propofol与肺血管

propofol与肺血管 : Am J Vet Res. 2003 Jul;64(7):913-7. Related Articles, Links Cardiovascular effects of propofol alone and in combination with ketamine for total intravenous anesthesia in cats. Ilkiw JE, Pascoe PJ. Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. OBJECTIVE: To compare cardiovascular effects of equipotent infusion doses of propofol alone and in combination with ketamine administered with and without noxious stimulation in cats. ANIMALS: 6 cats. PROCEDURE: Cats were anesthetized with propofol (loading dose, 6.6 mg/kg; constant rate infusion [CRI], 0.22 mg/kg/min) and instrumented for blood collection and measurement of blood pressures and cardiac output. Cats were maintained at this CRI for a further 60 minutes, and blood samples and measurements were taken. A noxious stimulus was applied for 5 minutes, and blood samples and measurements were obtained. Propofol concentration was decreased to 0.14 mg/kg/min, and ketamine (loading dose, 2 mg/kg; CRI, 23 microg/kg/min) was administered. After a further 60 minutes, blood samples and measurements were taken. A second 5-minute noxious stimulus was applied, and blood samples and measurements were obtained. RESULTS: Mean arterial pressure, central venous pressure, pulmonary arterial occlusion pressure, stroke index, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, oxygen delivery index, oxygen consumption index, oxygen utilization ratio, partial pressure of oxygen in mixed venous blood, pH of arterial blood, PaCO2, arterial bicarbonate concentration, and base deficit values collected during propofol were not changed by the addition of ketamine and reduction of propofol. Compared with propofol, ketamine and reduction of propofol significantly increased mean pulmonary arterial pressure and venous admixture and significantly decreased PaO2. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of propofol by CRI for maintenance of anesthesia induced stable hemodynamics and could prove to be clinically useful in cats. PMID: 12856778 [PubMed - in process] : Anesth Analg. 2003 Jun;96(6):1589-97, table of contents. Related Articles, Links The contribution of the coronary concentrations of propofol to its cardiovascular effects in anesthetized sheep. Zheng D, Upton RN, Martinez AM. Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital/University of Adelaide, North Terrace, Adelaide, Australia. da.zheng@adelaide.edu.au Linking physiological pharmacokinetic models to models of the cardiovascular system requires knowledge of the sites in the body that mediate a drug's cardiovascular effects. We examined the role of the coronary concentrations of propofol. Nine sheep anesthetized with isoflurane (2%) were instrumented acutely for cardiovascular measurements. In a random crossover design, they were administered ramped coronary artery (CA) infusions of propofol to selectively enrich the myocardium (as indicated by the coronary sinus blood concentration) or IV infusions to achieve the same concentration range in all sites of the body. Reductions in left ventricular myocardial contractility (LV dP/dt(max)) and mean arterial blood pressure were linearly related to the propofol concentration. For the CA route, LV dP/dt(max) was reduced by 52 mm Hg/s for each milligram per liter increase in coronary sinus propofol concentration. For the IV route, the reduction in LV dP/dt(max) was equivalent to that with the CA route, showing that the coronary propofol concentration was the major contribution to this effect. For the CA route, mean arterial blood pressure was reduced by 0.6 mm Hg for each milligram per liter. There was a larger reduction (2.5 mm Hg x mg(-1) x L(-1)) for the IV route. Therefore, this effect was predominantly mediated by propofol concentrations elsewhere in the body. IMPLICATIONS: With use of selective coronary artery infusions in sheep, the coronary concentrations of propofol were shown to be the major contributor to the cardiac depression caused by propofol but were a less significant contributor to the hypotension caused by this drug. Models of the cardiovascular effects of propofol should account for these relationships. PMID: 12760980 [PubMed - indexed for MEDLINE] : Anesthesiology. 2002 Dec;97(6):1557-66. Related Articles, Links Propofol increases pulmonary artery smooth muscle myofilament calcium sensitivity: role of protein kinase C. Tanaka S, Kanaya N, Homma Y, Damron DS, Murray PA. Center for Anesthesiology Research FF40, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. BACKGROUND: Vascular smooth muscle tone is regulated by changes in intracellular free Ca2+ concentration ([Ca2+]i) and myofilament Ca2+ sensitivity. These cellular mechanisms could serve as targets for anesthetic agents that alter vasomotor tone. This study tested the hypothesis that propofol increases myofilament Ca2+ sensitivity in pulmonary artery smooth muscle (PASM) via the protein kinase C (PKC) signaling pathway. METHODS: Canine PASM strips were denuded of endothelium, loaded with fura-2/AM, and suspended in modified Krebs-Ringer's buffer at 37 degrees C for simultaneous measurement of isometric tension and [Ca2+]i. RESULTS: The KCl (30 mm) induced monotonic increases in [Ca2+]i and tension. Verapamil, an L-type Ca2+ channel blocker, attenuated KCl-induced increases in [Ca2+]i and tension to an equal extent. In contrast, propofol attenuated KCl-induced increases in [Ca2+]i to a greater extent than concomitant changes in tension and caused an upward shift in the peak tension-[Ca2+]i relation. Increasing extracellular Ca2+ in the presence of 30 mM KCl resulted in similar increases in [Ca2+]i in control and propofol-pretreated strips, whereas concomitant increases in tension were greater during propofol administration. The Ca2+ ionophore, ionomycin (0.1 microm), increased [Ca2+]i to approximately 50% of the value induced