The present study was undertaken to evaluate the effects of methoxamine on force development and adenyl cyclase activity in cat ventricular myocardium. Methoxamine produced a dose-related increase in force development of isometrically contracting cat papillary muscles. The positive inotropic effects of methoxamine were not altered by beta-adrenergic blockade (propranolol), or catecholamine depletion by prior reserpinization, but were completely prevented by alpha-adrenergic blockade (phentolamine or ergotamine). Neither ergotamine, phentolamine, nor methoxamine had any direct effects on adenyl cyclase activity. Phentolamine did not attenuate the increase in force development produced by paired electrical stimulation, suggesting that it does not block the entry of calcium into the muscle. In summary, methoxamine produced a dose-related increase in force development of the cat papillary muscle that was selectively blocked by alpha-adrenergic receptors in ventricular myocardium.

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1. Data are presented which demonstrate that progressive antithrombin activity results from the interaction of three factors: antithrombin, an antithrombin inhibitor, and a platelet factor. In plasma, the antithrombin is held inactive by combination with inhibitor so that no free antithrombic activity is present. When platelets are disrupted—namely, in clotting—the platelet factor made available binds the inhibitor, releasing antithrombin to react with thrombin. 2. Antithrombin was isolated from plasma in the 70-75 per cent ammonium sulfate fraction. It was relatively heat stable at 56-57 C. for 5 minutes and was not soluble in perchloric acid. 3. Inhibitor was isolated from plasma in the 30-50 per cent ammonium sulfate fraction. It was inactivated at 56-57 C. for 5 minutes. It was soluble in perchloric acid in which it was purified by a factor of 300. 4. Platelet factor was present in the sedimentable fragments of platelets.

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SummaryHeparin accelerated the activity of isolated or unopposed antithrombin. Neither calcium, platelets nor inhibitor were required. Optimal activity was at minimal concentrations.Heparin was not consumed or altered in the process of thrombin neutralization by heparinized plasma. The full heparin activity was manifest when additional plasma antithrombin was supplied.Thrombin neutralization was noted to be a function of the plasma antithrombin concentration. It was unrelated to the heparin concentration. Heparin did not increase the total antithrombic activity in samples with either very small or large quantities of thrombin and antithrombin.The heparin influenced thrombin neutralization only in the presence of antithrombin. It did not affect the thrombin-fibrinogen reaction. Polybrene blocked the heparin effect when added to the antithrombin, but did not affect heparin action when added subsequently to the fibrinogen substrate.