Tl+-ions: influence on cardiac contractility

Attention has recently focussed on the heavy metal thallium as an environmental contaminant of increasing importance. From accidental or suicidal ingestions of thallium it has been known for many years that cardiovascular disorders regularly emerge, and for this reason, a variety of investigations of cardiological interest have been conducted. Amongst these, the effects of thallium on the contractile force of isolated myocardial tissues have been studied. Previous experiments were all carried out at concentrations far beyond those encountered during intoxication and yielded controversal data. We therefore reinvestigated the effects of thallium on myocardial tissue at levels between l0(-8) and 10(-3) M, thus covering the range of thallium concentrations encountered after uptake from a polluted environment through those seen after unintentional or intentional ingestion to levels at which previous studies were performed. Sheep interventricular cordis muscles were used at a stimulation frequency of 0.4 Hz showing three types of responses to thallium exposure. From a total of 32 experiments in 15% of all cases thallium caused a persistent increase in contractility which tended to decrease with time and thallium concentration but always remained greater than the control value. 50% of the experiments showed a progressive loss of contractile force with time and thallium concentration, despite transient increases in contractility which lasted for only 2-5 min after the application of each new thallium concentration. A combination of these types of reaction was observed in the remaining experiments in that a low thallium concentrations myocardial contractility increased considerably but then decreased progressively with time and thallium concentration. Guinea pig papillary muscles were used to test one thallium concentration only for up to 75 min. At 10(-8) M there was no effect, at 10(-7), 10(-6), 10(-5) M Tl+ there were positive inotropic transients followed by an inotropic decay; at 10(-4) M Tl+ only a progressive decrease of contractility was observed. The relationships between time and thallium concentration at different rates of stimulation were examined in two series of experiments at 0.1, 0.2, 0.4, 1.0, and 2.0 Hz. The effects of thallium were accelerated with increased beating rate and the decay of contraction also proceeded to markedly lower levels. In the rested state, thallium was also very effectual; this was illustrated in two series of experiments in which after 10 min intervals of quiescency 15 or more test stimuli were applied at different beating rates (0.1 to 2.0 Hz). The configurations of the resulting staircase phenomena were analyzed with respect to control behavior for each frequency of the test stimuli and for each thallium concentration. These results suggested an involvement of the slow inward current. The steady state values after quiescency showed a pronounced thallium-induced decay similar to that obtained at high constant stimulation rates...