The mechanism of the positive chronotropic action of diethyl ether on rat atria.

Diethyl ether elicited a dose-dependent increase in the intrinsic frequency of contraction of isolated rat atrial preparations. The maximum effect (plus 34 per cent) occurred with 230 mg ether/100 ml medium. This ether concentration corresponds to a partial pressure of 29.2 mm Hg or 3 MAC. The positive chronotropic action of ether was not reduced in atria obtained from rats pretreated with reserpine (4 mg/kg, ip) although this treatment markedly reduced the effect of tyramine on frequency of contraction. The positive chronotropic response to 0.01 muM isoproterenol was inhibited by the beta-adrenergic antagonist 0.3 mgM dl-propranolol but remained unimpaired in the presence of 0.3 mgM d-propranolol (a much weaker antagonist). In contrast, the atrial response to ether was similar in the presence of either d- or dl-propranolol. Atropine, in concentrations that completely blocked the negative chronotropic action of acetylcholine, did not increase the frequency of contraction, suggesting that the positive chronotropic effect of ether is not due to an atropine-like activity of ether. Our results indicate that the positive chronotropic effect of ether on isolated rat atrial preparations is not mediated via catecholamine release, nor does it represent direct stimulation of beta-adrenergic receptors or block of cholinergic receptors. (Key words: Anesthetics, volatile, diethyl ether; Heart, atria, diethyl ether.).