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At least 145 records · Page 8Linked to original sources

Interaction between cholinergic and nitrergic vasodilation: a novel mechanism of blood pressure control.

OBJECTIVE: Cholinergic vasodilation has been thought to play little if any role in the regulation of blood pressure in humans. Autonomic denervation potentiates the vasoconstriction evoked by nitric oxide synthase inhibition in humans, but the mechanism is unclear. We hypothesized that this may be related to loss of neuronal, non-nitric-oxide-dependent vasodilation. METHODS: To test this hypothesis, we examined effects of cholinergic blockade on blood pressure, heart rate and peripheral vascular responses to systemic infusion of the nitric-oxide-dependent vasoconstrictor L-NMMA (0.5 mg/kg/min over 15 min) in eight normal subjects. RESULTS: The L-NMMA-induced increase in mean (+/-S.E.) arterial pressure was roughly three times larger (P=0.002) in the presence than in the absence of cholinergic blockade (38+/-6 vs. 13+/-2 mmHg). Similarly, the increase in systemic and calf vascular resistance was more than twofold larger during L-NMMA-atropine. This potentiation was specific for nitric-oxide-dependent vasoconstriction, because atropine did not alter the responses to phenylephrine infusion. Cholinergic blockade also altered (P=0.004) the heart rate response to nitric oxide synthase inhibition; during L-NMMA alone heart rate decreased by 10+/-2 beats/min, whereas during L-NMMA-atropine infusion it increased by 14+/-4 beats/min. CONCLUSION: Cholinergic mechanisms play an important hitherto unrecognized role in offsetting the hypertension and cardiac sympathetic activation caused by nitric oxide synthase inhibition in humans. Decreased parasympathetic activity and impaired nitric oxide synthesis characterize several cardiovascular disease states, as well as normal aging. The conjunction of these two defects could trigger sudden death and contribute to the hypertension of the elderly.

Adrenergic beta-Antagonists↗

Decompensated ureteropelvic junction obstruction in renal allograft.

We report a case of complete obstruction at the ureteropelvic junction in a renal allograft 6 months after related kidney transplantation. Surgical treatment consisted of a Foley nondismembered Y-V pyeloplasty. Although the donor harbored undetected bilateral, mild, ureteropelvic junction stenosis, as established by review of the excretory urogram that was performed before nephrectomy, the remaining kidney functioned well, as confirmed by renal function and morphological appearance on a repeat excretory urogram. The possible mechanisms of ureteropelvic junction decompensation, the most crucial of which appears to be autonomic denervation of the allograft, are discussed.

Adult↗

Incomplete sympathic reinnervation of the orthotopically transplanted human heart: observation up to 13 years after heart transplantation.

OBJECTIVE: Heart transplantation (HTx) is associated with autonomic denervation of the donor heart. Sympathetic reinnervation (RI) as defined by the presence of functional nerve terminals occurs only if sympathetic ganglia outside the heart are connected with nerve terminals in the transplanted heart. The purpose of this study was to define the incidence and functional consequences of RI over time after HTx. The activity and distribution of norepinephrine (NE) uptake sites were assessed by positron emission tomography (PET) imaging. Symptom limited exercise testing was performed by bicycle-ergometer. METHODS: Forty-seven patients (m:f=42:5, 47.6+/-8. 2 years, age range 27-65 years) were investigated between 2 months and 13.6 years after HTx using PET and the NE analogue C-11-hydroxyephedrine (HED). Tracer uptake was quantified using dynamic imaging protocols yielding regional HED retention fraction. A regional value above 7%/min (+/-2.5 SD above the mean value of denervated hearts) was considered evidence for RI. The functional significance of RI was investigated in 34 patients (m:f=30:4, 49. 3+/-8.4 age range 27-62 years) by symptom limited exercise testing. Cardiac catheterization was performed at the time of PET imaging. RESULTS: RI could not be assessed in the first year after HTx, in 11% in the second year and in 80% of the patients from the third year on. Retention values plateaued then. In all time intervals, beyond the third year, not reinnervated patients were found. RI remained incomplete and was always restricted to the anterior wall of the left ventricle. Extent of retention of the left ventricle revealed a large individual range up to 66%, averaging of 20%. Recipient age at the time of HTx, reinnervated patients were 5.5 years younger than not reinnervated ones, proved as the only significant influencing factor for RI (P<0.05). Dividing patients into scintigraphically reinnervated (n=20) and not reinnervated (n=14), reinnervated patients displayed during exercise a higher maximal heart rate (137+/-14 vs. 123+/-20/min, P<0.05), heart rate increase (40+/-15 vs. 28+/-13/min, P<0.05), max. oxygen consumption (1674+/-424 vs. 1279+/-308 ml/min, P<0.01) and anaerobic threshold (887+/-170 vs. 717+/-183 mlO(2)/min, P<0.01) than not reinnervated ones. A correlation between transplant vasculopathy and RI could not be demonstrated. CONCLUSION: ++: RI assessed by PET and the NE analogue HED is time dependent, incomplete, displays a typical pattern and demonstrates a broad individual spread. Furthermore, RI enhances functional parameters of exercise testing.