by 60 mm KCl. Under these conditions, propofol (10, 100 microm) caused increases in tension equivalent to 11 +/- 2 and 28 +/- 3% of the increases in tension in response to 60 mM KCl, whereas [Ca2+]i was slightly decreased. Similar effects were observed in response to the PKC activator, phorbol 12-myristate 13-acetate (PMA, 1 microm). Specific inhibition of PKC with bisindolylmaleimide I before ionomycin administration decreased the propofol- and PMA-induced increases in tension and abolished the propofol- and PMA-induced decreases in [Ca2+]i. Selective inhibition of Ca2+ -dependent PKC isoforms with Go 6976 also attenuated propofol-induced increases in tension. CONCLUSION: These results suggest that propofol increases myofilament Ca2+ sensitivity in PASM, and this effect involves the PKC signaling pathway.PMID: 12459685 [PubMed - indexed for MEDLINE] : Clin Exp Pharmacol Physiol. 2002 Nov;29(11):1015-7. Related Articles, Links Propofol differently alters vascular reactivity in normotensive and hypertensive rats. Samain E, Clichet A, Bouillier H, Chamiot-Clerc P, Safar M, Marty J, Renaud JF.Department of Medical Research, CNRS ESA 8078, Marie Lannelongue Hospital, University of Paris, Le Plessis-Robinson, France. emmanuel.samain@bjn.ap-hop-paris.fr1. The effect of propofol on arterial tone in hypertension is poorly understood. We examined the effect of increasing concentrations of propofol (5.6 x 10-8 to 2.8 x 10-3 mol/L) on isometric tension developed by noradrenaline (10-7 mol/L)-contracted aortic rings from 12-week-old Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. In both WKY rats and SHR, propofol induced a dose-dependent inhibition of contraction induced by noradrenaline, but the amplitude of relaxation was larger in the SHR than in WKY rats. 3. The effects of propofol was endothelium independent in WKY rats, whereas in SHR relaxation induced by propofol was greater in endothelium-intact than in endothelium-denuded rings. 4. In conclusion, we found significant differences in the effect of propofol in hypertensive rats, which may be related to differences in structural and functional properties of the arterial wall observed in hypertension. PMID: 12366394 [PubMed - indexed for MEDLINE] : Acta Anaesthesiol Scand. 2002 May;46(5):481-7. Related Articles, Links Comment in: Acta Anaesthesiol Scand. 2002 May;46(5):479-80.• Microvascular changes during anesthesia: sevoflurane compared with propofol. Bruegger D, Bauer A, Finsterer U, Bernasconi P, Kreimeier U, Christ F.Clinic for Anesthesiology, Ludwig Maximilians University Munich, Germany.BACKGROUND: We have developed a non-invasive computer-assisted venous congestion plethysmograph to measure the microvascular parameters in the lower limbs. This enables the assessment of microvascular changes following the induction of standardized anesthesia with either sevoflurane or propofol. METHODS: In a prospective randomized trial we measured the capillary filtration coefficient (CFC), isovolumetric venous pressure (Pvi), an index of the balance of Starling forces, and limb blood flow 24 h preoperatively, immediately after induction of anesthesia and on the 1st and 2nd postoperative day. Anesthesia was maintained with either 1.0% sevoflurane and 5 microg/kg/h remifentanil or propofol (3 mg/kg/h), and 5 microg/kg/h remifentanil in 20 female patients undergoing breast surgery. RESULTS: Preoperatively we found no significant differences between the mean CFC values of the sevoflurane group (3.7+/-0.3 ml/min 100 ml tissue/mmHg x 10-3=CFCU) and the propofol group (3.5+/-0.3 CFCU). In the sevoflurane group CFC decreased significantly to 2.9+/-0.2 CFCU, whereas it was unchanged in the propofol group. Both groups revealed a significant reduction in Pvi during steady-state anesthesia. Limb blood flow remained unchanged. There was an overall significant positive correlation between the perioperative fluid substitution and the difference between the preoperative and intraoperative CFC values (r = 0.64, P<0.01). CONCLUSION: The decreased CFC in response to sevoflurane may result in less extravasation of fluids into the interstitial space, thereby reducing intraoperative fluid requirements. These data suggest that sevoflurane may be the preferred anesthetic agent in subjects susceptible to large intraoperative fluid shifts. Publication Types: Clinical Trial • Randomized Controlled Trial • PMID: 12027839 [PubMed - indexed for MEDLINE] : Anesthesiology. 2002 Mar;96(3):688-98. Related Articles, Links Propofol attenuates beta-adrenoreceptor-mediated signal transduction via a protein kinase C-dependent pathway in cardiomyocytes. Kurokawa H, Murray PA, Damron DS. Center for Anesthesiology Research, Division of Anesthesiology and Critical Care Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.BACKGROUND: Activation of beta adrenoreceptors by catecholamines is an important mechanism for increasing the inotropic state of the heart. The objectives of the current study were to investigate the effects of propofol on beta-adrenoreceptor-mediated increases in cardiomyocyte intracellular Ca2+ concentration ([Ca2+]i), cell shortening, L-type Ca2+ current (ICa) and cyclic adenosine monophosphate (cAMP) accumulation. The authors also investigated the site of action of propofol in the beta-adrenoreceptor signaling pathway, as well as the role of protein kinase C (PKC), and tested the hypothesis that propofol would inhibit the beta-adrenoreceptor signaling pathway via a PKC-dependent mechanism. METHODS: Freshly isolated ventricular myocytes were obtained from adult rat and guinea pig hearts. Myocyte shortening (video edge detection) and [Ca2+]i (fura-2, 340/380 ratio) were monitored simultaneously in individual cells. Conventional whole cell patch clamp analysis was used to measure the ICa in individual myocytes. cAMP production was assessed in suspensions of