CONCURRENT NITROGLYCERIN ADMINISTRATION DECREASES THROMBOLYTIC POTENTIAL OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR

[摘要] 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-mu-g/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 < 0.02), and the duration of reperfusion much shorter (11 +/- 17 versus 42 +/- 16 min, p < 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 < 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 < 0.01). In addition, whole blood platelet aggregation decreased significantly with administration of rt-PA alone, but not with administration of rt-PA with nitroglycerin (0.23 +/- 0.57 and 5.26 +/- 6.23-omega, respectively, p < 0.02). Peripheral blood platelet count decreased during thrombus formation in all dogs; with administration of rt-PA alone, platelet counts stabilized but continued to decrease with concurrent administration of nitroglycerin with rt-PA (mean platelet counts at the end of rt-PA infusion 7.23 +/- 1.68 and 4.78 +/- 3.00 x 10(8)/ml, respectively, p < 0.02), suggesting continued sequestration of platelets in the intracoronary thrombus. In four additional dogs nitroglycerin was given after rt-PA-induced thrombolysis, but nitroglycerin failed to sustain coronary artery reperfusion. This study shows that 1) nitroglycerin given concurrently with rt-PA may have a detrimental effect on the thrombolytic potential of rt-PA, probably because of the reduction in plasma t-PA concentrations, and 2) nitroglycerin given after rt-PA-induced thrombolysis does not prevent coronary artery reocclusion.

[发布日期] 1991-03-01