Nielsen T T, Bagger J P, Thomassen A
Br Heart J. 1986 Feb;55(2):140-7. doi: 10.1136/hrt.55.2.140.
Ten patients with chronic effort angina and coronary artery disease (luminal diameter reduction greater than 75%) were stressed by atrial pacing (140 beats/minutes) before and 15 minutes after intravenous propranolol (mean dose 7.4 mg). Myocardial substrate exchange of oxygen, blood lactate, plasma free fatty acids, citrate, glucose, glutamate, and alanine as well as coronary sinus blood flow were measured. Coronary sinus blood flow, oxygen consumption, and systemic haemodynamics did not change after propranolol. Propranolol did not influence arterial lactate concentration, and it reduced the arterial concentration of free fatty acid by 37% and increased that of glutamate by 21%. During pacing myocardial lactate extraction increased in all 10 patients; in two lactate release was converted to lactate uptake. Propranolol reduced free fatty acid uptake and increased glutamate uptake during pacing. For both substances the changes in aortocoronary sinus differences or in uptake or both correlated positively with the changes in their delivery to the heart from extracardial sources (arterial concentrations/loads). In the unstressed state before pacing, aortocoronary sinus lactate differences correlated inversely with free fatty acid differences and positively with those of glutamate. During pacing the relation between lactate and glutamate differences remained positive while the inverse correlation between lactate and free fatty acid differences was lost. Myocardial citrate release was halved during pacing and recovery. Propranolol did not influence alanine or glucose exchanges. An improved myocardial lactate extraction after propranolol administration may be secondary to decreased free fatty acid uptake or increased glutamate uptake or both. In the unstressed state both mechanisms may be of importance. During pacing induced ischaemia, increased glutamate uptake is more likely than reduced free fatty acid uptake to be the mechanism responsible for the improvement in myocardial lactate extraction. The propranolol mediated alterations in myocardial substrate exchanges may reflect the extracardial effects of the drug.
10例患有慢性劳力性心绞痛和冠状动脉疾病（管腔直径缩小大于75%）的患者，在静脉注射普萘洛尔（平均剂量7.4毫克）前及注射后15分钟，通过心房起搏（140次/分钟）进行负荷试验。测量了心肌对氧、血乳酸、血浆游离脂肪酸、柠檬酸、葡萄糖、谷氨酸和丙氨酸的底物交换以及冠状窦血流量。普萘洛尔注射后，冠状窦血流量、氧消耗和全身血流动力学未发生变化。普萘洛尔不影响动脉血乳酸浓度，使动脉游离脂肪酸浓度降低37%，使谷氨酸浓度升高21%。在起搏过程中，所有10例患者的心肌乳酸摄取均增加；其中2例患者的乳酸释放转变为乳酸摄取。普萘洛尔在起搏过程中减少了游离脂肪酸摄取，增加了谷氨酸摄取。对于这两种物质，主动脉-冠状窦差异或摄取量的变化或两者的变化与它们从心外来源输送到心脏的变化（动脉浓度/负荷）呈正相关。在起搏前的非负荷状态下，主动脉-冠状窦乳酸差异与游离脂肪酸差异呈负相关，与谷氨酸差异呈正相关。在起搏过程中，乳酸和谷氨酸差异之间的关系仍为正相关，而乳酸和游离脂肪酸差异之间的负相关消失。起搏和恢复过程中，心肌柠檬酸释放减半。普萘洛尔不影响丙氨酸或葡萄糖交换。普萘洛尔给药后心肌乳酸摄取改善可能继发于游离脂肪酸摄取减少或谷氨酸摄取增加或两者兼有。在非负荷状态下，这两种机制可能都很重要。在起搏诱导的缺血过程中，谷氨酸摄取增加比游离脂肪酸摄取减少更可能是心肌乳酸摄取改善的机制。普萘洛尔介导的心肌底物交换改变可能反映了该药物的心外效应。
