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At least 127 records · Page 7Linked to original sources
PubMed1992

Effect of dexmedetomidine, an alpha 2-adrenergic agonist, in the isolated heart.

Dexmedetomidine (DM) was studied in the isolated dog heart in the form of a Starling heart-lung preparation, (HLP). Hearts were subjected to increased loading by (a) increasing cardiac output, and (b) increasing systemic resistance. Results are depicted by cardiac function curves, prepared by plotting left atrial pressure against either systemic cardiac output or mean arterial pressure. DM, given in divided doses up to 44 micrograms, had no effect on heart rate or cardiac function, nor did injection of 0.5 mg of atipamezole, a selective alpha 2-antagonist. Additional injections of very large doses of DM, up to 4,444 micrograms, caused an increase in heart rate and a leftward shift of the function curves, ie, positive chronotropic and inotropic effects. Plasma catecholamine levels increased markedly between the 444 micrograms and the 4,444 micrograms cumulative doses of DM. Administration of 1 mg of prazosin had no effect, but 1 mg of propranolol returned the rate to baseline and markedly shifted function curves to the right and depressed their slopes. Thus, whereas low doses (corresponding to between 1 and 30 micrograms/kg in intact animals) of DM, given acutely IV, have been shown to depress cardiac function in intact and denervated dogs, this effect is not due to a direct effect on the myocardium. High doses, far beyond doses maximally effective in intact animals and man, release catecholamines from cardiac stores. Plasma DM levels after low doses in the HLP were between 1 to 10 times those seen in intact animals and human volunteers after the usual doses given clinically for their central effects. Because DM caused no myocardial depressant effect in the isolated, blood-perfused canine HLP, decreases in cardiac function seen after this drug is given to intact and autonomically denervated dogs must be due to factor(s) other than a direct action on the myocardium.

Adrenergic alpha-Agonists↗
PubMed1997

Effects of cardiac autonomic imbalance on postnatal changes in the electrocardiographic Q-T interval in conscious swine.

The effects of partial autonomic denervation of the heart rate and Q--T interval were examined during maturation in swine. Four groups of newborns were prepared: right stellate ganglionectomy (RSG), left stellate ganglionectomy (LSG), right cardiac vagotomy (RCV) and sham-operated. Swine were studied postsurgically for eight weeks. Unexpected deaths of unknown cause occurred in five of the 20 denervated swine but in none of the 10 sham-operated controls. Prolongation of the Q--T interval was greatest in RSG animals and least in RCV as compared to controls. The results indicate that we have successfully developed an animal model of a long Q--T syndrome in swine.

Animals↗
PubMed1980

Mucociliary clearance in patients with chronic autonomic failure.

Mucociliary clearance was measured in four patients with chronic autonomic failure and normal ventilatory function using a method of scanning the clearance of inhaled polystyrene particles tagged with 99mTc. Previous surgical and experimental evidence has suggested that autonomic denervation might be expected to impair clearance. However, the four patients in this study showed no significant difference in clearance rate compared to groups of sex-matched control subjects. A fifth patient was found to have impaired mucociliary clearance. However she had the symptoms and ventilatory function of smoking-related chronic obstructive bronchitis, a condition which has previously been shown to impair mucociliary clearance.

Adult↗
PubMed1994

Dependency of blood pressure upon cardiac filling in patients with severe postural hypotension.

Autonomic denervation of the vascular bed results theoretically in a stronger dependency of blood pressure upon intravascular volume, and the study described aimed at an investigation of the relation between cardiac filling and arterial blood pressure in patients with severe postural hypotension. Seven patients were studied during head-up tilt at three different tilt angles using intra-arterial blood pressure recordings and estimates of left ventricular volumes by radioisotope ventriculography. Blood pressure fell dramatically during head-up tilt due to reductions in cardiac output unopposed by vasoconstriction. The reduction in cardiac output resulted from reductions in left ventricular end-diastolic volumes with unchanged left ventricular ejection fractions and only moderate increments in heart rate. The study was demonstrated that blood pressure is strongly dependent upon cardiac filling in severe autonomic dysfunction, and that volume expansion is an important measure against postural hypotension.

Aged↗
PubMed1996

Reflex sympathetic dystrophy: does sympathetic dysfunction originate from peripheral neuropathy?

BACKGROUND: Sympathetic dysfunction in reflex sympathetic dystrophy (RSD) has been purported to consist of an afferently-induced increase in efferent sympathetic nerve impulses (somato-sympathetic reflex) and/or denervation-induced supersensitivity to catecholamines. In addition, both the central and peripheral nervous systems have been claimed to be involved. It was the aim of this study to obtain more insights into these underlying mechanisms. METHODS: In the affected extremeties of 42 patients with RSD we investigated as indirect measures of sympathetic (dys)function: (1) skin blood flow and the vasoconstrictive response to dependency of skin microvessels by means of laser Doppler flowmetry (distal to the site of trauma), (2) relative distention of the brachial artery and changes in relative distention consequent to a cold pressor test by means of ultrasonic vessel wall tracking (proximal to the site of trauma), and (3) arterial blood pressures by means of the Finapres technique. Both provocation tests induce a sympathetically mediated response. Patients were divided into three categories according to their perception of skin temperature in their injured limb (stage I, stationary warmth sensation; stage II, intermittent warmth and cold sensation; or stage III, stationary cold sensation). RESULTS: Distal to the site of trauma, when compared with controls, skin blood flow was increased at stage I and decreased at stages II and III, whereas the vasoconstrictive response to dependency was impaired at all three stages. Proximally, when compared with controls, relative distention of the brachial artery and its response to the cold pressor test were decreased at all three stages. No differences were observed in pulse pressure between patient groups and controls. CONCLUSIONS: These results suggest that sympathetic dysfunction in extremities of patients with RSD distal to the site of trauma consists of hypersensitivity to catecholamines at stages II and III as a result of autonomic denervation at stage I, whereas proximal to the site of trauma sympathetic nerve impulses may be increased at all three stages.

Adult↗
PubMed1997

Cardiac muscarinic receptor function in rats with cirrhotic cardiomyopathy.

The pathogenesis of cirrhotic cardiomyopathy remains unclear. Because ventricular contractility is dependent on the interplay of stimulatory beta-adrenergic and inhibitory muscarinic receptors, we aimed to examine a possible role of muscarinic M2 receptor overactivity in a rat model of cirrhotic cardiomyopathy. Cirrhosis was induced by bile duct ligation (BDL), while controls underwent sham operations. Contractile responses to the muscarinic agonist carbachol were measured in situ in the autonomic-denervated pithed rat and in vitro in isolated ventricular papillary muscles. Ventricular sarcolemmal plasma membranes were isolated by sucrose density gradients, and muscarinic receptor characteristics were studied using 1-[N-methyl-3H]scopolamine (NMS). Membrane adenylyl cyclase activity was tested by a protein binding assay. Maximum first time derivative of peak ventricular systolic pressure (+dP/dt) for sham-operated and cirrhotic rats at baseline was 3,599 +/- 296 versus 1,226 +/- 63 mm Hg/sec (P < .01). Maximum first time derivative of ventricular diastolic relaxation (-dP/dt) for sham and cirrhotic rats at basal levels was -3,040 +/- 235 versus -864 +/- 59 (P < .01). The +dP/dt(max), and -dP/dt(max) responses to carbachol were blunted in the cirrhotic rats. The cirrhotic papillary muscles showed significantly less inhibition to incremental doses of carbachol than control rat muscles. Likewise, isoproterenol-stimulated membrane adenylyl cyclase activity was significantly less inhibited by carbachol doses in the cirrhotic rats. Membrane M2 receptor density and binding affinity in cirrhotic rat hearts were similar to controls. We conclude that muscarinic responsiveness was blunted in cirrhotic hearts, but this was not caused by receptor down-regulation, suggesting changes in postreceptor factors. These changes in muscarinic function are likely compensatory, and M2 receptor overactivity is not involved in the genesis of cirrhotic cardiomyopathy.

Adenylyl Cyclases↗
PubMed1990

Effects of hysterectomy on bowel and bladder function.

A case control study compared the bowel habit of 91 post-hysterectomy women with paired controls from the same family doctor practice. More cases had an abnormal bowel frequency, a firmer stool consistency and assessed themselves as having abnormal bowel function, predominantly constipation after hysterectomy, than controls. Significantly more cases than controls had consulted a doctor because of constipation but there was no significant difference in laxative usage. There was a significant short-term association between decreased bowel frequency and increased urinary frequency after hysterectomy. This became highly significant in those patients who developed chronic symptoms. Oophorectomy, unilateral or bilateral, did not significantly affect bowel habit other than to intensify the change in stool consistency. The hypothesis is discussed that the post-hysterectomy effects on bowel and bladder function may have a common aetiology in a degree of autonomic denervation of both viscera.

Adult↗
PubMed1982

Training-induced bradycardia and intrinsic heart rate in rats.

After 10 weeks of treadmill training, female Sprague-Dawley rats had developed a bradycardia at exercise on submaximal work loads. This bradycardia was also present after autonomic denervation and in isolated perfused heart preparations. The heart weight/body weight ratio was increased in these trained animals compared to untrained littermates. Sympathectomized, trained rats developed the same degree of cardiac hypertrophy, but their heart rate after denervation and in the isolated heart was the same as in sympathectomized, untrained rats. It is concluded that the bradycardia of trained and thereafter denervated animals seen in this and a previous investigation represents an adaptation within the heart itself, since it was present in the isolated heart. These results thus provide further evidence for a non-neural component in training-induced bradycardia. Since the trained sympathectomized rats had a cardiac hypertrophy but no reduction of intrinsic heart rate, it seems likely that the myocardial mass is of minor importance for the level of intrinsic heart rate.

Adaptation, Physiological↗
PubMedDate not supplied

Postcolectomy syndromes.

Resection of the colon and rectum may produce both transient and permanent alterations in colonic function. Furthermore, the nature of some operative techniques may result in autonomic denervation of the rectum and associated pelvic viscera. An understanding of the mechanism of injury and the subsequent functional abnormalities is necessary to provide adequate therapy.

Anastomosis, Surgical↗
PubMed1998

Absorption, excretion, and distribution of plant sterols after proximal gut resection and autotransplantation of porcine ileum.

Contribution of different gut segments to plant sterol absorption, adaptation of plant sterol absorption after partial small bowel resection, and effects of gut transplantation (necessitates extrinsic autonomic denervation and lymphatic disruption) on plant sterol biodynamics are unclear. We studied the consequences of massive proximal small bowel resection and autotransplantation of the remaining ileum on the adaptive absorption and biodynamics of plant sterols. Dietary, fecal, biliary, hepatic and plasma plant sterols, fecal elimination and absorption of cholesterol, small bowel morphology, and intestinal transit were determined before (n = 5) and at 4, 8, and 14 wk after resection of the proximal 75% of the jejunoileum (n = 15) and autotransplantation of the remaining ileum (n = 15) or transection (n = 5). Proximal gut resection significantly reduced cholesterol absorption efficiency; percentage absorption and biliary secretion of plant sterols; plasma, biliary and hepatic campesterol-to-cholesterol proportions; and sitosterol proportions in plasma and bile. Autotransplantation of the remaining ileum further significantly decreased cholesterol absorption efficiency; percentage absorption and biliary secretion of campesterol; campesterol proportions in plasma, bile and liver; and plasma proportions of sitosterol while increasing fecal excretion of neutral and acidic steroids. Plasma proportions of the two plant sterols, but absorption of just campesterol, were gradually improved with increasing cholesterol absorption and villus height after proximal gut resection; the same result was observed to a lesser degree after ileal autotransplantation. In addition, significant positive correlations were found between percentage cholesterol and campesterol absorption and the plasma plant sterol proportions in both proximal resection groups, between campesterol absorption and ileal villus height in the resection group, and between campesterol absorption and intestinal transit time in the autotransplantation group. In conclusion, plasma campesterol and sitosterol closely reflect absorption of cholesterol and plant sterols from intact and autotransplanted ileum during adaptation to proximal gut resection. A loss of proximal gut absorptive surface impairs cholesterol and campesterol absorption more than sitosterol absorption, the latter being apparently less dependent on available jejunal villus surface area.

Animals↗
PubMed1990

Ventriculoarterial coupling influences regional contractility.