Carbon Radioisotopes↗

A study of the origin of the electric activity of the rectum: is it neurogenic or myogenic?

The rectum possesses electric activity, the origin of which is yet undetermined. The current study investigates the possible source of these waves. Three electrodes were sutured serially to the serosal surface of the rectum in 10 dogs. The rectal pressure was measured by a perfused catheter. Simultaneous recordings of the electric activity and rectal pressure were done before and after bilateral pelvic ganglionectomy and rectal myotomy. Regular slow waves or pacesetter potentials (PPs) followed by inconsistent action potentials (APs) were recorded. They exhibited the same frequency, amplitude and velocity from three electrodes in the individual animal. APs were associated with minor rectal pressure rise. After pelvic ganglionectomy, PPs and APs were recorded but with irregular frequency, amplitude and conduction, a picture of 'rectoarrhythmia'. The rectoarrhythmic waves were registered proximally but not distally to the myotomy. In conclusion, the rectal electric waves persist after bilateral pelvic ganglionectomy but exhibit a 'rectoarrhythmic' pattern. This is suggested to indicate that the waves are not initiated by, but may be under the control of, the extrarectal autonomic innervation. A 'pacemaker' is postulated to exist at the rectosigmoid junction triggering impulses that spread in the rectal wall along the muscle bundles or the myenteric nerve plexus.

Action Potentials↗

Desensitization and sequestration of human m2 muscarinic acetylcholine receptors by autoantibodies from patients with Chagas' disease.

Chronic Chagas' disease is associated with pathologic changes of the cardiovascular, digestive, and autonomic nervous system, culminating in autonomic denervation and congestive heart failure. Previously, circulating autoantibodies that activate signaling by cardiac muscarinic acetylcholine receptors (mAChRs) have been described. However, it remains unclear whether the chagasic IgGs directly interact with the m2 mAChRs (predominant cardiac subtype), and, if so, whether chronic exposure of the mAChRs to such activating IgGs would result in receptor desensitization. Here we performed studies with purified and reconstituted hm2 mAChRs and demonstrate that IgGs from chagasic serum immunoprecipitated the mAChRs in a manner similar to an anti-m2 mAChR monoclonal antibody tested in parallel. The chagasic antibodies did not directly interact with the ligand binding site, because the binding of radiolabeled antagonist was unchanged by the addition of the chagasic IgG. In intact cells stably expressing the hm2 mAChR, the chagasic IgGs, but not normal IgGs, mimicked the ability of the agonist acetylcholine to induce two effects associated with agonist-induced receptor desensitization: a decrease in affinity for agonist binding to m2 mAChR and sequestration of the hm2 mAChRs from the cell surface. The results demonstrate that the chagasic IgGs can directly interact with and desensitize m2 mAChRs and provide support for the hypothesis of autoimmune mechanisms having a role in the pathogenesis of Chagas' cardioneuromyopathy.

Animals↗

Cardiovascular effects of tiapamil (Ro 11-1781), a new calcium-entry blocker.

