Complete stunning in hypertrophied guinea pig heart. Defects in sarcolemmal calcium influx.
Isolated sham control as well as hypertrophied guinea pig hearts were subjected to global ischemia and reperfusion. Developed force declined to zero during 5 min of ischemia without any significant change in resting tension in both sham control and hypertrophied hearts. Upon reperfusion, control hearts showed nearly complete recovery of developed force within 20 min, whereas hypertrophied hearts during this time showed no contractile function, i.e., "a complete stunning" was observed. A continued reperfusion of the stunned hypertrophied hearts ultimately resulted in complete recovery of force within 40-60 min. Data on myocardial cation content showed a relative calcium deficiency in the stunned hearts (3.4 mumol/gm dry wt) as compared to sham control hearts (5.3 mumol/gm dry wt). Stunning could be reversed sooner by isoproterenol (100 microns), and low Na+ (35 and 60 mM) perfusion. Recovery of contractile function by low Na+ was blocked by amiloride (0.17-1.2 mM) in a dose-dependent manner. Perfusion with Bay K8644 (0.1-10 microM) as well as low (0.62 mM) and high (2.5 mM) extracellular calcium concentrations failed to reverse stunning. The pharmacological interventions that were able to reverse the stunning condition also increased the myocardial calcium content. Although the possibilities of a sarcoplasmic reticular dysfunction and/or reduced sensitivity of myofilaments are not excluded, data suggest that a defect in calcium influx across the sarcolemma is an important factor in "complete stunning." It is suggested that this "potential sarcolemmal defect" in the hypertrophied heart, which is unmasked by the ischemic stress, may also represent an early abnormality in the pathogenesis of heart failure.
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
A K
AK
Dhalla
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N
Khaper
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PK
Singal
D000818:Animals; D002118:Calcium / Q000502:physiology; D006332:Cardiomegaly / Q000503:physiopathology*; D006168:Guinea Pigs; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015427:Reperfusion Injury / Q000503:physiopathology; D012964:Sodium / Q000502:physiology
D012964:Sodium; D002118:Calcium