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Histaminergic vasodilatation in the hindlimb of the dog

University of British Columbia

Thirty-four dogs were anesthetized with sodium pentothal i.v. and maintained with i.v. alpha-chloralose. Neuro-muscular blockade was accomplished with gallamine triethiodide (Flaxedil). Respiratory PCO₂ was monitored continuously while artificial ventilation at a rate of 1 5 cpm and appropriate tidal volume was adjusted to maintain expiratory P CO₂ between 38 and 40 mm Hg. Blood gas analysis (P CO₂, PC₂ and pH) allowed maintenance of blood pH between 7.35 and 7.45 by periodic administration of i.v. sodium bicarbonate. Blood volume was maintained with Dextran 75 when necessary. Body temperature was monitored continuously with an esophageal thermister and maintained automatically with heating elements in the operating table. Arterial vascular isolation of the hindlimbs was accomplished by ligating all major branches of the aorta below the renal arteries except the external iliac arteries. The dog's own blood, taken from a cannula in the abdominal aorta just distal to the renal arteries, was perfused at constant flow into cannulae in the external iliac arteries through separate pumps. Each external iliac artery pressure was monitored separately (Fig. 1). A bilateral laminectomy allowed access to the L₅, ₆ and ₇ spinal segments for electrical stimulation of their ventral roots after section of the corresponding dorsal root. In 26 dogs monophasic square wave stimulation (3 to 10V, 3 msec, 8 to 20 Hz) of the ventral root of L₅, L₆ or L₇ induced:1) a decrease in the perfusion pressure (PP) in the ipsilateral hindlimb (-41.8 - 2.7 mm Hg; mean - SE); 2) a decrease in the PP in the contralateral hindlimb (-32.2 - 2.7); 3) a fall in the aortic pressure (-15.6 - 0.7). (Fig.. 3). Similar effects were observed on stimulation of the peripheral stump of the ventral root. The above described vascular effects of ventral root stimulation were resistant to intra-arterial injections of cholinergic and beta-adrenergic blocking agents administered directly into the hindlimb perfusion lines. The effectiveness of the blockades was tested with direct intra-arterial injections of the appropriate agonists. Antihistaminics (diphenhydramine and mepyramine) similarly administered and tested did abolish the response in doses which did not suppress vascular-reactivity to acetylcholine or isoproterenol. These experiments do not provide a clear explanation of the mechanisms responsible for the contralateral vasodilatation or the fall in aortic pressure. The presence of significant anastomotic channels connecting either the two hindlimbs and/or the hindlimbs with the rest of-the body was excluded. Contralateral vasodilatation might perhaps be explained by the presence of nerve fibres crossing the midline in. the fused impar ganglion of the dog. The drop in aortic pressure was not due to the activation of afferent fibres coursing in the ventral roots, nor to the peripheral release of a vasodilator substance since the onset of the phen-omenom was too fast to be explained on these grounds. The possibility exists that the drop in aortic pressure is due to the activation by the stimulated efferent fibres of some afferent nervous pathways carrying inhibitory impulses to the vasomotor centers. The present experiments, however, do not provide data supporting or excluding this hypothesis. The experimental results strongly suggest that the described vasodilatation may be mediated by histamine released directly or indirectly by the activation of fibres coursing into the lower-ventral roots.

Text

2010-02-01

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http://hdl.handle.net/2429/19507

Physiology

University of British Columbia

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