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The cardiovascular alpha adrenergic receptors evoke vasoconstriction, the cardiovascular beta receptors evoke vasodilation and cardiac stimulation. All blood vessels have both alpha and beta receptors. In some areas, for example skin and kidney, the alpha receptors predominate. In some vascular beds, for example the nutrient vessels in skeletal muscle, beta receptors predominate. In other beds, such as coronary, visceral, and connective tissue both receptors are active. The cardiovascular effects of adrenergic agonists depend on which receptor they act on. Phenylephrine is specific for alpha receptors. Isoproterenol is specific for beta receptors. Epinephrine and norepinephrine act on both. The real value of knowing the receptor specificity of each agonist is that side effects can more easily be predicted. For example, adrenergic cardiac stimulants are antiasthmatics. Therefore, adrenergic antiasthmatics can produce excessive cardiac stimulation. For the future, agonists that are not only receptor-specific but also tissue-specific will be developed. The first of these in the United States is terbutaline. The rest of the world has in addition a similar drug, salbutamol. No one knows if this drug will be approved for use by American physicians.

The hemodynamic responses to mephentermine were studied in dogs anesthetized with pentobarbital and in those treated with gallamine. Observations were made in normotensive animals and in animals made hypotensive by intravenous hexamethonium. Mephentermine regularly caused an increase in cardiac output and arterial pressure regardless of the control state of the animal. Calculated peripheral resistance increased in 18 of the 22 experiments. In this study, mephentermine raised the level of arterial pressure by increasing both cardiac output and peripheral resistance.

The antifibrillary actions of Ambonestyl, quinidine, and mephentermine were studied on spontaneous ventricular fibrillation and on surgically induced ventricular fibrillation in the hypothermic dog. In addition, combinations of these agents were studied on spontaneous ventricular fibrillation in hypothermia. Mephentermine in a dose of 3 mg./Kg. significantly reduced the frequency of spontaneous ventricular fibrillation, whereas Ambonestyl and quinidine were not effective. When combined with either Ambonestyl or quinidine, mephentermine exerted the same antifibrillary effect. Surgically induced ventricular fibrillation in hypothermia was significantly reduced by quinidine (12 mg./Kg.) but not by Ambonestyl or mephentermine. The results indicate that the two situations (spontaneous and surgically induced fibrillation in hypothermia) are not entirely similar, that prevention of one does not imply prevention of the other, and that the factors predisposing the heart to fibrillation are different in the two conditions.

1. 1. Mephentermine (Wyamine) a new pressor substance with theoretical norepinephrine-like activity has been shown to produce a rapid predictable pressor response in volunteer human beings (controls) and dogs. 2. 2. With the doses employed, there was little or no direct action upon the heart as measured by changes in rate, rhythm, and irritability. 3. 3. Side reactions such as cerebral stimulation, pupillary changes, blood sugar changes, respiratory stimulation, and metabolic rate increase were absent or insignificant. 4. 4. The cardiac output was relatively unaltered and heart work was increased in normal and hypotensive patients. Coronary flow in dogs was increased even under constant coronary perfusion pressure. 5. 5. Mephentermine appears to be a suitable drug for use in treating acute hypotensive states, especially shock following myocardial infarction. It has proved effective in sustaining blood pressure in cardiovascular operations without producing arrhythmias.

1.1. Shock accompanying myocardial infarction is associated with a mortality of approximately 80 per cent. 2.2. Pressor amines were administered to eighteen patients in shock accompanying myocardial infarction. ∗ Mephentermine (Wyamine), in a preliminary study, was found to be a safe effective pressor substance with little direct effect upon myocardial irritability in the doses employed. Seventeen patients were treated with mephentermine (three also received ephedrine) and one received ephedrine alone. 3.3. A pressor response was produced in sixteen patients. Fourteen emerged from the shock state with marked clinical improvement for more than two days. However, seven succumbed to secondary complications two to twenty-six days later. Seven patients recovered sufficiently to be discharged from the hospital. 4.4. Pressor therapy did not produce congestive failure in patients not previously in failure, nor did it aggravate pre-existing failure. 5.5. The use of pressor amines in the treatment of shock accompanying myocardial infarction appears to rest upon a firm clinical basis.

This case history was presented because of two separate etiological factors producing shock, namely, gram-negative ( Aerobacter aerogenes ) bacteremia and myocardial infarction. In this case, shock was preceded by convulsive seizure and coarse tremors of the right arm and leg, instead of the usual occurrence late in the course of events. This was interpreted as an early toxic manifestation of impending gram-negative bacteremia with shock. Of special interest is the marked leukemoid reaction (73,750 white blood cells per cubic millimeter), with metaraminol bitartrate suspect. Leukemoid reaction does not occur in gram-negative bacteremia, which is more likely to produce hemolytic reactions. Leukemoid reaction of this degree is not characteristic of myocardial infarction. Other causes of sepsis were ruled out. The hypotensive state was profound and prolonged for a total of 30 days and responded to conventional therapy. Adrenal insufficiency was suggested as a cause of prolonged hypotension but is not well documented by steroid levels reported or by the Thorn test.