Tg. Maddaford et Gn. Pierce, MYOCARDIAL DYSFUNCTION IS ASSOCIATED WITH ACTIVATION OF NA+ H+ EXCHANGE IMMEDIATELY DURING REPERFUSION/, American journal of physiology. Heart and circulatory physiology, 42(5), 1997, pp. 2232-2239
Amiloride analogs block Na+/H+ exchange and thereby protect the heart
from myocardial ischemia-reperfusion injury. It is unclear whether dru
gs must be present before ischemia to be cardioprotective. After 60 mi
n of global ischemia in the coronary-perfused right ventricular wall (
RVW), as little as 1 min of exposure to dimethyl amiloride (DMA) immed
iately at the time of reperfusion protected the RVW. Delaying the drug
attenuated the cardioprotection. If DMA was introduced in an ischemic
solution near the end of ischemia, the cardioprotective effects were
augmented. If the drug was washed out of the RVW vascular space before
ischemia, cardioprotection was not observed. In contrast, in whole he
arts, preischemic perfusion of the drug was necessary for cardioprotec
tion and the cardioprotection remained even if the drug was washed out
before ischemia. We conclude that Na+/H+ exchange is active and contr
ibutes to contractile dysfunction during the first seconds of reperfus
ion. This is difficult to detect in the perfused whole heart, and the
washout data suggest that this may be due to a limitation in drug deli
very across the vascular wall. The data also suggest that the exchange
r is not as active during ischemia itself as it is during reperfusion.