Effect of vagotomy and thoracic sympathectomy on responses of the monkey to water immersion

Cardiopulmonary stretch receptors have been implicated as part of a reflex mechanism linking changes in blood volume to changes in renal excretion. Experiments were performed to determine whether total denervation of these receptors by combined cervical vagotomy and thoracic sympathectomy affects the renal responses of the monkey to head-out water immersion, a maneuver that translocates blood to the thorax and elicits an increase in renal salt and water excretion. Macaca fascicularis monkeys first underwent chronic bilateral thoracic sympathectomy or sham denervation performed in two stages a week apart. One to two weeks later, they were anesthetized with pentobarbital sodium, and the sympathectomized animals underwent bilateral cervical vagotomy. Control renal function did not differ between the two groups. Immersion of 90-min duration increased central venous and mean arterial pressures by similar amounts in both groups, but heart rate increased only in the sham-denervated animals. Denervation did not affect the magnitudes or delay the times of onset of the increases in urine flow, absolute and fractional sodium excretion, and osmolar and free water clearances occurring with immersion. These results demonstrate that in the anesthetized monkey cardiopulmonary receptors are not necessary for eliciting the renal responses to immersion.     

Rat heart GDNF: effect of chemical sympathectomy

Developmental studies indicate a role for GDNF in survival of motor, autonomic, and sensory neurons. However, no study attempted to demonstrate its participation in autonomic nerve regeneration. In this work, chemical sympathectomy by 6-hydroxydopamine provided the model for assessing heart GDNF expression during denervation and axonal regrowth. A glyoxylic acid-based histochemical technique evaluated the noradrenergic innervation. ELISA determined GDNF levels after concentrating heart homogenates. Light and ultrastructural in situ hybridization and immunocytochemistry were used for identifying cells expressing GDNF mRNA and protein. In control rats, the GDNF cardiac levels were significantly higher in 37-day-old animals in comparison with those aging 60 days. In sympathectomized rats, GDNF cardiac levels were significantly higher 7 days after sympathectomy and dropped to control levels at day 30. GDNF mRNA was expressed in atrial and ventricular myocytes from normal and sympathectomized rats. GDNF immunoreactivity occurred on atrial granules and quantitative analysis in electron micrographs confirmed ELISA-obtained data. In ventricular myocytes gold particles occurred sparsely. These findings constitute the first evidence for GDNF synthesis by cardiomyocytes and postulate a role for this factor soon after cardiac sympathetic denervation, probably in nerve regeneration. In atrial myocytes, GDNF is probably secreted by regulated pathway.     

迷走神经在心率变异性中的作用

采用功率谱和近似熵 (approximateentropy ,ApEn)的方法 ,分析清醒家兔在双侧迷走神经保留 ,右、左侧迷走神经切断以及双侧迷走神经同时切断时心搏间期 (RRI)的变化。结果显示 :双侧迷走神经保留时功率谱中高频功率 (HF)、低频功率 (LF)及ApEn值均高于双侧及单侧迷走神经切断时 (P <0 0 5 ) ,LF/HF比值最小 ;切断单侧迷走神经 ,ApEn变小 ,LF/HF比值在右侧迷走神经切断时增大 ,而切断左侧迷走时LF/HF比值无明显变化 ;双侧迷走神经切断后LF/HF比值最大 ,ApEn最低。结果表明 :心率变异主要由迷走神经调节 ,右侧迷走神经起主要作用 ;传统心率变异性测量方法与非线性方法所得结果一致     

Effect of sympathectomy on the heart pump function in rats during postnatal ontogenesis

The influence of guanetidine sympathectomy (30 mg/kg) on the heart pump function in rats during 3 weeks in postnatal ontogenesis has been investigated. Sympathectomy restrains age-dependent establishment of stroke volume, cardiac output and heart rate. The adaptation effects of regular physical training do not develop in the animals with sympathectomy, i.e. heart rate does not decrease and stroke volume does not increase. The initial stage of adaptation of the sympathectomized animals to physical training is accompanied by decrease in stroke volume and remarkable increase in heart rate which indicates the reduction of contractile activity in the myocardium.     

