Tune J D, Mallet R T, Downey H F
Department of Integrative Physiology, University of North Texas Health Science Center at Fort Worth 76107-2699, USA.
Am J Physiol. 1998 May;274(5):H1574-81. doi: 10.1152/ajpheart.1998.274.5.H1574.
This study determined the effects of insulin on myocardial contractile function and glucose metabolism during moderate coronary hypoperfusion. Coronary perfusion pressure (CPP) was lowered from 100 to 60, 50, and 40 mmHg in the left anterior descending coronary artery of anesthetized, open-chest dogs. Regional glucose uptake (GU), lactate uptake, myocardial O2 consumption, and percent segment shortening (%SS) were measured without (n = 12) or with intravenous (4 U/min, n = 12) or intracoronary insulin (4 U/min, n = 6). Glucose metabolites were also measured in freeze-clamped biopsies of control heart (n = 6) and hearts treated with intravenous insulin (n = 6) at the completion of the protocol (40 mmHg CPP). GU increased with intravenous and intracoronary insulin (P < 0.01). In all groups, GU was unaffected by reduced CPP, although lactate uptake decreased significantly (P < 0.01). Myocardial O2 consumption fell (P < 0.05) as CPP was lowered in all groups and was not altered significantly by intravenous or intracoronary insulin treatment. Without insulin, %SS decreased 72% (P < 0.05) at 40 mmHg CPP, but in hearts treated with intravenous and intracoronary insulin, %SS was not reduced (P > 0.05). Myocardial glycogen, alanine, lactate, and pyruvate contents were not significantly different in untreated hearts and hearts treated with intravenous insulin. Thus, in moderately ischemic canine myocardium, insulin markedly improved regional contractile function and did not appreciably increase the products of anaerobic glucose metabolism.
本研究确定了胰岛素在中度冠状动脉灌注不足期间对心肌收缩功能和葡萄糖代谢的影响。在麻醉开胸犬的左前降支冠状动脉中,将冠状动脉灌注压(CPP)从100 mmHg降至60、50和40 mmHg。在未使用胰岛素(n = 12)、静脉注射胰岛素(4 U/min,n = 12)或冠状动脉内注射胰岛素(4 U/min,n = 6)的情况下,测量局部葡萄糖摄取(GU)、乳酸摄取、心肌耗氧量和节段缩短百分比(%SS)。在实验结束时(CPP为40 mmHg),还在对照心脏(n = 6)和静脉注射胰岛素治疗的心脏(n = 6)的冷冻钳夹活检组织中测量了葡萄糖代谢产物。静脉注射和冠状动脉内注射胰岛素后GU增加(P < 0.01)。在所有组中,尽管乳酸摄取显著降低(P < 0.01),但GU不受CPP降低的影响。随着所有组中CPP的降低,心肌耗氧量下降(P < 0.05),静脉注射或冠状动脉内胰岛素治疗未使其发生显著改变。在无胰岛素的情况下,在40 mmHg CPP时%SS降低了72%(P < 0.05),但在静脉注射和冠状动脉内注射胰岛素治疗的心脏中,%SS未降低(P > 0.05)。未治疗的心脏和静脉注射胰岛素治疗的心脏中,心肌糖原、丙氨酸、乳酸和丙酮酸含量无显著差异。因此,在中度缺血的犬心肌中,胰岛素显著改善了局部收缩功能,且未明显增加无氧葡萄糖代谢产物。