The influence of isosorbide dinitrate on regional myocardial blood flow during acute coronary occlusion in the dog

Summary: We investigated the influence of isosorbide dinitrate (ISDN), alone and combined with methoxamine, on regional myocardial blood flow during acute coronary occlusion. Cardiac output, mean aortic pressure, and heart rate were kept constant in open chest, chloralose anaesthetised dogs so that coronary flow alterations would be relatively independent of haemodynamic effects. Regional myocardial blood flow was measured using 9 μm radioactive microspheres. Mean aortic pressure, left ventricular end diastolic pressure and maximum left ventricular dP/dt were unchanged by ISDN. Studies of ISDN (5mg) treatment before the second of two 10 min consecutive reversible ligations of the left anterior descending coronary artery (LAD) demonstrated: (1) ISDN infused 35 min before LAD ligation increased collateral coronary blood flow to ischaemic myocardium 27± 9% (P <0.05); (2) ISDN + methoxamine infused 35 min before LAD ligation increased collateral coronary blood flow to ischaemic myocardium 8 ± 4% (NS). ISDN(5mg) treatment 20 min after LAD ligation demonstrated: (1) collateral coronary blood flow to ischaemic myocardium increased 11 ± 7% (NS), 23± 5% (P <0.005) and 17± 5% (P <0.02) at 15, 30, and 45 min, respectively, after drug treatment when compared with blood flow measured just before drug treatment and collateral coronary blood flow 60, 75, and 90 min after drug treatment was not significantly different from control. The results suggest that preligation and postligation administration of ISDN significantly increases collateral coronary blood flow to ischaemic myocardium and the effect continues at least 45 min after treatment. In these studies the addition of methoxamine to ISDN did not further increase collateral coronary blood flow and in fact appeared to slightly decrease blood flow when compared with ISDN alone.