Abstract 12121: Impaired Contractile and Metabolic Recovery after Low-Flow Myocardial Ischemia in a Porcine Model of Metabolic Syndrome
Background: Patients with insulin resistance, such as those with metabolic syndrome, face a poor prognosis in acute coronary syndrome. This poor prognosis is not fully explained by pre-ischemic contractile dysfunction or extent of coronary atherosclerosis, raising the question whether abnormalities of myocardial metabolism impair contractile recovery after ischemia. This study utilized a porcine model that recapitulates many characteristics of clinical metabolic syndrome (MetSyn) to determine if myocardial contractile recovery is impaired after low-flow ischemia, and whether such impairment is accompanied by abnormal myocardial energy substrate metabolism.
Methods and Results: Micropigs (n=16) were assigned to control (low-fat, no added sugar) or intervention diet (25% coconut oil, 20% high-fructose corn syrup, but no added cholesterol). Intervention diet resulted in obesity, abnormal glucose tolerance, hypertension, and dyslipidemia, but not diabetes or atherosclerosis. After 7 months of diet, pigs were anesthetized and underwent 45 min low-flow regional ischemia and 120 min reperfusion. Contractile function (regional work by pressure-dimension loops) was similar at baseline and depressed to a similar extent by ischemia in both groups. However, at 120 min reperfusion, regional work recovered to 61±13% of baseline in controls, but to only 16±14% of baseline in MetSyn pigs (p=0.01). Mechanical/metabolic efficiency (regional work/MVO2) was not affected by ischemia/reperfusion in the control group, but fell to 24±13% of baseline in the MetSyn group after reperfusion (p=0.02). MetSyn hearts, compared with control hearts, utilized more fatty acids and less carbohydrate substrates. Specific activity of pyruvate dehydrogenase was similar in both groups without ischemia, unaffected by ischemia in control hearts, but reduced 42±7% by ischemia/reperfusion in MetSyn hearts (p=0.03).
Conclusion: In pigs with characteristics of metabolic syndrome, contractile recovery after low-flow myocardial ischemia is impaired, along with metabolism of carbohydrate substrates and pyruvate dehydrogenase activity. These findings may provide an explanation for the poor prognosis of patients with metabolic syndrome and acute coronary syndrome.
- © 2010 by American Heart Association, Inc.