myocytes using an enzyme immunoassay kit. RESULTS: Propofol (0.1-10 mum) had no effect on steady state [Ca2+]i, cell shortening, ICa, or cAMP production. In contrast, propofol caused dose-dependent decreases in isoproterenol-stimulated increases in [Ca2+]i, shortening, ICa, and cAMP. Forskolin-induced increases in [Ca2+]i, shortening, and cAMP production were not altered by propofol. PKC activation with phorbol myristate acetate attenuated isoproterenol-stimulated cAMP production. Inhibition of PKC with bisindolylmaleimide (broad range inhibitor) or Go 6976 (inhibitor of Ca2+-dependent PKC isoforms) abolished propofol-induced inhibition of isoproterenol-stimulated increases in [Ca2+]i, shortening, and cAMP production. CONCLUSIONS: Clinically relevant concentrations of propofol attenuate beta-adrenergic signal transduction in cardiac myocytes via inhibition of cAMP production. The inhibitory site of action of propofol is upstream of adenylyl cyclase and involves activation of PKC alpha. PMID: 11873046 [PubMed - indexed for MEDLINE] : Anesthesiology. 2001 Sep;95(3):699-707. Related Articles, Links Myocardial and coronary effects of propofol in rabbits with compensated cardiac hypertrophy. Ouattara A, Langeron O, Souktani R, Mouren S, Coriat P, Riou B. Department of Anesthesiology, Centre Hospitalier Universitaire La Miletrie, Poitiers, France. BACKGROUND: Myocardial effects of propofol have been previously investigated but most studies have been performed in healthy hearts. This study compared the cardiac effects of propofol on isolated normal and hypertrophic rabbits hearts. METHODS: The effects of propofol (10-1,000 microM) on myocardial contractility, relaxation, coronary flow and oxygen consumption were investigated in hearts from rabbits with pressure overload-induced left ventricular hypertrophy (LVH group, n = 20) after aortic abdominal banding and from sham-operated control rabbits (SHAM group, n = 10), using an isolated and erythrocyte-perfused heart model. In addition, to assess the myocardial and coronary effects of propofol in more severe LVH, hearts with a degree of hypertrophy greater than 140% were selected (severe LVH group, n = 7). RESULTS: The cardiac hypertrophy model induced significant left ventricular hypertrophy (136+/-21%, P < 0.05). The pressure-volume relation showed normal systolic function but an altered diastolic compliance in hypertrophic hearts. Propofol only decreased myocardial contractility and relaxation at supratherapeutic concentrations (> or = 300 microM) in SHAM and LVH groups. The decrease in myocardial performances was not significantly different in SHAM and LVH groups. Propofol induced a significant increase in coronary blood flow which was not significantly different between groups. In severe LVH group, the degree of hypertrophy reached to 157+/-23%. Similarly, the effects of concentrations of propofol were not significantly different from the SHAM group. CONCLUSIONS: Propofol only decreased myocardial function at supratherapeutic concentrations. The myocardial and coronary effects of propofol were not significantly modified in cardiac hypertrophy.PMID: 11575544 [PubMed - indexed for MEDLINE] : Anesthesiology. 2001 Jun;94(6):1096-104. Related Articles, Links Propofol increases myofilament Ca2+ sensitivity and intracellular pH via activation of Na+-H+ exchange in rat ventricular myocytes. Kanaya N, Murray PA, Damron DS. Center for Anesthesiology Research, Division of Anesthesiology and Critical Care Medicine, The Cleveland Clinic Foundation, Ohio 44195, USA. BACKGROUND: The objectives were to determine the extent and mechanism of action by which propofol increases myofilament Ca2+ sensitivity and intracellular pH (pHi) in ventricular myocytes. METHODS: Freshly isolated adult rat ventricular myocytes were used for the study. Cardiac myofibrils were extracted for assessment of myofibrillar actomyosin adenosine triphosphatase (ATPase) activity. Myocyte shortening (video edge detection) and pHi (2',7'-bis-(2-carboxyethyl)-5(6')-carboxyfluorescein, 500/440 ratio) were monitored simultaneously in individual cells field-stimulated (0.3 Hz) and superfused with HEPES-buffered solution (pH 7.4, 30 degrees C). RESULTS: Propofol (100 microM) reduced the Ca2+ concentration required for activation of myofibrillar actomyosin ATPase from pCa 5.7 +/- 0.01 to 6.6 +/- 0.01. Increasing pHi (7.05 +/- 0.03 to 7.39 +/- 0.04) with NH4Cl increased myocyte shortening by 35 +/- 12%. Washout of NH4Cl decreased pHi to 6.82 +/- 0.03 and decreased myocyte shortening to 52 +/- 10% of control. Propofol caused a dose-dependent increase in pHi but reduced myocyte shortening. The propofol-induced increase in pHi was attenuated, whereas the decrease in myocyte shortening was enhanced after pretreatment with ethylisopropyl amiloride, a Na+-H+ exchange inhibitor, or bisindolylmaleimide I, a protein kinase C inhibitor. Propofol also attenuated the NH4Cl-induced intracellular acidosis, increased the rate of recovery from acidosis, and attenuated the associated decrease in myocyte shortening. Propofol caused a leftward shift in the extracellular Ca2+-shortening relation, and this effect was attenuated by ethylisopropyl amiloride. CONCLUSIONS: These results suggest that propofol increases the sensitivity of myofibrillar actomyosin ATPase to Ca2+ (ie., increases myofilament Ca2+ sensitivity), at least in part by increasing pHi via protein kinase C-dependent activation of Na+-H+ exchange. PMID: 11465603 [PubMed - indexed for MEDLINE] : Anesthesiology. 