Cardiovascular Effects of Inhalational Anesthetics :

Brief episodes of ischemia render the heart more resistant to subsequent ischemia; this phenomenon has been called ischemic preconditioning. In some animal species, myocardial preconditioning appears to be due to activation of ATP-sensitive K+ (KATP) channels. The role played by KATP channels in preconditioning in humans remains unknown. The aim of this study was to establish whether glibenclamide, a selective KATP channel blocker, abolishes the ischemic preconditioning observed in humans during coronary angioplasty following repeated balloon inflations. Twenty consecutive patients undergoing one-vessel coronary angioplasty were randomized to receive 10 mg oral glibenclamide or placebo. Sixty minutes after glibenclamide or placebo administration, patients were given an infusion of 10% dextrose (8 mL/min) to correct glucose plasma levels or, respectively, an infusion of saline at the same infusion rate. Thirty minutes after the beginning of the infusion, both patient groups underwent coronary angioplasty. The mean values (+/- 1 SD) of ST-segment shifts on the surface 12-lead ECG and the intracoronary ECG were measured at the end of the first and second balloon inflations, both 2 minutes long. In glibenclamide-treated patients, the mean ST-segment shift during the second balloon inflation was similar to that observed during the first inflation (23 +/- 13 versus 20 +/- 8 mm, P = NS), and the severity of cardiac pain was greater (55 +/- 21 versus 43 +/- 23 mm on a scale of 0 to 100, P < .05). Conversely, in placebo-treated patients the mean ST-segment shift during the second inflation was less than that during the first inflation (9 +/- 5 versus 23 +/- 13 mm, P < .001), as was the severity of cardiac pain (15 +/- 15 versus 42 +/- 19 mm, P < .01). Blood glucose levels were significantly reduced 60 minutes after glibenclamide compared with those at baseline (53 +/- 9 versus 102 +/- 10 mg/100 mL, P < .001) in the glibenclamide group; however, before coronary angioplasty, blood glucose levels increased to 95 +/- 19 mg/100 mL, a value similar to that found in placebo group (96 +/- 11 mg/100 mL, P = NS). In humans, ischemic preconditioning during brief repeated coronary occlusions is completely abolished by pretreatment with glibenclamide, thus suggesting that it is mainly mediated by KATP channels.

The influence of anesthetic agents on the infarction process in the ischemic myocardium is unclear. This study evaluated the effects of three intravenous and three inhalational anesthetic agents on myocardial infarction within a quantified ischemic risk zone in rabbit hearts subjected to a standardized regional ischemia-reperfusion insult. Both in vitro and in situ rabbit models were used to investigate the effects of anesthetic agents on infarct size. In all rabbits the heart was exposed and a coronary artery surrounded with a suture to form a snare for subsequent occlusion. In in situ preparations, both intravenous and inhalational agents were tested, whereas only the latter were used in isolated hearts. Infarct size was determined by triphenyltetrazolium chloride staining. To determine whether an adenosine-mediated protective mechanism was involved, 8-(p-sulfophenyl)theophylline, an adenosine receptor blocker, was added to halothane-treated isolated hearts. Adenosine concentration in the coronary effluent was also measured in isolated hearts exposed to halothane. In other protocols, chelerythrine, a highly selective protein kinase C inhibitor, was administered to both halothane-treated and untreated isolated hearts. Infarcts in the three in situ groups anesthetized with halothane, enflurane, and isoflurane were about one half as large as infarcts in rabbits that underwent anesthesia with pentobarbital, ketamine-xylazine, or propofol. Volatile anesthetics also protected isolated hearts by a similar amount. Both adenosine receptor blockade and chelerythrine abolished cardioprotection from halothane in isolated hearts. Halothane treatment did not increase adenosine release. The volatile anesthetics tested protected the ischemic rabbit heart from infarction, in contrast to the three intravenous agents tested. Protection was independent of the hypotensive effect of the inhalational agents because halothane also protected isolated hearts, in which changing vascular tone is not an issue and coronary perfusion pressure is constant. Cardioprotection by volatile anesthetics depended on both adenosine receptors and protein kinase C, and thus is similar to the mechanism of protection seen with ischemic preconditioning.

Following brief periods (5-15 min) of total coronary artery occlusion and subsequent reperfusion, despite an absence of tissue necrosis, a decrement in contractile function of the postischemic myocardium may nevertheless be present for prolonged periods. This has been termed "stunned" myocardium to differentiate the condition from ischemia or infarction. Because the influence of volatile anesthetics on the recovery of postischemic, reperfused myocardium has yet to be studied, the purpose of this investigation was to compare the effects of halothane and isoflurane on systemic and regional hemodynamics following a brief coronary artery occlusion and reperfusion. Nine groups comprising 79 experiments were completed in 42 chronically instrumented dogs. In awake, unsedated dogs a 15-min coronary artery occlusion resulted in paradoxical systolic lengthening in the ischemic zone. Following reperfusion active systolic shortening slowly returned toward control levels but remained approximately 50% depressed from control at 5 h. In contrast, dogs anesthetized with halothane or isoflurane (2% inspired concentration) demonstrated complete recovery of function 3-5 h following reperfusion. Because the anesthetics directly depressed contractile function, additional experiments were conducted in which a 15-minute coronary artery occlusion was produced during volatile anesthesia; however, each animal was allowed to emerge from the anesthetized state at the onset of reperfusion. Similar results were obtained in these experiments, demonstrating total recovery of contractile function within 3-5 h following reperfusion. Thus, despite comparable degrees of contractile dysfunction during coronary artery occlusion in awake and anesthetized dogs, the present results demonstrate that halothane and isoflurane produce marked improvement in the recovery of segment function following a transient ischemic episode. Therefore, volatile anesthetics may attenuate postischemic left ventricular dysfunction occurring intraoperatively and enhance recovery of regional wall motion abnormalities during reperfusion.