Development of the linkage of beta-adrenergic receptors to cardiac hypertrophy and heart rate control: neonatal sympathectomy with 6-hydroxydopamine

Presynaptic neural projections are thought to participate in the maturation of postsynaptic sensitivity to neurotransmitters. In the current study, we have examined the effects of sympathectomy with 6-hydroxydopamine on the ontogeny of the linkage of beta-adrenergic receptors to cardiac growth and heart rate control in the rat. Destruction of sympathetic projections at birth compromised the ability of beta-receptor stimulation to evoke cardiac hypertrophy, a defect which persisted into young adulthood. The chronotropic response to beta-receptor activation, assessed by acute challenge with a submaximally-effective dose of isoproterenol, also exhibited a slowed development, but did eventually achieve normal sensitivity. In contrast, neonatal sympathectomy had only minor effects on resting heart rate, basal heart rate (the intrinsic rate in the absence of autonomic input) or maximal heart rate; these animals also showed beta-receptor desensitization of chronotropic action in response to chronic isoproterenol treatment. Chronic isoproterenol treatment itself lowered the basal heart rate, regardless of whether animals were normal or sympathectomized. Thus, during critical developmental periods, sympathetic input to beta-receptors selectively programmes the linkage between postsynaptic receptors, tissue growth and heart rate.     

Cardiorespiratory responses to chemical activation of right ventricular receptors

Previous reports have shown that activation of left ventricular receptors with sympathetic afferents elicits increases in respiratory output and arterial pressure. The purpose of the present study was to determine whether similar responses are produced by chemical activation of epicardial receptors in the right ventricle. Receptors were stimulated by applying either capsaicin (10 micrograms) or bradykinin (500 ng) to the epicardial surface of the right ventricle in anesthetized cats. Application of either chemical evoked an increase in respiratory output (phrenic nerve activity), a decrease in heart rate, and a nonsignificant increase in arterial pressure in intact cats. However, capsaicin and bradykinin produced significant increases in arterial pressure, heart rate, and respiratory output after bilateral cervical vagotomy. In contrast, a fall in both heart rate and arterial pressure with only small increases in respiratory output were evoked after bilateral removal of the stellate ganglia in cats with intact vagi. Only small responses to the chemical stimulation of right ventricular receptors persisted after combined vagotomy and stellate ganglionectomy. These findings suggest that 1) activation of epicardial receptors with sympathetic afferents originating in the right ventricle causes an increase in cardiorespiratory function, and 2) activation of right ventricular receptors with vagal afferents produces decreases in heart rate and arterial pressure.     

Age changes in rat vasomotor reflexes and sympathetic neuron ultrastructure following chemical sympathectomy]

Prolonged administration of guanethidine (20 mg/kg) to newborn rats caused a marked reduction in the number of cells in stellate ganglia. The administration of guanethidine for 14 days decreased the amount of cells to 30% of the normal (partial sympathectomy), and for 28 days--to 0.5% (complete sympathectomy). At the age of two months the blood pressure pressor reflexes to asphyxia and femoral nerve stimulation were absent in both groups of the sympathectomized animals. These responses, however, were restored in the partially sympathectomized animals at the age of four months. No restoration took place in the completely sympathectomized animals. The electron microscopic studies of neurons in the partially sympathectomized animals showed the presence of a great number of neurofibrils. According to literature data this fact was typical of cells in which an active growth of axon fibers took place.     

Acute renal function in chronically sympathectomized deoxycorticosterone acetate-treated miniature swine

