Correction of Acidosis

Left ventricular (LV) contractile dysfunction during acidosis has been reported to be almost reversible in crystalloidperfused hearts after correction of acidosis. In contrast, we have found that, in blood-perfused hearts, contractile function is paradoxically depressed after correction of acidosis with a transient overshoot of contractility during the recovery of pH. To clarify the mechanism of this phenomenon, we measured the LV contractility index (Em,,) and the relation between myocardial oxygen consumption (Vo2) and systolic pressure-volume area (PVA, a measure of the LV total mechanical energy) before and after induction and rapid correction of acidosis by CO2 loading (pH 7.00) and unloading in 13 excised cross-circulated canine hearts. During the rapid correction of acidosis in six control hearts, a severe transient overshoot of Em. (404% of acidosis) occurred. However, after correction of acidosis, Ema, and PVA were lower than the preacidosis values by 46% (P<.01) and 44% (P<.01) at the same LV volume. When the preacidosis E.,a, level was restored by Ca2+ infusion, the Vo2 intercept (PVA-independent Vo2) of the linear Vo2-PVA relation exceeded the control value by 18% (P<.05) with an unchanged Acidosis is known to decrease myocardial contrac4\ tility,1,2 and critical heart diseases frequently .L X1.. accompany acidosis. Nevertheless, the recovery process from acidosis has been controversial. Some studies in crystalloid-perfused acidotic hearts or myocardium have indicated that the influence of acidosis on myocardium is reversible.3'4 In contrast, studies in situ have suggested that the rapid correction of acidosis results in myocardial damage5 and unbalance in blood gas analysis data.6,7 In addition, the mechanisms of these unfavorable results after correction of acidosis are not known. Difficulties in stably maintaining acidosis and preventing cardiovascular responses by neural reflexes and humoral factors in situ8-10 seem to have limited the progress of research on this mechanism. Recently, left ventricular (LV) pressure-volume area (PVA) has been shown to represent the total Received November 1, 1993; accepted December 20, 1993. From the Departments of Cardiovascular Dynamics and Internal Medicine, National Cardiovascular Center, Suita, Osaka, Japan. Correspondence to Katsuya Hata, MD, The First Department of Internal Medicine, Kobe University School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650, Japan. Reprint requests to Yoichi Goto, MD, Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565, Japan. slope. In addition, the oxygen cost of contractility, defined as the slope of the relation between PVA-independent Vo2 and Ema,, increased by 83% (P<.01) after correction of acidosis, indicating that postacidosis myocardium requires higher Vo2 for nonmechanical activities for a unit increase in Ema,. Then, we hypothesized that these mechanoenergetic disorders after rapid correction of acidosis would result from Ca21 overload via accelerated Na+-Ca2' exchange due to the heavily operating Na+-H+ exchange system at the time of rapid pH recovery. To examine this hypothesis, dimethylamiloride, a selective Na+-H+ exchange inhibitor, was administered just before the correction of acidosis in the other seven hearts. The administration of dimethylamiloride completely prevented both the mechanical and energetic disorders after correction of acidosis. We conclude that rapid recovery of pH paradoxically depresses myocardial contractility and increases the oxygen cost of contractility through an activation of the Na+-H+ exchange system. (Circ Res. 1994;74:794-805.)