Direct Effect of High-dose Insulin on the Depressed Heart after Beta-blockade or Ischemia

Summary

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/100g LV) and myocardial oxygen consumption (MVO₂, ml O₂/beat/100g LV) were determined during incremental left ventricular balloon inflation before and after functional depression by betablockade (0.2 mg/kg propranolol) or 2 hours cardioplegic ischemia at 28 °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.

Key words

Beta-adrenergic receptors - Cardiac effects - High-dose insulin - Postischemic failure