We recently validated a swine model in which chronic treatment with 6-hydroxydopamine (6-OHDA) produced an effective sympathectomy. These sympathectomized swine demonstrated a significantly attenuated hypertensive response when treated with deoxycorticosterone acetate (DOCA). Because renal nerve activity is elevated and important in controlling renal function and blood pressure in the DOCA swine model, we wanted to study the effect of chronic sympathectomy on acute renal hemodynamics and tubular function. Kidney function was assessed in 14 DOCA-treated miniature swine, 8 of which were sympathectomized by chronic treatment with 6-OHDA, while 6 served as controls. Effective renal sympathectomy in this model has been previously confirmed by a significant reduction (97%) of norepinephrine in renal cortical tissue. When anesthetized, mean arterial pressure and renal blood flow were similar between the two groups. Glomerular filtration rate was lower by 43%, urine flow rate by 71%, sodium excretion by 66%, and potassium excretion by 48% in the 6-OHDA DOCA animals. All of these parameters were significantly different from the intact DOCA controls. These results indicate that anesthetized, chronically sympathectomized swine exhibit decreased renal excretory function. The changes in renal function may have been due to the development of a tubular or glomerular supersensitivity to circulating antinatriuretic factors, since the 6-OHDA group had a 28% greater pressor response to the alpha-agonist phenylephrine and a significantly greater fall in mean arterial pressure in response to alpha-blockade with prazosin when compared with the controls. These changes in renal function may also explain why the 6-OHDA animals demonstrated a slight increase in mean arterial pressure in response to DOCA. Because acute renal denervation in DOCA-treated swine produces a diuresis and natriuresis, this study affirms that there may be important functional differences in acutely versus chronically denervated kidneys for which the implications under normal physiologic conditions are unknown.     

Effect of bombesin upon plasma somatostatin-like immunoreactivity, insulin and glucagon in normal and chemically sympathectomized dogs

The present study was designed to determine the effects of intravenously infused bombesin (10 ng/kg/min) upon basal and postprandial plasma somatostatin-like immunoreactivity (SLI), glucagon, insulin and triglyceride levels in normal (n = 12) and chemically sympathectomized (n = 11) dogs. Basal plasma SLI, glucagon and insulin levels rose significantly during the infusion of bombesin in the normal dogs, and this was not altered by chemical sympathectomy. Bombesin infusion enhanced the postprandial SLI response, while attenuating the postprandial glucagon response by 50% and the insulin response in the early postprandial phase of the meal. Sympathectomy did not significantly alter the basal levels of these polypeptides, but augmented the postprandial plasma SLI response during the first 90 min, and reduced the postprandial glucagon response during the infusion of bombesin. The postprandial insulin response was not affected by sympathectomy. In both normal and chemically sympathectomized dogs the rise in postprandial triglyceride levels was attenuated by bombesin infusion.     

Compensatory-adaptive modifications of the C-cell apparatus of the thyroid in normal rats of various ages and in partial sympathectomy

Population of the thyroid C-cells, normal and at sympathectomy has been analyzed in 75 white male rats at the age of 1, 3 and 6 months by means of electron microscopical, morphometrical and radioimmunological methods. Partial sympathectomy has been performed using subcutaneous injection of guanethidine (15 mg/kg of body mass) during 14 days after birth. During the period from 1 up to 6 months of life in intact rats a decrease in C-cells functional activity is observed. Under conditions of sympathectomy in 30-day-old animals decreasing extrusion processes of the secretory material are observed. During successive periods of life (3 and 6 months) mechanisms of paracrinic evacuation of hormonal products enhance considerably, nuclear volume of the cells and number of C-cells in the field of vision increase. Their hyperplastic alterations in the sympathectomized thyroid gland are more pronounced in 3-month-old animals.     

Volume expansion potentiates cardiac sympathetic afferent reflex in dogs

Our previous study (27) showed that the cardiac sympathetic afferent reflex (CSAR) was enhanced in dogs with congestive heart failure. The aim of this study was to test whether blood volume expansion, which is one characteristic of congestive heart failure, potentiates the CSAR in normal dogs. Ten dogs were studied with sino-aortic denervation and bilateral cervical vagotomy. Arterial pressure, left ventricular pressure, left ventricular epicardial diameter, heart rate, and renal sympathetic nerve activity were measured. Coronary blood flow was also measured and, depending on the experimental procedure, controlled. Blood volume expansion was carried out by infusion of isosmotic dextran into a femoral vein at 40 ml/kg at a rate of 50 ml/min. CSAR was elicited by application of bradykinin (5 and 50 microg) and capsaicin (10 and 100 microg) to the epicardial surface of the left ventricle. Volume expansion increased arterial pressure, left ventricular pressure, left ventricular diameter, and coronary blood flow. Volume expansion without controlled coronary blood flow only enhanced the RSNA response to the high dose (50 microg) of epicardial bradykinin (17. 3 +/- 1.9 vs. 10.6 +/- 4.8%, P < 0.05). However, volume expansion significantly enhanced the RSNA responses to all doses of bradykinin and capsaicin when coronary blood flow was held at the prevolume expansion level. The RSNA responses to bradykinin (16. 9 +/- 4.1 vs. 5.0 +/- 1.3% for 5 microg, P < 0.05, and 28.9 +/- 3.7 vs. 10.6 +/- 4.8% for 50 microg, P < 0.05) and capsaicin (29.8 +/- 6.0 vs. 9.3 +/- 3.1% for 10 microg, P < 0.05, and 34.2 +/- 2.7 vs. 15.1 +/- 2.7% for 100 microg, P < 0.05) were significantly augmented. These results indicate that acute volume expansion potentiated the CSAR. These data suggest that enhancement of the CSAR in congestive heart failure may be mediated by the concomitant cardiac dilation, which accompanies this disease state.     