We studied the hemodynamic effects of the new calcium antagonist tiapamil (Ro 11-1781) in anesthetized open-chest dogs and compared them with those of verapamil. Increasing doses of tiapamil injected intravenously caused the following hemodynamic effects: increase in coronary flow and decrease in coronary vascular resistance, followed by decreases in heart rate, blood pressure, and total peripheral resistance. Tiapamil did not depress myocardial contractility over a rather wide dose range, while verapamil did. Tiapamil was more effective in increasing coronary flow than verapamil. Cardiac autonomic denervation did not modify the tiapamil-induced decrease in coronary vascular resistance and did not cause tiapamil to display negative inotropism. Both tiapamil and verapamil reduced the extent of S-T segment elevation in the epicardial electrocardiogram produced by transient occlusion of the left anterior descending coronary artery. Neither drug had this effect when heart rate was kept constant by atrial pacing. In contrast to nitroglycerin, tiapamil dilated small but not large coronary arteries. Tiapamil raised PO2 relatively more in the subendocardial than in the subepicardial layers of the myocardium. The hemodynamic and electrocardiographic effects of tiapamil were not changed by diphenylhydantoin and disopyramide or by pindolol, a beta-adrenoceptor blocking agent with intrinsic sympathomimetic activity. However, the decreases in heart rate and blood pressure in response to propranolol were enhanced by tiapamil.

Animals↗

The effect of posterior sagittal anorectoplasty and its variants on lower urinary tract function in children with anorectal malformations.

The effect of posterior sagittal anorectoplasty (PSARP) and its variants on lower urinary tract function was investigated urodynamically in 32 patients with anorectal malformations. In 27 patients urodynamic evaluation was performed before and after surgery and in 4 it was done postoperatively only. One child was clinically assessed with no postoperative urodynamic study. Minor postoperative changes in the specific preoperative urodynamic pattern were observed in 4 cases but the changes did not seem to be related to surgery. In 3 boys with rectourethral fistulas detrusor failure consistent with autonomic denervation was noted postoperatively. Standard posterior sagittal anorectoplasty was performed in 1 of the 3 boys and posterior sagittal anorectoplasty combined with additional transabdominal procedures was done in the other 2. In general our findings suggest that posterior sagittal anorectoplasty and its variants do not affect lower urinary tract function unless these surgical techniques are combined with major transabdominal procedures and extensive retrovesical dissection.

Anal Canal↗

Laparoscopic presacral neurectomy: a review.

Dysmenorrhea can be a severe and debilitating symptom in many women. Although most women may find adequate relief of symptoms from pharmacological approaches, there remain a few with resistant pain. Presacral neurectomy, although technically challenging, may be offered after other approaches are unsuccessful. The operation is now performed increasingly by the laparoscopic approach, which has revived this operation in some centers. The anatomy, technique, and indications as well as a review of the literature supporting this operation are reviewed. The potential complications of this operation are discussed also.

Autonomic Denervation↗

Hematologic abnormalities within the first week after acute isolated traumatic cervical spinal cord injury: a case-control cohort study.

STUDY DESIGN: Case-control cohort study. OBJECTIVE: To evaluate 1) the hematologic abnormalities within the first week following isolated acute cervical spine trauma or spinal cord injury (SCI); and 2) the influence of age, sex, and severity of SCI on these hematologic abnormalities. SUMMARY OF BACKGROUND DATA: Given that autonomic nervous system has a critical role in the regulation of the hematopoietic system, we sought to evaluate the potential association between hematologic abnormalities within the first week posttrauma and the severity of SCI. METHODS: All consecutive individuals with isolated acute cervical spine trauma admitted to our institution from 1998 to 2000 were reviewed. Exclusion criteria included preexisting medical comorbidities and polytrauma. The study population was divided into a SCI group and a control group (individuals with spine trauma without neurologic impairment). The SCI group was subdivided into patients with motor complete SCI (American Spinal Injury Association [ASIA] Grades A/B) and individuals with motor incomplete SCI (ASIA Grades C/D). RESULTS: There were 21 SCI individuals (15 male, 6 female; ages 17-83 years; mean, 57 years) and 11 controls (6 male, 5 female; ages 18-75 years; mean, 41 years). When controlled for age, SCI individuals showed a significantly higher frequency of reduced hemoglobin concentration (RHC), leukocytosis, lymphopenia, and thrombocytopenia than controls within the first week posttrauma. Blood hemoglobin concentration, lymphocyte, and platelet counts in the SCI group were significant lower than the controls. The SCI group showed a significant higher leukocyte count than the controls. The degree of RHC and lymphopenia was significantly correlated with the severity of SCI. CONCLUSION: Our results indicate that patients with isolated cervical SCI have significantly greater frequency of RHC, leukocytosis, lymphopenia, and thrombocytopenia than controls during the first week posttrauma. The degree of RHC and lymphopenia was significantly associated with the severity of SCI. While the mechanisms underlying these clinically important hematologic consequences of SCI remain undetermined, evidence from the literature suggests that acute autonomic denervation of the hematopoietic system could play a key role.

