Global and regional ventricular function following intracoronary application of papaverine

Intracoronary injection of papaverine is used to determine coronary flow reserve in patients. The present study was to investigate the effect of papaverine on the performance of myocardium with reduced flow reserve. In nine anaesthetized open-chest dogs a bypass from the aorta to the left circumflex coronary artery (LCX) was established. Left ventricular end-diastolic and aortic pressure, dP/dt, stroke volume, LCX blood flow, and ECG were monitored. The performance of a segment of subendocardial wall supplied by the LCX was assessed by sonomicrometry. Peak reactive hyperaemia after 15s bypass occlusion was 1.44 +/- 0.09 times the baseline flow (41 ml/min), indicating reduced coronary flow reserve. Papaverine was injected into the bypass (0.3, 0.6, 1.2, 2.5, 5.0 mg/ml, 1 ml in 15s). The maximum LCX flow following PAPA 0.3 mg was comparable to peak reactive hyperaemia, but 10-15% higher after injection of 0.6-5.0 mg papaverine. Systolic shortening of the myocardium (control: 17.5% of end-diastolic length) became reduced in a dose-dependent fashion (5-25%) for about 1 min following papaverine injection. Stroke volume (control: 0.94 +/- 0.12 ml/kg) was reduced by about 8%, left ventricular end-diastolic pressure (control: 6.2 +/- 0.8 mmHg) increased by 15%, and dP/dtmin (control: 1850 +/- 150 mmHg/s) was curtailed by 15-25%. The ECG showed a transient T inversion and S-T depression following papaverine administration and in one experiment ventricular fibrillation occurred after the injection of 2.5 mg papaverine. The observed effects of intracoronary papaverine are consistent with the theory of transient subendocardial ischaemia arising from a redistribution of blood flow from the subendocardial to the subepicardial layers, because of greater vasodilatory capacity in the latter than in the former.