Antiarrhythmic properties of acetaminophen in the dog

Mongrel dogs bred for research and weighing 25 +/- 3 kg were used to test the hypothesis that acetaminophen has antiar-rhythmic properties. Only ventricular arrhythmias defined by the Lambeth Conventions were investigated. Dogs were exposed either to 60 mins of regional myocardial ischemia followed by 180 mins of reperfusion (n = 14) or were administered a high dose of ouabain (n = 14). Both groups of 14 dogs were further divided into vehicle and acetaminophen treatment groups (n = 7 in each). During selected 10-min intervals, we recorded the numbers of ventricular premature beats, ventricular salvos, ventricular bigeminy, ventricular tachycardia (nonsustained and sustained), and we recorded the heart rate, systemic arterial blood pressure, and left ventricular function. Neither heart rate nor the number of ventricular arrhythmias differed significantly under baseline conditions. Conversely, the combined average number of ventricular ectopic beats during ischemia and reperfusion was significantly less in the presence of acetaminophen (28 +/- 4 vs. 6 +/- 1; P < 0.05). Similarly, percent ectopy during reperfusion in vehicle- and acetaminophen-treated dogs was 1.4 +/- 0.4 and 0.4 +/- 0.2, respectively (P < 0.05). The number of all ventricular ectopic beats except ventricular salvos was also significantly reduced in the presence of acetaminophen. Similar results were obtained with ouabain. Our results reveal that systemic administration of a therapeutic dose of acetaminophen has previously unreported antiarrhythmic effects in the dog.     

Ethanol-induced cardiac hypertrophy: effects of peripheral sympathectomy

The development of cardiac hypertrophy was examined in rats that had undergone sympathectomy with 6-hydroxydopamine. After 4 days, the rats were given severely intoxicating doses of ethanol or isocalorically paired quantities of maltose-dextrin by intubation at 8-h intervals up to 48 h. The ethanol and sugar intubations were applied in a nutritionally adequate, liquid diet mix. The extent of the peripheral sympathectomy was evident from the absence of detectable quantities of noradrenaline in hearts of animals injected with the neurotoxin and in the reduced levels of excreted noradrenaline. The adrenal medullary catecholamine contents of sympathectomized rats were unchanged in the absence of ethanol; there were reduced quantities of adrenaline in the medullae of rats given ethanol. The adrenal glands of rats given ethanol were larger than those from control animals. Urine samples from sympathectomized and control rats, given ethanol, displayed equivalent increases in excreted adrenaline and noradrenaline. Increases in relative cardiac weight were evident in hearts from sympathectomized animals after 4 days of sympathectomy, and this change reached significance in the hearts from 6-hydroxydopamine-treated rats after a further 2 days on the control diet. Hearts from animals exposed to ethanol showed a marked, rapid development of cardiomegaly; after 24 h there was an increased mass of some 17%, which was sustained over the remaining 24-h period. The proportion of cardiac protein did not differ in the large hearts from ethanol-treated animals and those from their controls, hence myocardial oedema could not account for the increase in weight.(ABSTRACT TRUNCATED AT 250 WORDS)     

Brain enzyme activity in irradiated sympathectomized rats

The results are reviewed from studies of activity of hexokinase (2.7.1.1.EC), dehydrogenase glucose-6-phosphate (1.1.1.49 EC), and cholinesterase (3.1.1.7 EC) in subcellular fractions of rat brain at the background of chemical sympathectomy induced by long-term administration of guanethidine and subsequent irradiation with a dose of 7 Gy. In conditions of sympathectomy, the enzyme activity is inhibited; in irradiated sympathectomized rats, activity of hexokinase and cholinesterase increases to reach the level of that of intact animals while dehydrogenase remains inhibited.     

