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Background: Endogenous production of bradykinin (BK) has been postulated to cause hemodynamic changes and cardiac pain during myocardial ischemia, presumably because of the stimulation of cardiac afferent fibers., Methods: To test the hypothesis that BK results in cardiac reflex responses and can cause the sensation of angina, 10 patients with and without coronary atherosclerosis had BK injected into their right (RCA) and left (LCA) coronary arteries in graded concentrations up to 10(-5) m. Patients were monitored for hemodynamic changes and the presence and quality of pain., Results: Intracoronary BK 10(-5) m caused a significant reduction in blood pressure in most patients with either injection into the RCA or LCA (RCA: 151 +/- 10/90 +/- 5 mm Hg to 119 +/- 11/70 +/- 6 mm Hg, LCA: 161 +/- 11/88 +/- 6 mm Hg to 118 +/- 10/65 +/- 6 mm Hg) that began 12 to 14 seconds after injection. Injection into the LCA also resulted in a significant increase in heart rate (69 +/- 4 to 81 +/- 7 beats/minute), while injection into the RCA did not. Pain occurred after changes in blood pressure in all but one patient, which was present in 5 of 9 patients with RCA injection and 8 of 9 patients with LCA injection, and was often associated with flushing and nausea. Pain caused by BK was not similar to previous clinical ischemic pain in the patients with coronary atherosclerosis., Conclusions: The absence of a chronotropic response associated with arterial hypotension following injection of BK into the RCA is consistent with activation of cardiac vagal afferents in the left ventricle. The latency and quality of pain in these patients following injection of BK suggests that, while BK is nociceptive, it likely is not the cause of angina in patients with myocardial ischemia.

The comparative timing of hemodynamic alterations by sublingual nitroglycerin administered by spray vs. tablet has not been studied. Similarly, the directly measured comparative effects on left ventricular pressures have not been reported. To investigate these issues, we analyzed 49 patients undergoing elective diagnostic cardiac catheterization who were randomized to receive 0.4 mg sublingual nitroglycerin by either spray or tablet. Before administration of contrast medium, control determinations of left ventricular end-diastolic and systolic pressures and heart rate were done. These parameters were then evaluated at half-minute intervals for 5 min. Left ventricular end-diastolic pressure was reduced similarly in both groups, with the reduction achieving significance at 1.5 min in the spray and 2.0 min in the tablet group. Lowering of the left ventricular systolic pressure was also similar in the two groups, reaching significance at 2.5 min with spray and 2.0 min with tablet. Heart rate increased significantly by 2.0 min in the tablet group but did not change in the spray group. These findings were not altered by the level of resting left ventricular end-diastolic pressure or use of chronic nitrates. Thus, we found nitroglycerin to be similarly effective in timing and extent of response whether administered by spray or tablet, though the difference in heart rate responses remains unexplained.