Reflex increase in renal nerve activity during acutely altered portal venous pressure

This study was designed to determine the reflex effects of renal nerve activity during acutely altered portal venous pressure in anesthetized dogs. Following inflation of a balloon in the main portal vein of animals with the neuraxis intact, mean blood pressure (MBP) fell significantly from 127 +/- 8 mm Hg to 101 +/- 7 mm Hg, while renal nerve activity (RNA) increased to 189 +/- 11%. This significant increase in RNA during inflation of the balloon was not entirely eliminated by either carotid sinus nerve (CSN) denervation (163 +/- 9% of the control level) or vagotomy (161 +/- 11% of the control level). The reflex increase in RNA observed with the combined denervation of the carotid sinus and vagal nerves (CSN + Va denervation) was 138 +/- 2% of the control level, and this level of RNA increase was significantly smaller compared to those in the other 3 groups (intact, CSN or Va denervated). Even when the portal venous pressure below caudal to the balloon was controlled at a pre-distension level by means of opening an artificial bypass constructed between the mesenteric vein and the femoral vein in the CSN + Va denervated group, the increased RNA response during inflation of the balloon remained. After hepatic denervation in the CSN + Va denervated group with the opening of the bypass, however, inflation of a balloon caused no significant changes in RNA, even when more profound hypotension existed during inflation of the balloon.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of mesenteric lymph reperfusion on neurotransmitter expression in brain tissue of a superior mesenteric artery occlusion shock rat model

BACKGROUND: Previous studies have shown that mesenteric lymph reperfusion (MLR) exacerbates brain injury in a rat model of superior mesenteric artery occlusion (SMAO) shock. However, little is known about the influence of MLR on neurotransmitter expression in brain tissue. OBJECTIVE: To observe the effect of MLR on brain tissue injury by measuring monoamine and cholinergic neurotransmitter levels.DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Institute of Microcirculation, Hebei North University, China; Research Room of Microcirculation and Laboratory of Biochemistry, Department of Pathophysiology, Basic Medical College, Hebei North University between December 2007 and March 2009.MATERIALS: Choline acetyltransferase (ChAT) and acetylcholine esterase (AChE) kits were provided by Nanjing Jiancheng Bioengineering Institute, China; dopamine (DA) and noradrenalin (NE) standards were provided by the National Institute for the Control of Pharmaceutical and Biological Products; HP1100 chromatograph of liquid was provided by Agilent, USA. METHODS: A total of 24 male, Wistar rats were randomly assigned to 4 groups: sham-surgery, MLR, SMAO, and MLR + SMAO groups, with 6 rats in each group. In the MLR or SMAO groups, the mesenteric lymph duct or superior mesenteric artery was blocked for 1 hour. In the MLR + SMAO group, the mesenteric lymph duct and superior mesenteric artery were occluded for 1 hour, followed by 2-hour reperfusion. ChAT and AChE levels were measured using the synthesized and hydrolyzed acetylcholine method, respectively. Liquid chromatography was employed to quantitatively analyze DA and NE levels, using relative retention time and the external standard method. MAIN OUTCOME MEASURES: ChAT, AChE, DA, and NE levels. RESULTS: AChE levels were significantly increased, but ChAT levels were significantly decreased in the MLR and MLR + SMAO groups following 2-hour reperfusion (P < 0.01). However, AChE activity in the MLR + SMAO group was greater than in the MLR group (P < 0.05). DA and NE levels were significantly decreased in the SMAO and MLR + SMAO groups (P < 0.01), while DA levels in the MLR + SMAO group were less than in the SMAO group (P < 0.05). CONCLUSION: MLR exacerbated brain injury in a rat model of SMAO shock, which correlated with the intestinal lymphatic pathway. MLR decreased DA levels, but increased AChE activity, in a rat model of SMAO shock.     

Fundamental rhythm of renal sympathetic nerve activity in anesthetized cats.

To examine the fundamental rhythms of sympathetic discharges, the periodicity of synchronized renal nerve activity (RNA) was measured in anesthetized cats. After filtering the RNA between 50-3000 Hz, rectification and integration the periodicity was calculated by measuring the peak to peak intervals. Two major periodicities were detected, a Tc rhythm between 6 and 25 c/s with a 43% probability and a Tb rhythm between 2 and 6 c/s with a 57% probability. The mean periods of Tc and Tb were 95 +/- 2 ms and 297 +/- 4 ms (+/- SE) respectively. Another techniques which has previously been used to assess the periodicity was also applied, in which the original neurogram was filtered between 0.08-3000 Hz and measured by power spectral analysis. However, this technique only identified the 2-6 c/s frequency and the faster Tc rhythm was undetected. Baroreceptor stimulation induced by noradrenaline decreased the probability of Tc and Tb modal components. Baroreceptor denervation led to an increase in the probability of the Tc rhythm and reduction in the Tb rhythm. These results support our model that the Tc rhythm reflects a fundamental periodicity of central origin and that the Tb rhythm reflects a periodicity of cardiac-related RNA, which is produced by reflex inhibition of the fundamental rhythm by periodic baroreceptor input.     