Effects of inspiratory loading on left ventricular myocardial blood flow and metabolism.

With airways obstruction, mean pleural pressure decreases. It has been postulated that associated increases in left ventricular afterload increase myocardial O2 demand (MvO2) and coronary blood flow (CBF). We tested this hypothesis in 12 anesthetized mixed-breed dogs. Through a median sternotomy, dogs were instrumented for the measurement of mean arterial pressure, cardiac output, and left anterior descending CBF. A catheter placed in the coronary sinus allowed sampling of left ventricular venous blood. MvO2 was calculated as CBF x (arteriovenous content difference), and coronary resistance was calculated as (mean arterial pressure)/CBF. After closure of the thoracotomy, animals were studied before and during inspiratory threshold loading (IL) of -20 to -25 cmH2O while breathing 100% O2 before and after bilateral cervical vagotomy. During IL, heart rate fell [approximately 20 beats/min (NS prevagotomy, P less than 0.05 postvagotomy)], arterial PCO2 increased [45 to 66 Torr prevagotomy, 45 to 50 Torr postvagotomy (P less than 0.01)], and arterial O2 content was unchanged. CBF increased with IL:41% prevagotomy (P less than 0.01), 18% postvagotomy (P less than 0.02). However, with IL, MvO2 did not increase significantly either pre- or postvagotomy. Coronary resistance decreased with IL [30% prevagotomy, 24% postvagotomy (P less than 0.01)]. In eight dogs, PCO2 was increased by increasing dead space while the animals were mechanically ventilated and paralyzed. Although there was little change in CBF, heart rate fell by an amount equal to that with IL. We conclude that 1) IL causes coronary vasodilation not related to changes in MvO2, PCO2, or vagal tone; 2) MvO2 does not increase with IL; and 3) decreased heart rate with IL is related to hypercapnia and/or acidosis.     

Chemical sympathectomy and diurnal fluctuations of noradrenaline calorigenic action in the rat

In the rat, in which a diurnal fluctuation of the sensitivity to noradrenaline was previously found, the effect of injected 6-hydroxydopamine (6-OHDA) was investigated. The heat production and catecholamines contents in the interscapular brown adipose tissue, heart and adrenals were measured. Chemical sympathectomy induces a disappearance of diurnal fluctuation in the sensitivity to injected noradrenaline. In these animals a lower capacity for heat production was found. However, a significant calorigenic effect of injected noradrenaline in 6-OHDA-treated animals was still present. In sympathectomized animals a depletion of noradrenaline from interscapular brown adipose tissue and the heart was observed. Besides, a change in adrenaline/noradrenaline ratio was found in the adrenals.     

Neonatal chemical sympathectomy attenuates fructose-induced hypertriglyceridemia and hypertension in rats

Experiments were performed to determine the pathogenic contribution of the peripheral sympathetic nervous system to fructose-induced hypertriglyceridemia, hyperinsulinemia and hypertension in rats. Neonatal chemical sympathectomy was performed in neonatal Sprague-Dawley rats (1-week old) by administration of guanethidine (50 microg/g, i.p.) 5 times per week for consecutive 3 weeks and nerve-intact rats were served as controls. Both groups of rats were fed a fructose-enriched diet for 9 weeks. The systolic blood pressure (SBP) and body weight were measured weekly and arterial blood samples were taken weekly for determinations of plasma insulin, glucose and triglyceride levels. The results showed that fructose feeding for one week significantly increased SBP in intact rats and sympathectomized rats (116+/-1 to 119+/-1 mmHg and 116+/-1 to 120+/-1 mmHg, respectively). SBP further increased thereafter in both groups. However, the increased SBP levels were significantly higher in intact group than in sympathectomized group after 5 weeks of fructose feeding. Fructose feeding for one week concurrently produced hypertriglyceridemia that preceded the appearance of hyperinsulinemia in both groups. The elevated plasma triglyceride levels were significantly lower in sympathectomized rats than in intact rats after 3 weeks of fructose feeding, whereas the elevated plasma insulin concentrations were not different between groups throughout fructose feeding period. Plasma glucose concentrations of both groups were comparable and remained unchanged throughout the study. These data indicate that neonatal chemical sympathectomy attenuated, but did not prevent, fructose-induced elevations in blood pressure and plasma triglyceride levels, suggesting a partial dependency of fructose-induced hypertriglyceridemia and hypertension on the integrity of the peripheral sympathetic nervous system (SNS) in rats.     

