Myocardial effects of adrenaline, isoprenaline and dobutamine at hypothermic conditions

The pharmacodynamic myocardial effects of adrenaline, isoprenaline and dobutamine were studied in isolated, perfused and spontaneously beating rabbit hearts at hypothermic conditions. Cardiac contraction amplitude increased from the control value at 37 degrees set equal to 100% to about 165% at 22 degrees, whereas contraction velocity decreased to 52%, frequency to 30% and oxygen consumption to about 19%. At 22 degrees all drugs produced pronounced positive inotropic and chronotropic effects. Em-values related to contraction velocity, frequency and oxygen consumption were for isoprenaline 152, 98 and 136%, respectively, for adrenaline 127, 100 and 198% and for dobutamine 120, 86 and 165%, respectively. The corresponding EC50-values decreased and a marked left-shift of the log-concentration response curves was observed as an expression of increased myocardial sensitivity to the drugs. Em for contraction velocity for dobutamine was distinctly reduced at 32 and 27 degrees and for adrenaline at 27 degrees in comparison to the increase seen at 22 and 37 degrees. Em for oxygen consumption showed for all drugs an increase at decreasing temperatures. The frequency-corrected QTc-interval decreased slightly to moderately during exposure to the drugs at hypothermic conditions. None of the drugs caused arrhythmias during the experiments. Coronary flow rate decreased only moderately at the higher drug concentrations at decreased temperatures. Dobutamine and adrenaline at 37 degrees and isoprenaline at 37 and 22 degrees caused an increase of Em for oxygen consumption that was slightly less than proportional to the increase of Em for contraction velocity.