Paradox of enhanced contractility in postischemic rat hearts with depressed function.
Depressed function of postischemic hearts may be related to incomplete recovery of coronary perfusion. To circumvent this factor we studied the properties of papillary muscles under controlled extracellular conditions. First, recovery of function was measured in postischemic rat hearts. Next, a muscle was dissected and superfused in a bath. After 40 min of ischemia, recovery of cardiac output was generally zero. Muscles from this group were relaxed or showed small contractures. After 20-30 min of ischemia recovery of coronary flow and cardiac output was 50-100%, and the isolated muscles showed the following properties (compared with Langendorff-perfused controls): 1) increased force at normal or low [Ca2+]; 2) action potential and postextrasystolic potentiation were unchanged, which indicates that Ca2+ influx per beat was unchanged; 3) the decay of potentiation was slowed, indicating a reduced rate of Ca2+ extrusion via Na(+)-Ca2+ exchange. This implies intracellular Ca2+ accumulation and explains the increased force. Postischemic enhancement of contractility (isovolumic pressure) was demonstrated also in whole heart preparations. We conclude that mild injury by preceding ischemia leads to enhanced contractility (Ca2+ accumulation), advanced injury to local contractures, and finally to a general contracture (Ca2+ overload). Recovery of heart function and coronary flow probably depends on the number and size of local contractures.
Schouten
V J
VJ
Department of Thorax Surgery, University of Leiden, The Netherlands.
Los
G J
GJ
Kuypers
P D
PD
Brinkman
C J
CJ
Huysmans
H A
HA
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006321:Heart / Q000503:physiopathology*; D007552:Isotonic Solutions / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D010210:Papillary Muscles / Q000473:pathology / Q000503:physiopathology; D051381:Rats
D007552:Isotonic Solutions; C037692:Tyrode's solution; D002118:Calcium