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...

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The sequence of events characterizing the onset and course of exercise-induced angina pectoris was studied in 10 patients with ischemic heart disease during cardiac catheterization. Exercise produced a precipitous rise in left ventricular end-diastolic pressure prior to the onset of angina and electrocardiographic ischemia. A corresponding abnormal increase in pulmonary artery pressure occurred. Cardiac output increased commensurate with the degree of exertion and was accompanied by a slight reduction in stroke volume. Left ventricular work and stroke work paralleled the changes in cardiac output and stroke volume. Determinants of myocardial oxygen consumption, that is, heart rate, left ventricular systolic pressure, and left ventricular first derivative, were monitored continuously and noted to increase by 43%, 20%, and 38%, respectively, prior to angina. Ischemic ST-segment depression corresponded closely in time with angina. Angina and electrocardiographic and hemodynamic abnormalities persisted throughout exercise. Two minutes after exercise, hemodynamic values returned to normal along with a reduction in intensity of angina; ST-segment abnormalities persisted until 4 minutes after exercise. Pathophysiological mechanisms occurring during angina are described, and differences from typical heart failure are discussed.

The hemodynamic effects of 10 mg of propranolol given intravenously (iv) were studied in 10 patients (group I) with coronary heart disease (CHD). These results were compared with the hemodynamic effects in a similar group of the nine (CHD) patients (group II) who were studied after administration of 0.6 mg of nitroglycerin and then after receiving 10 mg of propranolol iv with a second 0.6-mg dose of nitroglycerin. Measurements were obtained at rest and during exercise: before treatment, after nitroglycerin alone, after propranolol alone, and after nitroglycerin-propranolol in combination. Pretreatment exercise showed a 125% increase in mean pulmonary artery pressure (PAP) to 43 mm Hg and a 163% increase in left ventricular end-diastolic pressure (LVEDP) to 29 mm Hg. Nitroglycerin decreased PAP (–45%) and LVEDP (–66%); as did nitroglycerin-propranolol: PAP (–33%) and LVEDP (–38%). Nitroglycerin reduced tension-time index (TTI) –21%, and increased cardiac index (CI) +17%, heart rate (HR) +10%, left ventricular work index (LVWI) +11%, and left ventricular dp/dt (LV dp/dt) +22%. By contrast, nitroglycerin-propranolol reduced LVWI –14%, LV dp/dt –30%, TTI – 15%, and HR – 13% but did not significantly alter CI from pretreatment. Propranolol increased PAP to 40 mm Hg, did not change LVEDP at 29 mm Hg and decreased stroke index (SI) 16%. Nitroglycerin-propranolol diminished PA and LVED pressure and increased SI 14%. Effects of propranolol alone and of nitroglycerin-propranolol on HR, TTI, and LV dp/dt were not significantly different. Nitroglycerin-propranolol appears to have important advantages over nitroglycerin or propranolol alone. A reduction in HR, TTI, and LV dp/dt, determinants of myocardial oxygen consumption, concurrent with improved left ventricular function, demonstrates a beneficial synergistic hemodynamic action for nitroglycerin combined with propranolol.

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