ELectrophysiologic properties of bretylium tosylate on atrial myocardium.

The antifibrillatory property of bretylium tosylate was first observed in experimental atrial fibrillation, yet the cellular basis for this phenomenon has not been explored. The purpose of this study was to determine the electrophysiologic properties of bretylium tosylate on guinea pig atrial myocardium in the presence and absence of cholinergic influence. Bretylium (10(-6) M - 10(-4) M) produced a concentration-dependent prolongation of atrial action potential duration with a threshold concentration of 10(-5) M. This direct effect of bretylium was unaltered by blockade of beta-adrenergic receptors with propranolol (10(-6) M) or blockade of alpha-adrenergic receptors with phentolamine (10(-6) M). In a second series of experiments the muscarinic receptor blocking properties of bretylium were determined. Acetylcholine produced a concentration-dependent shortening of action potential duration in paced (200 ms) left atrial muscle strips. This well-recognized muscarinic effect was unaltered in the presence of bretylium (10(-6) M - 10(-3) M). These data indicate that bretylium tosylate physiologically exerts direct effects on the atrial myocardium to prolong action potential duration. This compound does not appear to physiologically antagonize the effects of acetylcholine and therefore its reported atrial antiarrhythmic properties cannot be explained by muscarinic receptor blockade.

Human diabetic endoneurial sorbitol, fructose, and myo-inositol related to sural nerve morphometry.

Fascicles of the sural nerve from each of 20 diabetic patients, mostly with maturity-onset diabetes, were studied by biochemical and pathological techniques, and results were compared to values found in nerve specimens from 15 healthy persons. The sorbitol and fructose content was much more variable in diabetic than in healthy nerves. More than one-third of the diabetic nerves had sorbitol and fructose values above the highest levels for controls. myo-Inositol and scyllo-inositol content was not reduced in diabetic nerves. The sorbitol, fructose, and inositol concentrations could not be related to clinical, neurophysiological, or pathological severity of neuropathy. A comparison of scored symptoms and signs and clinical neurophysiological studies against morphometric and teased fiber studies of sural nerve demonstrated that the former three provide sensitive and reliable measures of severity of neuropathy that can be used for controlled clinical trials of diabetic neuropathy. The presence and type of teased fiber abnormalities could be related to the duration of diabetes and to symptoms of neuropathy. In untreated diabetics without symptoms of neuropathy, a higher than normal frequency of teased fibers showing segmental demyelination and remyelination was found. Untreated diabetics with symptomatic neuropathy showed two kinds of abnormalities: fibers with segmental demyelination and remyelination and fibers undergoing axonal degeneration. In treated diabetics, who often had longstanding neuropathy, the most common abnormalities were fibers undergoing axonal degeneration.

Nitrous oxide neurotoxicity studies in man and rat.

To assess the effects of chronic exposure to low levels of nitrous oxide on neural function of man, the authors evaluated the neurologic condition, motor and sensory nerve conduction, and computerized tests of sensation of approximately half of the dentists in Rochester, Minnesota. Results of scored tests of neural function were not significantly different for dentists who used nitrous oxide extensively in their practices and dentists who did not. To assess the effects of chronic exposure to high levels of nitrous oxide on neural function and structure of experimental animals, groups of rats were exposed to 70 per cent N2O in 30 per cent oxygen for four hours, five days a week, for six months. Rats exposed to N2O and control rats showed no difference in well-being, in caudal nerve conduction, in axonal content and transport of acetylcholinesterase and dopamine-beta-hydroxylase, or in number and size distribution and pathologic abnormality of teased myelinated fibers. Although these results indicate a lack of peripheral nerve neurotoxicity of N2O in the rat, one cannot assume a similar lack of neurotoxicity in man with heavy exposures.