Reflex activity and muscle tone during elbow movements in patients with spastic paresis.

Reflex behavior and tension development in upper limb muscles were analyzed and comparisons made between the unaffected and spastic sides of patients with spastic hemiparesis. During sinusoidal (0.3-Hz) isometric or isotonic elbow tracking, with a control either of joint position or of torque, randomly timed displacements were induced (at one of three velocities) stretching either the activated flexor or the extensor muscles. On the spastic side, exaggerated short-latency reflexes were apparent, but in contrast, the amplitude of long-latency electromyography (EMG) responses was reduced. The latter responses were differentially modulated on the unaffected side, predominantly by the acceleration signal during control of position and more by the velocity signal during control of torque, while the mode of muscle contraction (isometric or isotonic) had little influence on this behavior. This difference in reflex modulation was lost on the spastic side. The functional consequence of this reduced EMG modulation could be difficulty in performing finely controlled arm movements. The ratio of torque to EMG activity during displacements was higher for both background and reflex-induced EMG on the spastic limb than on the unaffected side. This effect was more pronounced for the flexor than for the extensor muscles. Consequently, the development of spastic muscle hypertonia cannot be attributed to an increase in EMG activity. It is suggested that secondary to a supraspinal lesion, mechanical muscle properties change in such a way that the activated spastic muscle develops more tension when it is stretched.     

Long-range correlation of renal sympathetic nerve activity in both conscious and anesthetized rats

In this study we employed both detrended fluctuation analysis (DFA) and multiscale entropy (MSE) measurements to compare the long-range temporal correlation (LRTC) of multifibre renal sympathetic nerve activity (RSNA) between conscious and anesthetized Wistar rats. It was found that both methods showed the obvious LRTC properties in conscious state. Moreover, the scaling exponent of the RSNA in conscious rats was significantly higher than that in anesthetized rats. The results of MSE analysis showed that the entropy values, derived from the conscious group, increased on small time scales and then stabilized to a relatively constant value whereas the entropy measure, derived from anesthetized animals, almost monotonically decreased. This suggests that the fractal properties of underlying dynamics of the system have been reduced by anesthesia. The results demonstrate that apparently random fluctuations in multifibre RSNA are dictated by a complex deterministic process that imparts "long-term" memory to the dynamic system. However, this memory is significantly weakened by anesthesia.     

Histopathological effects of delayed reperfusion after middle cerebral artery occlusion in the anesthetized baboon

In patients with middle cerebral artery (MCA) territory stroke, attempts to recanalize the brain are currently being extended beyond the classic 3-h time window. Mechanical thrombectomy is particularly attractive as it may carry lesser risks of severe hemorrhagic transformation than thrombolysis. However, whether late reperfusion per se promotes hemorrhagic transformation and increases infarct volume as compared to permanent occlusion is unclear. There is no study of the histopathologic sequelae of late reperfusion following MCA occlusion (MCAo) in the non-human primate. Five young adult baboons completed a specially designed protocol of 20-h MCAo (under etomidate anaesthesia), followed by 4-week survival and finally perfusion-fixation. Infarct volume was measured histologically using validated stereological methods. The results were compared to our previously published series of 6 h and permanent MCAo performed with identical experimental and post mortem procedures. An infarct was present in each baboon, consistently involving the caudate head, internal capsule and putamen; the adjacent inferior frontal cortex was involved in one subject. Infarct volume was significantly larger than with 6 h MCAo, as expected, but did not differ from permanent MCAo. There was no evidence of hemorrhage around the infarcted area in any animal. We found that following a 20 h ischemic episode, the infarct volume was similar to that found with permanent occlusion, with no evidence of hemorrhagic transformation. Cautiously extrapolating to the human situation, our findings suggest that even late mechanical recanalization may not promote brain damage and could be considered in selected cases.     

