Concurrent nitroglycerin administration decreases thrombolytic potential of tissue-type plasminogen activator.
Dynamic coronary vasoconstriction may play a role in coronary artery reocclusion after successful thrombolysis. The effect of nitroglycerin on the thrombolytic effects of recombinant tissue-type plasminogen activator (rt-PA) was examined in dogs with an electrically induced occlusive coronary artery thrombus. Eleven dogs were randomly given rt-PA alone and seven rt-PA with nitroglycerin. The dose of rt-PA was 0.75 mg/kg body weight given over 20 min and the dose of nitroglycerin was 125 micrograms/min for 40 min. The reperfusion rate in the dogs given rt-PA alone was 73% (8 of 11 dogs) and that in the rt-PA plus nitroglycerin group was 57% (four of seven dogs) (p = NS). The time to thrombolysis (or reperfusion) in dogs receiving rt-PA plus nitroglycerin was 70% greater than in those receiving rt-PA alone (means +/- SD/29.8 +/- 9.9 versus 17.6 +/- 5.9 min, p less than 0.02), and the duration of reperfusion much shorter (11 +/- 17 versus 42 +/- 16 min, p less than 0.02). Peak coronary blood flow after reperfusion in dogs receiving rt-PA plus nitroglycerin was also less than in those receiving rt-PA alone (36 +/- 52 versus 63 +/- 20 ml/min, p less than 0.02). Reocclusion occurred in all dogs given rt-PA with nitroglycerin and in six of eight given rt-PA alone (p = NS). Plasma concentrations of rt-PA were lower when nitroglycerin was given with rt-PA alone (427 +/- 279 versus 1,471 +/- 600 ng/ml, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Mehta
J L
JL
Division of Cardiology, University of Florida College of Medicine, Gainesville 32610.
Nicolini
F A
FA
Nichols
W W
WW
Saldeen
T G
TG
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy*; D004285:Dogs; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D015425:Myocardial Reperfusion; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D012008:Recurrence; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000097:blood
D010959:Tissue Plasminogen Activator; D005996:Nitroglycerin