Pagani F D, Baker L S, Knox M A, Cheng H, Fink M P, Visner M S
Department of Surgery, University of Massachusetts Medical Center, Worcester.
Surgery. 1992 Jun;111(6):683-93.
Tumor necrosis factor-alpha (TNF alpha) has been implicated as an endogenous mediator of the cardiovascular manifestations of sepsis and septic shock. We studied the acute effects of a single dose (50 or 200 micrograms/kg) of intravenous recombinant human TNF alpha (rhTNF alpha) on myocardial function in halothane-anesthetized dogs. Regional cardiac dimensions were measured by using sonomicrometry. Intracavitary left ventricular, ascending aortic, and pulmonary artery pressures were measured by use of micromanometers. Cardiac index was determined by means of thermodilution. Myocardial performance was analyzed by assessing changes in the slope of the left ventricular end-diastolic length-stroke work relationship obtained by performing transient vena caval occlusions. Animals were resuscitated by means of normal saline solutions to maintain baseline regional end-diastolic length. Over a 3-hour period of observation, rhTNF alpha decreased systemic vascular resistance index, but the cytokine did not compromise intrinsic myocardial performance. The circulatory response to rhTNF alpha was a hyperdynamic state characterized by tachycardia, augmented cardiac index, and increased intrinsic myocardial contractility (leftward shift of the left ventricular end-diastolic length-stroke work relationship). In addition, rhTNF alpha caused systemic acidosis and increased plasma levels of prostacyclin metabolite (6-keto-prostaglandin F1 alpha). After the dose of rhTNF alpha large volumes of fluid were required to maintain baseline end-diastolic length. We conclude that in the acute setting, rhTNF alpha elicits abnormalities in peripheral vascular tone that are not accompanied by depression of myocardial function.
肿瘤坏死因子-α（TNFα）被认为是脓毒症和感染性休克心血管表现的内源性介质。我们研究了单剂量（50或200微克/千克）静脉注射重组人TNFα（rhTNFα）对氟烷麻醉犬心肌功能的急性影响。使用超声微测法测量局部心脏尺寸。使用微压计测量心腔内左心室、升主动脉和肺动脉压力。通过热稀释法测定心脏指数。通过评估短暂腔静脉阻塞后左心室舒张末期长度-搏功关系斜率的变化来分析心肌性能。通过生理盐水溶液对动物进行复苏，以维持基线局部舒张末期长度。在3小时的观察期内，rhTNFα降低了全身血管阻力指数，但该细胞因子并未损害心肌的固有性能。对rhTNFα的循环反应是一种高动力状态，其特征为心动过速、心脏指数增加和心肌固有收缩力增强（左心室舒张末期长度-搏功关系向左移位）。此外，rhTNFα导致全身酸中毒，并增加了血浆前列环素代谢物（6-酮-前列腺素F1α）水平。给予rhTNFα后，需要大量液体来维持基线舒张末期长度。我们得出结论，在急性情况下，rhTNFα引起外周血管张力异常，但不伴有心肌功能抑制。
