Acute Sympathectomy Research Articles

Effects of phenylephrine and ephedrine on pulmonary arterial pressure in patients with cervical or lumbar epidural anesthesia, or enflurane anesthesia.

The authors studied systemic and pulmonary hemodynamic changes with ephedrine (EP) or phenylephrine (PH) when used to normalize arterial hypotension resulting from acute sympathectomy due to cervical or lumbar epidural anesthesia, or enflurane anesthesia in 52 patients. Both EP (0.2±0.05 mg·kg-1) and PH (0.025±0.008 mg·kg-1) produced a significant increase in pulmonary arterial pressure (PAP) with a concomitant increase in arterial pressure (AP). In the patients anesthetized with cervical epidural block and NO2-O2, systolic PAP increased from 22±5 to 28±8 mmHg with EP and from 23±6 to 32±10 mmHg with PH in response to approximately 30 mmHg increase of AP, and the ratio of the increment of systolic PAP to systolic AP (ΔPAP/ΔAP) was 0.15±0.08 with EP and 0.20±0.13 with PH (P<0.05); these changes did not differ significantly from those observed in the patients having lumbar epidural or enflurane-N2O-O2 anesthesia. The influence on cardiac output (CO) differed significantly between EP and PH; EP increased CO in all three groups (P<0.05), while PH did not elicit any significant changes in CO. A significant relationship between PAP and AP was found in patients given EP; the regression equation was ΔPAP=0.22×ΔAP-2.9 (r=0.77). The relationship in patients given PH was less significant (r=0.38). The results indicated that EP and PH elicit pulmonary hypertensive effect similarly in the patients with a high level of epidural anesthesia and that although both drugs act differently (EP mainly due to increases in the blood flow and PH solely due to its pulmonary vasconstrictive action), the increases in PAP were predictable, to some extent, from the increase of AP in anesthetized humans without predominant cardiopulmonary disorders.

The Pathophysiology of Contractile Activity in the Chronic Decentralized Feline Bladder

Autonomous wave activity occurs in the decentralized bladder and may contribute to upper tract damage and incontinence. In order to clarify the poorly understood pathophysiology and neuropharmacology of autonomous waves, cats were prepared with L7-S3 ventrodorsal rhizotomy alone or with L7-S3 ventral rhizotomy with and without total sympathectomy. The incidence of autonomous waves was <15% 12 weeks after ventral or ventrodorsal rhizotomy, but acute sympathectomy at 13 weeks increased the incidence to 58% in these groups. With chronic sympathectomy the incidence was 100%. This suggests that the waves arise locally via a mechanism which is independent of L7-S3 dorsal roots, due to lack of a suppressive sympathetic pathway. Autonomous waves were inhibited by atropine after acute sympathectomy and by prazosin after chronic sympathectomy, but increased inhibition occurred after both drugs in either case. Adrenergic neuron depletion with 6-hydroxydopamine enhanced wave activity, which was incompletely inhibited by subsequent atropine. This implies that the peripheral reflex pathway has facilitatory α1-adrenergic, muscarinic and also noncholinergic nonadrenergic elements. Clinically, sensory or sympathetic damage caused incontinence, but sympathectomy also caused high pressure waves, which may cause upper tract damage and treatment resistant incontinence in patients.

Control of Detrusor Stiffness in the Chronic Decentralized Feline Bladder

The neuropharmacology of increased bladder stiffness, which may contribute to upper tract damage and incontinence, was investigated in 76 cats, β-blockade increased but combined α1-adrenergic with muscarinic blockade decreased filling phase stiffness in normal cats. Bladder wall stiffness during the early filling phase was unaffected by chronic S2 ventrodorsal rhizotomy or L7-S3 ventral rhizotomy, but was decreased when L7-S3 dorsal rhizotomy or total sympathectomy was combined with the ventral root lesion, implying that sacral dorsal roots and sympathetic efferents maintain normal detrusor stiffness. Acute sympathectomy increased stiffness in all the former 3 chronic groups, implying that a tonic or reflex sympathetic inhibition operates independently of the L7-S3 dorsal roots. Stiffness during early filling phase decreased with acute ventral rhizotomy. This change persisted with chronic sympathectomy but returned to normal if sympathetic nerves were left intact. These results suggest that bladder stiffness is modulated by tonic or reflexic sympathetic activity, which is influenced by L7-S3 afferents. Detrusor stiffness during the later stages of filling, which was decreased by acute sympathectomy in chronic groups but increased by chronic sympathectomy, was reduced by interference with adrenergic or muscarinic mechanisms after either lesion. Therefore, a peripheral pathway with facilitatory α1-adrenergic and muscarinic receptors is involved in the production of increased late stage stiffness after chronic sympathetic damage. We propose that the increased bladder stiffness seen in congenital sacral lesions may be analogous to the stiffness during late stages of filling reported here. Our results also imply that the presence of this increased stiffness is closely associated with chronic sympathetic damage. Whether the increased stiffness in congenital and traumatic neural lesions in humans arises from sympathetic damage remains to be determined.

