title: Regional myocardial ajmaline concentration and antiarrhythmic activity for ischaemia- and reperfusion-induced arrhythmias in rats.
abstract: 1. Antiarrhythmic actions of ajmaline against ischaemia (left coronary artery occlusion for 15 min) and subsequent reperfusion-induced arrhythmias were investigated in anaesthetized rats. 2. Ajmaline (2 mg kg-1, i.v.) was effective in suppressing ischaemia-induced arrhythmias whether given pre- or post-occlusion. 3. Ajmaline diminished the reperfusion-induced arrhythmias completely when given pre-occlusion but had little effect when given post-occlusion. 4. Reperfusion-induced increases in plasma enzyme activities of lactate dehydrogenase, glutamate-oxaloacetate transaminase and creatine phosphokinase were prevented more effectively when ajmaline was given pre-occlusion rather than post-occlusion. 5. Fifteen min post-occlusion, the ajmaline concentrations in the ischaemic ventricle were 18.42 +/- 1.66 and 1.18 +/- 0.15 micrograms g-1 for pre- and post-occlusion administration, respectively. However, ajmaline concentrations in whole blood and normal ventricle were not significantly different between pre- and post-occlusion administration. 6. We suggest that the beneficial effect of ajmaline against reperfusion-induced arrhythmias is related to the ischaemic myocardial concentration of ajmaline which is markedly affected by the time of drug administration (i.e. pre- and post-occlusion).
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Okumura
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: M
authors.initials: M
authors.lastname: Yasuhara
authors.forename: R
authors.initials: R
authors.lastname: Hori
mesh_terms: D000404:Ajmaline / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000097:blood; D003326:Coronary Circulation; D003327:Coronary Disease / Q000378:metabolism*; D003402:Creatine Kinase / Q000097:blood; D004562:Electrocardiography; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000889:Anti-Arrhythmia Agents; D000404:Ajmaline; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase