Left Vagotomy Research Articles

Right vagotomy alters heart rate variability temporarily and increases total choline levels in rats

Abstract Objectives The variability in the time intervals between heartbeats, known as heart rate variability (HRV), serves as a reflection of the intricate interplay between the sympathetic and parasympathetic neural systems. While the potential asymmetric effects of the left and right branches of the vagus nerve remain uncertain, this study aims to investigate the impact of unilateral, bilateral, and atropine interventions on HRV parameters and choline levels within cardiac tissue. Methods 40 male adult Wistar albino rats were randomly assigned to the five groups (each n=8): sham-operated, atropine, right vagotomy, left vagotomy, and bilateral vagotomy. Heart rate variability (HRV) analyses were conducted, and the levels of total choline/acetylcholine in heart tissues were quantified. Statistical analyses were performed to assess the results. Results The bilateral vagotomy and atropine groups exhibited higher heart rates and high frequency power (HF), along with reduced low frequency power (LF). Total power (TP) remained relatively unchanged. In the bilateral vagotomy group, DFAα1 was significantly elevated while DFAα2 was reduced significantly. SD1 and SampEn were significantly lower in both the bilateral vagotomy and atropine groups. Notably, the right vagotomy group displayed significant changes primarily in the 15th minute, particularly in time-domain parameters, HF, TP, and SD1, with a significant increase observed in total choline levels. Conclusions Our results revealed that asymmetrical vagal innervation induces distinct effects on heart rate variability parameters and total choline/acetylcholine levels in heart tissues. Our findings suggest that compensatory hemodynamic recovery, possibly driven by contralateral vagal overactivity, may contribute to these observed results.

Suprachiasmatic nucleus and vagus nerve trigger preovulatory LH and ovulation.

In the proestrus day, the neural and endocrine signals modulate ovarian function. This study shows vagus nerve plays a role in the multisynaptic pathways of communication between the suprachiasmatic nucleus and the ovaries where such neural information determines ovulation. The suprachiasmatic nucleus (SCN) regulates the activity of several peripheral organs through a parasympathetic-sympathetic pathway. Previously, we demonstrated that atropine (ATR) microinjection in the right SCN of rats during proestrus blocks ovulation. In the present study, we analysed whether the vagus nerve is one of the neural pathways by which the SCN regulates ovulation. For this, CIIZ-V strain cyclic rats on the day of proestrus were microinjected with a saline solution (vehicle) or ATR in the right or left SCN, which was followed by ventral laparotomy or ipsilateral vagotomy to the microinjection side. Some animal groups were sacrificed (i) on the same day of the surgery to measure oestradiol, progesterone and luteinizing hormone (LH) levels or (ii) at 24 h after surgery to evaluate ovulation. The left vagotomy in rats microinjected with ATR in the left SCN did not modify ovulation. In rats with ATR microinjection in the right SCN, the right vagotomy increased the levels of steroids and LH on the proestrus and ovulatory response. The present results suggest that the right vagus nerve plays a role in the multisynaptic pathways of communication between the SCN and the ovaries and indicate that such neural information participates in the regulation of the oestradiol and progesterone surge, which triggers the preovulatory peak of LH and determines ovulation.

Vagotomy decreases splenocytes and MHCII+/CD11B+ cells in the spleen

Abstract The Vagus Nerve is a major component, in conjunction with the spleen, in modulating the systemic anti-inflammatory response. Adrenergic fibers of the splenic nerve innervate the spleen, where they stimulate a distinct population of memory T cells. These memory T cells subsequently release ACh, thereby reducing macrophage activation and inhibiting TNFα. Therefore this pathway, as it relates to the spleen, is a two-neuron circuit: initiating first in the dorsal motor nucleus of the Vagus, subsequently synapsing at the celiac ganglion, and finally synapsing on the memory T cells. There are additional lines of evidence demonstrating cholinergic modulation of immune cells in the spleen. For example emerging evidence supports a regulating role of the vagus nerve in mobilizing marginal zone B cells and their subsequent secretion of antibodies, heralding an innate immune response. However, a direct link between splenic B cell number and the vagus nerve has not been previously established. Therefore, we assessed the effects of a left unilateral vagotomy on total splenocytes and MHCII+/CD11+ B cells in the spleen 3 days after vagotomy. Results The results indicate that at 3 days after left unilateral vagotomy, there is a significant decrease in the overall number of splenocytes. The results also show that this vagotomy results in a trend toward a significant reduction in MHCII+/CD11+ B cells in the spleen. Conclusions Our conclusions based upon these results show that there is a direct influence of left vagus nerve innervation on the number of splenic B cells and that left vagotomy results in an overall decrease in either the proliferation of splenocytes in general including the B-cells, or in cell death of splenocytes including the B cells.

Implication of the vagus nerve in breathing pattern during sequential swallowing in rats

The ventilatory pattern during sequential swallowing is influenced by the vagal activity. As the vagus nerve is paired and mixed, we aimed (1) to determine if vagal implication in swallowing and breathing coordination is symmetric. (2) to study the importance of vagal afferences in swallowing and breathing coordination. Sixty two Wistar rats (7–11weeks, 260–400g) were studied by barometric plethysmography. In the first part of the study, we determined the effects of a right cervical vagotomy and the effects of a left cervical vagotomy on ventilatory pattern at rest and during sequential swallowing (14 rats with right vagotomy, 14 rats with left vagotomy and 14 rats with sham surgery). Comparisons of ventilatory variables were made between right and left vagotomized animals. Thereafter, we determined the effects of electrical vagus nerve stimulation (VNS) on ventilatory pattern at rest and during sequential swallowing (10 rats with electrical VNS and 10 rats with sham VNS). We showed that a right or a left cervical vagotomy does not alter ventilation at rest, but induces during sequential swallowing a decrease in respiratory rate (RR) (p<0.001) and mean inspiratory flow (VT/TI) (p<0.01) compared to baseline. These modifications were not observed following sham surgery and there were no differences in ventilatory variables at rest and during sequential swallowing between right vagotomized rats and left vagotomized rats (p>0.05). Electrical VNS had no effect on ventilation at rest, but it minimized during sequential swallowing a decrease in RR related to a local alteration of the vagus nerve after placement of the electrodes as shown following sham VNS. In conclusion, the implication of vagus nerve in breathing pattern during sequential swallowing seems symmetric and influenced by activation of the vagal afferent pathway. These data can be useful when testing electrical VNS in swallowing disorders.

Vagal tone regulates cardiac shunts during activity and at low temperatures in the South American rattlesnake, Crotalus durissus.

The undivided ventricle of non-crocodilian reptiles allows for intracardiac admixture of oxygen-poor and oxygen-rich blood returning via the atria from the systemic circuit and the lungs. The distribution of blood flow between the systemic and pulmonary circuits may vary, based on differences between systemic and pulmonary vascular conductances. The South American rattlesnake, Crotalus durissus, has a single pulmonary artery, innervated by the left vagus. Activity in this nerve controls pulmonary conductance so that left vagotomy abolishes this control. Experimental left vagotomy to abolish cardiac shunting had no effect on long-term survival and failed to identify a functional role in determining metabolic rate, growth or resistance to food deprivation. Accordingly, the present investigation sought to evaluate the extent to which cardiac shunt patterns are actively controlled during changes in body temperature and activity levels. We compared hemodynamic parameters between intact and left-vagotomized rattlesnakes held at different temperatures and subjected to enforced physical activity. Increased temperature and enforced activity raised heart rate, cardiac output, pulmonary and systemic blood flow in both groups, but net cardiac shunt was reversed in the vagotomized group at lower temperatures. We conclude that vagal control of pulmonary conductance is an active mechanism regulating cardiac shunts in C. durissus.

Systemic Blood Flow Relations in Conscious South American Rattlesnakes

Estimating total systemic blood flow based on measurements from a single aortic arch is common practice in cardiovascular stud- ies on reptiles to avoid heavy instrumentation and consequent stress responses. This practice requires the validation of a specific correction factor that expresses the relationship between the measured blood flow and the blood flow to be estimated. Misleading estimations may occur when correction factors are used in different conditions from those they were originally measured. Despite recognized as a problem, such misleading estimations are common in physiology. In the present study, we derived values for correction factors to estimate systemic blood flow in the South American rattlesnake, Crotalus durissus, following recovery from anesthesia, using serial measurements of blood flow in the three main systemic arteries, left or distal right aortic arches and the carotid artery. Blood flow recorded in the left aortic arch provided the most reliable and less variable correction factors. Different from previously published, blood flow distribution in the systemic circulation varied with temperature. We suggest the use of the specific correction factors present in this paper for different experimental protocols and temperatures. Furthermore, we can affirm that unilateral left vagotomy, which effectively ablated control of right-left shunts, does not affect systemic blood flow distribution, so the same correction factors can be used.

