Tissue-type plasminogen activator alone or in combination with thromboxane A2 synthetase inhibitor for ischemic myocardium.
Although the efficacy of tissue-type plasminogen activator (t-PA) for coronary thrombolysis is well established, its direct cardioprotective effect - independent of its thrombolytic effect - is still controversial. In addition, the potentiation of t-PA's direct cardioprotective effect by thromboxane A2 synthetase inhibitor has recently been reported. In this study, the authors examined whether t-PA alone or in combination with DP1904, a thromboxane A2 synthetase inhibitor, is able to salvage ischemic myocardium via a direct action on myocardium. In addition, the effect of these interventions on intramyocardial hemorrhage in reperfused infarcts was assessed. A branch of the coronary artery of the rabbit was occluded for 30 mins and then reperfused for 72 h. Myocardial infarct size and 'area at risk' were determined by histology and fluorescent particles, respectively. The extent of intramyocardial hemorrhage was graded using scores. Rabbits were divided into three groups: control, t-PA and DP1904 plus t-PA. The t-PA was administered intravenously at 500 iu/kg/min for 30 mins starting 5 mins prior to reperfusion. DP1904 was injected intravenously at a dosage of 10 mg/kg every 24 h starting 2 hr prior to coronary occlusion. Mortality was similar and hemodynamic parameters and area at risk were comparable between all three groups. The myocardial infarct size as a percentage of area at risk was 44.5 +/- 3.8% (mean +/- standard error) (n = 9) in the control group, 41.6 +/- 4.6% in the t-PA group (n = 8) and 51.3 +/- 5.2% in DP1904 plus t-PA group (n = 8), not significantly different (ANOVA). Neither were the hemorrhage scores significantly different between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Ogawa
T
T
Second Department of Internal Medicine, Sapporo Medical College, Japan.
Miura
T
T
Tsuchida
A
A
Iwamoto
T
T
Urabe
K
K
Endoh
A
A
Iimura
O
O
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004359:Drug Therapy, Combination; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D011817:Rabbits; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage* / Q000627:therapeutic use; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D007093:Imidazoles; D013764:Tetrahydronaphthalenes; C056295:nafagrel; D010959:Tissue Plasminogen Activator; D013930:Thromboxane-A Synthase