Determination of effective and safe dose for intracoronary administration of nicorandil in dogs.
OBJECTIVE
The aim was to evaluate the effective and safe dosage for intracoronary administration of nicorandil (2-nicotinamidoethyl nitrate) in dogs.


METHODS
Five ml of saline with or without nicorandil (0.025, 0.25, 1.0 or 2.5 mg) was constantly infused into the left anterior descending coronary artery (LAD) in 1 min without blood flow reduction in group A (normoxic group, n = 5) and with 50% blood flow reduction of the control value in group B (ischaemic group, n = 5).


METHODS
10 mongrel dogs of either sex were used, weight 14.6-20.5 kg.


RESULTS
The myocardial weight of the perfused area was 33.2(SD 7.9) g. In group A, LAD blood flow increased from 28.4(8.6) to 86.3(25.0) ml.min-1, p less than 0.05, following intracoronary infusion of 0.25 mg nicorandil. Higher doses caused no further increase. In both groups, high doses (1.0 mg or more) suppressed regional myocardial contraction, expressed as % segment shortening, from 20.0(4.7) to 10.0(9.0)%, p less than 0.05, in group A, and from 12.7(8.5) to 6.5(5.6)%, p less than 0.05, in group B. Multiple ventricular premature beats developed in both groups only at the dose of 2.5 mg: 6.8(5.5) beats.min-1 in group A and 4.5(4.2) beats.min-1 in group B. Ventricular fibrillation developed in two dogs in group B. Nicorandil did not affect the local bipolar electrocardiogram of the subendo- and subepicardium in the perfused area in either group.


CONCLUSIONS
Intracoronary administration of 0.25 mg of nicorandil was effective for coronary vasodilatation without deleterious mechanical or electrical effects. Larger doses of the agent showed adverse effects depending on the dosages.
Kojima
S
S
Division of Cardiology and Clinical Research, Saitama National Hospital, Japan.
Ishikawa
S
S
Ohsawa
K
K
Mori
H
H
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D004562:Electrocardiography; D005260:Female; D007261:Infusions, Intra-Arterial; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D020108:Nicorandil; D014665:Vasodilator Agents / Q000008:administration & dosage*
D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil