The Effects of Adrenaline and Noradrenaline on the Metabolism and Performance of the Isolated Dog Heart

Abstract

In 16 dog heart-lung preparations modified to permit a more accurate measurement of coronary flow, adrenaline or noradrenaline was infused at a rate of 4 ,ug. base/min. After a 30-mmn. pause during which the increased oxygen consumption and heart rate, but not the coronary flow, returned to pre-infusion levels, the other sympathomimetic amine was infused for the same length of time. It was found that, mole per mole, noradrenaline is as effective, and probably more so, than adrenaline in raising the oxygen consumption of the heart-lung preparation. The positive chronotropic and coronary dilating action of both amines appear to be equal. It was observed that in any one experiment the second dose of the sympathomimetic amine was slightly more effective than the first dose in raising the oxygen consumption. The main actions of adrenaline on the heart are: positive inotropic and chronotropic effects, increased atrio-ventricular conduction, and increased excitability. In addition to these, there is the " calorigenic " effect. This is the increase in cardiac oxygen consumption which cannot be explained solely by the rise in heart rate and increase in work performed (for literature see Gollwitzer-Meier, Kramer and Kruger, 1936).All these effects of adrenaline need not have the same mechanism of action at the cellular or subcellular (enzymatic) level. Krayer (1949), for instance, has shown that the chronotropic action but not the inotropic action can be inhibited by veratramine. It is also conceivable that a certain dose of adrenaline would evoke one effect and not the other. The mechanism of the coronary dilating action of adrenaline is not completely understood and it is not clear to what extent the vasodilatation is due to the rise in cardiac metabolism.In this study a comparison has been made between the "calorigenic," chronotropic, and coronary dilating actions of (-)-adrenaline and (-)-noradrenaline on the dog heart-lung preparation and the effect of these compounds on the phosphorus compounds of the heart. Furthermore, a study has been made of the effect of graded doses of adrenaline, to see if the inotropic action can be separated from the calorigenic action. This study appeared important in view of statements often encountered in the clinical literature that (a) adrenaline raises the blood pressure mainly by virtue of its action on the heart, increasing the cardiac output, whereas noradrenaline acts peripherally; (b) adrenaline is contraindicated in the treatment of cardiogenic shock as it increases myocardial oxygen consumption and produces symptoms of coronary

Some Factors Influencing the Recovery of Isolated Myocardium From Acute Anoxia

“…Pletscher (1961) noted an increase in the blood pyruvate and lactate levels when monoamine oxidase inhibitors were given to human subjects. Fawaz & Tutunji (1960) also found that adrenaline and noradrenaline were approximately equal in their effect on the oxygen consumption of the dog heart-lung preparation. In the work described in this paper, both these amines depressed the recovery of contraction when present in the anoxic phase.…”

Comparison of Equipressor Doses of Norepinephrine, Epinephrine, and Phenylephrine on Septic Myocardial Dysfunction

“…6 Nevertheless, when looking at the effects of norepinephrine on heart contractile performance, it appears as efficient as epinephrine. 13,14 Experimental data on isolated myocardial heart tissues have shown that norepinephrine is inotropic and lusitropic at low and high concentrations whereas epinephrine increases inotropism at low concentration and decreases the latter at high concentration. This is explained by a differing action on ␤-2 receptors because both Gs and Gi pathways are stimulated by epinephrine, whereas only Gs is stimulated by norepinephrine.…”

Comparative Study of Inotropic Effects of Catecholamines on Blood-perfused Canine Papillary Muscle

“…Changes in heart rate together with changes in venous return, stroke volume and peripheral resistance might modify the true isotropic effect of catecholamines. Heart rate has not been controlled ordinarily in the in situ experiments (Crismon and Tainter 1938, Lands and Howard 1952, Goldberg et al 1953, Cotten and Pincus 1955, Fawaz and Tutunji 1960. It has been reported that isoproterenol exhibited the most potent isotropic effect among catecholamines in the rabbit (Lands and Howard 1952) and in the dog (Moran 1966).…”

“…The inotropic potencies of catecholamines, naturally occurring and synthetic, have been determined in various preparations of mammalian ventricular muscle, i.e., isolated papillary muscles (Garb 1950, Lee andYu 1964), heart-lung prepara tion (Crismon andTainter 1938, Fawaz andTutunji 1960) and hearts in situ (Goldberg et al 1953, Cotten and Pincus 1955, Moran 1966. While isoproterenol was found to be the most potent catecholamine (Lands andHoward 1952, Moran 1966), differences in potencies between epinephrine and norepinephrine occur among various species of animals.…”