Volume 42, Number 4, 171-178, DOI: 10.1007/s00592-005-0198-7

Cardiac function and ischaemic tolerance during acute loss of metabolic control in the diabetic BB Wor rat

T. L. Broderick and P. Poirier

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Abstract

The effect of loss of metabolic control, by with-holding insulin treatment, on reperfusion recovery of cardiac function following ischaemia was studied in the spontaneously diabetic “BB” Wor rat. The study involved a group of insulin-treated diabetic BB rats (insulin-treated) and diabetic BB rats in which insulin treatment was withheld 24 h prior to study (insulin-withdrawn). Hearts were isolated and perfused at a constant left atrial filling pressure of 15 cm H2O and aortic afterload resistances of 100 and 140 cm H2O. Hearts were then subjected to 20 min of ischaemia followed by 30 min of reperfusion. Withdrawing insulin treatment from the BB Wor rat resulted in a dramatic increase in the levels of plasma glucose and free fatty acids. Hearts from these rats perfused under aerobic conditions demonstrated reductions in heart rate, positive and negative dP/dt, cardiac output and left ventricular minute work, whereas diastolic pressure was elevated. Following ischaemia, recovery of cardiac function in the insulin-treated BB Wor rat returned to preischaemic levels, whereas hearts from insulin-withdrawn rats displayed impaired recovery. Throughout reperfusion, heart rate, positive dP/dt, cardiac output and left ventricular minute work remained significantly lower in hearts from insulin-withdrawn rats compared to treated rats. Our results indicate that acute loss of metabolic control increases the sensitivity of the heart to ischaemia, even in the acutely diabetic BB Wor rat.

Key words  BB Wor - Insulin - Free fatty acids - Cardiac - Ischaemia

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