Momomura S, Nagai Y, Ogawa T, Bessho M, Yamashita H, Serizawa T
Second Department of Internal Medicine, University of Tokyo, Japan.
J Mol Cell Cardiol. 1993 May;25(5):551-62. doi: 10.1006/jmcc.1993.1065.
To study the responses of myocardial function and metabolism to hypoxia in normal hamsters and cardiomyopathic hamsters (Bio 14.6), left ventricular pressure was measured in an isolated isovolumically beating heart preparation, and myocardial high energy phosphates (ATP and creatine phosphate), inorganic phosphate, and intracellular pH were also measured by 31P nuclear magnetic resonance spectroscopy. In 20-week-old cardiomyopathic hamsters, the heart weight was increased and the baseline left ventricular developed pressure, peak positive dP/dt, and peak negative dP/dt were decreased, indicating depression of left ventricular function. In control hamsters, left ventricular end-diastolic pressure rose markedly (+481 +/- 70%), and left ventricular developed pressure decreased (-57 +/- 6%) during 30 mins period of hypoxic perfusion. Correspondingly, myocardial content of ATP (-42 +/- 17%) and creatine phosphate (-48 +/- 14%) was decreased and that of inorganic phosphate was increased (+185 +/- 127%). Intracellular pH was also decreased (-0.20 +/- 0.13). In contrast, cardiomyopathic hamsters, showed a relatively slight increase in left ventricular end-diastolic pressure (+106 +/- 83%, P < 0.01 vs. control hamsters), although the decrease in left ventricular developed pressure (-50 +/- 5%) was comparable to that in control hamsters. The recovery of left ventricular end-diastolic pressure and developed pressure during reoxygenation was better in cardiomyopathic hamsters. The decrease in myocardial ATP (-13 +/- 26%, P < 0.01 vs. control hamsters), the increase in inorganic phosphate (+95 +/- 88%, P < 0.05 vs. control hamsters), and the decrease in intracellular pH (-0.06 +/- 0.06, P < 0.01 vs. control hamsters) during hypoxia were much less marked in cardiomyopathic hamsters. Only the decrease in creatine phosphate (-32 +/- 16%) was comparable to that in control hamsters. Thus, in cardiomyopathic hamsters, the deterioration of left ventricular diastolic function, systolic function, and myocardial energy metabolism during hypoxia was mild compared with the change in control healthy hamsters. This increased tolerance of cardiomyopathic hearts to hypoxia may be related to alterations in myocardial contractile proteins and/or energy utilization, or substrate availability.
为研究正常仓鼠和心肌病仓鼠（Bio 14.6）心肌功能和代谢对缺氧的反应，在离体等容搏动心脏标本中测量左心室压力，并用31P核磁共振波谱法测量心肌高能磷酸盐（ATP和磷酸肌酸）、无机磷酸盐和细胞内pH值。在20周龄的心肌病仓鼠中，心脏重量增加，基线左心室舒张末压力、最大正dP/dt和最大负dP/dt降低，表明左心室功能受抑制。在对照仓鼠中，缺氧灌注30分钟期间，左心室舒张末压力显著升高（+481±70%），左心室舒张末压力降低（-57±6%）。相应地，心肌ATP含量（-42±17%）和磷酸肌酸含量（-48±14%）降低，无机磷酸盐含量增加（+185±127%）。细胞内pH值也降低（-0.20±0.13）。相比之下，心肌病仓鼠左心室舒张末压力升高相对较小（+106±83%，与对照仓鼠相比P<0.01），尽管左心室舒张末压力降低（-50±5%）与对照仓鼠相当。心肌病仓鼠复氧期间左心室舒张末压力和舒张末压力的恢复情况更好。缺氧期间，心肌病仓鼠心肌ATP降低（-13±26%，与对照仓鼠相比P<0.01）、无机磷酸盐增加（+95±88%，与对照仓鼠相比P<0.05）和细胞内pH值降低（-0.06±0.06，与对照仓鼠相比P<0.01）的程度要小得多。只有磷酸肌酸降低（-32±16%）与对照仓鼠相当。因此，与对照健康仓鼠的变化相比，心肌病仓鼠在缺氧期间左心室舒张功能、收缩功能和心肌能量代谢的恶化程度较轻。心肌病心脏对缺氧耐受性的增加可能与心肌收缩蛋白和/或能量利用或底物可用性的改变有关。
