Sharma A C, Motew S J, Farias S, Alden K J, Bosmann H B, Law W R, Ferguson J L
Department of Physiology & Biophysics, College of Medicine University of Illinois at Chicago 60612-7342, USA.
J Mol Cell Cardiol. 1997 May;29(5):1469-77. doi: 10.1006/jmcc.1997.0386.
Cardiovascular derangements during sepsis may arise from a mismatch between endothelin (ET) and nitric oxide (NO). We hypothesized that progression of chronic peritoneal sepsis would affect cardiac performance and would modulate the concentrations of NO and ET in the heart and plasma. Male Sprague-Dawley rats (340-390 g) were catheterized and made septic with a cecal slurry (200 mg/kg: i.p.). Heart rate, mean arterial pressure, and plasma ET and nitrite/nitrate (NOX) were determined at 0, 4, 8, 12, 24, and 48 h after induction of sepsis. Septic rats were found to have tachycardia at 48 h following induction of sepsis. Mean arterial pressure and pulse pressure were not altered in septic and non-septic rats. In a separate series of experiments, the function of isolated hearts from septic and non-septic rats was assessed at preload pressures of 2, 5, and 10 mmHg. Sepsis produced a significant decrease in rates of pressure development and relaxation (+/-dP/dt) at 24 and 48 h as compared to the hearts of non-septic rats. In septic rats, plasma concentrations of ET were significantly increased at t = 4, 8, 12 h as compared to basal values, and at 12 h as compared to non-septic rats, and returned to basal levels at 24 and 48 h. In contrast, circulating NO levels did not become elevated until t = 8 h and remained elevated throughout the remaining times. In the left ventricle, the concentration of ET was found to be significantly increased both in septic and non-septic rats at 4 and 8 h as compared to t = 0 h. In the left ventricles of non-septic rats, ET levels returned to baseline values at 12 h, while in septic rats, the concentration of ET remained significantly elevated until 12 h. In septic rats, left ventricular NO levels were found to be significantly increased at t = 12 h. It appeared that induction of sepsis contributed to an imbalance in the plasma concentration of ET and NO 12 h after the induction of sepsis. However, a similar imbalance was not observed in the left ventricle. It is concluded from these observations that peritoneal sepsis in a chronic rat model produced a divergence of plasma NO and ET levels. This suggests a homeostatic imbalance between vasoactive mediators, i.e. ET and NO, could contribute to the cardiovascular derangements that occur during sepsis.
脓毒症期间的心血管紊乱可能源于内皮素（ET）与一氧化氮（NO）之间的失衡。我们推测慢性腹膜脓毒症的进展会影响心脏功能，并调节心脏和血浆中NO和ET的浓度。将雄性Sprague-Dawley大鼠（340 - 390克）插管，并通过盲肠匀浆（200毫克/千克：腹腔注射）使其发生脓毒症。在诱导脓毒症后的0、4、8、12、24和48小时测定心率、平均动脉压、血浆ET和亚硝酸盐/硝酸盐（NOX）。发现脓毒症大鼠在诱导脓毒症后48小时出现心动过速。脓毒症大鼠和非脓毒症大鼠的平均动脉压和脉压没有改变。在另一系列实验中，在2、5和10 mmHg的预负荷压力下评估脓毒症大鼠和非脓毒症大鼠离体心脏的功能。与非脓毒症大鼠的心脏相比，脓毒症在24和48小时时导致压力上升和松弛速率（±dP/dt）显著降低。在脓毒症大鼠中，与基础值相比，血浆ET浓度在t = 4、8、12小时时显著升高，与非脓毒症大鼠相比在12小时时显著升高，并在24和48小时时恢复到基础水平。相比之下，循环NO水平直到t = 8小时才升高，并在其余时间一直保持升高。在左心室中，与t = 0小时相比，脓毒症大鼠和非脓毒症大鼠在4和8小时时ET浓度均显著升高。在非脓毒症大鼠的左心室中，ET水平在12小时时恢复到基线值，而在脓毒症大鼠中，ET浓度直到12小时仍显著升高。在脓毒症大鼠中，左心室NO水平在t = 12小时时显著升高。似乎脓毒症的诱导导致脓毒症诱导后12小时血浆中ET和NO浓度失衡。然而，在左心室中未观察到类似的失衡。从这些观察结果得出结论，慢性大鼠模型中的腹膜脓毒症导致血浆NO和ET水平出现差异。这表明血管活性介质即ET和NO之间的稳态失衡可能导致脓毒症期间发生的心血管紊乱。
