Key result
Food restriction or ACE inhibition fails to reduce infarct size or preserve contractility in diabetic mice.
Why the study?
Food restriction and angiotensin-converting enzyme inhibition are standard therapies in diabetic and metabolic syndrome patients, but their effects on cardiac ischemia-reperfusion injury have never been investigated.
Does food restriction or ACE inhibition reduce infarct size and preserve cardiac contractility after ischemia-reperfusion injury in diabetic and metabolic syndrome mouse models?
Does food restriction or ACE inhibition reduce infarct size and preserve cardiac contractility after ischemia-reperfusion injury in diabetic and metabolic syndrome mouse models?
In mouse models of type II diabetes and metabolic syndrome, 12 weeks of food restriction or ACE inhibition did not reduce infarct size following ischemia-reperfusion injury.
No cardioprotection from food restriction or ACE inhibition in diabetic mouse IR models; leaves open translation to human diabetes.
BACKGROUND: The number of patients with diabetes or the metabolic syndrome reaches epidemic proportions. On top of their diabetic cardiomyopathy, these patients experience frequent and severe cardiac ischemia-reperfusion (IR) insults, which further aggravate their degree of heart failure. Food restriction and angiotensin-converting enzyme inhibition (ACE-I) are standard therapies in these patients but the effects on cardiac IR injury have never been investigated. In this study, we tested the hypothesis that 1° food restriction and 2° ACE-I reduce infarct size and preserve cardiac contractility after IR injury in mouse models of diabetes and the metabolic syndrome. METHODS: C57Bl6/J wild type (WT) mice, leptin deficient ob/ob (model for type II diabetes) and double knock-out (LDLR-/-;ob/ob, further called DKO) mice with combined leptin and LDL-receptor deficiency (model for metabolic syndrome) were used. The effects of 12 weeks food restriction or ACE-I on infarct size and load-independent left ventricular contractility after 30 min regional cardiac ischemia were investigated. Differences between groups were analyzed for statistical significance by Student's t-test or factorial ANOVA followed by a Fisher's LSD post hoc test. RESULTS: Infarct size was larger in ob/ob and DKO versus WT. Twelve weeks of ACE-I improved pre-ischemic left ventricular contractility in ob/ob and DKO. Twelve weeks of food restriction, with a weight reduction of 35-40%, or ACE-I did not reduce the effect of IR. CONCLUSION: ACE-I and food restriction do not correct the increased sensitivity for cardiac IR-injury in mouse models of type II diabetes and the metabolic syndrome.
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Mieren et al. (2012) studied Type II diabetes and metabolic syndrome (n=145). Food restriction or ACE-inhibition (captopril) vs. Untreated mice was evaluated on Infarct size (% of area at risk) and load-independent left ventricular contractility after ischemia-reperfusion. Twelve weeks of food restriction or ACE inhibition did not reduce infarct size or preserve cardiac contractility after ischemia-reperfusion injury in mouse models of type II diabetes and the metabolic syndrome.
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