Adolescent↗

Severe peripheral neuropathy and elevated plantar pressures causing foot ulceration in pituitary gigantism.

We report two patients with treated pituitary gigantism and peripheral neuropathy, one of whom has chronic foot ulceration. Detailed neurophysiological assessment was performed on both patients. The patient with foot ulceration had clinical and neurophysiological evidence of severe neuropathy, whereas the patient without ulceration had only neurophysiological abnormalities. The sweating response to acetylcholine was markedly impaired in the feet of both patients, suggesting pedal autonomic denervation. Neither patient had evidence of diabetes mellitus and detailed investigation failed to reveal an alternative cause of peripheral neuropathy. Optical pedobarography revealed abnormally high pressure (> 10 kg/cm2) under the metatarsal heads of both patients, one such area coinciding with the area of ulceration. Thus in pituitary gigantism elevated plantar pressures may contribute to the development of foot ulceration when severe peripheral neuropathy is present. Furthermore, as in diabetes mellitus, impaired sweating may also increase the risk of ulceration as the resultant dry skin may develop fissures.

Adult↗

Autonomic neuropathy and the pathogenesis of glaucoma in diabetes mellitus.

In order to determine whether ocular hypertension and glaucoma may be a complication of autonomic neuropathy in diabetes mellitus, 30 asymptomatic diabetic patient volunteers were studied. A correlation was sought between reduced anterior chamber depth which is thought to predispose to the development of glaucoma, and two markers of autonomic dysfunction, loss of sinus arrhythmia and reduced diameter of dark adapted pupils. A significant correlation was found between reduced chamber depth and pupil diameter arrhythmia (r = 0.36, p = 0.025) and between chamber depth and pupil diameter (r = 0.45, p = 0.006). As expected, there was also a significant correlation between sinus arrhythmia and pupil diameter (r = 0.68, p less than 0.001). The correlation between pupil diameter and sinus arrhythmia, and between pupil diameter and chamber depth was preserved after the data were adjusted for age (r = 0.54, p less than 0.001 and r = 0.35, p = 0.03, respectively), while that between sinus arrhythmia and chamber depth was lost (r = 0.23, NS). No association was found between intraocular pressure and either marker of autonomic dysfunction, but intraocular pressure was not abnormal (less than 22 mmHg) in any individual case. These data suggest that autonomic denervation of the eye in diabetes may be associated with alteration of anterior chamber depth.

Adult↗

Optimal cardiac pacing after heart transplantation.

The transplanted heart is characterized physiologically by autonomic denervation, chronotropic incompetence, intermittent episodes of allograft rejection, and frequently by diastolic dysfunction. Sinus node dysfunction resulting in bradycardia is common in the early postoperative period following standard orthotopic cardiac transplantation. Bradycardia tends to remit spontaneously but there are no factors that accurately identify patients who will need long-term pacing. Patients in whom bradycardia persists beyond the second postoperative week despite treatment with theophylline require permanent pacemaker implantation. It has been observed that chronotropic incompetence and diastolic dysfunction are important determinants of exercise capacity following heart transplantation. Pacing that restores chronotropic competence improves exercise capacity, confirming the importance of impaired heart rate response. As in other settings, pacing that preserves atrioventricular (AV) synchrony results in increased cardiac output. For these reasons when pacing is necessary we recommend the DDDR mode (AAIR if intact AV nodal conduction is present) so that the 30%-50% of patients who remain pacemaker-dependent long-term obtain maximal benefit from their transplant.

Animals↗

Nitric oxide and thyroid gland: modulation of cardiovascular function in autonomic-blocked anaesthetized rats.