The purpose of this study was to adjudicate whether concomitant manipulation of inotropic state and arterial elastance influences linear indices of regional contractility. Fifteen autonomically denervated open-chest porcine hearts were instrumented with midmyocardial ultrasonic crystals and aortic and left ventricular chamber microamanometers. Linear left anterior descending coronary artery regional stroke work vs preload relationships (RSW) were generated by 10-sec vena caval occlusion at control and altered contractile states (either dopamine, 5 micrograms/kg/min, or propranolol, 0.2 mg/kg) and following arterial elastance variation (phenylephrine or nitroprusside), effecting an average 30% change in mean arterial pressure (MAP). Global contractility (dP/dt) was doubled (227% of control) by dopamine and halved (35% of control) by propranolol at constant preload (end-diastolic volume, end-diastolic pressure) and afterload (MAP). Regional contractility (RSW slope) was increased from 135 +/- 11 to 211 +/- 28, P less than 0.01, by dopamine, but unchanged with propranolol (106 +/- 10 vs 118 +/- 14, NS). Bidirectional changes in aortic elastance depressed the dopamine-augmented RSW slope (115 +/- 17, nitroprusside; 132 +/- 14, phenylephrine; P less than 0.01 vs dopamine). These differences were attenuated by propranolol infusion (98 +/- 7, nitroprusside; 132 +/- 9, phenylephrine; NS vs propranolol). Thus, optimizing ventriculoarterial coupling should supersede simple afterload manipulation in perioperative cardiac support.

Animals↗
PubMed1981

Acute hypoglycemia in man: neural control of pancreatic islet cell function.

Acute hypoglycemia is associated with stimulation of the pancreatic alpha cells and a concurrent, prolonged suppression of insulin secretion by the beta cells. The islets receive a rich autonomic innervation and may therefore be subject to control by adrenergic and cholinergic mechanisms. The role of such neuroregulation of pancreatic islets in response to hypoglycemia has been examined in normal subjects, in subjects with a preganglionic sympathectomy due to traumatic tetraplegia, and in tetraplegic subjects given atropine to induce effective dual autonomic denervation. The normal rise of plasma norepinephrine following hypoglycemia was absent in both groups of tetraplegic subjects, providing evidence of a complete sympathectomy. Blood glucose recovery was significantly impaired only in the group of tetraplegic patients given atropine. Changes in plasma C-terminal glucagon-like immunoreactivity (C-GLI) and C-peptide immunoreactivity (CPR) following hypoglycemia were commensurate with blood glucose levels and were not significantly influenced by islet denervation. These observations suggest that neuroregulation of human islet cell function in response to hypoglycemia may be of limited importance and that stimulation of glucagon secretion may occur independent of cholinergic vagal control.

Acute Disease↗
PubMed1992

Dental and oral findings in patients with familial dysautonomia.

Familial dysautonomia is an inherited autosomal recessive disease found almost exclusively in Ashkenazi Jews. It is characterized by selective damage to the sensory, motor, and autonomic peripheral nervous system. The main clinical features include decreased pain sensation, impaired temperature and blood pressure regulation, lack of tearing, absent tendon reflexes, and fungiform papillae on the tongue. The purpose of this study was to explore in depth and to verify the oral and dental status in familial dysautonomia. Twenty-two patients and 44 match-paired healthy persons of Ashkenazi descent were examined. Patients and parents had only little concern for their oral condition. Caries prevalence was lower than normal and plaque accumulation increased in all patients. Dental trauma was found in 59% of the patients, and 32% showed orodental self-mutilation. Dental age was within normal range, and dental arch measurements implied proportionally small jaws and little crowding. The low caries rate may be related to the known "hypersalivation" in familial dysautonomia and/or a possible change in the salivary composition and content, caused by chronic autonomic denervation.

Adolescent↗
PubMed1993

The effect of chronic decentralization on the enkephalin immunoreactive plexus around penile ganglionic neurons.

Target organ responses to sympathetic nerve stimulation are altered following partial decentralization of the pelvic plexus in the rat. One possible explanation for the new responses is that nerve injury has led to a reorganization of synaptic connections within pelvic ganglia. Since one measure of synaptic influence is the occurrence of a pericellular plexus of varicose fibers around autonomic ganglion cells, the present study has used immunocytochemistry for enkephalin (ENK), a peptide present in nerve fibers in the pelvic plexus, to follow changes in the innervation of penile ganglionic neurons after interruption of preganglionic pathways. Penile ganglion cells were located by the injection of the tracer Fluorogold into the penile crura. Four days after lesion of the pelvic nerve, innervation of penile neurons falls from 76% to 20%. This number increases however, to 31% in chronically (6 weeks) lesioned animals. In the totally decentralized ganglia, ENK immunoreactive (IR) fibers enclose fewer than 12% of the penile neurons 4 days after nerve lesion. However, this value rises to 35% in the chronically decentralized pelvic ganglion. Therefore, recovery of an enkephalin plexus occurs irrespective of whether the pelvic nerve, or both the hypogastric and pelvic nerve have been cut. Although these findings suggest sprouting within partially decentralized ganglia, the similar incidence of an ENK plexus in ganglia subjected to chronic partial or total decentralization indicates that preganglionic fibers are not responsible for the emergent fibers.

