HEMODYNAMIC EFFECTS OF TYRAMINE

¹ Departments of Pharmacology and Anesthesiology, Temple University School of Medicine, Philadelphia, Pennsylvania

The aim of this study was to provide a clearer definition of the cardiovascular actions of tyramine in intact conscious as well as anesthetized dogs, and where possible to localize the major cardiovascular sites of action. In pentobarbitalized open-chest dogs, pressor doses of tyramine HCl i.v. increased heart rate, cardiac output and force of myocardial contraction. Total peripheral resistance first increased, but then decreased despite the persistence of a pressor response. In unanesthetized trained dogs, using the rate of rise (first derivative) of left ventricular pressure as an index of myocardial contractile response, the responses to tyramine were similar except that heart rate decreased. In addition, the pattern of response with respect to cardiac output and total peripheral resistance was not the same in all animals. During the latter part of the pnesson response, cardiac output was the major determinate of pressure in the majority of animals. Local vasoconstrictor and positive inotropic cardiac effects of tyramine were demonstrated by regional i.a. injections of subpressor doses in anesthetized dogs: pressure/flow ratios increased in renal, mesentenic and femoral vascular beds when minimal doses were injected, respectively, into the renal, superior mesenteric and femoral artery; the force of left ventricular contraction increased when minimal doses were injected into the circumflex branch of the left coronary artery. The hypothesis that tyramine acts indirectly via catecholamine release is supported by the findings that local (renal) vasoconstrictor responses, myocardial contractile responses and pressor responses were reduced by reserpine pretreatment. The results in both anesthetized and unanesthetized animals indicate that both cardiac and vasoconstrictor responses to tyramine must be taken into account whenever the pressor effect is used in analyzing the actions of tyramine and the modification of its action by other drugs.