Arrhythmias and alpha 1-adrenoceptor binding characteristics of the guinea-pig perfused heart during ischaemia and reperfusion

Abstract

Guinea-pig isolated hearts were perfused by the Langendorff method. Low flow (10%) global ischaemia for 30 min induced ventricular tachycardia (VT) and fibrillation (VF) in 87.5 and 37.5% respectively of the hearts. The onset times for VT and VF were 15.7 +/- 1.0 and 23.5 +/- 1.6 min respectively. On reperfusion the incidences of VT and VF were 81.3 and 75.0% and occurred after 16.0 +/- 1.5 and 35.0 +/- 4.9 s of reperfusion. In those hearts exhibiting arrhythmias, [3H]-prazosin binding to alpha 1-adrenoceptors of ventricular membrane fractions was measured and compared with normally perfused time-matched controls. There was no significant change in dissociation constant (KD) or density Bmax, of binding throughout the control perfusion period. Similarly, the KD (0.38 +/- 0.06 nM) and Bmax (15.5 +/- 1.4 fmol/mg protein) values obtained during ischaemia did not differ significantly from the corresponding control values (0.48 +/- 0.05 nM and 15.8 +/- 1.5 fmol/mg protein). Also, at 1 min of reperfusion the KD (0.42 +/- 0.04 nM) and Bmax (19.3 +/- 2.0 fmol/mg protein) values were not significantly different from the time-matched controls (0.38 +/- 0.09 nM and 20.1 +/- 2.6 fmol/mg protein). The same result was obtained if the crude membrane fraction pelleted by the initial slow spin was used. Thus, although cardiac arrhythmias are induced by ischaemia and reperfusion of the guinea-pig isolated perfused heart and previous studies have shown these to be susceptible to alpha-adrenoceptor blockade, they are not accompanied by an increase in alpha 1-adrenoceptor affinity or density.