Restoration of prostacyclin synthase in vascular smooth muscle cells after aspirin treatment: regulation by epidermal growth factor.

Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation and plays an important role in maintenance of vascular homeostasis. Aspirin irreversibly inactivates prostacyclin synthetase by acetylating the enzyme. Recovery of the enzyme following inactivation by aspirin was studied in rat aorta smooth muscle cells in tissue culture. Confluent cultures superfused with [14C]arachidonic acid, synthesized prostacyclin (PGI2) together with prostaglandins E2, D2, and F2 alpha. Brief treatment with physiological levels of aspirin (0.2 mM) completely inactivated prostacyclin synthesis. Following aspirin removal and addition of fresh growth medium, PGI2 synthesis recovered rapidly with a T 1/2 of only 30-40 min, compared to a doubling time of 24-30 hr for the cells. Recovery of PGE2, PGD2, and PGF2a synthesis paralleled that of PGI2, confirming that cyclooxygenase rather than endoperoxide-prostacyclin isomerase was the labile component. Recovery of PGE2 synthesis after aspirin was blocked by cycloheximide but not by actinomycin D. Recovery of aspirin-inactivated cells required a non-dialyzable component present in serum. All samples tested, including fetal bovine, new-born calf, human, and guinea pig, showed the activity. Fresh serum also induced a cycloheximide-sensitive 2- to 3-fold increase in cyclooxygenase levels in resting confluent cells within 1 to 2 hr. Serum factor was also required to restore PG synthesis after aspirin-inactivation in other cells, including 3T3 mouse fibroblasts, SV40-3T3 and K-Balb 3T3 transformed mouse fibroblasts, NRK rat kidney cells, and REF-9 rat embryonic fibroblasts. The activity was thermolabile, and was completely removed from the medium by growing cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Limitation of infarct size with thrombolytic agents--electrocardiographic indexes.

Forty-four patients with acute transmural myocardial infarction underwent cardiac catheterization 4.7 +/- 1.3 hours (+/- SD) after the onset of persistent chest discomfort. Thirty-nine patients had total occlusion of infarct-related vessels; 27 of these 39 had successful intracoronary thrombolysis. Twenty of these 27 patients (74%) had reperfusion arrhythmia. Accelerated idioventricular rhythm was most often observed with reperfusion of all myocardial zones, while sinus bradycardia and hypotension accompanied reperfusion of the inferoposterior left ventricle. Three patients with spontaneous accelerated idioventricular rhythm had patient, stenosed, infarct-related vessels on the initial coronary angiogram. Patients with unsuccessful intracoronary thrombolysis did not demonstrate these specific arrhythmias. While there is rapid control of injury current with successful intracoronary thrombolysis, Q waves develop rapidly after reperfusion; however, in the days after intracoronary thrombolysis, there is a decline in Q wave with partial regrowth in R wave amplitude in some patients. Thus, specific arrhythmias, most notably accelerated idioventricular rhythm, are useful markers for the occurrence and timing of successful coronary arterial recanalization. In addition, rapid control of injury current and partial regrowth of R waves are electrocardiographic markers of myocardial salvage.

Reperfusion arrhythmia: a marker of restoration of antegrade flow during intracoronary thrombolysis for acute myocardial infarction.

We studied the effects of coronary recanalization on arrhythmogenesis in patients undergoing intracoronary thrombolysis during the early hours of myocardial infarction. Catheterization, ventriculography, coronary angiography, and intracoronary streptokinase infusion were performed in 22 patients. Twenty-one of 22 had thrombotic total occlusion of the infarct-related transient thrombolysis with reocclusion by the end of the procedure. In 12 of these 17 patients, restoration of antegrade coronary flow was accompanied by transient arrhythmia. In these 12 patients coronary angiography within seconds of onset of arrhythmia showed vessel patency in a previously totally occluded coronary artery. Two additional patients developed arrhythmias during streptokinase infusion but after reperfusion had already been established. Accelerated idioventricular rhythm was most often noted. Sinus bradycardia and atrioventricular block with hypotension occurred during restoration of flow in arteries supplying the inferoposterior left ventricle. These arrhythmias may be useful noninvasive markers of successful reperfusion during thrombolytic therapy in acute myocardial infarction.