Critical Care Medicine Department, Clinical Center National Institutes of Health Bethesda MD USA.
Division of Cardiology Duke University Medical Center Durham NC USA.
J Am Heart Assoc. 2024 Aug 6;13(15):e034027. doi: 10.1161/JAHA.123.034027. Epub 2024 Aug 5.
High levels of catecholamines are cardiotoxic and associated with stress-induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction.
Purpose-bred beagles received intrabronchial (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 μg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine-stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High-dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular-aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800-fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular-aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped.
Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion-induced ischemia. However, epinephrine itself has potentially harmful long-lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.
儿茶酚胺水平升高具有心脏毒性，并与应激诱导性心肌病有关。我们使用一种可复制与人类脓毒性休克相关的 10 天可逆性心肌病的脓毒性休克模型，研究了儿茶酚胺对微循环灌注和心功能障碍的影响。
目的饲养的比格犬接受支气管内（n=30）或盐水（n=6）治疗。然后，将脓毒症动物随机分为肾上腺素（1μg/kg/min，n=15）或盐水（n=15）输注组，从 4 小时到 44 小时。在 92 小时内收集连续心脏磁共振成像、儿茶酚胺水平和肌钙蛋白数据。对随机接受盐水（n=15 中的 8 例）或肾上腺素（n=15 中的 8 例）的脓毒症动物进行连续腺苷应激灌注心脏磁共振成像。给予大剂量镇静剂以抑制内源性儿茶酚胺释放。尽管儿茶酚胺水平在整个过程中基本保持在正常范围内，但在 48 小时时，接受盐水治疗的脓毒症动物与非脓毒症动物相比，左心室射血分数、周向应变和心室-主动脉偶联仍显著恶化。与接受盐水输注的脓毒症动物相比，接受肾上腺素输注的脓毒症动物的血浆肾上腺素水平增加了 800 倍，但肾上腺素对左心室射血分数、周向应变或心室-主动脉偶联没有显著的进一步恶化作用。接受盐水治疗的脓毒症动物的微循环储备显著增加，而肌钙蛋白水平没有升高。接受肾上腺素治疗的脓毒症动物的水肿减少，微循环灌注减弱，肌钙蛋白水平升高，且在肾上腺素输注停止后数小时仍持续升高。
脓毒症期间的心功能障碍主要不是由于内源性或外源性儿茶酚胺升高，也不是由于微血管灌注减少引起的缺血。然而，肾上腺素本身在脓毒症期间具有潜在的有害的持久缺血作用，包括在停止输注后持续存在的心脏微血管灌注受损。
