Chess-Williams R G, Sheridan D J, Broadley K J
Department of Pharmacology, Welsh School of Pharmacy, University of Wales College of Cardiff, UK.
J Mol Cell Cardiol. 1990 May;22(5):599-606. doi: 10.1016/0022-2828(90)90961-z.
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.
采用Langendorff法对豚鼠离体心脏进行灌注。低流量（10%）全心缺血30分钟分别使87.5%和37.5%的心脏诱发室性心动过速（VT）和室颤（VF）。VT和VF的起始时间分别为15.7±1.0分钟和23.5±1.6分钟。再灌注时，VT和VF的发生率分别为81.3%和75.0%，且分别在再灌注16.0±1.5秒和35.0±4.9秒后发生。在那些出现心律失常的心脏中，测定了[³H] - 哌唑嗪与心室膜部分α₁ - 肾上腺素能受体的结合情况，并与正常灌注的时间匹配对照组进行比较。在整个对照灌注期间，结合的解离常数（KD）或密度Bmax均无显著变化。同样，缺血期间获得的KD（0.38±0.06 nM）和Bmax（15.5±1.4 fmol/mg蛋白）值与相应的对照值（0.48±0.05 nM和15.8±1.5 fmol/mg蛋白）无显著差异。此外，在再灌注1分钟时，KD（0.42±0.04 nM）和Bmax（19.3±2.0 fmol/mg蛋白）值与时间匹配对照组（0.38±0.09 nM和20.1±2.6 fmol/mg蛋白）也无显著差异。如果使用最初低速离心沉淀的粗膜部分，也会得到相同的结果。因此，尽管豚鼠离体灌注心脏的缺血和再灌注会诱发心律失常，且先前的研究表明这些心律失常易受α - 肾上腺素能受体阻断的影响，但它们并未伴随着α₁ - 肾上腺素能受体亲和力或密度的增加。