Loss of the ability to control right-to-left shunt does not influence the metabolic responses to temperature change or long-term fasting in the South American Rattlesnake Crotalus durissus.

Abstract In the undivided ventricle of noncrocodilian reptiles, the blood perfusing the systemic circulation is a controlled combination of oxygenated pulmonary blood, flowing from left to right across the heart, and relatively deoxygenated systemic blood, flowing from right to left. A clear inverse correlation has been experimentally established between metabolic demand and the magnitude of right-to-left cardiac shunt in several reptile groups. Unilateral left vagotomy renders the single effective pulmonary artery of the South American rattlesnake (Crotalus durissus) unable to adjust the magnitude of blood flow to the lung. This provides a unique model for investigation of the long-term consequences of abolition of the cardiac shunt in a squamate reptile. Rattlesnakes-vagotomized on the left or right side or sham operated-were exposed to long-term food deprivation or temperature change. Loss of control of the cardiac shunt following selective vagotomy did not change the progressive decrease in body mass or the onset of identifiable fasting stages. Resting metabolic rate and the increase in oxygen uptake measured during spontaneous or forced activity were also unchanged. The responses to reductions in temperature (from 30° to 20° or 15°C) in adult snakes or juvenile snakes were similarly unaffected by vagal transection. These data support rejection of the hypothesis that adjustment of the cardiac shunt is central to the control metabolic rate in squamate reptiles.

Pten deletion in RIP-Cre neurons protects against type 2 diabetes by activating the anti-inflammatory reflex.

Inflammation has a critical role in the development of insulin resistance. Recent evidence points to a contribution by the central nervous system in the modulation of peripheral inflammation through the anti-inflammatory reflex. However, the importance of this phenomenon remains elusive in type 2 diabetes pathogenesis. Here we show that rat insulin-2 promoter (Rip)-mediated deletion of Pten, a gene encoding a negative regulator of PI3K signaling, led to activation of the cholinergic anti-inflammatory pathway that is mediated by M2 activated macrophages in peripheral tissues. As such, Rip-cre(+) Pten(flox/flox) mice showed lower systemic inflammation and greater insulin sensitivity under basal conditions compared to littermate controls, which were abolished when the mice were treated with an acetylcholine receptor antagonist or when macrophages were depleted. After feeding with a high-fat diet, the Pten-deleted mice remained markedly insulin sensitive, which correlated with massive subcutaneous fat expansion. They also exhibited more adipogenesis with M2 macrophage infiltration, both of which were abolished after disruption of the anti-inflammatory efferent pathway by left vagotomy. In summary, we show that Pten expression in Rip(+) neurons has a critical role in diabetes pathogenesis through mediating the anti-inflammatory reflex.

Changes in intestinal endocrine cells in the mouse after unilateral cervical vagotomy.

The effect of right or left unilateral cervical vagotomy on the intestinal endocrine cells was studied in 23 mice at 2 and 8 weeks after operation, respectively. The results were compared with that from 10 sham operated mice. Various types of endocrine cells in duodenum and proximal colon were detected by immunohistochemistry and quantified by computerized image analysis. In mouse duodenum, chromogranin-, CCK/gastrin-, GIP- and somatostatin-cells were significantly decreased at 2 weeks after right vagotomy, but returned to the control levels at 8 weeks. Serotonin-cells were reduced at both 2 and 8 weeks after right vagotomy. The amount of the duodenal endocrine cells did not change after left vagotomy with the exception of secretin-cells, which were diminished at 8 weeks after both right and left vagotomy. In the proximal colon, chromogranin-cells were also decreased at 2 weeks after right vagotomy. Serotonin-cells were reduced at 8 weeks after left vagotomy but not right vagotomy. There was no significant difference between the unilaterally vagotomized and the sham operated mice with regard to PYY- and glucagon-cells. It was concluded that vagotomy affected the intestinal endocrine cells in mouse. The influence was more pronounced in the small intestine than the proximal colon. The right vagus nerves seemed to exert more effect on the intestinal endocrine cells than the left ones.

