Negative inotropic effects of ATP on the isometric contractions of isolated rat heart muscle.

The effects of ATP on the isometric contractions of isolated rat left ventricular papillary muscle were studied. Exogenously administered ATP had an immediate onset, an abrupt response, progressive recovery and produced dose-related depression in the peak developed tension, maximum rate of tension development and relaxation, which were statistically significant. There were no significant changes in the resting tension, time to peak tension and relaxation time, except for a significantly prolonged relaxation time at the highest concentration of ATP. In the studies of interactions of ATP and either epinephrine or Ca(++), we observed that ATP seemed to interfere with the inotropic effect of epinephrine, while Ca(++) antagonized the negative inotropic action of ATP. We conclude that the site of negative inotropic action of ATP is most likely on the cell membrane, where ATP interferes with Ca(++) flux, and that ATP interferes with the positive inotropic action of epinephrine.

Antiarrhythmic and hemodynamic responses to adenosine triphosphate during infusion of epinephrine in dogs anesthetized with halothane.

The effects of adenosine triphosphate (ATP) on cardiovascular responses to epinephrine were evaluated in dogs anesthetized with halothane. The dose of epinephrine required to induce arrhythmias averaged 1.05 +/- 0.52 microgram/kg/min. The dose of ATP required to abolish these arrhythmias averaged 1.64 +/- 0.67 mg/kg/min. ATP had not only an antiarrhythmic effect but also antagonized epinephrine-induced increases in heart rate, systemic vascular resistance, mean arterial blood pressure, and further increased cardiac index. ATP had, however, no significant effect on epinephrine-induced increases in myocardial contractility.

Polymyxin B and heart muscle.

The effects of the polypeptide antibiotic, polymyxin B, on myocardial contractility were studied in t;e isolated rat heart muscle. Five different doses of polymyxin B were tested. There were no changes in contractility with does ranging from the clinical therapeutic value to three times greater. There was an initial increase and then depression with a dose six times greater than the therapeutic dose. There was no direct competitive interaction between polymyxin B and halothane or Ca2+. This suggests that polymyxin B does not depress the myocardium in clinical doses and does not interfere with Ca2+ influx at the myocardial cell membrane.

Hiccup and ephedrine.

Twelve patients who developed hiccup during anaesthesia and surgery were treated successfully with an intravenous injection of ephedrine 5 mg (eleven cases) or 10 mg (one case). In nine patients ephedrine was successful after traditional methods had been tried and failed, and in three patients ephedrine was the only agent given. We conclude that ephedrine is a safe and easy mode of treatment for intractable hiccup during anaesthesia and surgery.

Effects of certain antibiotics on isometric contractions of isolated rat heart muscle.

The direct effects of potassium-penicillin-G, kanamycin, streptomycin and chloramphenicol on isometric contraction of isolated rat heart muscle were examined. Potassium-penicillin-G did not depress myocardial contractility but rather increased it. Those increases are not due to penicillin itself but due to a small amount of K+ in potassium-penicillin-G. Kanamycin and streptomycin did show not only direct myocardial depressants effects but concentration-dependent depressions. The depression produced by kanamycin could be restored to normal by adding Ca++ to the bath solution. Chloramphenicol did not show any significant concentration-dependent depression in our studies. We conclude that it is important to be aware of the potential depression of cardiac function by antibiotics, particularly in patients who have diminished cardiac reserve and who are undergoing surgical procedures under anesthesia which may also depress cardiac function.

Interaction of halothane and antibiotics on isometric contractions on rat-heart muscle.

Halothane (H), kanamycin (KM), streptomycin (SM), and chloramphenicol (CM) had direct negative inotropic effects on isometric contractions of isolated rat-heart muscles. Potassium penicillin-G did not show any significant changes in isometric contractions. The depression produced by these antibiotics was characterized by an abrupt onset, rapid progression, and rapid complete recovery, which suggests direct physicochemical rather than metabolic effects. On the other hand, the depression produced by H progressed slowly. When KM, SM, or CM were combined with H, there was a greater depression in isometric contractions than seen in the absence of H, suggesting that the innate characteristics of the antibiotics are augmented when any of them is administered together with halothane.

Fluroxene and isolated heart muscle.

The direct myocardial effects of fluroxene were examined in isometrically and isotonically contracting isolated rat heart muscle. MAC, the minimum anesthetic concentration needed to prevent movement in response to tail clamping, was found to be 5.0 vol per cent fluroxene in the rat. At 4.6 vol per cent fluroxene, peak developed isometric tension and maximum rate of tension development were decreased 29 and 24 per cent, respectively. At 11 vol per cent, the depressions were 39 and 33 per cent. At 26.4 vol per cent, the depressions were around 60 per cent. Vmax (the maximum shortening velocity of unloaded muscle) of the force-velocity relation was unaltered by fluroxene concentrations of 0.8, 4.6, and 11 vol per cent. Even at 26.4 vol per cent, the depression in Vmax was only 25 per cent. Po (the maximum force at zero velocity), work, and power were lowered much more, with reductions ranging from 15 to 27 per cent at 4.6 vol per cent, from 40 to 42 per cent at 11.0 vol per cent, and from 65 to 69 per cent at the 26.4 vol per cent. Series elastic extension was unchanged at 0.8 and 4.6 vol per cent fluroxene, but was decreased 16 per cent at 11.0 vol per cent and 46 per cent at 26.4 vol per cent fluroxene. The data indicate the fluroxene has a direct negative inotropic effect that is associated with increased series elastic stiffness, but does not involve Vmax of the force-velocity relation until quite high anesthestic concentrations are reached. Comparative studies were also carried out with halothane. MAC for halothane in the rat was 1.0 vol per cent. The relative potency of halothane compared with fluroxene in depression of Vmax was 13.2, and its relative potency in depression of Po, 4.0.