B.J. Gannon

A new method of destroying adrenergic nerves in adult animals using guanethidine

1 The structure of sympathetic neurones in the rat has been examined with histological, fluorescence histochemical and electron microscopical methods after chronic treatment for 6 weeks with guanethidine (25 or 30 mg/kg/day i.p.). 2 Less than 2% of the nerve cell bodies in the superior cervical ganglion remained at this time and in these cells the mitochondria were badly damaged. Few fluorescent adrenergic nerve fibres were found outside the central nervous system. This situation persisted even 4 months (the longest period studied) after cessation of treatment. 3 This procedure is proposed as a new method of producing sympathectomy. It has the advantage of being applicable to adult animals in a variety of experimental and pathological situations. It is uniquely advantageous for denervation of the male reproductive tract.

Excitatory adrenergic innervation of the fish heart

Abstract 1. 1. The innervation of the heart of the trout (Salmo trutta and S. iredius) has been studied with fluorescent histochemical and physiological methods. 2. 2. Catecholamine-containing nerves were revealed by the histochemical technique in the sinus venosus, atrium and ventricle. 3. 3. Stimulation of the vagus nerve or the ductus Cuvieri (especially at high-pulse frequency and duration) produced inhibition of the heart, which was blocked by atropine. After atropine treatment an excitatory response was revealed, which was blocked by guanethidine, bretylium or pronethalol. 4. 4. Stimulation of the vagus nerve or ductus Cuvieri at low-pulse frequency (less than 4 p/sec) and short duration produced excitatory effects even in preparations not treated with atropine. 5. 5. It is suggested that the cardiac branch of the vagus nerve contains both inhibitory cholinergic and excitatory adrenergic nerves.

Adrenergic Innervation of Bowel in Hirschsprung's Disease

The adrenergic innervation of normal and aganglionic regions of bowel from patients with Hirschsprungs disease was investigated by a fluorescent histochemical technique. In normal bowel the adrenergic nerves end about intramural ganglion cells. In aganglionic bowel the adrenergic nerves form a dense varicose plexus in both muscularis externa and muscularis mucosae. It is suggested that the cause of megacolon in Hirschsprungs disease is due to a lack of nervous pathways controlling the intrinsic reflexes, which is probably congenital in origin.

Degeneration of adrenergic neurons following guanethidine treatment: an ultrastructural study.

SummaryThe degeneration of peripheral adrenergio neurons of the rat following chronic treatment with high doses of guanethidine has been described at the ultrastructural level. Neurons exhibiting three different degenerative appearances have been distinguished and evidence is presented that these represent sequential phases in the degeneration of individual neurons. These phases are referred to as“primary degeneration”, in which mitochondrial damage, extensive depletion of cytoplasmic organelles and swelling of the cell body occurred; the“transient growth phase”, characterised by proliferation of some organelles and by hyperplasia of neuronal processes; and“secondary degeneration”, in which the final breakdown and condensation of the neuronal contents occurred. Many of the characteristics of the “transient growth phase” and of “secondary degeneration” are comparable to those observed in studies of growth and degeneration respectively. Since the neuronal mitochondria represent a primary site of action of guanethidine, degeneration may be initiated by lowered energy metabolism within the neuron. This degenerative action of guanethidine is selective for adrenergic neurons, at least in the tissues studied; degeneration of other cell types, including cholinergic, purinergic and sensory neurons, was not observed.

Prolonged hypotension and ultrastructural changes in sympathetic neurones following guanacline treatment

Abstract Changes in systemic blood pressure, catecholamine levels, fluorescent histochemistry and ultrastructure of sympathetic nerves both during and after cessation of chronic treatment of rats with guanacline (5 mg/kg/day) were examined. Comparative studies were also carried out on guanethidine. The systemic blood pressure fell steadily for the first 9–14 weeks in both guanethidine and guanacline-treated animals. Following cessation of drug treatment, the blood pressure of guanethidine-treated animals rose rapidly to normal levels, in contrast to guanacline-treated animals in which the rise was slow. Sections of sympathetic ganglion cells from guanacline-treated rats exhibited strong yellow autofluorescence which was shown by electron microscopy to consist of a massive deposition of lipoprotein granules (comparable to ‘aging pigment’). These granules were still present 12 weeks following cessation of treatment. No comparable changes were observed in guanethidine-treated animals. It is suggested that the cellular effects of guanacline might be related to the postural hypotension which persists in humans some months after withdrawal of therapy.

Changes in the physiology and fine structure of the taenia of the guinea‐pig caecum following transplantation into the anterior eye chamber

1. The taenia of the guinea‐pig caecum has been used as a model to study the re‐establishment of autonomic innervation following transplantation into the anterior eye chamber. The ultrastructure, the histochemical localization of noradrenaline and acetylcholinesterase and the pharmacology of transmission to the taenia have been examined 1 day to 16 weeks following transplantation. Both ganglion‐free strips of the taenia and caecal wall segments including the underlying Auerbachs plexus were used.