The Mechanism of Cardiac Failure in Experimental Myocardial Infarction

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Introduction: Following myocardial infarction (MI), the uninvolved, remote myocardium (RM) may fail. The most general cause would seem to be either a failure of the contractile apparatus due to the increased load placed on the RM or a fall in myocardial energy levels because demand exceeds supply. To distinguish between the two, we infused ribose, the rate limiting component for AMP synthesis and hence ATP levels, but not itself a fuel, in a rat model of MI. The RM which fails would be structurally normal. Function was assessed by echocardiography and at the conclusion of the experiment, RM biopsies were taken. Hypotheses: (1) An energy supply/demand imbalance causes failure of the RM following an MI and (2) dysfunction can be at least partially prevented by increased AMP synthesis. Methods: Lewis rats (N=7 for each group) had central venous infusion pumps placed and 1 day later, the left anterior descending artery was ligated just distal to the circumflex artery, resulting in infarction of 35% of the LV. Ribose was infused for 2 weeks. Echo analysis was carried out at 0, 2, and 4 weeks. ATP was determined by NADP reduction. Results: In this model, MI produced LV dysfunction with thinning and dilation. Ribose reduced RM and LV dysfunction following MI as shown. Myocardial ATP levels were better preserved with ribose.

EF=ejection fraction; LVV=LV volume; s=systolic; d=diastolic; PWT=posterior wall thickness; *p<0.05.