The hemodynamic effects of tetramethylpyrazine were examined in 27 anesthetized open chest dogs with electromagnetic flowmeter probes on the left circumflex coronary artery and ascending aorta. Tetramethylpyrazine, 2-15 mg/kg i.v., caused prominent systemic and coronary vasodilation, with a maximum reduction of mean aortic pressure from 92 ± 5 mm Hg during control conditions to 62 ± 7 mm Hg (p < 0.01), a peak increase in cardiac output from 3.0 ± 0.4 to 4.1 ± 0.7 L/min (p < 0.05), and a peak reduction of systemic vascular resistance from 2.450 ± 400 to 1.210 ± 329 dyne·s·cm-5 (p < 0.01). Simultaneously, heart rate increased from 143 ± 9 to 174 ± 8 beats/min (p < 0.01), and maximum left ventricular dP/dt increased from 2.410 ± 120 to 4.020 ± 60 mm Hg/s (p < 0.01). Dose-related increases of coronary blood flow occurred from 37.3 ± 3.7 to a maximum of 74.1 ± 6.6 ml/min (p < 0.01), while mean coronary vascular resistance decreased from 1.770 ± 240 to 700 ± 260 dyne·s·cm-3 (p < 0.01). Myocardial oxygen consumption increased in proportion to the increase in coronary blood flow. Following β-adrenergic blockade with propranolol (1 mg/kg. i.v.), ganglionic blockade with hexamethonium, or catecholamine depletion with reserpine (1.0 mg/kg. i.p.), the systemic and coronary vasodilator effects of tetramethylpyrazine persisted, but the increases in heart rate, maximum left ventricular dP/dt, and myocardial oxygen consumption were markedly attenuated. These data demonstrate that tetramethylpyrazine has potent vasodilating activity in both systemic and coronary circulations. However, the increases in heart rate, maximum left ventricular dP/dt, and myocardial oxygen consumption produced by tetramethylpyrazine appear principally related to reflex activation of the sympathetic nervous system by the drug.
- Blood pressure
- Left ventricular afterload
- Myocardial blood flow
- Myocardial oxygen consumption