Increases in NPY in non-sympathetic nerve fibres supplying rat mesenteric vessels after immunosympathectomy

The effect of nerve growth factor (NGF) deprivation on developing peripheral peptide-containing nerves has been examined in Wistar rats. Animals were treated from birth for 7 days with antibodies to NGF (10 μl/g body weight) and killed at 4 or 8 weeks of age. The nerves of the mesenteric and femoral blood vessels, vas deferens and bladder were viewed with histochemical and immunohistochemical techniques. The effectiveness of anti-NGF treatment was monitored by viewing catecholamine (CA)-containing nerves, which were virtually absent from the blood vessels, but were little affected in the vas deferens and bladder in both age groups. Immunoreactivity for substance P and calcitonin gene-related peptide was slightly reduced in the blood vessels. Immunoreactivity for neuropeptide Y (NPY) was reduced in the femoral blood vessels by 88% at both ages, but reductions in NPY immunoreactivity (NPY-IR) in the mesenteric vessels varied with age. In the mesenteric artery at 4 weeks, NPY-IR was reduced by 96% from control values, but at 8 weeks it was reduced by only 37%. Acute sympathectomy with 6-OHDA treatment reduced NPY-IR in the mesenteric artery by 98% at 4 weeks and 93% at 8 weeks. It is proposed that the increase in NPY-IR but not CA-containing nerves in the mesenteric artery between 4 and 8 weeks after immunosympathectomy is due to compensatory innervation from a non-sympathetic source (probably enteric neurons) that is available to mesenteric, but not to femoral blood vessels.

Neuropeptide Y in non-sympathetic nerves of the rat: Changes during maturation but not after guanethidine sympathectomy

Non-sympathetic neuropeptide Y-containing nerves were demonstrated by their persistence after destruction of sympathetic nerve terminals by acute 6-hydroxydopamine treatment for 48 h. In order to examine whether these neuropeptide Y-containing nerves reinnervate tissues following the loss of sympathetic nerves we administered guanethidine sulphate to one-week-old rat pups for three weeks to produce a complete and long-lasting sympathectomy and we monitored the innervation of the superior cervical ganglion, mesenteric vein, vas deferens and urinary bladder by noradrenaline- and neuropeptide Y-containing nerves two and 16 weeks later (assay and histochemical observations). By two weeks the reduction in neuropeptide Y content of tissues was similar to the reduction after acute sympathectomy with 6-hydroxydopamine treatment, indicating that there was no early reinnervation by non-sympathetic neuropeptide Y-containing nerve fibres at a time when sensory transmitters increase. Furthermore, there was no reinnervation by neuropeptide Y-containing nerve fibres by the time these sympathectomized animals had reached maturity, 16 weeks after cessation of treatment. Neuropeptide Y levels increased in the superior cervical ganglion with normal maturation but decreased in the prostatic end of the vas deferens. A non-sympathetic source of neuropeptide Y demonstrated in the immature rat vas deferens was no longer evident in the mature animal.