2001 May;94(5):833-9. Related Articles, Links Propofol potentiates phenylephrine-induced contraction via cyclooxygenase inhibition in pulmonary artery smooth muscle.Ogawa K, Tanaka S, Murray PA. Division of Anesthesiology and Critical Care Medicine, The Cleveland Clinic Foundation, Ohio 44195, USA. BACKGROUND: The authors previously demonstrated in vivo that the pulmonary vasoconstrictor response to the a agonist phenylephrine is potentiated during propofol anesthesia compared with the conscious state. The current in vitro study tested the hypothesis that propofol potentiates phenylephrine-induced contraction by inhibiting the synthesis and/or activity of vasodilator metabolites of the cyclooxygenase pathway. METHODS: Canine pulmonary arterial rings were suspended for isometric tension recording. Intracellular calcium concentration ([Ca2+]i) was measured in pulmonary arterial strips loaded with acetoxylmethyl ester of fura-2. After phenylephrine-induced contraction, propofol (10(-7) to 10(-4) M) was administered in the presence or absence of the cyclooxygenase inhibitor ibuprofen (10(-5) M). The effects of propofol on the arachidonic acid and prostacyclin relaxation-response curves were assessed. The amount of 6-keto prostaglandin F1alpha (stable metabolite of prostacyclin) released from pulmonary vascular smooth muscle in response to phenylephrine was measured with enzyme immunoassay in the presence or absence of propofol and ibuprofen. RESULTS: Propofol potentiated phenylephrine-induced contraction in pulmonary arterial rings in a concentration-dependent and endothelium-independent manner. In endothelium-denuded strips, propofol (10(-4) M) increased tension by 53+/-11%, and increased [Ca2+]i by 56+/-9%. Ibuprofen also potentiated phenylephrine-induced contraction but abolished the propofol-induced increases in tension and [Ca2+]i. Propofol had no effect on the relaxation response to prostacyclin, whereas propofol and ibuprofen attenuated the relaxation response to arachidonic acid to a similar extent. Phenylephrine markedly increased 6-keto prostaglandin F1alpha production, and this effect was virtually abolished by propofol and ibuprofen. CONCLUSION: These results suggest that propofol potentiates alpha-adrenoreceptor-mediated pulmonary vasoconstriction by inhibiting the concomitant production of prostacyclin by cyclooxygenase. PMID: 11388535 [PubMed - indexed for MEDLINE] : Anaesthesia. 2001 Mar;56(3):266-71. Related Articles, Links Cardiovascular effects of intravenous propofol administered at two infusion rates: a transthoracic echocardiographic study.Bilotta F, Fiorani L, La Rosa I, Spinelli F, Rosa G. Department of Anaesthesia and Intensive Care, Policlinico Umberto I, University La Sapienza, Rome, Italy. bilotta@tiscalinet.it We assessed the haemodynamic changes after a propofol infusion at two rates in low-risk unpremedicated patients (ASA I-II). To determine contractility changes and loading conditions, we measured the ejection fraction, end-systolic quotient and fractional shortening on transthoracic echocardiograms. We studied 40 patients undergoing peripheral neurosurgical procedures under general anaesthesia induced by propofol alone (total dose 2.5 mg.kg-1). Patients were randomly assigned to receive propofol at an infusion rate of 10 mg.s-1; or 2 mg.s-1. Haemodynamic data were recorded simultaneously immediately before propofol infusion, at the end of infusion, and 5 and 10 min after the infusion ended. The higher infusion rate induced a larger decrease in mean arterial pressure than the lower infusion rate (- 20% vs. - 10% from baseline, p = 0.01). In both groups, global and segmental ventricular function remained unchanged throughout the study. In both groups, there were markedly reduced end-systolic quotients--presumably related to diminished afterload, and in the higher infusion-rate group a significant reduction in fractional shortening--presumably related principally to diminished preload. Publication Types: •Clinical Trial •Randomized Controlled Trial PMID: 11251436 [PubMed - indexed for MEDLINE] : J Cardiothorac Vasc Anesth. 2002 Dec;16(6):709-14. Related Articles, Links A combination of intrathecal morphine and remifentanil anesthesia for fast-track cardiac anesthesia and surgery.Bowler I, Djaiani G, Abel R, Pugh S, Dunne J, Hall J. Department of Anesthesia, University Hospital of Wales, United Kingdom.OBJECTIVE: To determine if the combined remifentanil and intrathecal morphine (RITM) anesthetic technique facilitates early extubation in patients undergoing coronary artery bypass graft (CABG) surgery. DESIGN: Prospective, randomized, controlled clinical trial. SETTING: Referral center for cardiothoracic surgery at a university hospital. PARTICIPANTS: Patients (n = 24) undergoing first-time elective CABG surgery. INTERVENTIONS: Two groups represented RITM (n = 12) and fentanyl-based (controls, n = 12) anesthesia. Premedication was standardized to temazepam, 0.4 mg/kg, and anesthesia was induced with etomidate, 0.3 mg/kg, in both groups. The RITM group received remifentanil, 1 microg/kg bolus followed by 0.25 to 1 microg/kg/min infusion, and intrathecal morphine, 2 mg. The control group received fentanyl, 12 microg/kg in 3 divided doses. Anesthesia was maintained with isoflurane and pancuronium in both groups. After completion of surgery, the remifentanil infusion was stopped. Complete reversal of muscle relaxation was ensured with a nerve stimulator, and a propofol infusion, 0.5 to 3 mg/kg/h, was started in both groups. All patients were transferred to the intensive care unit (ICU) to receive standardized postoperative care. Intensivists and ICU nurses were blinded to the group assignment. Propofol infusion was stopped, and the tracheal extubation was accomplished when extubation criteria were fulfilled. MEASUREMENTS AND MAIN RESULTS: Both groups were similar with respect to demographic data and surgical characteristics. Extubation times were 156 +/- 82 minutes and 258 +/- 91 minutes in the RITM and control groups (p = 0.012). Patients in the RITM group exhibited lower visual analog scale pain scores during the first 2 hours after extubation (p < 0.04). Morphine requirements during the 