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首页> 外文期刊>Physiological Reports >Opposite diastolic effects of omecamtiv mecarbil versus dobutamine and ivabradine co‐treatment in pigs with acute ischemic heart failure
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Opposite diastolic effects of omecamtiv mecarbil versus dobutamine and ivabradine co‐treatment in pigs with acute ischemic heart failure

机译：奥美卡地美卡比与多巴酚丁胺和伊伐布雷定对急性缺血性心力衰竭猪的舒张作用相反

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Acute ischemic cardiogenic shock is associated with poor prognosis, and the impact of inotropic support on diastolic function in this context is unclear. We assessed two suggested new inotropic strategies in a clinically relevant pig model of ischemic acute heart failure (AHF): treatment with the myosin activator omecamtiv mecarbil (OM) or dobutamine and ivabradine (D+I). Left ventricular (LV) ischemia was induced in anesthetized pigs by coronary microembolization ( n ?=?12). The animals then received OM (bolus 0.75?mg/kg, followed by 0.5?mg/kg per h) ( n ?=?6) or D+I (5? μ g/kg per min + 0.29?±?0.16?mg/kg) ( n ?=?6), respectively. Ischemia reduced the stroke volume (SV), despite the increased left atrial pressure associated with impaired LV early relaxation, systolic dilatation, and LV late diastolic stiffness. Both treatments improved systolic ejection, but only D+I increased the SV from 26?±?5 to 33?±?5?mL. D+I enhanced LV early relaxation (Tau; from 45?±?11 to 29?±?4?msec) and prolonged the diastolic time (DT) from 338?±?60 to 352?±?40?msec. In contrast, OM prolonged Tau (42?±?5 to 62?±?10?msec) and shortened the DT (from 326?±?68 to 248?±?84?msec). Our data suggest that enhanced early relaxation by D+I improves LV pump function in postischemic acute heart failure. In contrast, OM worsened lusitropy in this model.
机译：急性缺血性心源性休克与预后不良有关，在这种情况下，肌力支持对舒张功能的影响尚不清楚。我们在临床相关的缺血性急性心力衰竭（AHF）猪模型中评估了两种建议的新的正性肌力策略：用肌球蛋白活化剂奥美加替卡比（OM）或多巴酚丁胺和伊伐布雷定（D + I）治疗。麻醉的猪通过冠状动脉微栓塞术诱发左心室（LV）缺血（n = 12）。然后，动物接受OM（推注0.75？mg / kg，然后每小时0.5？mg / kg）（n == 6）或D + I（5？μg/ kg /分钟+0.29？±？0.16？）。 （mg / kg）（n≥6）。尽管左心房压力升高与左室早期舒张功能受损，收缩期扩张和左室舒张末期僵硬相关，但缺血仍降低了卒中体积（SV）。两种治疗均能改善收缩期射血，但只有D + I使SV从26？±？5增加到33？±？5？mL。 D + I增强了LV的早期放松（Tau;从45？±？11到29？±？4？msec），舒张时间（DT）从338？±？60延长到352？±？40？msec。相反，OM延长了Tau（42？±？5到62？±？10？msec）并缩短了DT（从326？±？68到248？±？84？msec）。我们的数据表明，D + I增强的早期舒张改善了缺血性急性心力衰竭中的左室泵功能。相比之下，OM在该模型中加剧了光致各向异性。

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