Postnatal changes in calcium and amylase of rat salivary glands, including calcium changes with senescence

Postnatal changes occur in glandular Ca concentration of rat parotid and submandibular glands. At 4 days of age, Ca concentration was low in both glands (only one-third to one-half that of adults) and increased gradually with age. The pattern of change was generally similar for male and female rats, but in submandibular gland, adult levels of 9–10 m-equiv./kg were reached by weaning, whereas for parotid gland, a gradual increase in Ca concentration occurred with adult levels of 9–10 m-equiv./kg reached by 7 weeks of age. The pattern of change was the same whether Ca concentration was expressed per kg wet or dry weight albeit water content changed with age. The changes in Ca concentration of parotid paralleled the age-associated increases in amylase activity of parotid gland. Amylase activity of submandibular gland was much less than that of parotid and similarly low at all ages examined, and did not parallel the age-associated increases in Ca concentration. The regulatory role of the sympathetic innervation on glandular Ca concentration was examined by effecting surgical denervation of parotid and submandibular glands at 8 days of age, and then determining Ca concentration of the denervated glands at 32 days. A three-fold increase in Ca concentration, similar to that following acute sympathectomy in adults, occurred in submandibular gland but no change was seen in parotid. An unexpectedly high concentration of Ca was also found in submandibular (but not parotid) gland of old rats.

Circulatory responses to airway stimulation and cervical epidural blockade.

In order to investigate the effects of acute cardiac sympathectomy, the circulatory responses due to tracheal intubation and broncho-carinal stimulation were compared in lightly anesthetized, paralyzed patients who had either cervical (n = 18) or lumbar epidural blockade (n = 18), or neither (n = 12). The mean analgesic levels obtained using 2% mepivacaine with epinephrine were C4-T8 in the cervical group, and T7-S1 in the lumbar group. Increases in arterial blood pressure (AP) and heart rate (HR) due to laryngoscopy were significant (P less than 0.01) but similar in the three groups of patients. Broncho-carinal stimulation by a suction catheter did not produce noticeable changes in AP and HR in the cervical group; significant increases were observed in the other two groups (P less than 0.01). It was concluded from this study that acute sympathectomy induced in part by cervical or lumbar epidural block does not attentuate circulatory responses due to laryngoscopy and tracheal intubation. The cervical blockade, however, can prevent such responses due to broncho-carinal stimulation without predominant vagotonic reflexes; this may be attributed to the interruption of sympathetic afferents to the spinal cord at the epidural level.

Effect of acute sympathectomy by epidural anesthesia on the canine coronary circulation.

The effects of reversible sympathetic neural blockade of the canine myocardium under control conditions and in the presence of decreased coronary blood flow and after myocardial infarction were investigated in 17 dogs. A multiple-microsphere technique was used to measure distribution of blood flow in the myocardium. Epidural blockade was associated with the following changes in the ratio of endocardial to epicardial blood flow: under control conditions, no change; after 50 per cent decrease in coronary flow, 18 per cent increase in endocardial/epicardial ratio; after myocardial infarction at unrestricted coronary flow, 43 per cent ratio increase; after myocardial infarction and 50 per cent decrease in coronary flow, 76 per cent increase of endocardial/epicardial ratio. These effects appear to be independent of systemic factors, and may result from alterations in tone of transmural resistance vessels. In addition, cervicothoracic epidural blockade resulted in a decrease in systemic pressure and an increase in coronary vascular resistance as myocardial oxygen demand decreased. When systemic pressure was restored these effects were abolished. In the presence of myocardial infarction, epidural blockade had less effect on systemic pressure and left ventricular filling pressure was decreased. With decreased coronary flow, sympathetic blockade redistributed coronary blood flow, favoring sympathetic blockade redistributed coronary blood flow, favoring the endocardium in both the normal and the infarcted heart.

Influence of the cerebrovascular sympathetic innervation on regional flow, autoregulation, and blood-brain barrier function.

Experiments have been done on rats, rabbits and baboons to elucidate the role of the cranial sympathetic nerves originating in the superior cervical ganglia in the regulation of local cerebral blood flow, including its autoregulation, and in blood-brain barrier functions. Flow was measured by the [14C] ethanol technique, thermoclearance, and xenon-133 clearance. Blood-brain barrier functions were studied by the extravasation of an Evan's blue-albumin complex and by calculation of brain uptake index for two compounds (noradrenaline and inulin). Electrical stimulation of the sympathetic nerves reduces regional flow to a degree that is related to the amount of local perivascular innervation. The breakthrough of autoregulation during induced systemic hypertension is prevented by bilateral stimulation of the superior cervical ganglia. Acute sympathectomy markedly enhances the vascular penetration both at normotension (tested by brain uptake index for noradrenaline and inulin) and rapidly induced hypertension (evidenced by extravasation of Evans' blue). This extravasation of Evans' blud during acute hypertension can be counteracted by sympathetic nerve stimulation. The results give further support for the view that the cranial sympathetic nerves afford an efficient control of the cerebrovascular bed.

Chemical sympathectomy and two-way escape and avoidance learning in the rat.

Six experiments are reported on the effects of 2,4,5-trihydroxyphenylethyl-amine (6-hydroxydopamine) on two-way escape and avoidance learning. Rats were tested on either escape or avoidance learning at 80 days of age after chemical sympathectomy at birth or 40 or 80 days of age. Neonatal and chronic sympathectomy (at 40 days), but not acute sympathectomy (at 80 days), resulted in depressed escape learning. Avoidance learning was affected by neonatal sympathectomy and partially by acute sympathectomy. The results have implications for the role of the autonomic nervous system in escape-avoidance learning.

Acute sympathectomy by 6-hydroxydopamine in the adult rat: effects on cardiovascular conditioning and fear retention.

Acute sympathectomy by 6-hydroxydopamine in the adult rat: effects on cardiovascular conditioning and fear retention.

Action of angiotensin on sympathetic nerve endings in isolated blood vessels.

THE recent experimental findings1,2 of a diminished effect of administered angiotensin on blood pressure after acute sympathectomy or pretreatment with reserpine have directed attention to a possible relationship between the effects of angiotensin and the sympathetic nerve system. In dogs, McCubbin and Page3 described an effect of angiotensin on the sympathetic nervous system resulting in an enhanced response to agents and procedures which cause release of endogenous noradrenaline. Later, Lewis4 observed an angiotensin-induced release of catecholaminas from the suprarenal medulla of cats. In connexion with this finding he tentatively discussed an action of angiotensin at the vascular wall by local liberation of catecholamines from the sympathetic nerve endings. The two kinds of experiments (a and b) presented here were undertaken to obtain further information on the relationship between angiotensin and the sympathetic vasomotor action.

Cardiac Effects of Angiotensin II

The injection of angiotensin II, 1.0 mcg./Kg., into pentobarbital anesthetized dogs produced a significant increase in systolic and diastolic blood pressures and myocardial blood flow, a slight increase in the force of right ventricular contraction, and no significant effects on heart rate. Cardiac output was initially decreased; but within 80 to 100 seconds after angiotensin II administration, a secondary rise was noted. The rise in diastolic pressure was significantly greater than that of the systolic pressure at the 5 per cent level. The coronary flow increase appeared to be dependent entirely on the increase in diastolic blood pressure. In coronary perfusion studies, angiotensin II produced myocardial vasoconstriction when injected either intravenously or intra-arterially. These effects were mediated by both direct musculotropic actions and the sympathetic nervous system since acute sympathectomy reduced, but did not abolish, the activity of angiotensin II. The sympathetic component of the cardiovascular effects of angiotensin II appear to be via the alpha receptors since nethalide markedly potentiated the activity of angiotensin II. The effect of pretreatment with phenoxybenzamine, atropine, or dichloroisoproterenol on the cardiovascular responses to angiotensin II was also evaluated.

Effect of acute sympathectomy on responses to angiotensin and norepinephrine.

The vasopressor response to angiotensin administered intra-arterially to the perfused hindquarters of the dog was reduced significantly after acute sympathectomy. Responses to norepinephrine and tyramine remained unchanged. Similar results were obtained following gangliouic blockade with hexamethonium and cervical spinal transection. After the response to augiotensin was reduced following sympathectomy, the cut lumbar sympathetic nerves were stimulated electrically. During the period of stimulation, an increase in the vasoconstrictor effect to angiotensin was obtained, but complete restoration to the control magnitude was not seen consistently. Possible mechanisms for the reduction in the response to angiotensin following sympathectomy are discussed. The present evidence suggests that the tonic discharge of normally functioning sympathetic nerves is capable of facilitating the response to angiotensin and that sympathectomy results in an abolition of this effect.