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Regression of cardiac hypertrophy normalizes glucose metabolism and left ventricular function during reperfusion
R B Wambolt1, S L Henning, D R English
1Cardiovascular Research Laboratory, University of British Columbia-St Paul's Hospital, Vancouver, Canada.
Insights
Regression of cardiac hypertrophy using enalapril normalized myocardial glucose metabolism and improved left ventricular function during reperfusion in rats. This suggests that reversing cardiac hypertrophy can restore heart function after ischemia.
Area of Science:
- Cardiology
- Metabolic Research
- Pharmacology
Background:
- Cardiac hypertrophy, often caused by pressure overload, is linked to altered myocardial glucose metabolism and impaired left ventricular function during reperfusion.
- The reversibility of these metabolic and functional deficits following regression of cardiac hypertrophy remains unclear.
Purpose of the Study:
- To investigate the effect of pharmacologically induced regression of cardiac hypertrophy on myocardial glucose metabolism and post-ischemic heart function.
- To determine if normalizing cardiac hypertrophy can restore normal glucose metabolism and left ventricular function during reperfusion.
Main Methods:
- Isolated working hearts from male Sprague-Dawley rats subjected to aortic banding (to induce hypertrophy) or sham operation were studied.
- Hearts were treated with or without enalapril maleate to induce regression of hypertrophy.
- Myocardial glucose metabolism (glycolysis and oxidation) and heart function were assessed during pre-ischemic perfusion and reperfusion following global ischemia.
Main Results:
- Untreated aortic-banded hearts showed significant hypertrophy, accelerated glycolysis, and reduced function post-reperfusion compared to controls.
- Enalapril treatment successfully regressed cardiac hypertrophy, normalizing heart weight.
- In enalapril-treated rats, rates of glycolysis were normalized, and left ventricular function during reperfusion was restored to control levels.
Conclusions:
- Pharmacological regression of pressure-overload cardiac hypertrophy effectively normalizes abnormal myocardial glucose metabolism.
- Reversal of cardiac hypertrophy also restores left ventricular function during the reperfusion period.
- These findings highlight the potential for therapeutic interventions targeting hypertrophy regression to improve outcomes in ischemic heart disease.
Abstract:
It is not yet known if the alterations in myocardial glucose metabolism and the exaggerated left ventricular dysfunction that occur during reperfusion in hypertrophied hearts are reversible. Thus, we studied isolated working hearts from aortic-banded (n = 29) and sham-operated control (n = 32) male Sprague-Dawley rats with or without enalapril maleate treatment (25.6 +/- 0.8 mg/kg per day, p.o.) to determine the effect of regression of cardiac hypertrophy on myocardial glucose metabolism and post-ischemic heart function. Hearts were perfused with buffer containing 1.2 mM palmitate, 11 mM [5-3H]/[U-14C]-glucose, 0.5 mM lactate and 100 microU/ml insulin. Glucose metabolism [rates of glycolysis (3H2O production) and rates of oxidation (14CO2 production) of exogenous glucose] and heart function (heart rate x peak systolic pressure) were measured during 30 min pre-ischemic perfusion and 60 min of reperfusion following 20 min of global, no-flow ischemia. Hearts from untreated aortic-banded rats were hypertrophied, being 27.6 +/- 1.8% larger than hearts from untreated control rats. Enalapril treatment caused regression of cardiac hypertrophy that normalized heart weight in aortic-banded rats. Rates of glycolysis of exogenous glucose in hearts from untreated aortic-banded rats were accelerated compared to rates in hearts from untreated control rats during pre-ischemic perfusion (4391 +/- 97 v 2652 +/- 69 nmol glucose/min per g dry wt, respectively, P < 0.05) and reperfusion (2402 +/- 58 v 1597 +/- 88 nmol glucose/min per g dry wt. respectively, P < 0.05). In contrast, rates of glycolysis of exogenous glucose in hearts from enalapril-treated aortic-banded rats were normalized before and after ischemia. Rates of glycolysis of exogenous glucose in hearts of control rats were not affected by enalapril treatment. Oxidation of exogenous glucose was not different among groups either before or after ischemia. Function of hearts from untreated aortic-banded rats at the end of reperfusion was significantly less than that of hearts from untreated control rats (23.9 +/- 2.6 v 32.2 +/- 0.7 mmHg x beats per min/1000, respectively, P < 0.05). As with myocardial glucose metabolism function of hearts from aortic-banded rats treated with enalapril was normalized during reperfusion. Thus, pharmacologically induced regression of pressure-overload cardiac hypertrophy normalizes glucose metabolism as well as left ventricular function during reperfusion.