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Hypercholesterolemia attenuates postischemic ventricular dysfunction in the isolated rabbit heart.
Verónica D'Annunzio1, Martín Donato, Melina Sabán
1Institute of Cardiovascular Pathophysiology, Department of Pathology, Faculty of Medicine, University of Buenos Aires, Argentina.
Molecular and Cellular Biochemistry
|July 15, 2005
Summary
High cholesterol diets in animals reduce heart muscle contractility before ischemia. However, this condition paradoxically protects against stunning post-ischemia, an effect that disappears when contractility is normalized.
Area of Science:
- Cardiovascular Physiology
- Metabolic Research
Background:
- The impact of chronic cholesterol administration on myocardial stunning remains understudied.
- Hypercholesterolemia is a known risk factor for cardiovascular diseases, affecting cardiac function.
Purpose of the Study:
- To investigate the effect of a cholesterol-enriched diet on post-ischemic ventricular dysfunction in isolated rabbit hearts.
- To determine if hypercholesterolemia alters the response of the myocardium to ischemia-reperfusion injury.
Main Methods:
- Isolated rabbit hearts were subjected to aerobic perfusion or global ischemia followed by reperfusion.
- Animals were divided into normocholesterolemic and hypercholesterolemic groups, with the latter fed a 1% cholesterol diet for 4 weeks.
- Ventricular function, including left ventricular developed pressure (LVDP) and end-diastolic pressure, was monitored. Isoproterenol was used to match pre-ischemic inotropic states.
Main Results:
- Hypercholesterolemic hearts exhibited reduced basal inotropism (LVDP) compared to normocholesterolemic hearts.
- Despite lower pre-ischemic LVDP, hypercholesterolemic hearts showed attenuated systolic dysfunction after reperfusion when expressed as a percentage of baseline.
- When pre-ischemic contractility was normalized between groups, the protective effect against post-ischemic systolic alterations disappeared. Left ventricular end-diastolic pressure increased significantly in control and matched groups but not in the hypercholesterolemic group.
- No significant differences in infarct size or relaxation parameters (tau) were observed between groups.
Conclusions:
- Chronic cholesterol administration in rabbits leads to reduced pre-ischemic myocardial contractility.
- Hypercholesterolemia appears to attenuate myocardial stunning post-ischemia, likely due to the reduced pre-ischemic inotropic state.
- The observed beneficial effect on post-ischemic function in hypercholesterolemic animals is abolished when baseline contractility is normalized, suggesting it is not an intrinsic protective mechanism against ischemia-reperfusion injury itself.