24 hours after extubation were 2.5 +/- 3 mg in the RITM group and 16 +/- 11 mg in the control group (p = 0.0018). Sedation scores were lower in the RITM group during the first 3 hours after extubation (p < 0.03). Pulmonary function tests as assessed by spirometry were better in the RITM group at 6 and 12 hours after extubation (p < 0.04). There were no significant differences in PaO(2) and PaCO(2) after extubation between the 2 groups. None of the patients had episodes of apnea during the immediate 24-hour postextubation period. Two patients from the RITM group required reintubation on the second and sixth postoperative days. There were no differences in ICU and hospital length of stay between the 2 groups. CONCLUSION: Implementation of the RITM technique provided earlier tracheal extubation, decreased level of sedation, excellent analgesia, and improved spirometry in the early postoperative period. The impact of RITM on ICU and hospital length of stay and potential cost benefits require further evaluation. Copyright 2002, Elsevier Science (USA). All rights reserved. Publication Types: •Clinical Trial •Randomized Controlled Trial PMID: 12486651 [PubMed - indexed for MEDLINE] 1: Pediatr Cardiol. 2001 Nov-Dec;22(6):488-90. Epub 2001 Dec 04.Related Articles, Links Propofol does not modify the hemodynamic status of children with intracardiac shunts undergoing cardiac catheterization.Gozal D, Rein AJ, Nir A, Gozal Y. Department of Anesthesiology and Critical Care Medicine, Hadassah University Hospital and the Hebrew University School of Medicine, Post Office Box 12000, Jerusalem 91120, Israel. gozaly@mdz.huji.ac.il Immobility and cardiovascular stability are required for cardiac catheterization. Pediatric patients need a type of sedation that also allows spontaneous ventilation without supplemental oxygen. Propofol has been adequate in hemodynamically stable patients with congenital heart disease undergoing cardiac catheterization. However, mild systemic hypotension caused by propofol may increase a preexisting right-to-left shunt. The aim of this study is to evaluate, in pediatric patients scheduled for cardiac catheterization, the effects of propofol on systemic and pulmonic circulations. Fifteen patients aged 18 months to 9 years were studied. After a fast of 4-6 hours for solid food, the patient arrived at the cardiac catheterization suite, where an IV catheter was placed. Usual monitoring was used. For sedation, without supplemental oxygen, patients received 1 mg/kg of fentanyl followed by propofol (1-2 mg/kg) titrated to immobility during preparation of the groin. A continuous infusion of propofol (100 mg/kg/min) was also started to obtain immobility during the procedure. Hemodynamic data, including systemic venous, pulmonary artery and vein, aortic saturations, and pressures, were recorded; Qp and Qs were calculated. The same set of data was re-corded 4 minutes after discontinuation of propofol and when the patient was responding to tactile stimuli. Despite lower pressures during propofol infusion, as compared with those pressures measured after discontinuation of propofol, the extent of the intracardiac shunt remained unchanged. Propofol seems to be an adequate sedative agent for pediatric patients undergoing cardiac catheterization, including those with intracardiac shunts. PMID: 11894151 [PubMed - indexed for MEDLINE] : Hiroshima J Med Sci. 2001 Sep;50(3):61-4. Related Articles, Links Propofol relaxes extrapulmonary artery but not intrapulmonary artery through nitric oxide pathway. Tanaka H, Yamanoue T, Kuroda M, Kawamoto M, Yuge O. Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Hiroshima University, Japan. htank@hiroshima-u.ac.jp The object of this study was to compare vasorelaxing responses to propofol by the intrapulmonary artery (IPA) and the extrapulmonary artery (EPA), and to identify the mechanisms of action. Rat pulmonary arterial rings were isolated and suspended in organ chambers where isometric tension development was measured under optimal resting tension. All pulmonary arterial rings were pre-contracted with phenylephrine. Propofol (Diprivan) and the vehicle (10% Intralipid) were administered cumulatively in the presence or absence of N(omega)-nitro-L-arginine methyl ester (L-NAME). Sodium nitroprusside (SNP), a nitric oxide donor, was administered cumulatively. Propofol relaxed both EPA and IPA in a dose dependent manner (p<0.05), while the vehicle alone showed no effect. The vasorelaxing responses to propofol were significantly higher in EPA than IPA at higher concentrations (10(-4) M and 10(-4.5) M) (p<0.05), and were decreased by L-NAME in EPA (p<0.05), though it had no effect in IPA. The concentration for SNP causing 50% relaxation was not significantly different between the two arteries. We concluded that the response of smooth muscle to nitric oxide was the same between EPA and IPA; however, the vasorelaxing mechanisms of propofol seemed to be different between them at higher doses, suggesting that a mechanism exists and operates through the nitric oxide pathway. PMID: 11720164 [PubMed - indexed for MEDLINE] : Acta Anaesthesiol Scand. 