Plunkett M D, Hendry P J, Anstadt M P, Camporesi E M, Amato M T, St Louis J D, Lowe J E
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
J Thorac Cardiovasc Surg. 1996 Jul;112(1):8-13. doi: 10.1016/s0022-5223(96)70171-x.
The effect of chronic hypoxia on neonatal myocardial metabolism remains undefined. With a new neonatal piglet model, we determined changes in myocardial metabolism during global ischemia after chronic hypoxia. Five-day-old piglets (N = 30) were randomly assigned to two groups and exposed to an atmosphere of 8% oxygen or to room air for 28 days before they were killed. Left ventricular myocardium was then analyzed at control and at 15-minute intervals during 60 minutes of global normothermic ischemia to determine high-energy phosphate levels, glycogen stores, and lactate accumulation. Time to peak ischemic myocardial contracture was measured with intramyocardial needle-tipped Millar catheters as a marker of the onset of irreversible ischemic injury. Results showed an initially greater level of myocardial adenosine triphosphate in the hypoxic group (27 +/- 1.2 vs 19 +/- 1.8 micromol/gm dry wt, p = 0.001) and a delay in adenosine triphosphate depletion during 60 minutes of global ischemia compared with the control group. Initial energy charge ratios (1/2 adenosine diphosphate + adenosine triphosphate/adenosine monophosphate + adenosine diphosphate + adenosine triphosphate) were also greater in the hypoxic group (0.96 +/- 0.01 vs 0.81 +/- 0.04, p = 0.01) and remained so throughout global ischemia. Initial glycogen stores were greater in the hypoxic group (273 +/- 13.3 vs 215 +/- 14.7 micromol/gm dry weight, p = 0.02) when compared with the control group. Lactate levels in the hypoxic group were initially higher (19.1 +/- 6.4 vs 8.9 +/- 3.1 micromol/gm dry weight, p = 0.001) compared with control levels and remained elevated throughout 60 minutes of ischemia. Time to peak ischemic contracture was prolonged in the hypoxic group (69.5 +/- 1.8 vs 48.9 +/- 1.4 minutes, p = 0.001) compared with the controls group. These data show that chronic hypoxia results in significant myocardial metabolic adaptive changes, which in turn result in an improved tolerance to severe normothermic ischemia. These beneficial effects are associated with elevated baseline glycogen storage levels and an accelerated rate of anaerobic glycolysis during ischemia.
慢性缺氧对新生儿心肌代谢的影响尚不明确。利用一种新的新生仔猪模型，我们确定了慢性缺氧后全心缺血期间心肌代谢的变化。将5日龄仔猪（N = 30）随机分为两组，在处死前分别置于8%氧气环境或室内空气中28天。然后在正常体温下进行60分钟全心缺血期间，分别在对照时以及每隔15分钟对左心室心肌进行分析，以确定高能磷酸水平、糖原储备和乳酸积累情况。使用心肌内尖端带有Millar导管测量缺血性心肌挛缩达到峰值的时间，作为不可逆缺血性损伤开始的标志。结果显示，缺氧组心肌三磷酸腺苷的初始水平较高（27±1.2对19±1.8微摩尔/克干重，p = 0.001），与对照组相比，在60分钟全心缺血期间三磷酸腺苷耗竭出现延迟。缺氧组的初始能量电荷比（1/2二磷酸腺苷+三磷酸腺苷/一磷酸腺苷+二磷酸腺苷+三磷酸腺苷）也更高（0.96±0.01对0.81±0.04，p = 0.01），并且在整个全心缺血期间一直保持如此。与对照组相比，缺氧组的初始糖原储备更多（273±13.3对215±14.7微摩尔/克干重，p = 0.02）。缺氧组的乳酸水平最初高于对照组（19.1±6.4对8.9±3.1微摩尔/克干重，p = 0.001），并且在60分钟缺血期间一直保持升高。与对照组相比，缺氧组缺血性挛缩达到峰值的时间延长（69.5±1.8对48.9±1.4分钟，p = 0.001）。这些数据表明，慢性缺氧会导致显著的心肌代谢适应性变化，进而提高对严重正常体温缺血的耐受性。这些有益作用与缺血期间升高的基线糖原储存水平以及加速的无氧糖酵解速率有关。
