Effect of stepwise normalization of perfusate pH on post-ischemic functional recovery and Ca2+ overload in isolated rat hearts.

Abstract

The purpose of this study was to examine whether initial acidic reperfusion after ischemia followed by stepwise normalization of perfusate pH could improve functional recovery and to assess whether this is associated with a reduction in Ca2+ overload. Isolated rat hearts were subjected to global ischemia for 25 min, followed by 30 min of reperfusion. In the control group (Group C), the perfusate pH was 7.4 throughout reperfusion. In the acidic groups, the perfusate pH was 6.8 for the first 5 min, 7.1 for the second 5 min, and 7.4 for the remainder of reperfusion. Acidic buffer was produced either by adding HCl (metabolic acidosis, Group MA) or by bubbling with gas containing 12 to 24% CO2 (respiratory acidosis, Group RA). The recovery of ventricular function, Ca2+ uptake, and energy metabolites were analyzed. Thirteen of the 15 hearts in Group C, 14 of the 15 in MA and 8 of the 15 in RA recovered regular cardiac rhythm at the end of reperfusion. In these hearts which exhibited normal rhythm, the percent recovery in developed pressure was higher (MA: 73 +/- 8, RA: 68 +/- 6, C: 51 +/- 5%, p < 0.05) and left ventricular end-diastolic pressure was lower (MA: 5.1 +/- 1.4, RA: 5.9 +/- 1.3, C: 14.2 +/- 2.7 mmHg, p < 0.05) in the acidic groups. The improved recovery was associated with a significant reduction in Ca2+ uptake which persisted with the restoration of normal pH. These results demonstrate that early acidic reperfusion enhances contractile recovery and diminishes Ca2+ overload. Moreover, these salutary effects are maintained after stepwise normalization of the perfusate pH to physiological values.