Veit S, Poethko C, Heidelmeyer C F, Brückner J B
Klinik für Anaesthesiologie und operative Intensivmedizin, Klinikum Rudolf Virchow, Freie Universität Berlin.
Anaesthesist. 1993 Sep;42(9):597-604.
Ornipressin (POR 8), referred to below as OR, is a synthetic derivative of natural vasopressin. It was introduced into clinical practice to replace epinephrine as a local vasoconstrictor because OR was presumed to produce fewer undesirable side-effects. However, mayor cardiovascular complications following local infiltration of OR have been reported in recent time. Beside increased blood pressure and changes in heart rate, there is evidence that the systemic effects of OR include a distinct vasopressor activity on coronary arteries. This study was planned to investigate the effects of OR in haemodynamics and the coronary vascular system. METHODS. The effects of OR on systemic haemodynamics and coronary circulation were studied in nine anaesthetized closed-chest mongrel dogs. Anaesthesia was administered using N2O/O2 (FiO2:0.33) and enflurane (1.0 vol% endtidal). Saline-filled catheters were used to measure intravascular pressures. Left ventricular pressure change (dP/dt) was monitored with a tip catheter manometer. Cardiac output (CO) was determined using thermodilution and coronary sinus blood flow, using a Pitot catheter. Recording of baseline values was followed by bolus injection of OR (0.03 U/kg) and changes in haemodynamics were measured for 90 min at fixed time intervals. Statistical analysis was performed by analysis of variance for repeated measures. A value of P < or = 0.05 was considered to indicate statistical significance. RESULTS. Significant maximum changes occurred within 3-5 min after administration of OR. Systolic and diastolic arterial pressures increased by 33% and 39%, respectively. With only minor changes in heart rate, cardiac output markedly decreased by 44% and total peripheral resistance increased by 159%. Impaired pump function of the left ventricle became obvious by a decrease in maximum dP/dt, a decrease in ejection fraction by 35%, and a concomitant sharp increase in left ventricular enddiastolic pressure by 68% and in endosystolic volume by 41%. At the same time, OR produced a marked impairment of coronary perfusion. Myocardial blood flow fell by 32%, while coronary vascular resistance rose by 112%. Increased myocardial oxygen demand and reduced oxygen supply resulted in very low values of coronary venous oxygen saturation (< 20%). CONCLUSIONS. Systemic effects of OR are characterized by a sharp rise in arterial blood pressure. Concomitantly a decrease of myocardial contractility leads to a compromised left ventricular function with marked increases in left ventricular enddiastolic pressure. These haemodynamic changes are associated with an imbalance of myocardial oxygen demand and delivery due to the distinct OR-induced coronary constriction. With regard to the deterioration of systemic and cardiac haemodynamics the indications and use of ornipressin in clinical practice need to be reevaluated.
去氨加压素（POR 8，以下简称OR）是天然血管加压素的合成衍生物。它被引入临床实践以取代肾上腺素作为局部血管收缩剂，因为据推测OR产生的不良副作用较少。然而，最近有报道称局部注射OR后出现了主要的心血管并发症。除了血压升高和心率变化外，有证据表明OR的全身作用包括对冠状动脉有明显的升压活性。本研究旨在调查OR对血流动力学和冠状动脉系统的影响。方法：在9只麻醉的闭胸杂种犬中研究OR对全身血流动力学和冠状动脉循环的影响。使用N2O/O2（FiO2：0.33）和恩氟烷（呼气末浓度1.0 vol%）进行麻醉。使用充盐水的导管测量血管内压力。用顶端导管压力计监测左心室压力变化（dP/dt）。使用热稀释法测定心输出量（CO），用皮托管测定冠状窦血流量。记录基线值后，静脉推注OR（0.03 U/kg），并在固定时间间隔内测量90分钟的血流动力学变化。采用重复测量方差分析进行统计分析。P≤0.05的值被认为具有统计学意义。结果：给药后3 - 5分钟内出现显著的最大变化。收缩压和舒张压分别升高33%和39%。心率仅有轻微变化，心输出量显著下降44%，总外周阻力增加159%。左心室泵功能受损表现为最大dP/dt降低、射血分数降低35%，同时左心室舒张末期压力急剧升高68%，收缩末期容积增加41%。与此同时，OR导致冠状动脉灌注明显受损。心肌血流量下降32%，而冠状血管阻力上升112%。心肌需氧量增加和氧供应减少导致冠状静脉血氧饱和度极低（<20%）。结论：OR的全身作用表现为动脉血压急剧升高。同时心肌收缩力下降导致左心室功能受损，左心室舒张末期压力显著升高。这些血流动力学变化与OR引起的明显冠状动脉收缩导致的心肌氧供需失衡有关。鉴于全身和心脏血流动力学的恶化，临床实践中去氨加压素的适应证和使用需要重新评估。
