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Endogenous modulators of platelet aggregability and vascular tone may play a part in coronary-artery disease. We therefore measured the release of prostaglandins and thromboxane into the coronary circulation in patients with various kinds of cardiac disease. Simultaneous coronary-sinus (CS) and ascending-aortic (AO) blood samples were obtained from 60 patients for measurement of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha, a prostaglandin I2 metabolite) and of thromboxane B2 (TxB2). Samples from 45 of these patients were also tested for prostaglandin E2 (PGE2) and lactate. Patients with unstable angina pectoris who reported chest pain within 24 hours of study had higher TxB2 CS/AO ratios (5.8 +/- 2.8, mean +/- S.D.) than patients whose most recent anginal pain was more than 96 hours before study (1.3 +/- 0.6; P less than 0.05), than those with nonischemic chest pain (1.2 +/- 0.4; P less than 0.05), or with valvular or congenital nonischemic heart disease (1.2 +/- 0.6; P less than 0.05). Those whose most recent anginal pain occurred 24 to 96 hours before study were distributed bimodally: the majority had low TxB2 CS/AO ratios (range, 0.5 to 2.1) like the patients in the three aforementioned groups, whereas a few had markedly elevated values (range, 10.5 to 46.6). The 6-keto-PGF1 alpha and PGE2 CS/AO ratios and myocardial lactate extraction were not significantly different among the five groups. These data suggest that local thromboxane release is associated with recent episodes of angina in patients with unstable angina pectoris, but whether this release is a cause or an effect is not yet known.

Thromboxane A2 exerts powerful effects on vascular smooth muscle tone and platelet aggregability. Previous studies have demonstrated increases in transcardiac thromboxane B2 (a stable thromboxane A2 metabolite) in patients with unstable angina and recent chest pain. To determine whether these increases in transcardiac thromboxane B2 are unique to the unstable anginal syndrome or are merely a consequence of ongoing myocardial ischemia, simultaneous ascending aortic and coronary sinus blood samples were obtained for quantitation of thromboxane B2 in 52 patients with a history of chest pain. Provocation was performed with (1) rapid cardiac pacing in 23 patients, (2) cold pressor stress in 19 patients, and (3) sustained isometric exertion in 10 patients. Of the 52 patients, only 5 had a substantial (greater than 3-fold) increase in coronary sinus thromboxane B2 in response to provocation: 1 had unstable angina and chest pain during the previous 48 hours and 4 had a myocardial infarction within the previous 6 weeks. Similarly, only 7 had a greater than 3-fold increase in the coronary sinus/aortic thromboxane B2 ratio in response to provocation: 1 had unstable angina and recent chest pain, 5 had a recent myocardial infarction, and 1 had both of these. There were no other clinical features unique to these patients. The remaining patients with similar diagnoses did not develop a marked increase in coronary sinus thromboxane B2 or the coronary sinus/aortic thromboxane B2 ratio with provocation. None of the 35 patients with stable ischemic heart disease or nonischemic chest pain syndromes had a substantial increase in coronary sinus thromboxane B2 or the coronary sinus/aortic thromboxane B2 ratio (p less than 0.001 for both coronary sinus thromboxane B2 and the coronary sinus/aortic thromboxane B2 ratio in comparison with the 17 patients with recent unstable angina or myocardial infarction). Thus, generous amounts of thromboxane B2 are released into the coronary circulation after provocation in some patients with unstable angina or recent myocardial infarction but not in those with stable ischemic heart disease or nonischemic chest pain syndromes.

We investigated the relationship between glucose levels and platelet thromboxane production or aortic prostacyclin production, using radioimmunoassay (RIA) to measure thromboxane B2 and 6-keto-PGF1 alpha. We found a direct relationship (p less than .05) between plasma glucose levels and thromboxane A2 production by arachidonate stimulated platelets in platelet rich plasma of normal mice. However, when mice were deprived of food overnight, the glucose level fell but the TxB2 production rose significantly. Moreover, mice with streptozotocin diabetes had significantly elevated glucose levels, but normal TxB2 production, which also rose significantly after fasting. Thus in our laboratory both fasting and diabetes nullify or reverse the direct relationship between glucose levels and TxB2 production seen in normal fed mice. This makes it difficult to ascribe the correlation between glucose and TxB2 levels in normal fed animals to cause and effect. RIA revealed an inverse correlation between glucose levels and 6-keto-PGF1 alpha production which was highly significant in aortas taken from fasted mice and stimulated for 10 minutes with 0.1 mM arachidonate. This inverse correlation was present with either normal or diabetic aortas. Moreover, fasting increased the production of 6-keto-PGF1 alpha. However there was a significant elevation of 6-keto production by aortas of mice with diabetes of 5-6 weeks duration, compared to aortas of normal mice. Therefore either diabetes in these mice reversed a normal inhibitory effect of glucose on 6-keto production, or else the inverse correlation between glucose levels and 6-keto production does not represent a cause and effect relationship between the two variables.

Thromboxane A2 may play a role in coronary arterial spasm, unstable angina, myocardial infarction, cardiac arrhythmias, and sudden death. Although previous studies have examined peripheral, aortic, and coronary sinus concentrations of its stable metabolite, thromboxane B2 (TxB2), it is unknown, first, if blood sampling through long catheters alters the concentration of TxB2 and second, if peripheral levels of this prostanoid reflect its intracoronary production and release. In order to answer these questions, paired blood samples were obtained through an 18-gauge needle and a No. 7 or 8 French 110 to 125 cm catheter from the arterial (14 patients) and venous (16 patients) circulations; in addition, coronary sinus and peripheral venous samples were obtained in 16 patients and aortic samples were obtained in 14 of these patients. All samples were analyzed to TxB2 by radioimmunoassay. Blood sampling through long catheters did not systematically alter the concentrations of arterial TxB2 (needle, 85.5 +/- 67.5 pg/ml [mean +/- SD]; catheter, 62.3 +/- 40.9 pg/ml; p = 0.20) or venous TxB2 (needle, 182.5 +/- 170.5 pg/ml; catheter, 521.4 +/- 1536.0 pg/ml; p = 0.39). Peripheral venous TxB2 levels did not correlate with TxB2 levels in coronary sinus (r = 0.01) or the TxB2 coronary sinus/aortic ratios (r = 0.21). Thus blood sampling through long catheters across the coronary bed is both a reliable and necessary method for assessing intracoronary TxB2 production in patients with ischemic heart disease.