REPEATED, TRANSIENT LACTATE EXPOSURE DOES NOT PRECONDITION RAT MYOCARDIUM

The precise mechanism of the cardioprotective effect of ischemic preco nditioning (IPC) is still unclear, although various mechanisms have be en suggested, including activation of ATP-dependent potassium (K-ATP) channels by adenosine and protein kinase C as well as increased expres sion of heat shock protein (HSP). Increasing evidence suggests that la ctate, which accumulates during IPC periods, can activate several of t hese ''triggers'' of preconditioning. We tested whether repeated expos ure to lactate, producing tissue lactate concentrations similar to tho se during brief ischemic periods, could contribute to IPC benefits. Fi ve isolated rat hearts were subjected to a previously reported IPC pro tocol composed of two 5-min ischemia-reperfusion cycles; another five hearts served as controls; and six hearts underwent a ''lactate-precon ditioning'' protocol, consisting of two 5-min exposures to 15 mM lacta te and two 5-min periods of reflow with a lactate-free buffer. Subsequ ently all hearts underwent 30 min of normothermic, total ischemia foll owed by 30 min of reflow at a constant perfusion pressure of 80 mmHg ( 1 mmHg = 133.3 Pa). Lactate exposure resulted in tissue lactate levels similar to those during ischemia in ischemia-preconditioned hearts (1 0.5 +/- 0.6 versus 10.5 +/- 1.2 mu mol/g wet weight, mean +/- SEM). Ho wever, the recovery of left ventricular developed pressure (DevP) foll owing 30 min of total ischemia was significantly higher in the IPC hea rts than in either the control or lactate-exposed hearts, reaching 56. 8 +/- 3.4, 14.2 +/- 6.8, and 9.5 +/- 3.6%, respectively, of the baseli ne values. There was no significant difference between lactate-precond itioned and control hearts. End-diastolic pressure (EDP) was significa ntly lower during reperfusion in IPC hearts than in lactate-exposed an d control hearts, with no significant differences between the latter t wo groups (36.2 +/- 3.5, 82.0 +/- 2.9, and 81.2 +/- 8.5 mmHg, respecti vely). In contrast with the proposed hypothesis, repeated, transient l actate exposure resulting in tissue lactate levels similar to ischemic preconditioning did not improve contractile recovery after a prolonge d ischemic period in this model.