This assay measures picogram quantities of catechol drugs and endogenous catecholamines in body tissues and fluids. The catechols are converted to their 3H-O-methyl metabolites during incubation with 3H-S-adenosylmethionine then separated by solvent extraction and thin-layer chromatography. Most drugs containing the catechol structure can be radiolabeled and separated from norepinephrine and epinephrine by this technique to provide simultaneous measurement of endogenous and exogenously administered catechols. The disposition of isoproterenol in tissues and fluids of man and experimental animals is measured to illustrate the utility of this assay. The reactivity of several commonly administered catechol drugs with COMT is described and the possible implications discussed.

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Atrial muscle of guinea pigs was used to study the inotropic influences of substituting a tris(hydroxymethyl)-aminomethane-buffered solution aerated with 100% O2 for a bicarbonate-buffered solution aerated with 95% O2-5% CO2 under otherwise equivalent in vitro conditions. Basal values of isometric contractile tension and its first derivative (dT/dt) were smaller and time to peak tension and time to 90% relaxation were longer in Tris- than in bicarbonate-bathed muscles. Both groups responded similarly to changes in stimulation frequently (0.1--2.2 Hz) and Ca2+ concentration (1.0--7.0 mM); however, maximal inotropic responses to these variables were smaller in the Tris-bathed atria. The negative inotropic effects of D600 and gentamicin were greater in the Tris group. Tris-bathed atria developed pulsus alternans when exposed to Mn2+ or a reduced Ca2+ concentration, whereas pulsus alternans did not occur in the bicarbonate group. A transient increase in contractility occurred in bicarbonate-bathed atria after treatment with 0.125 mM Mn2+, but only a negative response occurred in the Tris group. Thus important, and seemingly Ca2+-dependent, differences exist between the inotropic influences of Tris and bicarbonate solutions that may affect the utility of Tris-buffered (and/or bicarbonate deprived) heart muscle for studying certain inotropic interventions.

Isolated heart muscle preparations are useful in the study of cardiac toxicities of drugs and environmental chemicals: such tissues allow assessment of chemical effects on heart muscle that is free from indirect in vivo influences that can mask or even accentuate cardiac responses measured in the intact animal. In the present study, left atria of guinea pigs were used to demonstrate a direct cardiac depressant effect of greater-than-therapeutic concentrations of several aminoglycoside antibiotics. The toxic effect of these antibiotics seems to be a calcium-dependent event, and may prove useful to characterize contractile responses of the heart. Other antibiotic agents can also depress cardiovascular function, as summarized in this report, but mechanisms of action have not been clearly defined.

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