Herzog C A, Aeppli D P, Bache R J
J Am Coll Cardiol. 1984 Dec;4(6):1174-83. doi: 10.1016/s0735-1097(84)80135-7.
The effect of beta-adrenergic blockade with timolol (40 micrograms/kg) on myocardial blood flow during rest and graded treadmill exercise was assessed in 12 chronically instrumented dogs 10 to 14 days after myocardial infarction was produced by acute left circumflex coronary artery occlusion. During exercise at comparable external work loads, the heart rate-systolic blood pressure product was significantly decreased after timilol, with concomitant reductions of myocardial blood flow in normal, border and central ischemic areas (p less than 0.001) and increases in subendocardial/subepicardial blood flow ratios (p less than 0.05). In addition to the blunted chronotropic response to exercise, timolol exerted an effect on myocardial blood flow that was not explained by changes in heart rate or blood pressure. At comparable rate-pressure products during exercise, total myocardial blood flow was 24% lower after timolol (p less than 0.02) and flow was redistributed from subepicardium to subendocardium in all myocardial regions. Thus, timolol altered myocardial blood flow during exercise by two separate mechanisms: a negative chronotropic effect, and a significant selective reduction of subepicardial perfusion independent of changes in heart rate or blood pressure with transmural redistribution of flow toward the subendocardium.
在12只经长期仪器植入的犬中，于急性左旋冠状动脉闭塞造成心肌梗死后10至14天，评估了噻吗洛尔（40微克/千克）进行β-肾上腺素能阻滞对静息和分级运动时心肌血流的影响。在同等外部工作负荷的运动过程中，噻吗洛尔给药后心率-收缩压乘积显著降低，同时正常、边缘和中央缺血区域的心肌血流减少（p<0.001），心内膜下/心外膜下血流比值增加（p<0.05）。除了对运动的变时反应减弱外，噻吗洛尔对心肌血流产生了一种不能用心率或血压变化来解释的影响。在运动过程中同等的心率-血压乘积时，噻吗洛尔给药后总心肌血流降低24%（p<0.02），且所有心肌区域的血流都从心外膜重新分布到心内膜下。因此，噻吗洛尔通过两种不同机制改变运动时的心肌血流：负性变时效应，以及与心率或血压变化无关的显著的心外膜灌注选择性降低，血流跨壁重新分布向心内膜下。
