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Direct effect of high-dose insulin on the depressed heart after beta-blockade or ischemia
Insights
High-dose insulin (HDI) reversed beta-blocker effects on canine hearts, improving function without increasing oxygen use. HDI did not affect ischemically depressed hearts, suggesting limited direct cardiac benefits.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Beta-adrenergic blockade and cardioplegic ischemia impair cardiac function.
- The direct cardiac effects of high-dose insulin (HDI) remain incompletely understood.
Purpose of the Study:
- To investigate the direct cardiac effects of HDI on canine hearts.
- To determine if HDI can reverse functional depression induced by beta-blockade or ischemia.
Main Methods:
- Canine hearts underwent cardiopulmonary bypass and functional assessment (peak developed pressure, coronary blood flow, myocardial oxygen consumption).
- Hearts were functionally depressed using either propranolol (beta-blockade) or cardioplegic ischemia.
- HDI was administered, and cardiac function and metabolism were reassessed under a glucose clamp.
Main Results:
- HDI reversed the negative inotropic effects of propranolol, restoring 80% of control function and normalizing heart rate.
- HDI did not alter systolic function or heart rate in ischemically depressed hearts.
- Myocardial oxygen consumption (MVO2) did not increase with HDI, even when systolic function improved.
Conclusions:
- HDI can reverse beta-adrenergic blockade-induced negative inotropy without augmenting myocardial oxygen utilization.
- Direct cardiac inotropic stimulation by HDI is unlikely in post-ischemic, non-diabetic myocardium, apart from systemic effects.
- The findings suggest potential therapeutic applications of HDI in specific cardiac conditions, distinct from its metabolic actions.
Abstract:
The direct cardiac effects of high-dose insulin (HDI) were assessed in 13 canine hearts supported by cardiopulmonary bypass. Isovolumic peak developed pressure (PDP, mmHg), coronary blood flow (CBF, ml/beat/100 g LV) and myocardial oxygen consumption (MVO2, ml O2/beat/100 g LV) were determined during incremental left ventricular balloon inflation before and after functional depression by beta-blockade (0.2 mg/kg propranolol) or 2 hours cardioplegic ischemia at 28 degrees C. The 2 regimens gave an overall functional reduction of 46 +/- 3% and 42 +/- 2%, respectively. The hearts were then challenged with an aortic root bolus of 1000 IU insulin. A glucose clamp was maintained at physiological levels. Insulin reversed the negative inotropic effect of propranolol to 80% of control function and normalized heart rate. Despite the significant amelioration of systolic function by HDI, MVO2 indexed for cardiac effort did not change. Neither systolic function nor heart rate was changed in the ischemically depressed hearts. In conclusion, HDI reverses the negative inotropic effect of beta-adrenergic receptor blockade without augmenting oxygen utilization. Apart from effects ascribable to systemic vasodilation and metabolic shifts, no direct cardiac inotropic stimulation can be expected on the post-ischemically depressed, nondiabetic myocardium unless there is a persistent negative effect of beta-blockers.