We have previously reported that acute administration of N(G)-nitro-l-arginine methyl ester (L-NAME) increases the mean arterial pressure (MAP) and heart rate (HR) in autonomic-blocked (CAB) anaesthetized rats. In the present study we examined whether thyroid and adrenal glands are involved in these pressor and chronotropic responses. Sprague-Dawley rats were studied after bilateral vagotomy and ganglionic blockade with hexamethonium (10 mg kg(-1)), and stabilization of MAP with infusion of phenylephrine (PE) (6 microg kg(-1) min(-1)). The rats were divided into groups: L, CAB; PE, CAB + PE bolus (6 microg kg(-1)); L-TX, thyroidectomy + CAB; L-AX, adrenalectomy + CAB; TX, only thyroidectomy; C, CAB. L, L-AX and L-TX groups received a bolus of l-NAME (7.5 mg kg(-1)). Triiodothyronine (T3), thyroxin (T4) and thyrotropin (TSH) levels were measured in L and L-TX rats before and after l-NAME administration. Reduced nicotamide adenine dinucleotide (NADPH) diaphorase activity was determined in heart and aorta of the TX group. The pressor response induced by l-NAME was similar in all groups. l-NAME-induced-tachycardia was associated with this rise in MAP. Adrenalectomy did not modify this chronotropic response, but it was attenuated by thyroidectomy. Thyroidectomy by itself decreased the circulating levels of T3 but it had no effect on the plasma levels of T4 and TSH. L and L-TX groups showed similar levels of circulating T4 and TSH, meanwhile the plasma level of T3 decreased in the L group. Nitric oxide synthase (NOS) activity in atria as well as in aorta was greater in the TX group compared with C. When autonomic influences are removed, the thyroid gland modulates intrinsic heart rate via a mechanism that involves, at least in part, the nitric oxide pathway.

Anesthesia↗

A mathematical model of sinus node function: validation by recording of sinus node electrograms.

We have applied a mathematical function to model sinus node recovery after atrial pacing at different cycle lengths in 13 autonomically denervated, anesthetized canines. This model provides "pure" indexes of sinoatrial conduction and of suppression of automaticity. We compared sinoatrial conduction computed from the model (SACTc) with sinoatrial conduction measured directly utilizing a catheter recording the sinus node electrogram (SACTd) to test the validity of the model. We used both the model and the sinus node electrogram to further define events after pacing. There was close agreement between SACTc and SACTd with correlation coefficients at pacing cycle lengths of 20 and 50% below resting of 0.86 (P < 0.0001) and 0.78 (P < 0.0001), respectively. We verified that the conventional sinus node recovery time is due both to suppression of automaticity and prolongation of sinoatrial conduction. Sinoatrial conduction time returned rapidly to normal over 1-3 beats, whereas automaticity recovered exponentially over 20-40 postpacing intervals. The model accurately describes postpacing phenomena and has the potential to provide a useful adjunct to the measurement of the sinus node electrogram for assessment of sinus node function in the experimental laboratory.

Animals↗

Autonomic control of skeletal muscle blood flow at the onset of exercise.

The purpose of this study was to determine whether the autonomic nervous system is involved in skeletal muscle vasodilation at the onset of exercise. Mongrel dogs (n = 7) were instrumented with flow probes on both external iliac arteries. Before treadmill exercise at 3 miles/h, 0% grade, hexamethonium (10 mg/kg) and atropine (0.2 mg/kg) or saline was infused intravenously. Ganglionic blockade increased resting heart rate from 87 +/- 5 to 145 +/- 8 beats/min (P < 0.01) and reduced mean arterial pressure from 100 +/- 4 to 88 +/- 5 mmHg (P < 0.01). During steady-state exercise, heart rate was unaffected by ganglionic blockade (from 145 +/- 8 to 152 +/- 5 beats/min), whereas mean arterial pressure was reduced (from 115 +/- 4 to 72 +/- 4 mmHg; P < 0.01). Immediate and rapid increases in iliac blood flow and conductance occurred with initiation of exercise with or without ganglionic blockade. Statistical analyses of hindlimb conductance at 5-s intervals over the first 30 s of exercise revealed a statistically significant difference between the control and ganglionic blockade conditions at 20, 25, and 30 s (P < 0.01) but not at 5, 10, and 15 s of exercise. Hindlimb conductance at 1 min of exercise was 9.21 +/- 0.68 and 11.82 +/- 1.32 ml. min(-1). mmHg(-1) for the control and ganglionic blockade conditions, respectively. Because ganglionic blockade did not affect the initial rise in iliac conductance, we concluded that the autonomic nervous system is not essential for the rapid vasodilation in active skeletal muscle at the onset of exercise in dogs. Autonomic control of skeletal muscle blood flow during exercise is manifested through vasoconstriction and not vasodilation.

