DIABETES WITH AND WITHOUT KETOACIDOSIS ON RIGHT ATRIAL PACEMAKER RATEAND AUTONOMIC RESPONSIVENESS

Experiments were designed to determine whether insulin-dependent diabe tes mellitus (IDDM) alters direct chronotropic effects of adrenergic a nd cholinergic agonists and whether the observed changes are associate d with hyperglycemia or combined hyperglycemia and ketoacidosis. Diabe tes was induced by intravenous administration of 45, 50, or 65 mg/kg s treptozotocin (STZ). Rats treated with 65 mg/kg STZ had higher levels of blood glucose and ketones compared with the levels of the other gro ups. Right atria were isolated 12 wk after administration of STZ and b athed in Krebs-Henseleit solution. Basal spontaneous pacemaker rate wa s diminished in preparations isolated from diabetic rats. The maximum pacemaker rate observed during exposure to isoproterenol or norepineph rine was also depressed in preparations from diabetic animals; however , the increase in rate and half-maximal effective concentration values for each agent were not affected. The sensitivity to the negative chr onotropic action of acetylcholine was enhanced by IDDM, whereas the re sponse to carbachol(a cholinergic agonist not readily metabolized by a cetylcholinesterase) was not changed. No significant differences were observed when we compared preparations isolated from diabetic animals with and without ketoacidosis. In summary, these data suggest 1) that IDDM is associated with a diminished basal spontaneous pacemaker witho ut changes in the responsiveness to adrenergic and cholinergic recepto r activation and 2) that ketoacidosis does not play a role in the obse rved alterations.