Prabhu S D
Department of Medicine/Cardiology, University of Texas Health Science Center, San Antonio 78284-7872, USA.
Cardiovasc Res. 1998 Dec;40(3):483-91. doi: 10.1016/s0008-6363(98)00201-6.
Although the myocardial force-interval and relaxation-interval relations are considered to be mechanical expressions of myocardial Ca2+ handling, correlation of these phenomena with altered Ca2+ kinetics in the intact state is limited. Thus, I sought to determine the impact of selective impairment of physiologic sarcoplasmic reticulum Ca2+ release, achieved by the use of the drug ryanodine, on these relations in the intact animal.
Twelve dogs instrumented with left ventricular manometers and piezoelectric dimension crystals were studied before and after ryanodine (4 micrograms/kg intravenously). End-systolic elastance was measured at paced heart rates of 120-180 bpm to determine the force-frequency response. Mechanical restitution and relaxation restitution were determined by measuring contractile (single beat elastance) and relaxation (peak negative dP/dt) responses for beats delivered at graded extrasystolic intervals, with normalized responses expressed as a function of extrasystolic interval.
Ryanodine accelerated mechanical restitution (time constant 60.3 +/- 3.9 versus 81.7 +/- 10.1 ms, p < 0.05) and reduced maximal contractile response (107.5 +/- 2.1 versus 122.1 +/- 5.7%, p < 0.05), slowed early relaxation restitution (time constant 65.5 +/- 13.8 versus 36.8 +/- 3.8 ms, p < 0.05) without changing late relaxation restitution kinetics, and amplified the force-frequency response (end-systolic elastance, 180 bpm, 19.4 +/- 4.3 versus 11.4 +/- 1.2 mm Hg/ml, p < 0.05).
These findings suggest that in the intact animal, Ca2+ handling by the sarcoplasmic reticulum is a primary determinant of mechanical restitution and early relaxation restitution, but not late relaxation restitution. Conversely, ryanodine induced augmentation of the force-frequency response indicates a central role for sarcolemmal Ca2+ influx in producing frequency potentiation.
尽管心肌力-间期和舒张-间期关系被认为是心肌钙处理的力学表现，但在完整状态下，这些现象与改变的钙动力学之间的相关性有限。因此，我试图确定通过使用药物雷诺丁选择性损害生理性肌浆网钙释放对完整动物中这些关系的影响。
对12只植入左心室压力计和压电尺寸晶体的狗在静脉注射雷诺丁（4微克/千克）前后进行研究。在120-180次/分钟的起搏心率下测量收缩末期弹性，以确定力-频率反应。通过测量在分级早搏间期传递的搏动的收缩（单次搏动弹性）和舒张（最大负dP/dt）反应来确定机械恢复和舒张恢复，标准化反应表示为早搏间期的函数。
雷诺丁加速了机械恢复（时间常数60.3±3.9对81.7±10.1毫秒，p<0.05）并降低了最大收缩反应（107.5±2.1对122.1±5.7%，p<0.05），减慢了早期舒张恢复（时间常数65.5±13.8对36.8±3.8毫秒，p<0.05），而不改变晚期舒张恢复动力学，并放大了力-频率反应（收缩末期弹性，180次/分钟，19.4±4.3对11.4±1.2毫米汞柱/毫升，p<0.05）。
这些发现表明，在完整动物中，肌浆网的钙处理是机械恢复和早期舒张恢复的主要决定因素，但不是晚期舒张恢复的决定因素。相反，雷诺丁诱导的力-频率反应增强表明肌膜钙内流在产生频率增强中起核心作用。
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