2001 Sep;45(8):1006-10. Related Articles, Links Dose-response relationship of propofol on mid-latency auditory evoked potentials (MLAEP) in cardiac surgery. Palm S, Linstedt U, Petry A, Wulf H. Clinic for Anaesthesiology and Operative Intensive Care, Christian-Albrechts-University Kiel, Germany. palm@anaesthesie.uni-keil.de BACKGROUND: Propofol-sufentanil anaesthesia has become popular during cardiac surgery for its titrability and short recovery time. Avoidance of awareness is a major goal during cardiac surgery. We therefore investigated the dose-response relationship of propofol and cortical responses (mid-latency auditory evoked potentials, MLAEP). METHODS: One hundred patients undergoing cardiac surgery were investigated. Basic anaesthesia was performed with sufentanil (4.5 microg kg(-1) h(-1)) / flunitrazepam (9 microg kg(-1) h(-1)) infusion (control group); the other groups received in addition a loading dose of propofol 2 mg kg(-1) and a maintainance infusion of 1-3.5 mg kg(-1) h(-1). MLAEP were evaluated by using Pa/Nb-amplitudes and Nb-latencies. Haemodynamics were monitored by ECG, arterial blood pressure and cardiac function with pulmonary artery catheterization. RESULTS: In the control group, median amplitude of MLAEP decreased by 50% with a wide range, but were detectable in >90% of patients throughout surgery. Propofol suppressed amplitude Pa/Nb of MLAEP dose dependently. With 3.5 mg kg(-1) h(-1) amplitudes disappeared in >40% of patients throughout cardiac surgery. Median Nb-latencies increased in the control group from 44 to a range from 50 to 60 ms. In groups with propofol >2 mg kg(-1) h(-1), Nb-latencies, detectable in the patients without complete suppression of MLAEP, increased to median 60 ms. Haemodynamic parameters and cardiac function did not differ among the groups. The use of vasopressors was not increased even with the highest propofol dose used. CONCLUSION: The dose-response effect of propofol on auditory evoked potentials reveals that combining a loading dose of 2 mg kg-1 with a consecutive infusion of 3.5 mg kg(-1) h(-1) significantly suppresses MLAEP during cardiac surgery. Thus, auditory information may not be processed and awareness with recall becomes unlikely.PMID: 11576053 [PubMed - indexed for MEDLINE] Related Articles, Links 1: Anesthesiology. 2001 Sep;95(3):681-8. Propofol attenuates capacitative calcium entry in pulmonary artery smooth muscle cells. Horibe M, Kondo I, Damron DS, Murray PA. Center for Anesthesiology Research, Division of Anesthesiology and Critical Care Medicine, The Cleveland Clinic Foundation, Ohio 44195, USA. BACKGROUND: Depletion of intracellular Ca2+ stores results in capacitative Ca2+ entry (CCE) in pulmonary artery smooth muscle cells (PASMCs). The authors aimed to investigate the effects of propofol on CCE and to assess the extent to which protein kinase C (PKC) and tyrosine kinases mediate propofol-induced changes in CCE. METHODS: Pulmonary artery smooth muscle cells were cultured from explants of canine intrapulmonary artery. Fura 2-loaded PASMCs were placed in a dish (37 degrees C) on an inverted fluorescence microscope. Intracellular Ca2+ concentration was measured using fura 2 in PASMCs using a dual-wavelength spectrofluorometer. Thapsigargin (1 microM), a sarcoplasmic reticulum Ca2+-adenosine triphosphatase inhibitor, was used to deplete intracellular Ca2+ stores after removing extracellular Ca2+. CCE was activated when extracellular Ca2+ (2.2 mM) was restored. RESULTS: Thapsigargin caused a transient increase in intracellular Ca2+ concentration (182+/-11%). Restoring extracellular calcium (to induce CCE) resulted in a peak (246+/-12% of baseline) and a sustained (187+/-7% of baseline) increase in intracellular Ca2+ concentration. Propofol (1, 10, 100 microM) attenuated CCE in a dose-dependent manner (peak: 85+/-3, 70+/-4, 62+/-4%; sustained: 94+/-5, 80+/-5, 72+/-5% of control respectively). Tyrosine kinase inhibition (tyrphostin 23) attenuated CCE (peak: 67+/-4%; sustained: 74+/-5% of control), but the propofol-induced decrease in CCE was still apparent after tyrosine kinases inhibition. PKC activation (phorbol 12-myristate 13-acetate) attenuated CCE (peak: 48+/-1%; sustained: 53+/-3% of control), whereas PKC inhibition (bisindolylmaleimide) potentiated CCE (peak: 132+/-11%; sustained: 120+/-4% of control). Moreover, PKC inhibition abolished the propofol-induced attenuation of CCE. CONCLUSION: Tyrosine kinases activate and PKC inhibits CCE in PASMCs. Propofol attenuates CCE primarily via a PKC-dependent pathway. CCE should be considered a possible cellular target for anesthetic agents that alter vascular smooth muscle tone. PMID: 11575542 [PubMed - indexed for MEDLINE] : Anesthesiology. 2001 May;94(5):833-9. Related Articles, Links Propofol potentiates phenylephrine-induced contraction via cyclooxygenase inhibition in pulmonary artery smooth muscle.Ogawa K, Tanaka S, Murray PA. Division of Anesthesiology and Critical Care Medicine, The Cleveland Clinic Foundation, Ohio 44195, USA. BACKGROUND: The authors previously demonstrated in vivo that the pulmonary vasoconstrictor response to the a agonist phenylephrine is potentiated during propofol anesthesia compared with the conscious state. The current in vitro study tested the hypothesis that propofol potentiates phenylephrine-induced contraction by inhibiting the synthesis and/or activity of vasodilator metabolites of the cyclooxygenase pathway. METHODS: Canine pulmonary arterial rings were suspended for isometric tension recording. Intracellular calcium concentration ([Ca2+]i) was measured in pulmonary arterial strips loaded with acetoxylmethyl ester of fura-2. After phenylephrine-induced contraction, propofol (10(-7) to 10(-4) M) was administered in the presence or absence of the cyclooxygenase inhibitor ibuprofen (10(-5) M). The effects of propofol on the arachidonic acid and prostacyclin relaxation-response curves were assessed. The amount of 6-keto prostaglandin F1alpha (stable metabolite of prostacyclin) released from pulmonary vascular smooth muscle in response to phenylephrine was measured with enzyme immunoassay in the presence or absence of propofol and ibuprofen. RESULTS: Propofol potentiated phenylephrine-induced contraction in pulmonary arterial rings in a concentration-dependent and endothelium-independent manner. In endothelium-denuded strips, propofol (10(-4) M) increased tension by 53+/-11%, and increased [Ca2+]i by 56+/-9%. Ibuprofen also potentiated phenylephrine-induced contraction but abolished the propofol-induced increases in tension and [Ca2+]i. Propofol had no effect on the relaxation response to prostacyclin, whereas propofol and ibuprofen attenuated the relaxation response to arachidonic acid to a similar extent. Phenylephrine markedly increased 6-keto prostaglandin F1alpha production, and this effect was virtually abolished by propofol and ibuprofen. CONCLUSION: These results suggest that propofol potentiates alpha-adrenoreceptor-mediated pulmonary vasoconstriction by inhibiting the concomitant production of prostacyclin by cyclooxygenase. PMID: 11388535 [PubMed - indexed for MEDLINE] : Anesthesiology. 