Effects of unilateral cervical vagotomy on antral endocrine cells in mouse.

The present study was carried out to investigate the effect of unilateral cervical vagotomy on the antral endocrine cells in mouse. Fifty-four mice were randomly divided into three groups, 18 in each, for left or right cervical vagotomy, or sham operation as controls. The animals were sacrificed 2, 4, and 8 weeks after the operation, respectively. Chromogranin-, gastrin/CCK-, serotonin-, and somatostatin-cells were detected by immunohistochemistry and quantitated by computerised image analysis. The results showed that the number of chromogranin-cells was decreased in both left and right vagotomized mice after 4 weeks and remained at the same level after 8 weeks. The numbers of gastrin-, serotonin- and somatostatin-cells did not change after right vagotomy. However, the numbers of gastrin- and somatostatin-cells were decreased after left vagotomy, whereas no change was found in serotonin-cells. Endocrine cells with vacuolated cytoplasm and pyknotic nuclei were also observed during the course of time. The alteration in the antral endocrine cells observed in this study seemed to be dynamic and depended on the observation time after the operation as well as the denervated branches of the vagus nerve. This may explain, at least partially the contradictory results obtained earlier by different investigators.

Ablation of the ability to control the right-to-left cardiac shunt does not affect oxygen consumption, specific dynamic action or growth in rattlesnakes,Crotalus durissus

The morphologically undivided ventricle of the heart in non-crocodilian reptiles permits the mixing of oxygen-rich blood returning from the lungs and oxygen-poor blood from the systemic circulation. A possible functional significance for this intra-cardiac shunt has been debated for almost a century. Unilateral left vagotomy rendered the single effective pulmonary artery of the South American rattlesnake, Crotalus durissus, unable to adjust the magnitude of blood flow to the lung. The higher constant perfusion of the lung circulation and the incapability of adjusting the right-left shunt in left-denervated snakes persisted over time, providing a unique model for investigation of the long-term consequences of cardiac shunting in a squamate. Oxygen uptake recorded at rest and during spontaneous and forced activity was not affected by removing control of the cardiac shunt. Furthermore, metabolic rate and energetic balance during the post-prandial metabolic increment, plus the food conversion efficiency and growth rate, were all similarly unaffected. These results show that control of cardiac shunting is not associated with a clear functional advantage in adjusting metabolic rate, effectiveness of digestion or growth rates.

The effects of DBcAMP on the expression of eNOS, iNOS and TGF-beta in rat heart tissue

Dibutryl (DB) adenosine 3′,5′-cyclic monophosphate (cAMP) is an important modulator of physiological functions. To determine the protective effects of DBcAMP on heart tissue, we evaluated changes in immunoreactivity of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and transforming growth factor-beta (TGF-β) in left cervical vagotomized rats treated with DBcAMP. Male rats were divided into four groups. In Group 1, animals were subjected to a left cervical vagotomy. Group 2 received a 1 ml bolus injection of 15 ml/kg DBcAMP in addition to the left vagotomy. DBcAMP alone was given to Group 3 and Group 4 was the control group. For each animal, mean arterial pressure (MAP) and heart rate (HR) were measured. For indirect immunohistochemistry, anti-eNOS, anti-iNOS, and anti-TGF-β primary antibodies were used. In Group 1, MAP and HR values decreased slightly. In Groups 2 and 3, DBcAMP induced a statistically significant drop in HR and MAP. In Group 1, strong eNOS, iNOS, and TGF-β immunoreactivities were observed. Immunostaining intensities decreased in Groups 2 and 3. The results of the study reported here suggest that increased immunoreactivities of eNOS, iNOS, and TGF-β might contribute to the effects on the heart tissue after left vagotomy and imply that DBcAMP acts on heart tissue via nitric oxide.

