Wakefield T W, Ucros I, Kresowik T F, Hinshaw D B, Stanley J C
Department of Surgery, University of Michigan Medical Center.
J Vasc Surg. 1989 Jun;9(6):772-7.
Protamine sulfate has been observed to interfere with the control of isolated mitochondrial respiration in vitro. This study was designed to determine if oxygen consumption changes in intact animals occur in vivo during protamine administration. Oxygen consumption was assessed in seven dogs anticoagulated with heparin (150 IU/kg) and reversed 30 minutes later with protamine sulfate (1.5 mg/kg). Oxygen saturations measured included arterial (SaO2 arterial), mixed venous (SvO2 systemic), jugular (SvO2 jugular), portal (SvO2 portal), and coronary (SvO2 coronary). Cardiac output (CO) and carotid artery flow determinations allowed calculation of systemic oxygen consumption (VO2 systemic) and cerebral oxygen consumption VO2 cerebral. Hemodynamic measurements included arterial blood pressure (BP), pulmonary artery systolic and diastolic pressures (PAS, PAD), and heart rate (HR). Protamine sulfate administration resulted in hypotension (delta BP -64 mm Hg), pulmonary hypertension (delta PAS + 13 mm Hg, delta PAD + 11 mm Hg), and bradycardia (delta HR -30). Shortly after protamine administration, CO fell 54% and carotid artery flow fell more than 50%, yet declines in SvO2 systemic and SvO2 jugular were not observed. In fact these parameters increased 3% and 2%, respectively. VO2 systemic fell 55% and VO2 cerebral fell 57%. Similarly, SvO2 portal and SvO2 coronary increased 6% and 9%, respectively. Significant correlations existed between changes in VO2 systemic and BP (r = 0.05, p less than 0.001), HR (r = 0.3, p less than 0.01, PAD (r = -0.3, p less than 0.05, and CO (r = 0.8, p less than 0.001). Impaired oxygen utilization was most evident during the first 5 minutes after protamine administration. This investigation, for the first time, establishes that protamine sulfate decreases in vivo oxygen consumption, a finding that may account for certain of the drug's adverse side effects.
已观察到硫酸鱼精蛋白在体外会干扰离体线粒体呼吸的控制。本研究旨在确定在给动物注射硫酸鱼精蛋白的过程中，完整动物体内的耗氧量是否会发生变化。对7只经肝素（150 IU/kg）抗凝、30分钟后用硫酸鱼精蛋白（1.5 mg/kg）进行逆转的狗的耗氧量进行了评估。测量的氧饱和度包括动脉血氧饱和度（SaO2动脉）、混合静脉血氧饱和度（SvO2全身）、颈静脉血氧饱和度（SvO2颈静脉）、门静脉血氧饱和度（SvO2门静脉）和冠状动脉血氧饱和度（SvO2冠状动脉）。通过测定心输出量（CO）和颈动脉血流量，可以计算全身耗氧量（VO2全身）和脑耗氧量VO2脑。血流动力学测量包括动脉血压（BP）、肺动脉收缩压和舒张压（PAS、PAD）以及心率（HR）。注射硫酸鱼精蛋白导致低血压（血压变化量δBP -64 mmHg）、肺动脉高压（PAS变化量δPAS + 13 mmHg，PAD变化量δPAD + 11 mmHg）和心动过缓（心率变化量δHR -30）。在注射硫酸鱼精蛋白后不久，CO下降了54%，颈动脉血流量下降超过50%，但未观察到全身SvO2和颈静脉SvO2下降。事实上，这些参数分别增加了3%和2%。VO2全身下降了55%，VO2脑下降了57%。同样，门静脉SvO2和冠状动脉SvO2分别增加了6%和9%。VO2全身的变化与血压（r = 0.05，p < 0.001）、心率（r = 0.3，p < 0.01）、PAD（r = -0.3，p < 0.05）和CO（r = 0.8，p < 0.001）之间存在显著相关性。在注射硫酸鱼精蛋白后的前5分钟内，氧利用受损最为明显。这项研究首次证实硫酸鱼精蛋白会降低体内耗氧量，这一发现可能解释了该药物的某些不良反应。
