Cunningham M J, Apstein C S, Weinberg E O, Vogel W M, Lorell B H
Cardiac Muscle Research Laboratory, Boston University School of Medicine, Massachusetts.
Circ Res. 1990 Feb;66(2):406-15. doi: 10.1161/01.res.66.2.406.
Myocardial hypertrophy can result in increased sensitivity toward the development of mechanical dysfunction during hypoxia. Alterations in glycolytic metabolism may contribute to this. We studied the response to 15 minutes of hypoxia in hypertrophied (deoxycorticosterone-salt hypertension model) and nonhypertrophied rat hearts and examined the influence of a high glucose (27.5 mM) and insulin (100 mU/ml) concentration. In response to hypoxia in the presence of a normal glucose concentration (5.5 mM), left ventricular end-diastolic pressure was higher in hypertrophied than in nonhypertrophied hearts (65 +/- 6 vs. 44 +/- 4 mm Hg; p less than 0.05). Perfusion with high glucose and insulin blunted the rise in left ventricular end-diastolic pressure in both hypertrophied and nonhypertrophied hearts and abolished the difference in diastolic dysfunction between groups during hypoxia (26 +/- 2 vs. 32 +/- 4 mm Hg, respectively; p = NS). At end hypoxia in the presence of a normal glucose concentration, developed pressure was more depressed in hypertrophied than in nonhypertrophied hearts (11 +/- 1 vs. 18 +/- 1% of baseline, respectively; p less than 0.05). Perfusion with high glucose and insulin resulted in improved function in both groups during hypoxia such that a greater impairment of developed pressure was no longer present in the hypertrophied versus nonhypertrophied hearts (21 +/- 1 vs. 24 +/- 2% of baseline, respectively; p = NS). At the end of hypoxic perfusion in the presence of a normal glucose concentration, hypertrophied hearts were producing 38% less lactate than nonhypertrophied hearts. Perfusion with high glucose and insulin increased lactate production in both groups and equalized lactate production between groups. Thus, the greater deterioration in hemodynamic function in hypertrophied hearts compared with nonhypertrophied hearts during hypoxia is associated with lower lactate production. Both the exaggerated hemodynamic dysfunction and deficient lactate production can be ameliorated by perfusion with a high glucose concentration and insulin.
心肌肥大可导致在缺氧期间对机械功能障碍发展的敏感性增加。糖酵解代谢的改变可能对此有影响。我们研究了肥大（脱氧皮质酮-盐高血压模型）和非肥大大鼠心脏对15分钟缺氧的反应，并考察了高葡萄糖（27.5 mM）和胰岛素（100 mU/ml）浓度的影响。在正常葡萄糖浓度（5.5 mM）存在的情况下对缺氧的反应中，肥大心脏的左心室舒张末期压力高于非肥大心脏（65±6 vs. 44±4 mmHg；p<0.05）。用高葡萄糖和胰岛素灌注可使肥大和非肥大心脏的左心室舒张末期压力升高均减弱，并消除缺氧期间两组间舒张功能障碍的差异（分别为26±2 vs. 32±4 mmHg；p=无显著性差异）。在正常葡萄糖浓度存在的情况下缺氧结束时，肥大心脏的舒张压力比非肥大心脏下降更明显（分别为基线的11±1% vs. 18±1%；p<0.05）。用高葡萄糖和胰岛素灌注可使两组在缺氧期间功能得到改善，使得肥大心脏与非肥大心脏相比不再存在更大的舒张压力损害（分别为基线的21±1% vs. 24±2%；p=无显著性差异）。在正常葡萄糖浓度存在的情况下缺氧灌注结束时，肥大心脏产生的乳酸比非肥大心脏少38%。用高葡萄糖和胰岛素灌注可增加两组的乳酸产生，并使两组间乳酸产生量相等。因此，与非肥大心脏相比，肥大心脏在缺氧期间血流动力学功能的更大恶化与较低的乳酸产生有关。通过高葡萄糖浓度和胰岛素灌注，过度的血流动力学功能障碍和乳酸产生不足均可得到改善。