Mesenteric lymph reperfusion may exacerbate brain injury in a rat model of superior mesenteric artery occlusion shock

BACKGROUND:The intestinal lymphatic pathway and intestinal ischemia/reperfusion are mainly involved in mesenteric lymph duct ligation or drainage; moreover,intervention by reducing the lymph liquid reflux might relieve lung and other organ dysfunction induced by intestinal ischemia/reperfusion; however,research addressing mesenteric lymph reperfusion (MLR) and brain injury has not yet to be reported.OBJECTIVE:To observe the effect of MLR on brain tissue in a rat model of superior mesenteric artery occlusion (SMAO) shock,and to explore the molecular mechanism of MLR.DESIGN,TIME AND SETTING:A randomized,controlled,animal experiment at a neuro-pathophysiology level was performed at the Institute of Microcirculation,Hebei North University; Department of Pathophysiology,Basic Medical College; Department of Pathology,the First Hospital of Hebei North University between December 2007 and March 2009.MATERIALS:Adenosine triphosphate (ATP) standard was provided by the National Institute for the Control of Pharmaceutical and Biological Products; lactic acid (LA),superoxide dismutase (SOD),malonaldehyde (MDA),nitrogen monoxidum (NO),nitric oxide synthase (NOS),myeloperoxidase (MPO) and ATPase assay kits were provided by Nanjing Jiancheng Bioengineering Institute,China.METHODS:A total of 24 male Wistar rats were randomly divided into four groups.In the sham-surgery group (n = 6),both the mesenteric lymph duct and the superior mesenteric artery were not blocked; in the MLR group (n = 6),the mesenteric lymph duct was occluded for 1 hour followed by 2-hour reperfusion; in the SMAO group (n = 6),the superior mesenteric artery was occluded for 1 hour followed by 2-hour reperfusion; in the MLR + SMAO group (n = 6),both the mesenteric lymph duct and superior mesenteric artery were occluded for 1 hour followed by 2-hour reperfusion.MAIN OUTCOME MEASURES:Mean arterial blood pressure prior to and following ischemia/reperfusion; brain tissue morphology levels of LA,MDA,SOD,NO,NOS,MPO,ATPase and ATP following reperfusion.RESULTS:MLR did not cause changes in mean arterial blood pressure,brain tissue morphology,LA,MDA,NO,ATP,SOD,NOS,MPO and ATPase.However,SMAO caused a rapid decrease and gradual increase of mean arterial blood pressure.Neuronal necrosis,degeneration and swelling were observed in brain tissue.Contents of MDA,NO,LA and ATP as well as activities of NOS and MPO were significantly increased (P< 0.05),but activities of SOD and Na+-K+-ATPase were significantly decreased (P < 0.05).MLR aggravated neuronal damage in a rat model of SMAO shock.Following MLR,mean arterial blood pressure was significantly decreased (P < 0.05),contents of MDA and NO as well as activities of NOS and MPO were significantly increased (P <0.05),but activities of Ca2+-ATPase,Mg2+-ATPase and Ca2+-Mg2+-ATPase as well as ATP content were significantly decreased (P< 0.05).CONCLUSION:MLR aggravates brain injury in a rat model of SMAO shock,which correlates with oxygen-derived free radical injury,NO synthesis and release,sequestration of neutrophilic granulocytes,decreasing activity of cell membrane pumps and energy metabolism dysfunction.Pathogenesis of the intestinal lymphatic pathway should be thoroughly investigated to prevent ischemia/reperfusion injury.     

Noninvasive quantification of superior mesenteric artery blood flow during sympathoneural activation in normal subjects

The role of the splanchnic circulation in normal subjects during sympathoneural activation induced by stimuli which either raise (mental arithmetic, cold pressor test, isometric exercise) or maintain (head-up tilt) blood pressure has been studied by measuring superior mesenteric artery blood flow using a noninvasive Doppler ultrasound method in 18 normal subjects. Cardiac, systemic and regional haemodynamic changes were simultaneously studied. Blood pressure rose with the pressor tests and was maintained with head-up tilt. There was a significant fall in superior mesenteric artery blood flow with a rise in vascular resistance during each stimulus incidating active constriction. In six subjects, after 2 months measurements were repeated in an identical study. Superior mesenteric artery blood flow measurements in this study were closely correlated with the initial results. These changes, in a large vascular bed, are likely to be of importance in the overall haemodynamic response during sympathoneural stimuli which either raise or maintain blood pressure.     

Effect of chemoreceptor stimulation on the periodicity of renal sympathetic nerve activity in anesthetized cats.

