Clozel J P, Holck M, Osterrieder W, Burkard W, Da Prada M D
Pharmaceutical Research Department, F Hoffmann-La Roche & Co Ltd, Basel, Switzerland.
Cardiovasc Res. 1987 Sep;21(9):688-95. doi: 10.1093/cvr/21.9.688.
Responsiveness to catecholamines and alterations in myocardial beta adrenoceptors were determined in rats with chronic myocardial infarction. Myocardial infarction was produced by ligating the left main coronary artery. Three weeks after myocardial infarction, when left ventricular function was impaired, catecholamine responsiveness was determined by measuring the effects of isoprenaline in the conscious animal, the isolated perfused heart, the isolated right atria, and the right papillary muscles. The catecholamine content and the density and affinity of beta adrenergic receptors [( 3H]dihydroalprenolol binding) were determined in non-ischaemic myocardium (ventricular septum). In conscious rats isoprenaline induced the same tachycardia in the sham operated as in the rats with infarction, but it induced only a slight increase of myocardial contractility because of a high basal sympathetic tone. In isolated perfused hearts, right atria, and right papillary muscles isoprenaline increased contractile force and heart rate with the same EC50 in both groups. However, in the infarcted group the maximal increase of contractile force induced by isoprenaline was smaller because of mechanical limitation due to the infarction. The catecholamine content was decreased in non-ischaemic myocardium and beta adrenergic density was increased by 30% (p less than 0.02) without any change of affinity. Thus in rats chronic myocardial infarction does not change the responsiveness of the non-ischaemic myocardium to isoprenaline and is not associated with a downregulation of the beta adrenoceptors.
在患有慢性心肌梗死的大鼠中，测定了对儿茶酚胺的反应性以及心肌β肾上腺素能受体的变化。通过结扎左冠状动脉主干造成心肌梗死。心肌梗死后三周，当左心室功能受损时，通过测量异丙肾上腺素对清醒动物、离体灌注心脏、离体右心房和右乳头肌的作用来测定儿茶酚胺反应性。在非缺血心肌（室间隔）中测定儿茶酚胺含量以及β肾上腺素能受体的密度和亲和力[（3H）二氢阿普洛尔结合]。在清醒大鼠中，异丙肾上腺素在假手术组和梗死组中引起相同的心动过速，但由于基础交感神经张力高，它仅引起心肌收缩力轻微增加。在离体灌注心脏、右心房和右乳头肌中，异丙肾上腺素在两组中以相同的EC50增加收缩力和心率。然而，在梗死组中，由于梗死导致的机械限制，异丙肾上腺素诱导的收缩力最大增加较小。非缺血心肌中的儿茶酚胺含量降低，β肾上腺素能密度增加30%（p<0.02），亲和力无任何变化。因此，在大鼠慢性心肌梗死中，非缺血心肌对异丙肾上腺素的反应性未改变，且与β肾上腺素能受体的下调无关。
