We have previously reported that the negative inotropic effects of hyperthermia (42 °C) on left ventricular (LV) mechanoenergetics using the excised, cross-circulated rat heart model. Here, we investigated the role of TRPV1 on LV mechanoenergetics in hyperthermia. We analyzed the LV end-systolic pressure-volume relation (ESPVR) and the linear relation between the myocardial oxygen consumption per beat (VO2) and the systolic pressure-volume area (PVA; a total mechanical energy per beat) during infusion of capsazepine (CPZ) in hyperthermia, or capsaicin (Cap) under 300 bpm pacing. LV ESP decreased in each LV volume and the resultant downward-shift of LV ESPVR was suppressed by CPZ infusion in hyperthermia-hearts. In Cap-treated hearts, LV ESPVR shifted downward from the control ESPVR, similar to hyperthermia-hearts. The slopes of VO2-PVA relationship were unchanged. The VO2 intercepts in hyperthermia-hearts did not decrease because of decreased E-C coupling VO2, and inversely increased basal metabolic VO2, which was suppressed by CPZ, though the VO2 intercepts in Cap-treated hearts significantly decreased. The levels of phosphorylated phospholamban at serine 16 decreased significantly in hyperthermia-hearts, as well as Cap-treated hearts. These results indicate that a Cap-induced decrease in the LV contractility, like in cases of hyperthermia, are due to the down-regulation of the total calcium handling in E-C coupling, suggesting that negative inotropic effect in hyperthermia-heart is, at least in part, mediated through TRPV1 signaling pathway.

中文翻译：

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高温对大鼠左心室负性肌力作用的潜在机制：TRPV1的作用。

我们先前曾报道过，使用切除的交叉循环大鼠心脏模型，高热（42°C）对左心室（LV）机械能的负性肌力作用。在这里，我们研究了TRPV1对热疗中LV机械能的作用。我们分析了辣椒素（输注）过程中的左室收缩末期压力-容积关系（ESPVR）以及每搏心肌耗氧量（VO2）和收缩压容积（PVA;每搏总机械能）之间的线性关系。 CPZ）或300 bpm起搏下的辣椒素（Cap）。LV ESP在每个LV体积中均减小，并且通过CPZ输注热疗心脏抑制了LV ESPVR的下降。在接受Cap治疗的心脏中，LV ESPVR从对照ESPVR向下移动，类似于热疗心脏。VO2-PVA关系的斜率没有变化。由于EC耦合VO2的减少，热疗心脏中的VO2截距并没有减少，而基础代谢VO2却相反地增加，这被CPZ所抑制，尽管Cap治疗的心脏中的VO2截距显着降低。在热疗心脏以及Cap治疗的心脏中，丝氨酸16处的磷酸化lambban水平显着降低。这些结果表明，Cap诱导的LV收缩力下降，如在热疗中一样，是由于EC耦合中总钙处理的下调所致，这表明热疗心脏的负性肌力作用至少在部分是通过TRPV1信号通路介导的。并逆转了基础代谢VO2的增加，这被CPZ抑制，尽管Cap治疗的心脏中的VO2截获量明显减少。在热疗心脏以及Cap治疗的心脏中，丝氨酸16处的磷酸化lambban水平显着降低。这些结果表明，Cap诱导的LV收缩力下降，如在热疗中一样，是由于EC耦合中总钙处理的下调所致，这表明热疗心脏的负性肌力作用至少在部分是通过TRPV1信号通路介导的。并逆转了基础代谢VO2的增加，这被CPZ抑制，尽管Cap治疗的心脏中的VO2截获量明显减少。在热疗心脏以及Cap治疗的心脏中，丝氨酸16处的磷酸化lambban水平显着降低。这些结果表明，Cap诱导的LV收缩力下降，如在热疗中一样，是由于EC耦合中总钙处理的下调所致，这表明热疗心脏的负性肌力作用至少在部分是通过TRPV1信号通路介导的。以及盖帽治疗的心脏。这些结果表明，Cap诱导的LV收缩力下降，如在热疗中一样，是由于EC耦合中总钙处理的下调所致，这表明热疗心脏的负性肌力作用至少在部分是通过TRPV1信号通路介导的。以及盖帽治疗的心脏。这些结果表明，Cap诱导的LV收缩力下降，如在热疗中一样，是由于EC耦合中总钙处理的下调所致，这表明热疗心脏的负性肌力作用至少在部分是通过TRPV1信号通路介导的。