Sevoflurane-mediated modulation of oxidative myocardial injury.

Introduction: Volatile anesthetics offer protection when administered throughout an ischemic injury. We examined how volatile anesthetics modulate the cardiac myocytic injury associated with hydrogen peroxide. Methods: Forty-eight Long-Evans rats were divided into four groups depending on the treatment: none (CONT), Glibenclamide (GLB); Sevoflurane (SEV); or GLB+SEV. Each group was further divided into two, one of which was exposed to hydrogen peroxide (H2O2). Oral GLB was administered 48 hours before myocardial isolation. All rats were anesthetized by intraperitoneal injection of Ketamine, and the hearts were harvested after heparinization. Cardiomyocytes were isolated using a combination of mechanical mincing and enzymatic digestion. After isolation, the aliquots of cells were exposed to H2O2 and FeSO4 for 30 minutes. The cell suspensions were then bubbled for 10 minutes with 100% oxygen and 1.5% SEV if appropriate. Apoptosis was detected by fluorescein-bound annexin-V (ANX-V), necrosis by propidium iodide, and ELISA assessed caspase-3 activity in all groups. Results: There was an increase in apoptosis, necrosis, and caspase-3 activity in the cells following exposure to hydrogen peroxide. SEV reduced the rate of cell necrosis and apoptosis. Pretreatment with GLB did not alter the effects of SEV. Similarly, caspase-3 activity did not change with GLB, although SEV administration reduced this enzymatic activity in response to hydrogen peroxide. Conclusion: In this oxidant injury model, we demonstrated that incubating isolated cardiomyocytes with SEV profoundly diminished H2O2-induced apoptotic and necrotic cells compared to their CONTs. These results support the hypothesis that KATP channels are not the sole mediators associated with anesthetic preconditioning.

The comparative myocardial protection by propofol and isoflurane in an in vivo model of ischemia reperfusion.

BACKGROUND: Anesthetic Agents protect the heart from ischemic injury during perioperative period. We evaluated the protective effects of 2 anesagents on myocardial ischemia -reperfusion injury in rabbit models. METHODS: 58 anesthetized and mechaniventilated rabbits randomly received isoflurane (ISO) 2%, propofol (PRP), or were observed as the control group for 15 minutes. We applied vascular tourniquet around the left anterior descending artery (LAD). Myocardium was reperfused for 4 hours. Derivative of pressure over time (dP/dT(max)), left ventricular pressure (dLVP), isovolumetric relaxation time (Tau), and segment shortening (SS) were measured over the ischemic and non-ischemic regions of left ventricle (LV). Cardiac troponin I (cTnI), tissue concentrations of tumor necrosis factor á (TNFá), myeloperoxidase activity assay (MPO), and tissue malonyl dialdehyde (MDA) concentrations were measured as indices of cellular injury and inflammatory response. RESULTS: dP/dT(max) values significantly decreased during ischemia. Following reperfusion, dP/dT(max), dLVP, and Tau remained depressed in the control animals. Both PRP and ISO restored the function of the myocardium globally. CONCLUSION: Only ISO improved the recovery of the ischemic myocardium during reperfusion. The effects of PRP were global in nature and involved compensatory hypercontractile state in nonischemic regions of the myocardium. Implication. PRP and ISO protect the heart against an ischemic injury, but only ISO preserves the function of the myocardium at the ischemic region. The survival rate of the PRP-treated group versus the ISO-treated group supports the claim that PRP has smaller contribution to recovery from myocardial ischemia.

Anesthetic myocardial protection with sevoflurane.

OBJECTIVE: To examine the role of sevoflurane in myocardial protection in patients undergoing coronary artery bypass graft (CABG) surgery. DESIGN: Prospective, randomized, controlled, double-blinded study. SETTING: Veterans Administration Medical Center (VAMC), Buffalo, New York. SUBJECTS: Twenty-one patients undergoing CABG were included in the study. Eleven patients were randomized to receive sevoflurane, and 10 patients served as controls. INTERVENTION: Total intravenous anesthesia was provided for both study and control groups by infusion of propofol, fentanyl, and midazolam. Sevoflurane 2% was added to the cardioplegia solution in the experimental group. MEASUREMENTS AND MAIN RESULTS: Neutrophil beta-integrins (CD11b/CD18), tumor necrosis factor alpha (TNF-alpha), and interleukin (IL)-6 were measured as indicators of the inflammatory response to myocardial ischemia-reperfusion injury. Blood samples were obtained from the aorta and coronary sinus before (T1) and immediately after cardiopulmonary bypass (CPB) (T2) and, in addition, from a peripheral artery 6 hours (T3) after CPB. Myocardial function was determined in all patients at each time point. Left ventricular stroke work index (LVSWI) was calculated as an estimation of left ventricular function. Left ventricular regional wall motion abnormality (RWMA) was assessed by transesophageal echocardiography at T1 and T2 time points. TNF-alpha was detectable only in the control group in arterial samples at T3. IL-6 levels (pg/mL) were found to be lower in the sevoflurane group compared with controls at T2 arterial circulation (38.2 +/- 21.1 v 60.6 +/- 19.1, p < 0.05) as well as in the coronary circulation (38.4 +/- 19.9 v 118.2 +/- 23.5, p < 0.01) at T2. CD11b/CD18 increased 79% after CPB in the control group while only increasing 36% in the sevoflurane group (p < 0.05). The post-CPB LVSWI was back to its baseline values in the sevoflurane group, whereas it was still significantly depressed in the control group. Eight of 10 patients in the control group showed a transient new-onset RWMA in either the septal or anteroseptal regions. Only 2 of 11 patients in the sevoflurane group showed transient RWMA of the LV. CONCLUSIONS: Sevoflurane decreases the inflammatory response after CPB, as measured by the release of IL-6, CD11b/CD18, and TNF-alpha. Myocardial function after CPB, as assessed by RWMA and LVSWI, was also improved with sevoflurane. The role of sevoflurane in myocardial protection and the inflammatory response to myocardial reperfusion should be considered.