Stunned myocardium after rapid correction of acidosis. Increased oxygen cost of contractility and the role of the Na(+)-H+ exchange system.
Left ventricular (LV) contractile dysfunction during acidosis has been reported to be almost reversible in crystalloid-perfused 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 (Emax) 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 Emax (404% of acidosis) occurred. However, after correction of acidosis, Emax and PVA were lower than the preacidosis values by 46% (P < .01) and 44% (P < .01) at the same LV volume. When the preacidosis Emax 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 slope. In addition, the oxygen cost of contractility, defined as the slope of the relation between PVA-independent VO2 and Emax, increased by 83% (P < .01) after correction of acidosis, indicating that postacidosis myocardium requires higher VO2 for nonmechanical activities for a unit increase in Emax. Then, we hypothesized that these mechanoenergetic disorders after rapid correction of acidosis would result from Ca2+ 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.
Hata
K
K
Department of Cardiovascular Dynamics, National Cardiovascular Center, Osaka, Japan.
Takasago
T
T
Saeki
A
A
Nishioka
T
T
Goto
Y
Y
D000138:Acidosis / Q000097:blood / Q000503:physiopathology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D004837:Epinephrine / Q000097:blood; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D009200:Myocardial Contraction / Q000502:physiology*; D017682:Myocardial Stunning / Q000097:blood / Q000503:physiopathology*; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption / Q000502:physiology*; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*; D016277:Ventricular Function, Left / Q000502:physiology*
D007773:Lactates; D017923:Sodium-Hydrogen Exchangers; D019344:Lactic Acid; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine