Effects of 6-Hydroxydopamine on the Canine Sinus Node

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Abstract
The acute effects of 6-hydroxydopamine (6-OH-DA) injected directly into the sinus node artery were studied in 57 dogs. The positive chronotropic effect of 6-OH-DA was intermediate between that of norepinephrine and that of tyramine, when these substances were compared on the basis of their ED50. The increase in heart rate produced by 6-OH-DA was inhibited by prior intranodal injection of propranolol and desmethylimipramine. At high doses, injection of 6-OH-DA was often associated with arrhythmias such as periodic slowing of the sinus rate, atrial premature beats, atrial fibrillation, and ventricular extrasystoles. In the 72 hours following injection of 1.5 mg 6-OH-DA, the norepinephrine content of the sinus node region decreased progressively. In agreement with the norepinephrine depletion, response to intranodally injected tyramine was significantly diminished. The number of fluorescent adrenergic nerve fibers was also reduced. Impaired norepinephrine uptake and enhanced release were also demonstrated by using tritiated norepinephrine. After 6-OH-DA treatment, response to right stellate stimulation was diminished, and the response to vagal stimulation was not altered. It was concluded that the local perfusion of the sinus node with 6-OH-DA produces a marked norepinephrine depletion of the perfused region compatible with a localized degeneration of the sympathetic nerve terminals.