2001 May;94(5):815-23. Related Articles, Links Pulmonary vascular effects of propofol at baseline, during elevated vasomotor tone, and in response to sympathetic alpha- and beta-adrenoreceptor activation. Kondo U, Kim SO, Nakayama M, Murray PA. Division of Anesthesiology and Critical Care Medicine, The Cleveland Clinic Foundation, Ohio 44195, USA. BACKGROUND: This in vivo study had two primary objectives. The first goal was to determine whether the pulmonary vascular effects of propofol depend on the preexisting level of vasomotor tone, and the second was to investigate the effects of propofol on the pulmonary vascular responses to sympathetic alpha- and beta-adrenoreceptor activation. METHODS: Thirty-one mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LPQ) relation. Left lung autotransplantation (LLA) was also performed in eight additional dogs to induce a long-term increase in pulmonary vascular resistance. LPQ plots were measured on separate days in the conscious state and during propofol anesthesia. LPQ plots were measured at baseline and when vasomotor tone was acutely increased with the alpha agonist, phenylephrine, or the thromboxane mimetic, U46619. In separate experiments, cumulative dose-response curves to alpha- (phenylephrine) and beta- (isoproterenol) adrenoreceptor agonists were generated in conscious and propofol-anesthetized dogs. RESULTS: Compared with the conscious state, propofol had no effect on the baseline LPQ relation in normal or post-LLA dogs. However, propofol caused pulmonary vasoconstriction (P < 0.05) when vasomotor tone was acutely increased with either phenylephrine or U46619 in normal or post-LLA dogs. The pulmonary vasoconstrictor response to alpha-adrenoreceptor activation was potentiated (P < 0.05) during propofol anesthesia, whereas the pulmonary vasodilator response to beta-adrenoreceptor activation was not altered. CONCLUSION: These results indicate that the pulmonary vascular response to propofol anesthesia is tone-dependent. During sympathetic activation, propofol may favor alpha-adrenoreceptor-mediated vasoconstriction over beta-adrenoreceptor-mediated vasodilation. PMID: 11388533 [PubMed - indexed for MEDLINE] : Anesthesiology. 2000 Aug;93(2):447-55. Related Articles, Links Propofol attenuates acetylcholine-induced pulmonary vasorelaxation: role of nitric oxide and endothelium- derived hyperpolarizing factors. Horibe M, Ogawa K, Sohn JT, Murray PA. Center for Anesthesiology Research, Division of Anesthesiology and Critical Care Medicine, The Cleveland Clinic Foundation, OH 44195, USA. BACKGROUND: The mechanism by which propofol selectively attenuates the pulmonary vasodilator response to acetylcholine is unknown. The goals of this study were to identify the contributions of endogenous endothelial mediators (nitric oxide [NO], prostacyclin, and endothelium-derived hyperpolarizing factors [EDHFs]) to acetylcholine-induced pulmonary vasorelaxation, and to delineate the extent to which propofol attenuates responses to these endothelium-derived relaxing factors. METHODS: Canine pulmonary arterial rings were suspended for isometric tension recording. The effects of propofol on the vasorelaxation responses to acetylcholine, bradykinin, and the guanylyl cyclase activator, SIN-1, were assessed in phenylephrine-precontracted rings. The contributions of NO, prostacyclin, and EDHFs to acetylcholine-induced vasorelaxation were assessed in control and propofol-treated rings by pretreating the rings with a NO synthase inhibitor (l-NAME), a cyclooxygenase inhibitor (indomethacin), and a cytochrome P450 inhibitor (clotrimazole or SKF 525A) alone and in combination. RESULTS: Propofol caused a dose-dependent rightward shift in the acetylcholine dose-response relation, whereas it had no effect on the pulmonary vasorelaxant responses to bradykinin or SIN-1. Cyclooxygenase inhibition only attenuated acetylcholine-induced relaxation at high concentrations of the agonist. NO synthase inhibition and cytochrome P450 inhibition each attenuated the response to acetylcholine, and combined inhibition abolished the response. Propofol further attenuated acetylcholine-induced relaxation after NO synthase inhibition and after cytochrome P450 inhibition. CONCLUSION: These results suggest that acetylcholine-induced pulmonary vasorelaxation is mediated by two components: NO and a cytochrome P450 metabolite likely to be an EDHF. Propofol selectively attenuates acetylcholine-induced relaxation by inhibiting both of these endothelium-derived mediators. PMID: 10910495 [PubMed - indexed for MEDLINE] þÿþÿþÿþÿ Show: Write to the Help Desk NCBI | NLM | NIH Department of Health & Human Services Freedom of Information Act | Disclaimer Jul 17 2003 11:42:11 : Anesthesiology. 