The effects of prolonged beta-adrenoceptor blockade on heart weight and cardiac intracellular potentials in rabbits.

Estimates were made in vivo in rabbits of the relative beta-receptor blocking potency and duration of action of propranolol and practolol. In further experiments groups of litter mates were injected twice daily with approximately equi-active amounts of propranolol or practolol, or with saline, for several weeks. The heart weights of the treated animals were significantly lower than those of the controls, the water contents were higher, and the dry weight differences were highly significant; -16.8% after 2 mg/kg bd propranolol for six weeks and -33.8% after 10 mg/kg practolol. (The treated animals grew less rapidly than the controls; when corrected for body weight these figures were -11.9% and -20.4%, respectively.) In the practolol group, but not the propranolol group, the duration of the atrial intracellular potentials was prolonged. There was no evidence that the prolonged treatment with either drug had a negative inotropic effect, or reduced positive inotropic responses to isoprenaline.

Chemosensitivity of cardiac muscle.

1. Measurements of contractions, conduction velocity and intracellular potential were made on isolated rabbit atria under four sets of conditions: high bicarbonate/high CO(2) (HH), low bicarbonate/low CO(2) (LL), high bicarbonate/low CO(2) (HL) and low bicarbonate/high CO(2) (LH). The ratio high/low was the same for the bicarbonate and CO(2) concentrations, so that HH had the same pH as LL.2. Acid solutions caused a fall of a few mV in the resting potential, but not in the overshoot. They reduced conduction velocity and rate of rise of the action potential. They depressed contractions, but prolonged the tail of the action potential.3. Alkaline solutions caused the converse changes, but, with the exception of the effect on the duration of the action potential, the relation with pH was markedly alinear, in that a rise in pH had much less effect than an equivalent fall.4. Statistical tests were devised to decide whether the observed changes were associated primarily with pH, P(CO(2) ) or bicarbonate. By far the strongest association was with external pH. Changes in P(CO(2) ), per se, had no significant effect.