PRETREATMENT WITH SEVOFLURANE IMPROVES HEART FUNCTION AFTER GLOBAL ISCHEMIA IN ISOLATED RAT HEART

Abstract

S88 INTRODUCTION: Ischemic preconditioning (IP) and some volatile anesthetics (halothane and isoflurane) have been shown to attenuate ischemia-reperfusion injury [1,2]. The aim of our study was to determine whether sevoflurane (Sevo) can cardio-protect isolated hearts when given before prolonged periods of global ischemia. METHODS: Following IACUC approval at the University of Utah, 15 male Sprague-Dawley rats (325-340g) were randomly assigned to 3 groups (n=5). The rats were anesthetized with 60mg/kg (ip) pentobarbital after which their hearts were removed, then perfused with a modified Krebs solution gassed with 7.5% CO2 balanced O (2) in a retrograde manner at a constant temperature (37[degree sign]C) and pressure (80mmHg). A latex balloon was placed into the left ventricle to obtain isovolumetric contraction. After 15 min of equilibration, each heart was randomly allocated to 1) IP group, two 5 min ischemic periods separated by 5 min of normal perfusion, 2) Sevo group, 20 min exposure to Sevo (1.7%, 1MAC), or 3) Control group, no pretreatment. Following pretreatment, each heart was exposed to a 20 min period of global normothermic ischemia, followed by 60min reperfusion. Left ventricular end diastolic pressure (LVEDP), ventricular peak systolic pressure (VPSP), left ventricular developed pressure (LVDP=VPSP-LVEDP), the first derivative of left ventricular pressure (+dp/dt), heart rate (HR), HRxLVDP, and perfusion flow were continuously recorded during the whole experiment. At the end of experiment, the hearts were placed in 10% formalin for histological examination using H&E staining to evaluate the degree of heart damage. RESULTS: At baseline, there were no statistically significantly differences (p>0.05) in hemodynamics among the three groups. After 30min and 60min of reperfusion, +dp/dt recovered to 80.47% and 69.28% of baseline values respectively in IP group; 48.63% and 29.88% respectively in Sevo group; and 9.43% and 8.92% respectively in the Control hearts (p<0.01). At 30 min and 60min of reperfusion, HRxLVDP product recovered 77.02% and 65.3% of baseline values in the IP group (p<0.01); 36.12% and 29.48% in the Sevo group (p<0.050); and only 9.88% and 8.74% respectively for the control group (Figure 1). However, the recovery of +dp/dt and HRxLVDP in Sevo group was significantly less than that in IP group (P<0.05). Histological examination (% of necrosis and edema index) showed less ischemic changes from hearts in IP and Sevo groups compared with Control hearts.Figure 1: Post-ischemic recovery of HRxLVDP at 30min and 60min Of reperfusion after 20min global ischemia. *P<0.05, **P<0.01 compared with Control hearts. #P<0.05 compared with IP hearts.DISCUSSION: Our data show pretreating hearts with Sevo before prolonged normothermic global ischemia offers moderate cardioprotection and improvement in heart function when compared to nonconditioned hearts. However, pretreatment with Sevo in the isolated heart model provides less cardiac protection from ischemia-reperfusion injury when compared to IP.