Ventricular function and cardiac hypertrophy after coronary thrombolysis with tissue-type plasminogen activator (t-PA) in dogs with coronary artery thrombi.
Subacute prognosis of cardiac function after thrombolysis with a modified tissue-type plasminogen activator (t-PA) YM866 was determined in dogs with coronary artery thromboses induced by injection of a thrombin, fibrinogen and autogenous blood mixture. The left ventricular ejection fraction (LVEF) decreased 30 min after occlusion and had not improved 1 week later. Examination after sacrifice revealed myocardial infarction as well as increases in both the left ventricular myocardial area and heart mass. Occluded coronary arteries reperfused by YM866 (0.1 mg kg(-1) i.v.) treatment 30 min after occlusion, by contrast, had improved LVEF and inhibited myocardial infarction development. In addition, the left ventricular myocardial area and heart mass were significantly reduced compared with the vehicle control group 1 week after administration. Although occluded coronary arteries reperfused by YM866 (0.1 mg kg(-1) i.v.) treatment 3 h after occlusion did not show an improvement in the LVEF or inhibition of myocardial infarction development, the left ventricular myocardial area and heart mass decreased significantly compared with the vehicle control group 1 week after administration. In conclusion, early reperfusion by t-PA treatment 30 min after occlusion improved the ventricular function and cardiac hypertrophy, whereas late reperfusion by t-PA treatment 3 h after occlusion did not improve the ventricular function but did inhibit hypertrophy in dogs with coronary artery thrombi.
Suzuki
M
M
Applied Pharmacology Research, Yamanouchi Pharmaceutical Co. Ltd, Tsukuba, Ibaraki, Japan.
Asano
H
H
Kimoto
A
A
Tanaka
H
H
Usuda
S
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000517:prevention & control*; D003328:Coronary Thrombosis / Q000150:complications / Q000188:drug therapy*; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects*
D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; C085027:pamiteplase