The unequal influences of the left and right vagi on the control of the heart and pulmonary artery in the rattlesnake,Crotalus durissus

Autonomic control of the cardiovascular system in reptiles includes sympathetic components but heart rate (f(H)), pulmonary blood flow (Q(pul)) and cardiac shunt patterns are primarily controlled by the parasympathetic nervous system. The vagus innervates both the heart and a sphincter on the pulmonary artery. The present study reveals that whereas both the left and right vagi influence f(H), it is only the left vagus that influences pulmonary vascular resistance. This is associated with the fact that rattlesnakes, in common with some other species of snakes, have a single functional lung, as the other lung regresses during development. Stimulation of the left cervical vagus in anaesthetised snakes slowed the heart and markedly reduced blood flow in the pulmonary artery whereas stimulation of the right cervical vagus slowed the heart and caused a small increase in stroke volume (V(S)) in both the systemic and pulmonary circulations. Central stimulation of either vagus caused small (5-10%) reductions in systemic blood pressure but did not affect blood flows or f(H). A bilateral differentiation between the vagi was confirmed by progressive vagotomy in recovered snakes. Transection of the left vagus caused a slight increase in f(H) (10%) but a 70% increase in Q(pul), largely due to an increase in pulmonary stroke volume (V(S,pul)). Subsequent complete vagotomy caused a 60% increase in f(H) accompanied by a slight rise in Q(pul), with no further change in V(S,pul). By contrast, transection of the right vagus elicited a slight tachycardia but no change in V(S,pul). Subsequent complete vagotomy was accompanied by marked increases in f(H), Q(pul) and V(S,pul). These data show that although the heart receives bilateral vagal innervation, the sphincter on the pulmonary artery is innervated solely by the left vagus. This paves the way for an investigation of the role of the cardiac shunt in regulating metabolic rate, as chronic left vagotomy will cause a pronounced left-right shunt in recovered animals, whilst leaving intact control of the heart, via the right vagus.

Vagotomy enhances experimental metastases of 4THMpc breast cancer cells and alters Substance P level

We have previously demonstrated that inactivation of capsaicin-sensitive sensory neurons enhances lung and heart metastases of breast carcinoma. Because a significant part of sensory innervation of lung tissue is supplied by the vagus nerve, we here examined the effects of unilateral mid-cervical vagotomy in the metastases of 4THMpc breast carcinoma and tissue Substance P (SP) levels. Balb-c mice were injected orthotopically with 4THMpc cells 1 week after vagotomy. Animals were sacrificed 27–30 days after injection of 4THMpc cells and the extent of metastases was determined. Unilateral vagotomy, right or left significantly increased the lung, liver and kidney metastases without altering the growth rate of the primary tumor. Heart metastases were increased only following left vagotomy. The changes in SP levels were somewhat surprising such that vagotomy actually increased while sham-operation decreased SP levels in lung. The effect of sham-operation was reversed by unilateral vagotomy demonstrating that vagal activity decreases total SP levels in the lung. Increased SP levels might be due to decreased degradation of the peptide. Presence of the tumor markedly increased SP level in the lung, which was more prominent in vagotomized animals. These results provide evidence that vagal activity may protect against metastatic disease.

Compensatory recovery of vagal control of hemodynamics after unilateral vagotomy

This study investigated whether each part of the heart is evenly innervated by the left or right vagus and observed the mechanism of compensatory recovery after unilateral cervical vagotomy. HR, BP, LVSP and +/-dp/dt max all decreased one week after left vagotomy, whereas only BP and -dp/dt max decreased one week after right vagotomy. Western blot analyses revealed that the expression of M(2) receptors in the left atrium and left ventricle was upregulated after subacute (1 week) left/right vagotomy. However, significantly more cholinesterase-positive nerves in LV and RV were seen one week after unilateral vagotomy compared to the sham-operated group. In addition, baroreflex sensitivity was increased after subacute right vagotomy. The decreasing effects of ACh (0.5 microg/kg) on LVSP and +/-dp/dt max (but not on HR and BP) were facilitated by subacute unilateral vagotomy. Our present experiments indicate that 1) the working myocardium is innervated bilaterally by the vagus, 2) ventricular contractility is influenced more by denervation of the left than the right vagus and 3) up-regulation of M(2) muscarinic receptors in the left heart, increase of cholinergic nerves, and high baroreflex sensitivity could be involved in the mechanism of compensatory hemodynamic recovery via contralateral vagus overactivity, thereby amplifying contralateral vagal activity and decreasing cardiac contractility.

