Haemodynamic effects of low and high doses of insulin during beta receptor blockade in dogs

Haemodynamic effects of small and high doses of insulin during beta receptor blockade were studied in nine dogs. Beta receptor blockade was induced by 0.5 mg/kg propranolol and caused depression of cardiac performance with a significant increase in left ventricular end-diastolic pressure (LVEDP) and a significant decrease in heart rate; maximum rate of left ventricular (LV) pressure rise (LVdP/dtmax), stroke volume and cardiac output. At 15 min, after beta receptor blockade, a bolus injection of 0.5 IU/kg of insulin, free of glucagon and calcium, was given followed by a continuous infusion of 0.5 IU/kg/h. After 30 min another bolus dose of 300 IU insulin was injected. Glucose and potassium were given to maintain physiological levels of these factors. Five minutes after a low dose of insulin there was a significant decrease in LVEDP (P less than 0.01), and a significant increase in LVdP/dtmax (P less than 0.01), in stroke volume (P less than 0.01) and in cardiac output (P less than 0.01). The other haemodynamic variables were not significantly changed. Administration of a high dose of insulin further, significantly, improved performance of the beta receptor blocked heart and caused a significant reduction in total peripheral resistance. In conclusion, insulin exerts inotropic and vasodilator effects which are dose-dependent and not related to adrenergic mechanisms.