EFFECTS OF ORNIPRESSIN ON CORONARY BLOOD- FLOW AND SYSTEMIC HEMODYNAMICS - EXPERIMENT USING ANIMAL-MODELS

Omipressin (POR 8), referred to below as OR, is a synthetic derivative of natural vasopressin. It was introduced into clinical practice to r eplace epinephrine as a local vasoconstrictor because OR was presumed to produce fewer undesirable side-effects. However, mayor cardiovascul ar 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 dist inct vasopressor activity on coronary arteries. This study was planned to investigate the effects of OR in haemodynamics and the coronary va scular system. Methods. The effects of OR on systemic haemodynamics an d coronary circulation were studied in nine anaesthetized closed-chest mongrel dogs. Anaesthesia was administered using N2O/O2 (F(i)O2:0,33) 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, u sing a Pitot catheter. Recording of baseline values was followed by bo lus injection of OR (0.03 U/kg) and changes in haemodynamics were meas ured for 90 min at fixed time intervals. Statistical analysis was perf ormed by analysis of variance for repeated measures. A value of P less -than-or-equal-to 0.05 was considered to indicate statistical signific ance. Results. Significant maximum changes occurred within 3-5 min aft er administration of OR. Systolic and diastolic arterial pressures inc reased by 33% and 39%, respectively. With only minor changes in heart rate, cardiac output markedly decreased by 44% and total peripheral re sistance increased by 159%. Impaired pump function of the left ventric le became obvious by a decrease in maximum dP/dt, a decrease in ejecti on fraction by 35%, and a concomitant sharp increase in left ventricul ar enddiastolic pressure by 68% and in endsystolic volume by 41%. At t he same time, OR produced a marked impairment of coronary perfusion. M yocardial blood flow fell by 32%, while coronary vascular resistance r ose by 112%. Increased myocardial oxygen demand and reduced oxygen sup ply resulted in very low values of coronary venous oxygen saturation ( < 20%). Conclusions. Systemic effects of OR are characterized by a sha rp rise in arterial blood pressure. Concomitantly a decrease of myocar dial contractility leads to a compromised left ventricular function wi th marked increases in left ventricular enddiastolic pressure. These h aemodynamic changes are associated with an imbalance of myocardial oxy gen demand and delivery due to the distinct OR-induced coronary constr iction. With regard to the deterioration of systemic and cardiac haemo dynamics the indications and use of ornipressin in clinical practice n eed to be reevaluated.