Portman M A, Standaert T A, Ning X H
Department of Pediatrics, University of Washington, Seattle 98195, USA.
J Clin Invest. 1995 May;95(5):2134-42. doi: 10.1172/JCI117902.
This study investigates the relation between myocardial oxygen consumption (MVO2), function, and high energy phosphates during severe hypoxia and reoxygenation in sheep in vivo. Graded hypoxia was performed in open-chested sheep to adjust PO2 to values where rapid depletion of energy stores occurred. Highly time-resolved 31P nuclear magnetic resonance spectroscopy enabled monitoring of myocardial phosphates throughout hypoxia and recovery with simultaneous MVO2 measurement. Sheep undergoing graded hypoxia (n = 5) with an arterial PO2 nadir of 13.4 +/- 0.5 mmHg, demonstrated maintained rates of oxygen consumption with large changes in coronary flow as phosphocreatine (PCr) decreased within 4 min to 40 +/- 7% of baseline. ATP utilization rate increased simultaneously 59 +/- 20%. Recovery was accompanied by marked increases in MVO2 from 2.0 +/- 0.5 to 7.2 +/- 1.9 mumol/g per min, while PCr recovery rate was 4.3 +/- 0.6 mumol/g per min. ATP decreased to 75 +/- 6% of baseline during severe hypoxia and did not recover. Sheep (n = 5) which underwent moderate hypoxia (PO2 maintained 25-35 mmHg for 10 min) did not demonstrate change in PCr or ATP. Functional and work assessment (n = 4) revealed that cardiac power increased during the graded hypoxia and was maintained through early reoxygenation. These studies show that (a) MVO2 does not decrease during oxygen deprivation in vivo despite marked and rapid decreases in high energy phosphates; (b) contractile function during hypoxia in vivo does not decrease during periods of PCr depletion and intracellular phosphate accumulation, and this may be related to marked increases in circulating catecholamines during global hypoxia. The measured creatine rephosphorylation rate is 34 +/- 11% of predicted (P < 0.01) calculated from reoxygenation parameters, which indicates that some mitochondrial respiratory uncoupling also occurs during the rephosphorylation period.
本研究调查了绵羊在体严重缺氧和复氧过程中心肌耗氧量（MVO2）、功能及高能磷酸化合物之间的关系。对开胸绵羊进行分级缺氧，将动脉血氧分压（PO2）调整至能量储备快速耗竭时的值。高时间分辨率的31P核磁共振波谱技术能够在整个缺氧和恢复过程中监测心肌磷酸盐，同时测量MVO2。经历分级缺氧（n = 5）且动脉PO2最低点为13.4±0.5 mmHg的绵羊，随着磷酸肌酸（PCr）在4分钟内降至基线的40±7%，冠状动脉血流量发生大幅变化，但耗氧率保持不变。ATP利用率同时增加了59±20%。复氧时MVO2显著增加，从2.0±0.5升至7.2±1.9 μmol/g每分钟，而PCr恢复率为4.3±0.6 μmol/g每分钟。严重缺氧时ATP降至基线的75±6%且未恢复。经历中度缺氧（PO2在25 - 35 mmHg维持10分钟）的绵羊（n = 5），PCr或ATP未出现变化。功能和做功评估（n = 4）显示，分级缺氧期间心脏功率增加，并在早期复氧过程中保持。这些研究表明：（a）尽管高能磷酸化合物显著快速减少，但体内缺氧时MVO2并未降低；（b）体内缺氧期间，在PCr耗竭和细胞内磷酸盐积累阶段，收缩功能并未降低，这可能与整体缺氧期间循环儿茶酚胺显著增加有关。根据复氧参数计算，测得的肌酸再磷酸化率为预测值的34±11%（P < 0.01），这表明在再磷酸化期间也发生了一些线粒体呼吸解偶联。
