Effects of alinidine on metabolic response to high-demand myocardial ischemia

Alinidine is a new bradycardic agent that interferes with ion channels and the i_f pacemaker current. To determine if alinidine had antiischemie effects unrelated to its bradycardic action, myocardial metabolism was studied during a pacing-stress test in 20 patients with coronary artery disease and angina pectoris, before and after intravenous infusion of alinidine (10 mg. n= 10; 50 mg, n= 10). When compared to the control pacing-stress test, the low dose of alinidine had no significant effect on aortic pressure, coronary sinus flow (-3%, NS), myocardial oxygen extraction, or myocardial lactate uptake. After the high dose of alinidine. aortic pressure and coronary sinus flow remained unchanged but the arteriocoronary sinus difference in oxygen content increased (12.2 ± 1.3 to 12.7 ± 1.4 ml/100 ml; p < 0.0002) above the values observed during the control pacing-stress test, while both the chemical lactate extraction fraction (- 19 ± 30 to 15 ± 21%. p < 0.025) and the L-[l-¹⁴C]lactate extraction fraction increased. Accordingly, the net myocardial lactate uptake (corrected for production) had increased from 14 ± 32 during the control pacing-stress test to 29 ± 24 μmol/min during the pacing repeated after the high dose of alinidine (p < 0.05). After the high dose of alinidine, the free fatty acid uptake also rose slightly (± 23%, NS) and the alanine production was reduced in 7 of 10 patients (-3.6 ± 1.7 to -1.4 ± 0.6 μmol/min: NS). Thus, independently of its effects on the sinus rhythm, administration of a high dose of alinidine improved oxygen extraction and reduced the signs of anaerobic metabolism during high-demand ischemia.