The effects of continuously administered intravenous propoxyphene chloride (15 mg X min-1) on ECG, systemic, pulmonary and coronary circulations and myocardial oxygenation were investigated in eight pentobarbital-anesthetized pigs. Circulatory shock, defined as a systolic blood pressure below 60 mmHg (8.0 kPa) and a cardiac output of approximately 2.0 l X min-1 X m-2, occurred after 675 to 2025 mg propoxyphene chloride. At the time when shock occurred plasma concentrations of propoxyphene ranged from 9.6 to 15.3 micrograms X ml-1 which is within the range of the lethal concentration observed in man. Statistically significant decreases were observed for the following variables: maximum rate of rise of left ventricular pressure dP/dt (-90%), mean arterial pressure (-73%), heart rate (-46%), cardiac index (-58%), stroke volume index (-22%), left ventricular stroke work index (-85%), right ventricular stroke work index (-63%) and systemic vascular resistance (-50%). Mean pulmonary arteriolar occlusion pressure increased (+42%), whereas mean right atrial pressure and pulmonary vascular resistance remained unchanged. The arteriovenous oxygen difference increased (+53%) and total body oxygen consumption decreased (-35%). The following coronary variables decreased: coronary sinus blood flow (-57%), coronary vascular resistance (-65%), myocardial oxygen consumption (-68%), myocardial oxygen extraction (-26%) and myocardial lactate extraction (-28%). Prolongation of the ECG PQ and QRS intervals were recorded shortly before shock appeared, and all animals were in sinus rhythm till the last minute before death. The results indicate that intravenously administered propoxyphene besides being a powerful negative inotropic and chronotropic agent, is also a potent systemic and coronary vasodilator.

The effects of enflurane with and without nitrous oxide on coronary haemodynamics and myocardial oxygenation were investigated in 11 patients with generalised atherosclerotic disease. Enflurane decreased systemic blood pressure (-50%) mainly by systemic vasodilation (SVR -41%) and to a lesser degree by impairment of cardiac performance (CO -27%). A change from 1MAC enflurane-nitrogen-oxygen (70/30) to 1MAC enflurane-nitrous oxide-oxygen (70/30) decreased blood pressure and cardiac output further (-16% and -14%). Enflurane-nitrogen-oxygen decreased coronary blood flow (-29%) and perfusion pressure (-47%). Coronary vascular resistance fell (-20%) along with decreases in myocardial oxygen consumption and extraction (-40% and -16%). Regional coronary blood flow measurements in four of the patients revealed maldistribution of blood flow. During enflurane-nitrous oxide-oxygen, myocardial oxygen consumption and extraction decreased further (-29% and -12%) without change in coronary blood flow or resistance. Myocardial ischaemia was observed in four patients during enflurane-nitrogen. During enflurane-nitrous oxide, ischaemia disappeared in two of the previously ischaemic patients and appeared in two not previously ischaemic. The regional blood flow maldistribution was abolished with nitrous oxide. It is concluded that enflurane is a powerful coronary vasodilator and in this respect slightly less potent than isoflurane. Enflurane may induce myocardial ischaemia by redistributing coronary blood flow and/or by producing hypotension. Nitrous oxide added to enflurane depresses cardiac function and augments the coronary vasodilatory effect of enflurane to a level at which coronary blood flow becomes totally pressure dependent.

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The hemodynamic and cardiometabolic effects of dopamine were evaluated in propoxyphene-induced circulatory shock in eight pentobarbital anesthetized pigs. Circulatory shock was induced by an infusion of propoxyphene chloride 15 mg . min-1 i.v. At shock, i.e. CI less than or equal to 2.0 l . min-1 . m-2 and/or MAP less than or equal to 60 mmHg, dopamine was infused at 10, 20, 40, 80 and 160 micrograms . kg-1 . min-1 with an interval between increments of 8 min. After 30 min at 160 micrograms . kg-1 . min-1, the infusion rate was reversibly decreased. The propoxyphene infusion of 15 mg . min-1 was continued throughout the study. Dopamine improved the circulation in seven animals; one animal died in refractory shock during dopamine infusion. Dopamine infusion at shock level resulted in an increase of the following variables (% of baseline value): MAP (69%), HR (109%), CI (138%) and SVI (129%). Normalisation was seen in MRAP (120%) and in MPAOP (100%). A profound decrease in systemic vascular resistance was unchanged. Increases were seen in left and right ventricular stroke work index, to 88% and 176% of baseline, respectively. Left ventricular dP/dt increased (170%). In the coronary circulation myocardial blood flow increased (133%) as did myocardial oxygen consumption (65%) concomitant with a decrease in myocardial oxygen uptake (41%), but coronary vascular resistance progressively decreased (38%). The myocardial propoxyphene extraction changed from +54% to -86% during peak dopamine infusion. In conclusion, dopamine reversed cardiac failure in propoxyphene overdose by a marked positive inotropic stimulation restoring contractility. A marked positive chronotropic stimulation maintained a sufficient cardiac index and a normal blood pressure in spite of a profound vasodilatation which was unresponsive to dopamine.