Mechanism of Action of Tris (Hydroxymethyl) Aminomethane on the Negative Inotropic Effect of Carbon Dioxide

Administration of isotonic THAM to the blood of the heart-lung preparation induced a decrease in the negative inotropic effect of CO 2 , suggested by the fact that, at constant stroke work, an increase in P co 2 of 26 ± 1.9 mm Hg was followed by an increase in left ventricular end-diastolic pressure (LVEDP) of 3.8 ± 0.2 mm Hg before the infusion of THAM; after THAM was given, a similar increase in P co 2 induced an increase in LVEDP of 1.8 ± 0.2 mm Hg (P<0.01). When pH was increased by 0.15 M NaHCO 3 , no changes in myocardial contractility or in the tolerance of the heart to CO 2 were found. On the other hand, hemodilution with isotonic sucrose reproduced the effect of THAM. Either sucrose or THAM produced a decrease in plasma Na. Myocardial contractility, previously increased by THAM or sucrose, returned to control after plasma Na was restored. When cat papillary muscles were immersed in Ringer's solution with normal (142 m M ) and low (112 m M ) Na concentration, it was observed that a similar increase in P co 2 originated a smaller decrease in contractility when the muscles were in the low Na solution. It is concluded that the effect of THAM in the present experiments is due, at least to an important extent, to changes in extracellular Na.