Serizawa T, Vogel W M, Apstein C S, Grossman W
J Clin Invest. 1981 Jul;68(1):91-102. doi: 10.1172/jci110258.
To clarify conflicting reports concerning the effects of ischemia on left ventricular chamber stiffness, we compared the effects of hypoxia at constant coronary perfusion with those of global ischemia on left ventricular diastolic chamber stiffness using isolated, perfused rabbit hearts in which the left ventricle was contracting isovolumically. Since chamber volume was held constant, increases in left ventricular end diastolic pressure (LVEDP) reflected increases in chamber stiffness. At a control coronary flow rate (30 ml/min), 2 min of hypoxia and pacing tachycardia (4.0 Hz) produced major increases in postpacing LVEDP (10+/-1 to 24+/-3 mm Hg, P < 0.01) and the relaxation time constant, T, (40+/-4 to 224+/-37 ms, P < 0.001), while percent lactate extraction ratio became negative (+ 18+/-2 to -48+/-15%, P < 0.001). Coronary perfusion pressure decreased (72+/-5 to 52+/-3 mm Hg, P < 0.01), and since coronary flow was held constant, the fall in coronary perfusion pressure reflected coronary dilation and a decrease in coronary vascular resistance. Following an average of 71+/-6s reoxygenation and initial heart rate (2.0 Hz), LVEDP and relaxation time constant T returned to control. Hypoxia alone (without pacing tachycardia) produced similar although less marked changes (LVEDP, 10+/-1 to 20+/-3 mm Hg; and T, 32+/-3 to 119+/-22 ms; P < 0.01 for both) and there was a strong correlation between LVEDP and T (r = 0.82, P < 0.001). When a similar degree of coronary vasodilatation was induced with adenosine, no change in LVEDP occurred, indicating that the increase in end diastolic pressure observed during hypoxia was not secondary to vascular engorgement, but due to an acute effect of hypoxia on the diastolic behavior of the ventricular myocardium. In contrast, global ischemia produced by low coronary flow (12-15 ml/min) resulted in a decrease in LVEDP, as well as a marked fall in left ventricular systolic pressure. In 14 global ischemia experiments, pacing tachycardia led to a further decline in left ventricular systolic pressure, and no increase was noted in postpacing LVEDP. Changes in lactate extraction ratio were much smaller in magnitude than with hypoxia and constant coronary perfusion. In two experiments (one at normal coronary flow and one at 15 ml/min), left ventricular systolic pressure did not change markedly from control when tachycardia was superimposed, and postpacing LVEDP showed a marked rise (to > 25 mm Hg), which gradually recovered over 1-2 min at the control heart rate. From these results, we conclude that left ventricular chamber stiffness increases when myocardial O(2) demand exceeds supply. This change is usually masked in ischemic (reduced coronary flow) preparations, perhaps because of reduced turgor of the coronary vascular bed, marked reductions in systolic work (and therefore myocardial O(2) requirements), and local accumulation of hydrogen ion and metabolites following acute severe reduction of coronary flow. The increased chamber stiffness during hypoxia is accompanied by marked slowing of relaxation, with increased diastolic pressure relative to volume persisting throughout diastole.
为澄清关于缺血对左心室腔僵硬度影响的相互矛盾的报道，我们在左心室等容收缩的离体灌注兔心脏中，比较了恒定冠状动脉灌注下缺氧与全心缺血对左心室舒张期腔僵硬度的影响。由于腔容积保持恒定，左心室舒张末期压力（LVEDP）的升高反映了腔僵硬度的增加。在对照冠状动脉流量（30 ml/min）下，2分钟的缺氧和起搏性心动过速（4.0 Hz）使起搏后LVEDP显著升高（从10±1 mmHg升至24±3 mmHg，P<0.01），舒张时间常数T也显著升高（从40±4 ms升至224±37 ms，P<0.001），而乳酸摄取率百分比变为负值（从+18±2%变为-48±15%，P<0.001）。冠状动脉灌注压力下降（从72±5 mmHg降至52±3 mmHg，P<0.01），由于冠状动脉流量保持恒定，冠状动脉灌注压力的下降反映了冠状动脉扩张和冠状动脉血管阻力的降低。在平均71±6秒的再氧合和初始心率（2.0 Hz）后，LVEDP和舒张时间常数T恢复到对照水平。单独缺氧（无起搏性心动过速）产生了类似但不太明显的变化（LVEDP从10±1 mmHg升至20±3 mmHg；T从32±3 ms升至119±22 ms；两者P均<0.01），且LVEDP与T之间存在强相关性（r = 0.82，P<0.001）。当用腺苷诱导相似程度的冠状动脉扩张时，LVEDP无变化，表明缺氧期间观察到的舒张末期压力升高并非继发于血管充血，而是由于缺氧对心室心肌舒张行为的急性影响。相比之下，低冠状动脉流量（12 - 15 ml/min）导致的全心缺血导致LVEDP降低，以及左心室收缩压显著下降。在14次全心缺血实验中，起搏性心动过速导致左心室收缩压进一步下降，起搏后LVEDP未升高。乳酸摄取率的变化幅度比缺氧和恒定冠状动脉灌注时小得多。在两个实验中（一个在正常冠状动脉流量下，一个在15 ml/min下），当叠加心动过速时，左心室收缩压与对照相比无明显变化，起搏后LVEDP显著升高（>25 mmHg），在对照心率下1 - 2分钟内逐渐恢复。从这些结果中，我们得出结论，当心肌氧需求超过供应时，左心室腔僵硬度增加。这种变化在缺血（冠状动脉流量减少）的标本中通常被掩盖，可能是因为冠状动脉血管床的膨胀减少、收缩功显著降低（因此心肌氧需求降低）以及冠状动脉流量急性严重减少后氢离子和代谢产物的局部积累。缺氧期间腔僵硬度增加伴随着舒张明显减慢，相对于容积的舒张压升高在整个舒张期持续存在。
