THE HEMODYNAMIC-EFFECTS IN PATIENTS WITH CORONARY-ARTERY DISEASE PRETREATED WITH AND WITHOUT CARDIOSELECTIVE BETA(1)-BLOCKADE

Patients with coronary artery disease undergoing coronary artery bypas s grafting can develop perioperative low cardiac output failure requir ing positive inotropic support. Commonly, the sympathetic amines, dopa mine, dobutamine or adrenaline are used in low-output state. However, patients on long-term cardioselective beta-blocking therapy may experi ence problems with such a treatment. Dopexamine, a new synthetic amine , possesses positive inotropic effects by indirect stimulation of the beta1-receptors and direct stimulation of the beta2-receptors. We ther efore studied the hemodynamic efficacy of dopexamine in patients with and without beta-receptor blockade. In 12 patients with coronary arter y disease classed as NYHA II or III six without any beta-blocker medic ation, and six with beta1-blocker medication (bisoprolol 5 mg), anesth esia was induced with high-dose fentanyl (0.05 mg/kg) and pancuronium (0.1 mg/kg). The patients were normoventilated with a mask (O2:air 1:1 , tidal volume 10 ml/kg with a rate of 10/min) for 5 min and then intu bated. Following intubation anesthesia was continued with 0.025 mg/kg/ h fentanyl. In anesthesia steady state the patients of both groups wer e treated with 2 mug/kg/min dopexamine over a period of 15 min and the n with 4 mug/kg/min dopexamine over a further period of 15 min. Measur ements of cardiovascular dynamics included heart rate (HR), cardiac in dex (CI), stroke volume index (SVI), mean arterial blood pressure (MAP ), coronary perfusion pressure (CPP), systemic vascular resistance (SV R), pulmonary artery pressure (PAP), pulmonary capillary wedge pressur e (PCWP), right atrium pressure (RAP), pressure work index (PWI) and a rterial-mixed venous oxygen content difference (AVDO2), which were mon itored or calculated by standard formulas. Data and electrocardiogram were taken at the following times 1) before induction of anesthesia (W ); 2) after induction of anesthesia and before administration of the c atecholamine (K); 3) 15 min after continuous infusion of 2 mug/kg/min dopexamine (Dpx 2 mug); 4) 15 min after continuous infusion of 4 mug/k g/min dopexamine (Dpx 4 mug). Dopexamine induced significant increases of cardiac index, stroke volume index and heart rate, a small decreas e of mean arterial pressure and a significant decrease of coronary per fusion pressure and systemic vascular resistance. Significant differen ces between both groups could not be evaluated. Pressure work index in creased in both groups with dopexamine treatment, and the increase was more pronounced in patients with bisoprolol medication. Nevertheless, in both groups the levels of PWI with dopexamine were not greater in the awake and calm patient. In neither group did we observe any ST-seg ment changes in the ECG or an increase in pulmonary capillary wedge pr essure. Dopexamine possesses a positive inotropic effect of nearly the same extent in patients with and without beta1-blockade pretreatment. Simultaneously, it induces an afterload reduction. The coronary perfu sion pressure decreased, but did not change differently in either grou p, and there were no signs of myocardial ischemia, as shown in changes of left ventricular filling pressure or in the ECG. Probably, the low ered wall tension by arterial vasodilatation counterbalances the augme ntation of myocardial oxygen consumption by the positive inotropic and chronotropic effects of dopexamine. In doses up to 4 mug/kg/min dopex amine acts mainly by stimulating beta2-receptors; therefore, its use s eems suitable in such subtypes of heart failure where down-regulation of beta1-receptors or a pretreatment with beta1-receptor blockers exis ts.