2000 Aug;93(2):437-46. Related Articles, Links Propofol selectively attenuates endothelium-dependent pulmonary vasodilation in chronically instrumented dogs.Kondo U, Kim SO, Murray PA. Center for Anesthesiology Research, Division of Anesthesiology and Critical Care Medicine, The Cleveland Clinic Foundation, OH 44195, USA. BACKGROUND: The objective was to investigate the effects of propofol anesthesia on the pulmonary vascular response to endothelium-dependent and -independent vasodilators, compared with the responses measured in the conscious state. METHODS: Twenty-six conditioned, male, mongrel dogs were instrumented long-term to measure the left pulmonary vascular pressure-flow relation. Pressure-flow plots were measured on separate days in conscious and propofol-anesthetized (5.0 mg/kg plus 0.5 mg. kg-1. min-1 intravenously) dogs at baseline, after preconstriction with the thromboxane mimetic U46619, and during the cumulative intravenous administration of endothelium-dependent (acetylcholine and bradykinin) and -independent (proline-nitric oxide) vasodilators. RESULTS: Propofol had no effect on the baseline pressure-flow relation compared with the conscious state. A lower (P < 0.05) dose of U46619 was necessary to achieve the same degree of preconstriction during propofol anesthesia. The pulmonary vasodilator responses to bradykinin and proline-nitric oxide were similar in the conscious and propofol-anesthetized states. In contrast, the pulmonary vasodilator response to acetylcholine was markedly attenuated (P < 0.01) during propofol anesthesia. The intralipid vehicle for propofol had no effect on the acetylcholine dose-response relation. CONCLUSION: These results suggest that propofol causes a specific defect in the signal transduction pathway for acetylcholine-induced pulmonary vasodilation. This defect involves the endothelial and not the vascular smooth muscle component of the response.PMID: 10910494 [PubMed - indexed for MEDLINE] : Anesth Analg. 1999 Dec;89(6):1411-6. Related Articles, Links The hemodynamic effects of propofol in children with congenital heart disease. Williams GD, Jones TK, Hanson KA, Morray JP. Department of Anesthesiology, University of Washington School of Medicine and Children's Hospital and Regional Medical Center, Seattle 98105, USA. We studied the hemodynamic effects of propofol during elective cardiac catheterization in 30 children with congenital heart disease. Sixteen patients were without cardiac shunt (Group I), six had left-to-right cardiac shunt (Group II), and eight had right-to-left cardiac shunt (Group III). The mean (+/-SD) ages were 3.8+/-3.1 yr (Group I), 3.2+/-3.7 yr (Group II), and 1.0+/-0.6 yr (Group III). After sedation and cardiac catheter insertion, hemodynamic data and oxygen consumption were measured before and after the administration of propofol (2-mg/kg bolus, 50- to 200-microg x kg(-1) x min(-1) infusion), and values were compared by using a paired t-test (significance: P < 0.05). After the propofol administration, systemic mean arterial pressure and systemic vascular resistance decreased significantly and systemic blood flow increased significantly in all patient groups; heart rate, pulmonary mean arterial pressure, and pulmonary vascular resistance were unchanged. Pulmonary to systemic resistance ratio increased (Group I, P = 0.005; Group II, P = 0.03; Group III, P = 0.10). In patients with cardiac shunt, propofol resulted in decreased left-to-right flow and increased right-to-left flow; the pulmonary to systemic flow ratio decreased significantly (Group II, P = 0.005; Group III, P = 0.01). Clinically relevant decreases in Pao2 (P = 0.008) and Sao2 (P = 0.01) occurred in Group III patients. We conclude that propofol can result in clinically important changes in cardiac shunt direction and flow. IMPLICATIONS: The principal hemodynamic effect of propofol in children with congenital heart defects is a decrease in systemic vascular resistance. In children with cardiac shunt, this results in a decrease in the ratio of pulmonary to systemic blood flow, and it can lead to arterial desaturation in patients with cyanotic heart disease. Publication Types: •Clinical Trial PMID: 10589618 [PubMed - indexed for MEDLINE] : Acta Anaesthesiol Scand. 1999 Apr;43(4):431-7. Related Articles, Links Responses to propofol in the pulmonary vascular bed of the rat.Kaye A, Anwar M, Banister R, Feng C, Turner K, Kadowitz P, Nossaman B. Department of Anesthesiology and Pharmacology, Tulane University Medical School, New Orleans, Louisiana, USA. BACKGROUND: Although a great deal is known about responses to propofol, controversy remains about its mechanism of action. The present study was undertaken to investigate the direct effects of 2,6-diisopropyl phenol, disodium edetate, and its intralipid emulsion in the rat pulmonary vascular bed and to better understand the mechanisms involved in propofol-mediated responses. METHODS: The effects of N omega-l-nitro-l-arginine benzyl ester (L-NABE), an inhibitor of nitric oxide synthase, of the cyclooxygenase blocker, meclofenamate, and the K + ATP channel antagonist, U-37883A, an ATP-sensitive potassium channel antagonist, on responses to propofol, acetylcholine, nitroglycerin, and isoproterenol were investigated in the isolated blood-perfused rat lung under low tone and high steady-state tone. RESULTS: Propofol produced a dose-dependent decrease in pulmonary arterial perfusion pressure. L-NABE significantly reduced vasodilator responses to acetylcholine, whereas the nitric oxide synthase inhibitor had no significant effect on responses to propofol. Meclofenamate significantly reduced vasodilator responses to arachidonic acid without effecting responses to propofol. Responses to propofol were not significantly changed in the presence of U-37883A, whereas U-37883A reduced vasodilator responses to levcromakalim. Additionally, 2,6-diisopropylphenol in a pure preparation as well as an intralipid preparation similar to propofol emulsion had no significant effect while disodium edetate had a dose-dependent depressor effect under high steady-state tone. CONCLUSION: Propofol has significant vasodilator activity in the pulmonary vascular bed of the rat but responses to propofol are not mediated or modulated by the release of nitric oxide, opening of K + ATP channels, or the release of vasodilator cyclooxygenase products. PMID: 10225077 [PubMed - indexed for MEDLINE]