Pump function of the feline left heart: changes with heart rate and its bearing on the energy balance

Abstract

The isolated perfused working rat heart model of cardiopulmonary bypass and ischaemic cardiac arrest has been used to investigate whether addition of various organic anti-oxidants to the St Thomas' Hospital cardioplegic solution can enhance the recovery of function of the rat myocardium after normothermic (37°C) global ischaemic arrest. Five anti-oxidants were studied: (i) ascorbate (1.0 and 10.0 mmol·litre⁻¹), (ii) methionine (1.0 and 10.0 mmol·litre⁻¹), (iii) reduced glutathione (1.0 and 10.0 mmol·litre⁻¹), (iv) dimethylthiourea (0.1, 1.0, 10.0 and 50.0 mmol·litre⁻¹), (v) N-2-mercaptopropionyl glycine (0.1, 1.0 and 10.0 mmol·litre⁻¹). The recovery of aortic flow in control hearts which were free of anti-oxidant was 50.7(SEM 0.5)%; ascorbate (1.0 or 10.0 mmol·litre⁻¹) improved this recovery to 72.1(1.7) and 70.2(0.3)% respectively; methionine (1.0 and 10.0 mmol·litre⁻¹) improved the recovery to 74.1(5.7)% and 67.7(1.7)%, respectively; reduced glutathione (1.0 and 10.0 mmol·litre⁻¹) improved the recovery to 66.7(1.4)% and 74.0(1.7)% respectively. In further studies, the addition of dimethylthiourea (0.1, 1.0 and 10.0 mmol·litre⁻¹) to the cardioplegic solution failed to improve recovery of aortic flow [47.3(8.0), 24.6(7.3), 48.0(7.7)% respectively] when compared to its anti-oxidant free control value of 40.4(6.1)% and at a concentration of 50.0 mmol·litre⁻¹ a very poor recovery of aortic flow of 7.7(4.8)% was observed. Mercaptopropionyl glycine (0.1, 1.0 and 10.0 mmol·litre⁻¹) also failed to improve the recovery of aortic flow [34.7(1.6), 34.7(7.7) and 25.6(5.4)% respectively]. Since biological membranes are highly permeable to dimethylthiourea and mercaptopropionyl glycine, it is possible that they accumulate in the intracellular compartment. However, ascorbate, methionine and reduced glutathione do not readily penetrate the cell membrane, so it is more likely that they exert their effects at an extracellular site. The results from this study might indicate that, if free radicals contribute to cell damage during reperfusion, an extracellular site may be involved.