Experimental congestive heart failure due to myocardial infarction: Sarcolemmal receptors and cation transporters

Summary

Rats, subsequent to loss of a large amount of left ventricular free wall due to surgically-induced myocardial infarction, form a good model of congestive heart failure. Since depressed cardiac pump function is the hallmark of heart failure, it is suspected that decreased influx of Ca²⁺ into the cardiac cell is responsible for depressed contractile function. Because Ca²⁺ movements in the sarcolemmal membrane are known to involve Ca²⁺-channels, Na⁺-Ca²⁺ exchange, Ca²⁺-pump, Na⁺-K⁺ ATPase, β-adrenoceptors and α-adrenoceptors directly or indirectly, the status of these mechanisms was examined by employing rats at different degrees of congestive heart failure. The left coronary artery was ligated and hearts were examined 4, 8, and 16 weeks later; sham-operated animals served as controls. The number of Ca²⁺ channels in the myocardium was depressed in moderate and severe stages of heart failure. Furthermore, depressions in sarcolemmal Na⁺-Ca²⁺ exchange activity and β-adrenoceptor number were associated with the development of early stages of heart failure, whereas sarcolemmal Na⁺-K⁺ ATPase activity was decreased and the number of aadrenoceptors was increased at moderate and severe stages. The Ca²⁺-pump activities were not altered in failing hearts. Thus it appears that changes in Na⁺-Ca²⁺ exchange as well as β-adrenoceptors and Ca²⁺ channels may contribute towards decreasing Ca²⁺ influx at early and moderate stages of congestive heart failure, respectively. On the other hand, changes in α-adrenoceptors and Na⁺-K⁺ ATPase may act as compensatory mechanisms for maintaining Ca²⁺ influx at moderate and late stages of congestive heart failure.

The research work reported in this study was supported by a grant from the Manitoba Heart and Stroke Foundation.