Ipsilateral vagotomy to unilaterally ovariectomized pre-pubertal rats modifies compensatory ovarian responses

The present study evaluates the participation of the vagus nerve in pre-pubertal rats with unilateral ovariectomy on puberty onset, and on progesterone, testosterone and estradiol serum levels, and the compensatory responses of the ovary. Unilateral vagotomy did not modify the onset of puberty in unilaterally ovariectomized rats. Ovulation rates of animals with the left vagus nerve sectioned and the left ovary in-situ was lower than in rats with only unilateral ovariectomy. Sectioning the left vagus to 32-day old rats with the left ovary in-situ resulted in lower compensatory ovarian hypertrophy than in rats with right unilateral ovariectomy. Twenty-eight or 32-day old animals with sectioning of the right vagus nerve and the right ovary in situ showed higher compensatory ovulation. Twenty-eight -day old rats with the right ovary in situ had higher progesterone and testosterone levels than animals of the same age with the left ovary in-situ. Compared to animals with the right ovary in situ, animals treated at 32-days of age, sectioning the ipsi-lateral vagus nerve resulted in higher progesterone levels. Higher progesterone levels were observed in 28- and 32 days old rats with the left ovary in situ and left vagus nerve sectioned. Thirty-two day old animals with the right ovary in situ and right vagus nerve sectioned had higher progesterone levels than rats of the same age with the left ovary in situ and left vagus nerve sectioned. Left vagotomy to 28-day old rats with the left ovary in situ resulted in higher testosterone levels, a reverse response to that observed in animals with sectioning of the right vagus and the right ovary in situ. Thirty-two day old rats with the left ovary in situ and left vagus nerve sectioned showed lower testosterone levels than animals without vagotomy and with the left ovary in situ.Twenty-eight -day old animals with the left vagus sectioned and left ovary in situ had lower estradiol serum levels than rats without unilateral vagotomy, a response similar to that observed in 32-day old rats with the right ovary in situ and right vagus nerve sectioned.Present results suggest an asymmetric regulation of steroid hormones secretion by the vagus nerve innervations in animals with unilateral ovariectomy, and those differences in testosterone serum levels observed are associated to the ovary remaining in-situ, vagal innervation and age when the animals were treated.

DOMINANT LEFT VAGAL CONTROL OF THE HEART INDUCES HEART RATE IRREGULARITIES

In a pilot study on the effect of decreased baroreflex sensitivity in well-trained long distance speedskaters we showed that directly after the contest period the sensitivity was significantly decreased. One month later, the sensitivity increased to almost normal values. In the first week after the contest period, 4 of the 9 speedskaters showed (pre)syncope behavior in a tilt table experiment. This was seen several minutes after tilting, in ongoing decrease of bloodpressure even until 50 mmHg, while heart rate was paradoxically further decreased. After 2 weeks, this behavior disappeared. We attributed this decreased sensitivity and syncope incidents to the increased vagal activity in rest as found in these athletes. It is well known that the right vagal nerve mainly influences the rhythmogenesis of the SA-node, while the left branch predominantly influences the conductivity of the AV-node. These effects will be amplified in the case of well-trained physical condition. In a study on the changes in baroreflex sensitivity, we compared the effect of acute increase in arterial bloodpressure in rats by phenylephrine infusion in cases of unilateral vagotomy. We showed that in cases of right vagotomy, with only the left vagal branch intact, the PQ interval increases 5 to 10 times more than in cases of left vagotomy. Also, in the right vagotomy cases, much more AV-blocking was found. These results suggest that in cases of predominantly left vagal nerve activity on heart rate control, increased vagal activity induces heart rate irregularities, while under normal conditions no irregularities were observed. The acute increase in pressure only increases vagal activity acutely, so after ten to twenty seconds the heart rate is normal again. Therefore we studied the effect of right vagotomy in endurance trained rats. For this study we used 20 rats with both vagal nerves intact: 10 sedentary for control and 10 were trained at 80% of maximal VO2 during 6 months, (BV-rats), and 20 rats in which the right vagal nerve was cut: 10 sedentary and 10 trained (RV-rats). Weekly ECG's were recorded about 5 hours after training. In the BV-rats, heart rate decreased significantly compared to control after 2 weeks, stabilizing at about 20% lower after 5 weeks. In the RV-rats, it took 5 weeks before they had a significantly lower heart rate, and after 7 weeks they stabilized at about 10% lower heart rate. All rats except one, had PQ intervals between 40 and 55 ms during the experiment. In several RV-rats, irregularities in AV conduction were seen. In one RV-rat, the PQ interval was increased directly after vagotomy from 45 to 65 ms. In the fourth week this rat died suddenly during a recording session. The AV conduction changed from first degree block to complete block. Ventricular rate was decreased progressively from 300 beats/min to about 150. After 1 minutes the rat was reanimated. In the period hereafter no other "sudden death" was observed, although it is well possible that in the absence of the investigator also this sudden death pattern occurs, which than was interrupted by life saving activity of the sympathatic nerves system. This study showed that in case of predominantly control of the heart by the left vagal branch, under increased vagal activity due to training or acute increase in arterial pressure, sudden death can occur under normal physiological conditions, due to the decreased sensitivity of the baroreflex.

