Department of Physiology, Charles University, Prague, Czech Republic.
Crit Care Med. 2010 Feb;38(2):579-87. doi: 10.1097/CCM.0b013e3181cb0f61.
To hypothesize that reduced L-type calcium current with consequent shortening of cardiac repolarization is present in a clinically relevant porcine model of hyperdynamic septic shock. Myocardial depression is a well-recognized manifestation of sepsis and septic shock. Reduction of L-type calcium current was demonstrated to contribute to the myocardial depression in endotoxemic rodents.
Laboratory animal experiments.
Animal research laboratory at a university.
Twenty-two domestic pigs of either gender.
In anesthetized, mechanically ventilated, and instrumented pigs, sepsis was induced by bacteremia (central venous infusion of live Pseudomonas aeruginosa) and continued for 22 hrs.
Electrocardiogram was recorded before and 22 hrs after induction of bacteremia. RR, QT, and QTc intervals were significantly shortened by sepsis. In vitro, action potentials were recorded in right ventricular trabeculae. Action potential durations were shortened in septic preparations. Tumor necrosis factor-alpha did not influence action potential durations. L-type calcium current was measured in isolated ventricular myocytes. Peak L-type calcium current density was reduced in myocytes from septic animals (8.3 +/- 0.4 pA/pF vs. 11.2 +/- 0.6 pA/pF in control). The voltage dependence of both L-type calcium current activation and inactivation was shifted to more negative potentials in myocytes from septic animals. Action potential-clamp experiments revealed that the contribution of L-type calcium current to the septic action potential was significantly diminished. In cardiac myocytes incubated with tumor necrosis factor-alpha, L-type calcium current was not further affected.
In a clinically relevant porcine model, hyperdynamic septic shock induced shortening of ventricular repolarization and reduction of L-type calcium current. The contribution of L-type calcium current to the action potential in septic ventricular myocytes was significantly diminished. Tumor necrosis factor-alpha probably did not contribute to this effect.
假设在临床上相关的猪高动力性脓毒性休克模型中存在 L 型钙电流减少，进而导致心脏复极化缩短。心肌抑制是脓毒症和脓毒性休克的一种公认表现。已证明 L 型钙电流减少导致内毒素血症啮齿动物的心肌抑制。
实验室动物实验。
大学动物研究实验室。
22 只雄性和雌性家猪。
在麻醉、机械通气和仪器监测的猪中，通过菌血症（静脉内输注活铜绿假单胞菌）诱导败血症，并持续 22 小时。
在诱导菌血症之前和之后 22 小时记录心电图。RR、QT 和 QTc 间期在败血症时显著缩短。在体外，记录右心室小梁的动作电位。败血症制剂中的动作电位持续时间缩短。肿瘤坏死因子-α（tumor necrosis factor-alpha）不影响动作电位持续时间。在分离的心室肌细胞中测量 L 型钙电流。来自败血症动物的心肌细胞中的峰值 L 型钙电流密度降低（8.3 +/- 0.4 pA/pF 与对照中的 11.2 +/- 0.6 pA/pF）。L 型钙电流激活和失活的电压依赖性在败血症动物的心肌细胞中更向负电位转移。动作电位箝位实验表明，L 型钙电流对败血症动作电位的贡献明显降低。在孵育有肿瘤坏死因子-α的心肌细胞中，L 型钙电流没有进一步受到影响。
在临床上相关的猪模型中，高动力性脓毒性休克引起心室复极缩短和 L 型钙电流减少。败血症心室肌细胞中 L 型钙电流对动作电位的贡献明显降低。肿瘤坏死因子-α可能不会对此产生影响。
