Yamamoto H, Avkiran M
Cardiovascular Research, Rayne Institute, St. Thomas' Hospital, London, England.
J Thorac Cardiovasc Surg. 1993 Jan;105(1):120-31.
The effect of pressure overload during postnatal development on (1) coronary reserve and (2) tolerance to cardioplegic arrest and hypothermic ischemia was investigated. Left ventricular pressure overload was induced in 1-week-old rats by aortic constriction (group AC), with control rats (group C) undergoing sham operation. Relative to group C rats, left ventricular weight/body weight ratio in group AC increased by 50% to 80% at 3 weeks of age and by 100% to 120% at 6 weeks of age. At these ages, hearts were isolated from group C and AC rats and Langendorff-perfused with bicarbonate buffer at perfusion pressures of 75 and 110 mm Hg, respectively. In the first study, minimal coronary vascular resistance was assessed during perfusion with adenosine (10 mumol/L). There was no difference in total minimal coronary vascular resistance between groups C and AC at 3 weeks of age. Total minimal coronary vascular resistance decreased with increasing cardiac mass between 3 and 6 weeks of age in group C (from 6.9 +/- 0.4 to 4.5 +/- 0.2 mm Hg/ml/min, p < 0.05), but not in group AC. Between these ages, minimal coronary vascular resistance per unit heart weight increased to a greater extent in group AC (from 2.9 +/- 0.2 to 7.0 +/- 0.3 mm Hg/ml/min/gm, p < 0.05) than in group C (from 1.8 +/- 0.0 to 2.7 +/- 0.1 mm Hg/ml/min/gm, p < 0.05). In the second study, hearts were arrested with St. Thomas' Hospital cardioplegic solution (15 degrees C) and subjected to hypothermic (15 degrees C) global ischemia (210 minutes at 3 weeks and 180 minutes at 6 weeks) followed by 65 minutes of reperfusion. At 3 weeks of age, coronary resistance profiles, changes in left ventricular end-diastolic pressure, and recoveries of left ventricular developed pressure during reperfusion were similar in groups C and AC. At 6 weeks of age, however, group AC had greater coronary resistance during reperfusion, a greater increase in left ventricular end-diastolic pressure (28 +/- 5 versus 1 +/- 1 mm Hg, p < 0.05), and consequently a reduced recovery of left ventricular developed pressure (50.7% +/- 3.6% versus 75.9% +/- 4.0%, p < 0.05) relative to group C. Thus 2 weeks of left ventricular pressure overload during neonatal development in the rat has little effect on coronary reserve and ischemic tolerance. Prolonged (5 weeks) pressure overload, however, results in postischemic diastolic dysfunction, which may be due to perfusion abnormalities during reperfusion.
研究了出生后发育过程中压力超负荷对（1）冠状动脉储备以及（2）心脏停搏和低温缺血耐受性的影响。通过主动脉缩窄在1周龄大鼠中诱导左心室压力超负荷（AC组），对照组大鼠（C组）接受假手术。相对于C组大鼠，AC组左心室重量/体重比在3周龄时增加50%至80%，在6周龄时增加100%至120%。在这些年龄，从C组和AC组大鼠分离心脏，分别在75和110 mmHg的灌注压力下用碳酸氢盐缓冲液进行Langendorff灌注。在第一项研究中，在用腺苷（10 μmol/L）灌注期间评估最小冠状动脉血管阻力。3周龄时C组和AC组之间的总最小冠状动脉血管阻力没有差异。C组在3至6周龄期间总最小冠状动脉血管阻力随心脏质量增加而降低（从6.9±0.4降至4.5±0.2 mmHg/ml/min，p<0.0），但AC组没有。在这些年龄之间，AC组每单位心脏重量的最小冠状动脉血管阻力比C组增加幅度更大（从2.9±0.2至7.0±0.3 mmHg/ml/min/gm，p<0.05）（从1.8±0.0至2.7±0.1 mmHg/ml/min/gm，p<0.05）。在第二项研究中，用圣托马斯医院心脏停搏液（15℃）使心脏停搏，并进行低温（15℃）全心缺血（3周时210分钟，6周时180分钟），然后再灌注65分钟。3周龄时，C组和AC组在再灌注期间的冠状动脉阻力曲线、左心室舒张末期压力变化以及左心室发育压力恢复情况相似。然而，在6周龄时，AC组在再灌注期间冠状动脉阻力更大，左心室舒张末期压力增加幅度更大（28±5对1±1 mmHg，p<0.05），因此相对于C组，左心室发育压力恢复降低（50.7%±3.6%对75.9%±4.0%，p<0.05）。因此，大鼠新生儿发育期间2周的左心室压力超负荷对冠状动脉储备和缺血耐受性影响很小。然而，长期（5周）压力超负荷会导致缺血后舒张功能障碍，这可能是由于再灌注期间的灌注异常所致。
