The effect of platelet-activating-factor antagonist TCV-309 on arrhythmias and functional recovery during myocardial reperfusion.
BACKGROUND
We investigated the effects of a platelet-activating-factor antagonist TCV-309, an antagonist of metabolites of ischemia, on arrhythmias and functional recovery during in-situ reperfusion in dogs.


METHODS
Open-chest anesthetized dogs were subjected to ligation of the left anterior coronary artery. Ischemia was maintained for 20 min after which reperfusion was allowed. A cardiac surface ECG was recorded continuously with the II limb lead. Monophasic action potential, left ventricular segment shortening measured by sonomicrometer, and left ventricular pressure were recorded simultaneously under atrial pacing (group A, n = 14). In a second group of dogs, TCV-309 (1 mg/kg) was administered before coronary artery occlusion (group B, n = 12). The hearts were constantly paced through the right atrium at 120 beats/min throughout all experiments. Measurements were continuously obtained from before drug administration to 30 min after reperfusion.


RESULTS
The 90% repolarization time of monophasic action potentials in group B revealed significant recovery compared with group A until the fifth minute after reperfusion (P < 0.02). Reduction of severe ventricular arrhythmias was observed during reperfusion in group B (P < 0.05). The percentage segment shortening and left ventricular pressure did not differ significantly between the groups.


CONCLUSIONS
The platelet-activating-factor antagonist had beneficial effects on arrhythmias but not on functional recovery during reperfusion after brief coronary artery occlusion in situ in dogs.
Tamura
K
K
Second Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Kimura
Y
Y
Tamura
T
T
Kitashiro
S
S
Izuoka
T
T
Tsuji
H
H
Iwasaka
T
T
Inada
M
M
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004562:Electrocardiography; D007546:Isoquinolines / Q000627:therapeutic use*; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011726:Pyridinium Compounds / Q000627:therapeutic use*; D017180:Tachycardia, Ventricular / Q000503:physiopathology / Q000517:prevention & control*; D044005:Tetrahydroisoquinolines; D014693:Ventricular Fibrillation / Q000503:physiopathology / Q000517:prevention & control*; D016277:Ventricular Function, Left / Q000187:drug effects*
D007546:Isoquinolines; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; D044005:Tetrahydroisoquinolines; C067430:TCV 309