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...

The results of this study compared favourably with the responses of patients treated with radiation therapy and chemotherapy. The study continues with accrual of additional patients.

We have reported that thromboxane B2 is present in plasma of Prinzmetal's angina patients measured by radioimmunoassay but is below detection limits, <0.5 pmol/ml, in normals. To determine whether this metabolite of thromboxane A2 (a coronary vasoconstrictor) is present in the peripheral blood in classical angina pectoris, we studied 14 patients with fixed obstructive coronary artery disease (2.5 lesions per patient) in whom angina was induced by atrial pacing. Thromboxane B2 at rest was barely detectable (0.537±0.16 pmol/ml), but rose during pacing (0.747±0.18 pmol/ml) and was maximal (p<0.05) 5–10 min after pacing (1.237±0.36 pmol/ml). In eight variant angina patients, resting levels of thromboxane B2 were not statistically different during spontaneous angina and angina‐free intervals (2.837±0.56 and 1.577±0.34 pmol/ml), but the mean 5–10 min after angina was higher than during angina (6.41 7±1.46 pmol). The means of preanginal, anginal, and postanginal samples were all higher than the corresponding means of the classical angina group, and thromboxane B2 levels in variant angina patients in the absence of angina, during angina, and 5–10 min after angina were all significantly higher (p<0.025) compared to the classical angina group measured prior to pacing. Unlike the case with variant angina, thromboxane B2 is indetectable in classical angina pectoris patients at rest. Furthermore, spontaneous angina in variant angina or pacing‐induced angina in classical angina pectoris are both followed by increased thromboxane B2, although the latter responses are smaller. The role of these phenomena in the pathogenesis of coronary artery spasm and ischemia remains to be clarified.

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The results of the present study are favourable in comparison with radiation therapy and chemotherapy. We believe that confirmation of these results through further studies may introduce a new promising treatment for incurable paediatric brain tumours.

Increases in endogenous free fatty acids (FFA) induced by several stimuli are associated with increases in platelet aggregates and platelet factor 4 in man. To determine if thromboxane (TxB) release is also an associated event, we measured plasma FFA and TxB₂ levels before and 5 min after bolus injection of 2,500 U of heparin prior to coronary arteriography in 27 patients with angina. Significant increases in FFA occurred in all patients (p < 0.02) and those with critical lesions (p < 0.01), while TxB₂ levels also rose (p < 0.02, p < 0.05, respectively). However, linear regression showed increases in FFA and TxB₂ were independent. The observed TxB₂ release may be due to lipolysis-induced exposure of vascular collagen or direct inhibition of platelet adenylate cyclase by heparin.

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