Differential effects of lactate and H+ on performance and metabolism in the rat heart

Although the effects of both high [H+] and high [lactate] ([L-]) are receiving attention under ischemia-reperfusion conditions, little is known about their effects in non-ischemic hearts. Isolated rat hearts were Langendorff-perfused at constant, unlimiting flow with media at two pH (7.4 and 7.0) and two [L-] (0 and 20 mM) in various sequences (n=6/group). We measured contractility, O2 uptake, diastolic pressure, and at the end of the protocol, tissue [L-] and pH. Perfusion with high [L-] raised tissue [L-] from 5.5±0.1 to 17.5±2.6 μmoles/heart (P<0.0001), whilst 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 affected by high [L-], but was reversibly depressed by high [H+] (P=0.004). Developed pressure declined by 20% in response to high [L-], low [H+], and high [L-] plus low [H+] (P=0.002). After withdrawing L-, pressure continued declining. In contrast, withdrawing H+ allowed partial recovery. The behaviour of diastolic pressure mirrored that of developed pressure. Although unaffected by high [L-], the O2 uptake was reversibly depressed by high [H+]. This suggests higher O2 cost per contraction in the presence of high [L-]. Conclusion: For similar acute contractility depression, high [L-] induces irreversible damage, likely at some point in the pathway of O2-utilization. By contrast, the effect of high [H+] appears reversible. These differential behaviours may have implications for heart function during heavy exercise, and ischemia-reperfusion events.