Anesthesia and analgesia
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Anesthesia and analgesia · Aug 1998
Modifications of the inotropic responses to alpha- and beta-adrenoceptor stimulation by propofol in rat myocardium.
Propofol induces cardiovascular depression but without significant effect on intrinsic myocardial contractility in many species. However, its interactions with adrenoceptor stimulation are unknown. We studied the effects of propofol (1 and 10 microg/mL) and its solvent on the inotropic response induced by phenylephrine (10(-8)-10(-4) M) or isoproterenol (10(-8)-10(-4) M) in rat left ventricular papillary muscles in vitro (Krebs-Henseleit solution, 29 degrees C, pH 7.40, calcium 0.5 mM, stimulation frequency 12 pulses/min). We also studied the lusitropic effects in isotonic and isometric conditions. In control groups, phenylephrine (127% +/- 3% of baseline; P < 0.05) and isoproterenol (169% +/- 11% of baseline; P < 0.05) induced a positive inotropic effect. Propofol (10 microg/mL) completely abolished the positive inotropic effect of phenylephrine (100% +/- 3% of baseline; P = not significant). In contrast, at the lowest concentration (1 microg/mL), propofol did not modify the positive inotropic effect of phenylephrine. Propofol did not modify the inotropic effect of isoproterenol. Propofol (10 microg/mL) enhanced the positive lusitropic effect of isoproterenol under low-load (P < 0.05) but not under high-load conditions. ⋯ A high concentration of propofol abolished the positive inotropic effect of alpha- but not beta-adrenoceptor stimulation and enhanced the positive lusitropic effect of beta-adrenoceptor stimulation.
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Anesthesia and analgesia · Aug 1998
Involvement of nitric oxide in peripheral antinociception mediated by kappa- and delta-opioid receptors.
Nitric oxide (NO) has been reported to enhance the analgesic effect of the peripherally administered mu-opioid receptor agonists, but the role of NO on the analgesic effect of the peripherally administered kappa and delta opioid receptor agonists is still unclear. We examined the effects of peripherally applied kappa- and delta-opioid receptor agonists and of their interactions with the NO-releasing drug, FK409, on the behavioral response to intraplantar injection of formalin in rats (the formalin test). The formalin injection results in a biphasic appearance of agitation behavior, consisting of the early (Phase 1; 0-9 min) and late (Phase 2; 10-60 min) responses. The active enantiomer of kappa-opioid receptor agonist, (-)U50,488H, dose-dependently suppressed the agitation response in both phases of the formalin test when applied peripherally. A peripheral delta-opioid receptor agonist, [D-Pen(2,5)] enkephalin (DPDPE), suppressed only Phase 2 of the formalin test. Local application of FK409 after the administration of a subthreshold dose of each opioid resulted in a dose-dependent decrease in the Phase 1, but not Phase 2, response to the formalin test for both agonists. Interactions between peripheral opioids and FK409 were reversed with both naloxone and carboxy-PTIO (NO scavenger). Systemic injections of either a kappa- or delta-agonist had no interaction with peripherally applied FK409. Peripheral FK409 alone did not have any significant effect on the formalin test. These data indicate that the antinociceptive effects of peripherally applied kappa- and delta-opioid agonists on the formalin test are potentiated by the local action of NO. ⋯ The analgesic effects of peripherally applied kappa- and delta-opioid receptor agonists during inflammation induced by formalin injection in the rat are, at least partly, mediated by the NO-cGMP pathway.
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Anesthesia and analgesia · Jul 1998
Randomized Controlled Trial Clinical TrialPulmonary effects of methylprednisolone in patients undergoing coronary artery bypass grafting and early tracheal extubation.
Numerous clinical studies suggest that methylprednisolone may facilitate early tracheal extubation after cardiac surgery, yet no investigation has rigorously examined the use of the drug in this setting. In this prospective, randomized, double-blind, placebo-controlled study, we examined the pulmonary effects of methylprednisolone in patients undergoing coronary artery bypass grafting (CABG) and early tracheal extubation. Sixty patients undergoing elective CABG and early tracheal extubation were randomized into two groups. Group MP patients received i.v. methylprednisolone (30 mg/kg during sternotomy and 30 mg/kg during initiation of cardiopulmonary bypass) and Group NS patients received i.v. placebo at the same two times. Perioperative management was standardized. Alveolar-arterial (A-a) oxygen gradient, lung compliance, shunt, and dead space were determined four times perioperatively. Postoperative tracheal extubation was accomplished at the earliest appropriate time. Both groups exhibited significant postoperative increases in A-a oxygen gradient and shunt (P < 0.000001 for each group) and significant postoperative decreases in dynamic lung compliance (P < 0.000001 for each group). Patients in Group MP exhibited significantly larger increases in postoperative A-a oxygen gradient (P = 0.001) and shunt (P = 0.001) compared with patients in Group NS. Postoperative alterations in dynamic lung compliance, static lung compliance, and dead space were not statistically significant between the groups. The time to postoperative tracheal extubation was prolonged in Group MP patients compared with Group NS patients (769 +/- 294 vs 604 +/- 315 min, respectively; P = 0.05). Methylprednisolone was associated with larger increases in postoperative A-a oxygen gradient and shunt, was unable to prevent postoperative decreases in lung compliance, and prolonged extubation time, which indicate that use of the drug may hinder early tracheal extubation in patients after cardiac surgery. ⋯ Traditionally, methylprednisolone has been administered to patients undergoing cardiac surgery to decrease postoperative pulmonary dysfunction. This study revealed that the drug is associated with larger increases in postoperative alveolar-arterial oxygen gradient and shunt and prolonged tracheal extubation time in patients undergoing coronary artery bypass grafting, which indicate that use of the drug may hinder early tracheal extubation.