Alterations in excitation-contraction coupling in chronically ischemic or hibernating myocardium.
In coronary artery disease, areas subtended by a severely stenotic artery or by collateral vessels can develop chronic contractile dysfunction in the absence of necrosis. This dysfunction is thought to be adaptive to the reduced flow reserve and can be reversible upon revascularization, hence the term 'hibernating' myocardium. In the present report, the underlying cellular mechanisms were studied in a pig with severe stenosis in the left circumflex coronary artery, resulting in hibernation in the distal myocardium.After six weeks, single cardiomyocytes were isolated enzymatically from the hibernating region (HIB) and their properties compared with those of cardiomyocytes from the same area in matched control pigs (CTRL). The amplitude of cell shortening during field stimulation (1 Hz) was reduced in HIB versus CTRL; the accompanying Ca(2+) transients were only modestly reduced. In whole cell recording, prolongation of action potential was observed in HIB. When this difference was excluded by using depolarizing steps of fixed duration in both HIB and CTRL, the Ca(2+) transients in HIB myocytes were reduced compared with CTRL. There was also a decrease in peak L-type Ca(2+) current in HIB. In intact cells, increasing the available Ca(2+) for contraction did not correct the contractile deficit in HIB, suggesting alterations to the myofilaments.In conclusion, in this pig model for hibernating myocardium, intrinsic remodelling of the myocytes with a unique profile of excitation-contraction coupling is demonstrated. Along with the changes observed in myocytes from the border zone of a myocardial infarction, or in the remote area, this specific phenotype adds to the diversity and complexity of the remodelling processes in ischemic cardiomyopathy.
Bito
Virginie
V
Laboratory of Experimental Cardiology.
Heinzel
Frank R
FR
Claus
Piet
P
Bijnens
Bart
B
Verbeken
Erik
E
Van der Velden
Jolanda
J
Stienen
Ger
G
Sipido
Karin R
KR