Patel D, Duke K, Light R B, Jacobs H, Mink S N, Bose D
Department of Medicine, University of Manitoba, Winnipeg, Canada.
J Crit Care. 2000 Jun;15(2):64-72. doi: 10.1053/jcrc.2000.7902.
In septic shock, myocardial dysfunction develops over the course of illness, but the mechanism of this depression is not clear. In this study, mechanisms of myocardial dysfunction were examined in a porcine model of Escherichia coli sepsis.
Animals were subjected to 4 hours of bacteria infusion (n = 5) (septic group) or saline infusion (n = 5) (nonseptic group), after which trabeculae were removed from the right ventricle and placed into a recirculating water bath. Measurements of steady-state contraction (SSC) were obtained at 0.5, 1, and 2 Hz. Indirect indices were used to assess abnormalities in myocardial calcium metabolism in sepsis. Extrasystoles (ES) were used to assess transsarcolemmal (TSL) calcium flux and were measured at 300 milliseconds, 400 milliseconds, and 500 milliseconds after the preceding stimulus. Postrest contraction (PRC) is an indicator of SR recirculation from the uptake to the release site and was obtained after interposing intervals of rest between steady-state beats at 0.5 Hz. Rapid-cooling contracture (RCC) is an indicator of sarcoplasmic reticulum (SR) content and was obtained at 0.5, 1, and 2 Hz and after interposing intervals of rest at 0.5 Hz.
SSC was not different between groups at 0.5 Hz, but compared with the nonseptic group, SSC decreased at 1 and 2 Hz in the septic group (P < .05). PRC and TSL were not different between groups. During rest intervals, calcium leaks out of SR through the ryanodine channel (ie, SR calcium release channel). In the septic group, as assessed by RCC, SR calcium leak was less than that found in the nonseptic group.
These results indicate that myocardial dysfunction in sepsis is frequency dependent, and that the mechanism is most likely caused by inhibition of SR calcium release owing to blockade of the ryanodine channel.
在脓毒性休克中，心肌功能障碍在疾病过程中逐渐发展，但其抑制机制尚不清楚。在本研究中，我们在大肠杆菌败血症猪模型中研究了心肌功能障碍的机制。
将动物分为两组，一组进行4小时的细菌输注（n = 5）（脓毒症组），另一组进行生理盐水输注（n = 5）（非脓毒症组）。之后，从右心室取出小梁并置于循环水浴中。在0.5、1和2 Hz频率下测量稳态收缩（SSC）。使用间接指标评估败血症中心肌钙代谢的异常情况。使用期前收缩（ES）评估跨肌膜（TSL）钙通量，并在前一个刺激后300毫秒、400毫秒和500毫秒测量。静息后收缩（PRC）是肌浆网从摄取部位到释放部位再循环的指标，在0.5 Hz的稳态搏动之间插入休息间隔后获得。快速冷却挛缩（RCC）是肌浆网（SR）含量的指标，在0.5、1和2 Hz频率下以及在0.5 Hz频率下插入休息间隔后获得。
两组在0.5 Hz时的SSC无差异，但与非脓毒症组相比，脓毒症组在1和2 Hz时的SSC降低（P < 0.05）。两组之间的PRC和TSL无差异。在休息间隔期间，钙通过兰尼碱通道（即SR钙释放通道）从SR中泄漏出来。通过RCC评估，脓毒症组的SR钙泄漏少于非脓毒症组。
这些结果表明，败血症中的心肌功能障碍是频率依赖性的，其机制很可能是由于兰尼碱通道的阻断导致SR钙释放受到抑制。
