ISOFLURANE AND HALOTHANE INCREASE ADENOSINE-TRIPHOSPHATE PRESERVATION, BUT DO NOT PROVIDE ADDITIVE RECOVERY OF FUNCTION AFTER ISCHEMIA, IN PRECONDITIONED RAT HEARTS

Background: Brief ischemic periods render the myocardium resistant to infarction from subsequent ischemic insults by a process called ischem ic preconditioning. Volatile anesthetics have also been shown to be ca rdioprotective if administered before ischemia. The effect of precondi tioning alone and combined with halothane or isoflurane on hemodynamic recovery and preservation of adenosine triphosphate content in isolat ed rat hearts was evaluated. Methods: Seven groups of isolated rat hea rts (n = 6 each) were perfused in a retrograde manner at constant temp erature and pressure. A latex balloon was placed in the left ventricle to obtain isovolumetric contraction. Heart rhythm, coronary flow, lef t ventricular pressure and its derivative dP/dt (positive and negative ), and developed pressure were monitored. The hearts were paced at 300 beats per minute. Each heart was randomly allocated to (1) a time-con trol group that received no ischemia, (2) an untreated group that rece ived 25 min of normothermic ischemia only, (3 and 4) an isoflurane gro up and a halothane group that received 40 min of anesthetic (2.2% and 1.5%, respectively) before ischemia; (5) a preconditioning group that received two 5-min periods of ischemia separated by 10 min of reperfus ion before ischemia; or (6 and 7) a isoflurane + preconditioning group and a halothane t preconditioning group that received anesthetic for 10 min at concentrations of 2.2% or 1.5%, respectively, before two 5-m in periods of ischemia separated by 10 min of reperfusion. All treated groups received 25 min of normothermic ischemia followed by 30 min of reperfusion. Results: The time-control group remained hemodynamically stable for the entire experiment, and the adenosine triphosphate cont ent was 18.3 +/- 1.7 (SEM) mu M/g at the end of 115 min. The untreated group had depressed recovery after 25 min of normothermic ischemia, a nd the developed pressure was significantly depressed and recovered on ly 30 +/- 9% (P < 0.001) of its preischemic value. There was also a si gnificant increase in the incidence of ventricular fibrillation (P < 0 .001). Adenosine triphosphate content was significantly lower in this group than in all other groups. Five minutes of ischemia in the precon ditioning group had little effect on hemodynamics and decreased develo ped pressure only 6.4%. Halothane depressed developed pressure by 16 /- 5% (P < 0.001), and isoflurane increased coronary flow by 145 +/- 9 % (P < 0.001) but had no significant hemodynamic effect. The treated g roups had significantly better recovery of postischemic function than did the untreated group. In the preconditioning group, developed press ure recovered to 85% of control and dP/dt+ to 87% of control. The addi tion of halothane or isoflurane to preconditioning did not provide add itional functional recovery but did increase the level of adenosine tr iphosphate preservation (13.1 +/- 1.1 and 12.4 +/- 1.1 mu M/g, respect ively). Conclusions: The results indicate that preconditioning, haloth ane, and isoflurane provide significant protection against ischemia. T he combination of preconditioning and halothane or isoflurane did not improve hemodynamic recovery but did increase preservation of adenosin e triphosphate.