Differential depression of myocardial function and metabolism by lactate and H+

The effects of both high blood H+ concentration ([H+]) and high blood lacta te concentration ([lactate]) under ischemia-reperfusion conditions are rece iving attention, but little is known about their effects in nonischemic hea rts. Isolated rat hearts were Langendorff perfused at constant flow with me dia at two pH values (7.4 and 7.0) and two [lactate] (0 and 20 mM) in vario us sequences (n = 6/group). Coronary flow and arterial O-2 content were kep t constant at levels that allowed hear-ts to function without O-2 supply li mitation. We measured contractility, O-2 uptake, diastolic pressure, and at the end of the protocol, tissue [lactate] and pH. Perfusion with high [lac tate] raised tissue [lactate] from 5.5 +/- 0.1 to 17.5 +/- 2.6 mu mol/heart (P < 0.0001), whereas decreasing the pH of the medium decreased tissue pH from 6.94 +/- 0.02 to 6.81 +/- 0.06 (P = 0.002). Heart rate was not affecte d by high [lactate] but was reversibly depressed by high [H+] (P = 0.004). Developed pressure declined by 20% in response to high [lactate], high [H+] , and high [lactate] + high [H+] (P = 0.002). After the high-[lactate] chal lenge was withdrawn, pressure continued to decline. In contrast, withdrawin g the high [H+] challenge allowed partial recovery. The behavior of diastol ic pressure mirrored that of developed pressure. Although unaffected by hig h [lactate], the O-2 uptake was reversibly depressed by high [H+]. This sug gests higher O-2 cost per contraction in the presence of high [lactate]. We conclude that for similar acute contractility depression, high [lactate] i nduces irreversible damage, likely at some point in the pathway of O-2 util ization. In contrast, the effect of high [H+] appears reversible. These dif ferential behaviors may have implications for heart function during heavy e xercise and ischemia-reperfusion events.