TY - JOUR
T1 - Effects of alinidine on metabolic response to high-demand myocardial ischemia
AU - Hanet, Claude
AU - Pouleur, Hubert
AU - Hue, Louis
AU - Caucheteux, Danielle
AU - Gurné, Olivier
AU - Maldague, Pierre
AU - Rousseau, Michel F.
PY - 1989/3
Y1 - 1989/3
N2 - Alinidine is a new bradycardic agent that interferes with ion channels and the if 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.
AB - Alinidine is a new bradycardic agent that interferes with ion channels and the if 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.
KW - Coronary artery disease
KW - Lactate
KW - Oxygen extraction
UR - http://www.scopus.com/inward/record.url?scp=0024538482&partnerID=8YFLogxK
U2 - 10.1097/00005344-198903000-00008
DO - 10.1097/00005344-198903000-00008
M3 - Article
C2 - 2471886
AN - SCOPUS:0024538482
SN - 0160-2446
VL - 13
SP - 405
EP - 411
JO - Journal of cardiovascular pharmacology
JF - Journal of cardiovascular pharmacology
IS - 3
ER -