Inhibition of fibrin-induced neurogenic pulmonary edema by previous unilateral left-vagotomy correlates with increased levels of brain nitric oxide synthase in the nucleus tractus solitarii of rats

In the course of investigations on mechanisms underlying development of neurogenic pulmonary edema (NPE), we have evaluated effects of nitric oxide (NO) in the central nervous system on incidence and severity in the fibrin-induced pulmonary edema model. Rats were left-unilaterally vagotomized 1, 2 and 4 weeks before injections of fibrinogen and thrombin into the cisterna magna, after cutting the right vagus nerve, grouped as LV1W, LV2W or LV4W, respectively. The brain NO synthase (NOS) mRNA level in the left medulla oblongata was elevated in the LV2W group, compared to the control, but decreased in the LV4W rats. Incidences of pulmonary edema were 100% in the control group, decreasing to 78% in LV1W group, 17% in LV2W group, and back to 72% in LV4W group. The lung water ratio, a parameter of severity, demonstrated a similar pattern of change as the incidence. The lowered incidence and severity obtained in the LV2W group were reversed by intracisternal injection of N ω-nitro- l-arginine methyl ester ( l-NAME). From these results, we propose that an increase in nitric oxide, possibly in the nucleus tractus solitarius 2 weeks after left vagotomy, may have an inhibitory action on the development of neurogenic pulmonary edema in rats.

Thoracoscopic left truncal vagotomy in the treatment of peptic post-anastomotic ulcer(U.P.P.O.) disease

Thoracoscopic left truncal vagotomy in the treatment of peptic post-anastomotic ulcer(U.P.P.O.) disease

Vagal modulation of epicardial coronary artery size in dogs. A two-dimensional intravascular ultrasound study.

Because the role of tonic vagus nerve activity in regulating conduit coronary artery size remains undefined, we investigated the response of epicardial coronary artery size to changes in resting vagal tone resulting from vagotomy and muscarinic receptor blockade. Using intravascular ultrasound to measure left circumflex coronary artery cross-sectional area continuously, we examined the effects of vagotomy on left circumflex cross-sectional area in nine dogs. Lumen area decreased 20% from 8.70 +/- 2.81 to 6.92 +/- 1.97 mm2 after right vagotomy, 17% to 7.19 +/- 2.80 mm2 after left vagotomy (both P < .05 versus baseline), and 38% to 5.42 +/- 2.00 mm2 after bilateral vagotomy (P < .05 versus unilateral vagotomy). Vasoconstriction occurred despite increases in heart rate and an unchanged rate-pressure product. In six additional dogs, after acetylcholine (100 micrograms/kg i.v.), lumen area increased by 18%, although heart rate, blood pressure, and rate-pressure product were unchanged. Vasodilation was prevented by prior muscarinic blockade with glycopyrrolate. With glycopyrrolate administration and heart rate control by pacing, lumen area decreased by 26% (P = .011). When stellate stimulation was performed in a third group of eight dogs with heart rate, blood pressure, and rate-pressure product controlled by a combination of pacing and exsanguination, there was no change in coronary area, thus precluding reflex sympathetic activation as a contributor to the vasoconstriction produced by vagal withdrawal. Vagus nerve activity maintains tonic dilation of the left circumflex coronary artery by muscarinic receptor activation. Each vagus nerve contributes approximately equally to the tonically dilated state. Vagotomy-induced vasoconstriction occurs independently of local metabolic factors and coronary distending pressure and is a result of cholinergic withdrawal rather than reflex sympathetic activation.