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 ischemic preconditioning. Volatile anesthetics have also been shown to be cardioprotective if administered before ischemia. The effect of preconditioning alone and combined with halothane or isoflurane on hemodynamic recovery and preservation of adenosine triphosphate content in isolated rat hearts was evaluated.


METHODS
Seven groups of isolated rat hearts (n = 6 each) were perfused in a retrograde manner at constant temperature and pressure. A latex balloon was placed in the left ventricle to obtain isovolumetric contraction. Heart rhythm, coronary flow, left 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-control group that received no ischemia, (2) an untreated group that received 25 min of normothermic ischemia only. (3 and 4) an isoflurane group 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 reperfusion before ischemia; or (6 and 7) a isoflurane+preconditioning group and a halothane+preconditioning group that received anesthetic for 10 min at concentrations of 2.2% or 1.5%, respectively, before two 5-min 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 content was 18.3 +/- 1.7 (SEM) microM/g at the end of 115 min. The untreated group had depressed recovery after 25 min of normothermic ischemia, and the developed pressure was significantly depressed and recovered only 30 +/- 9% (P < 0.001) of its preischemic value. There was also a significant 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 preconditioning group had little effect on hemodynamics and decreased developed 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 groups had significantly better recovery of postischemic function than did the untreated group. In the preconditioning group, developed pressure recovered to 85% of control and dP/dt+ to 87% of control. The addition of halothane or isoflurane to preconditioning did not provide additional functional recovery but did increase the level of adenosine triphosphate preservation (13.1 +/- 1.1 and 12.4 +/- 1.1 microM/g, respectively).


CONCLUSIONS
The results indicate that preconditioning, halothane, and isoflurane provide significant protection against ischemia. The combination of preconditioning and halothane or isoflurane did not improve hemodynamic recovery but did increase preservation of adenosine triphosphate.
Boutros
A
A
Department of Anesthesiology, State University of New York Health Science Center at Brooklyn 11203-2098, USA. aBoutros@NetMail.HSCBKLYN.edu
Wang
J
J
Capuano
C
C
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006221:Halothane / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control
D000255:Adenosine Triphosphate; D007530:Isoflurane; D006221:Halothane