Animals↗
PubMed1993

Effects of dexmedetomidine on systemic and coronary hemodynamics in the anesthetized dog.

In addition to central effects, which are the basis of their use in anesthesiology, alpha 2-adrenergic agonists have direct peripheral cardiovascular effects. Dexmedetomidine (DM) has been found to depress cardiac function in dogs, even after autonomic denervation. The present experiments evaluated the effects of DM on coronary flow, myocardial oxygen extraction, and cardiac function in intact, open chest dogs under enflurane anesthesia. Heart rate (HR), mean arterial pressure (MAP), left ventricular end-diastolic pressure (LVEDP), the first derivative of systolic left ventricular pressure (dP/dtmax), and flow in the left anterior descending coronary artery (CBF) were measured and continuously recorded. Cardiac output (CO), plasma catecholamines (CA), hemoglobin and oxygen saturation in arterial, mixed venous, and coronary sinus blood were measured at intervals. Cardiac index (CI), systemic vascular resistance index (SVRI), regional coronary vascular resistance (CVR), and oxygen concentration differences across the systemic [C(a-v)O2], and coronary [C(a-cs)O2] circulations were calculated. DM doses of 0.25, 0.5, 1.0, 2.0, and 4.0 micrograms/kg were given IV at 20-minute intervals. Measurements and samples were taken at peak drug effects and just prior to the next dose. The alpha 2-antagonist atipamezole, 0.5 mg/kg, was given after the last dose of DM. DM caused immediate dose-dependent increases in SVRI, CVR, LVEDP, C(a-v)O2, and C(a-cs)O2, and decreases in HR, and CI, with recovery between doses. DP/dtmax declined after the first two doses and stabilized thereafter, as plasma CA fell to minimal levels. Atipamezole completely reversed all changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed2005

Arrhythmias after orthotopic heart transplantation.

BACKGROUND: Arrhythmias frequently occur after orthotopic heart transplantation (OHT). METHODS AND RESULTS: The most common are ventricular premature complexes, atrial premature complexes, sinus or junctional bradycardia, atrial fibrillation, and atrial flutter, all of which have varying clinical significance depending on associated or causative conditions. Unique etiologic factors such as allograft rejection, transplant coronary artery disease, and altered anatomy and autonomic nervous system changes require that arrhythmias be treated differently after OHT compared with the general population. CONCLUSION: The potentially severe ramifications of allograft rejection and coronary artery disease make treatment of these disorders in the setting of arrhythmias as important as treating the arrhythmias themselves. At the same time, autonomic denervation and altered anatomy after transplantation complicate drug and device therapies.

Arrhythmias, Cardiac↗
PubMed1995

Evolution of the chronotropic response to exercise after cardiac transplantation.

The chronotropic response to exercise is abnormal in cardiac transplant recipients as a result of autonomic denervation. Differences in the response between recent transplant recipients and longer-term survivors have been described in previous cross-sectional studies. These changes have not been assessed directly using serial studies. The effect of sinus node dysfunction on the chronotropic response has not previously been determined. Thirty-one transplant recipients underwent serial treadmill exercise tests using the chronotropic exercise assessment protocol 3 and 6 weeks and 3 and 6 months after transplantation. Sinus node function was assessed using standard electrophysiologic techniques. The chronotropic response increased between 3 and 6 weeks after transplantation in all subjects. Six months after transplantation, there was a further marked increase in the response in a subgroup of 5 subjects. These subjects also had a dramatic decrease in heart rate on cessation of exercise. Three subjects had abnormal sinus node function. Although heart rates and chronotropic response were below average in these subjects, 2 other subjects with normal sinus node function on electrophysiologic testing had lower heart rates and worse chronotropic responses. Thus, the chronotropic response to exercise evolves over the first 6 weeks after cardiac transplantation in all subjects. In a number of recipients (16%), there is a marked increase in chronotropic response between 3 and 6 months, which suggests efferent sympathetic reinnervation. There was no clear difference in chronotropic response between subjects with and without evidence of sinus node dysfunction.

Adult↗