Viscerosomatic interaction induced by myocardial ischemia in conscious dogs.

Studies tested the hypothesis that myocardial ischemia induces increased paraspinal muscular tone localized to the T(2)-T(5) region that can be detected by palpatory means. This is consistent with theories of manual medicine suggesting that disturbances in visceral organ physiology can cause increases in skeletal muscle tone in specific muscle groups. Clinical studies in manual and traditional medicine suggest this phenomenon occurs during episodes of myocardial ischemia and may have diagnostic potential. However, there is little direct evidence of a cardiac-somatic mechanism to explain these findings. Chronically instrumented dogs [12 neurally intact and 3 following selective left ventricular (LV) sympathectomy] were examined before, during, and after myocardial ischemia. Circumflex blood flow (CBF), left ventricular contractile function, electromyographic (EMG) analysis, and blinded manual palpatory assessments (MPA) of tissue over the transverse spinal processes at segments T(2)-T(5) and T(11)-T(12) (control) were performed. Myocardial ischemia was associated with a decrease in myocardial contractile function and an increase in heart rate. MPA revealed increases in muscle tension and texture/firmness during ischemia in the T(2)-T(5) segments on the left, but not on the right or in control segments. EMG demonstrated increased amplitude for the T(4)-T(5) segments. After LV sympathectomy, MPA and EMG evidence of increased muscle tone were absent. In conclusion, myocardial ischemia is associated with significant increased paraspinal muscle tone localized to the left side T(4)-T(5) myotomes in neurally intact dogs. LV sympathectomy eliminates the somatic response, suggesting that sympathetic neural traffic between the heart and somatic musculature may function as the mechanism for the interaction.     

Effect of neonatal sympathectomy on the postnatal differentiation of the submandibular gland of the rat

Summary Right superior cervical sympathectomy was performed in one-day old rats. This operation had a small but definite effect on the postnatal development of the submandibular gland. The gland on the sympathectomized side weighed less and contained smaller amounts of DNA, RNA and protein than the contralateral intact gland. The postnatal development of acinar cells and granular convoluted ductal cells was retarded in the sympathectomized gland. The acinar cells which differentiated after the ganglionectomy were smaller than those in the contralateral intact gland and were filled with secretory granules but devoid of basal basophilia. The rate of cellular proliferation in the sympathectomized gland was, however, similar to that in the intact gland at various ages studied.Supported by Public Health Service Research Grant CA 17038 from the National Cancer Institute to Dr. T. Barka. The authors are indebted to Miss H. van der Noen and Mr. I. Borcsanyi for their assistance and to Dr. T. Barka for his suggestions regarding this paper     

Delayed development of hypertension and increased aortic relaxation in spontaneously hypertensive rats after neonatal sympathectomy

The effect of neonatal sympathectomy on vasodilator responses to acetylcholine (ACh) and cAMP has been studied in aortic rings of spontaneously hypertensive rats (SHR) and normotensive animals. The relaxation of intact SHR aorta in response to ACh and cAMP was 20-35% lower than that of normotensive rats. Sympathectomy in normotensive rats did not affect the level of blood pressure and aorta reactivity to Ach. In SHR, sympathectomy caused a decrease in blood pressure, while relaxation in response to ACh and cAMP increased, as compared to intact SHR, but remained lower than in normotensive rats. The data obtained suggest that the decrease in arterial pressure of sympathectomized SHR is a result not only of the reduction in sympathetic effects but also of the increase in smooth muscle relaxation.