Thromboxane release during pacing-induced angina pectoris: possible vasoconstrictor influence on the coronary vasculature.

Abstract

SUMMARY We developed a radioimmunoassay for plasma thromboxane B,, the metabolite of the coronary vasoconstrictor thromboxane A,. To see if thromboxane A, is produced during myocardial ischemia, we used atrial pacing to study 14 patients with greater than 75% occlusive coronary artery disease proved by arteriography. Paired samples were taken from the coronary sinus (CS) and an artery (A) for lactate and thromboxane B, analysis before pacing. During and after pacing at 140 beats/min, sampling was repeated. Before, during, immediately after and 10 minutes after pacing, percent myocardial lactate extractions (A-CS/A X 100) were 29.3 ± 3.7%, -21.1 ± 12.8%, -74.3 ± 20.3% and 25.1 + 3.5%, respectively (all changes p < 0.01). Before pacing, five patients had detectable coronary sinus or arterial thromboxane levels. During pacing, 18% and 40% increases occurred in coronary sinus and arterial blood, respectively (0.8 ± 0.1 to 0.9 ± 0.2 pmol/ml, and 0.5 0.2 to 0.7 ± 0.2 pmol/ml). Immediately after pacing, increases of 204% and 132% occurred in the coronary sinus and arterial blood (p < 0.05), respectively (2.3 ± 0.9 pmol/ml and 1.2 ± 0.4 pmol/ml). Ten minutes after pacing, thromboxane B, returned to prepacing levels. These data indicate that thromboxane A, is produced during pacing-induced myocardial ischemia and could alter regional coronary blood flow.ATRIAL PACING coupled with coronary sinus blood sampling has been used extensively to study angina pectoris.' During controlled tachycardia, induced myocardial ischemia is accompanied by increased concentrations of lactic acid,6 carbon dioxide,7 hydrogen ion,7 potassium6 and bradykinin.8 Fox et al.9 observed the release of adenosine from human hearts during angina induced by rapid atrial pacing. Subsequently, Berger et al.,10 in a similar experimental setting, reported the release of prostaglandin F from the coronary sinus during anginal provocation.Hamberg, Svensson and Samuelssonll described another prostaglandin, thromboxane A2, which has been found to have potent coronary vasoconstricting and platelet-aggregating ability.'2-14 Our development15 of a radioimmunoassay to measure thromboxane B,, the stable but inactive metabolite of thromboxane A2, led us to design an investigative protocol using rapid atrial pacing to determine if thromboxane release is involved in the cardiovascular response to ischemia. This study documents increases in both coronary sinus and arterial thromboxane B, concentrations during and after ischemia in patients with arteriographically proved, fixed coronary artery disease.Materials December of 1978 were studied by atrial pacing using a method previously reported,'6 followed by coronary arteriography and ventriculography. Descriptions of these patients are shown in table 1. All were judged to have unstable or accelerating angina pectoris and were candidates for emergency myocardial revascularization. After informed consent was obtained, catheterization of the coronary sinus was performed by means of a #7 Gorlin pacing catheter. An 18-gauge Te...

Coronary Vasoconstrictor and Vasodilator Actions of Arachidonic Acid in the Isolated Perfused Heart of the Rat

“…The role of TxA2 as a vasospastic agent leading to coronary insufficiency has been examined in humans and it was shown that TxB2 in the coronary sinus increased during angina pectoris electrically induced by tachycardia (Lewy, Wiener, Walinsky, Lefer, Silver & Smith, 1980). The coronary constriction would be located, particularly at the level of the arterioles, as it has been demonstrated in the hamster cheek pouch by the administration of the prostaglandin endoperoxide, PGH2 (Higgs, Cardinal, Moncada & Vane, 1979).…”

Effect of heparin bonding on catheter-induced fibrin formation and platelet activation.

“…1-5. 25 Several groups of investigators have reported that levels of TXB, the stable metabolite of TXA,, are elevated in coronary sinus blood of patients with variant angina.61 --Other investigators have reported elevated TXB2 levels in coronary sinus blood of patients with coronary artery disease after episodes of spontaneous angina, 17 19 in association with pacing-induced angina, 16 or within 24 hr of an episode of chest pain.27 Elevated BTG levels have been reported in coronary sinus blood of patients with coronary artery disease and have been interpreted as demonstrating abnormal platelet activation in the atherosclerotic coronary circulation. '5 In all these studies, blood samples were collected from the coronary sinus with woven Dacron catheters.…”

Effects of dazoxiben on exercise performance in chronic stable angina.

“…Miller and his group (Kumpuris et al, 1980) reported an increased production of platelet aggregates by dynamic exercise in patients with coronary heart disease. At the same time Lewy et al (1980) demonstrated an excessive release of thromboxane into the coronary sinus of patients with coronary heart disease, during pacing-induced angina.…”