Animals↗

Amyloid deposits inside myocardial fibers in transthyretin-Met30 familial amyloidotic polyneuropathy. A histological and biochemical study.

A case of severe cardiac involvement is reported in a patient affected with familial amyloidotic polyneuropathy due to the Portuguese type I variant (Val-->Met30) of the transthyretin (prealbumin) molecule. Echocardiographic and hemodynamic studies suggested the presence of a progressive infiltrative cardiomyopathy that was later confirmed by endomyocardial biopsy. Amyloid deposits were found in both intra- and extra-myofiber location and thought to be related to primary involvement of the heart. Norepinephrine content of myocardial bioptic specimens was about threefold lower than normal, indicating that autonomic denervation may contribute to the maintenance and progression of cardiomyopathy. A sample obtained from the sural nerve showed a loss of myelinated fibers along with accumulation of amyloid masses in the endoneurial space. This histopathologic pattern correlated with a sharp decrease in the activity of the enzyme subserving electrochemical conduction through the axonal membrane, Na+, K(+)-ATPase.

Amyloid↗

Pericardial prostaglandin biosynthesis prevents the increased incidence of reperfusion-induced ventricular fibrillation produced by efferent sympathetic stimulation in dogs.

This study tested the hypothesis that sympathetic neural stimulation increases the prevalence of reperfusion-induced ventricular fibrillation and explored the mechanisms by which this occurs and how it may be prevented. In anesthetized, autonomically denervated dogs, we examined the effects of bilateral ansae subclaviae stimulation (SS) and of induction of pericardial biosynthesis of prostaglandins, an intervention that reduces SS effects by acting at presynaptic sites. A 5-minute occlusion of the left anterior descending coronary artery distal to the first or second diagonal branch was performed during SS. Heart rate was maintained constant by atrial pacing. In the absence of SS, one of 23 dogs developed ventricular fibrillation during occlusion, and three of the remaining 22 dogs developed ventricular fibrillation upon reperfusion. SS did not increase the prevalence of occlusion-induced ventricular fibrillation (four of 23 dogs) but increased the prevalence of reperfusion-induced ventricular fibrillation (12 of the remaining 19 dogs, p = 0.01). SS did not affect occlusion-induced decrease in local electrogram amplitude recorded from the ischemic myocardium or myocardial blood flow to the ischemic myocardium during occlusion or reperfusion. SS, however, prevented occlusion-induced increase in diastolic excitability threshold. Instillation into the pericardial cavity of arachidonic acid solution (3 micrograms/ml) resulted in release of prostacyclin, measured by radioimmunoassay as a stable metabolite 6-ketoprostaglandin F1 alpha (63.1 +/- 11.3 ng/ml, n = 11, mean +/- SEM), and of prostaglandin E2 (7.0 +/- 0.9 ng/ml, n = 11). This pericardial solution blunted SS-induced increase in mean arterial blood pressure and reduced the prevalence of ventricular fibrillation during reperfusion (six dogs to one dog, p less than 0.05). Blood flow to the ischemic myocardium remained unaffected. Indomethacin, when added to the solution (3 micrograms/ml), reversed the effects of prostaglandin release and arrhythmia development. These data indicate that efferent sympathetic stimulation during a coronary occlusion and reperfusion sequence increases the prevalence of reperfusion-induced ventricular fibrillation that is reduced by pericardial biosynthesis of prostaglandins. Pericardial prostaglandin synthesis may serve as a unique antiarrhythmic function by regulating efferent cardiac sympathetic nerve effects.

Animals↗