The effect of chemoreceptor stimulation, with asphyxia (1 min), hypoxia (2 min) or hypercapnia (2 min), on the periodicity of synchronized renal sympathetic nerve activity (RNA) was examined in anesthetized cats before and after peripheral chemoreceptor and baroreceptor denervation. RNA was filtered between 50-3000 Hz, rectified and integrated. Time intervals, less than 500 ms, between synchronized interburst intervals were measured and used to produce periodicity histograms. Under control normoxia two major periodicities were evident, a Tc rhythm between 6 and 17 c/s comprising 34 +/- 5% (+/- SE) of measured intervals and a Tb rhythm between 2 and 6 c/s with a 66% probability. The mean periods of Tc and Tb were 110 +/- 6 ms and 299 +/- 7 ms respectively. The periodicity distribution and mean Tc and Tb rhythms for RNA discharge under various chemoreceptor stimulations were not significantly changed despite significant increases in arterial blood pressure in all cases. The amplitude and overall number of synchronized RNA peaks were however increased with chemoreceptor stimulation. When asphyxia was applied under a constant arterial pressure the periodicity of synchronized RNA still was not significantly altered. Baroreceptor and peripheral chemoreceptor denervation led to an increase in the probability of the Tc mode and reduction in the Tb mode, once again the application of chemoreceptor stimulation did not significantly alter the frequency distribution of synchronized RNA. The results indicate that chemoreceptor stimulation does not affect the 10 c/s fundamental rhythm and the stability of gate operators altering Tc/Tb proportions, although it can alter the number of active fibres and interacts with the baroreflexes to maintain RNA at elevated blood pressures. The results support our model that the Tc mode reflects a fundamental periodicity of central origin and the Tb mode a periodicity of cardiac related RNA, which is produced by the opening and closing of gate operators to the fundamental rhythm.     

Reflex control of renal nerve activity originating from the osmoreceptors in the hepato-portal region.

The reflex effects of hepatic osmoreceptors on the renal sympathetic nerve activity (RNA) were studied in 30 pentobarbital anesthetized, vagotomized and sino-aortic baroreceptor denervated (SAD + VD) rabbits. The changes in mean arterial pressure (MAP), heart rate (HR), and RNA were examined when 9% NaCl, 6.5% LiCl or 50% glucose solution was infused into the hepatic portal vein at a rate of 0.15 ml/kg/min for 10 min. Infusion of 9% NaCl solution into the hepatic portal vein increased the plasma osmolality by 10.8 +/- 1.0 mOsmol/kg from the control level in the blood of the hepatic portal vein and by 2.8 +/- 2.0 mOsmol/kg from the control level in the systemic blood. MAP was significantly elevated by 10.2 +/- 5.0 mmHg but HR did not change with hepatic portal infusion of 9% NaCl solution. Intraportal infusion of 9% NaCl solution significantly decreased the RNA by 28.6-34.2% from the control level, 6.5% LiCl solution by 28.6 +/- 4.7%, and 50% glucose solution by 26.2 +/- 3.0%. Femoral arterial infusion of hypertonic NaCl solution, however, did not evoke any significant change in RNA in SAD + VD rabbits. These findings suggest that increases in osmolality and NaCl concentration in the systemic circulation do not result in a decrease of RNA. Furthermore, after section of the anterior and posterior plexus of the hepatic nerve, hepatic portal infusion of hypertonic NaCl solution elicited no change in RNA. The present data indicate that an increase in osmolality in the hepatic portal venous blood results in a reflex decrease of RNA. This reflex may be important for restoration of a postprandial increase in osmolality.     

Effect of superior laryngeal nerve transection on pharyngeal muscle contraction timing and sequence of activity during eating and stimulation of the nucleus solitarius in dogs

The effect of unilateral or bilateral transection of the superior laryngeal nerve on the electromyographic activity in the hyopharyngeal, thyropharyngeal, and cricopharyngeal muscles was studied in 10 dogs during eating and during unilateral electrical stimulation of the solitary nucleus. In all groups of dogs, after unilateral or bilateral transection, there were some swallowing actions in which the sequence of activity in the pharyngeal muscles was disturbed during eating and during stimulation of the solitary nucleus. In the dogs in which the transection was unilateral, this fraction was 18% in the ipsilateral muscles during eating and 7% in the contralateral muscles. After bilateral transection it was 8% in the left muscles and 16% in the right muscles. The fractions were not significantly different when swallowing was evoked by stimulation of the solitary nucleus. Swallowing actions having a normal sequence of activity in these dogs were compared with those in a group of eight dogs in which the superior laryngeal nerves were intact. Contraction timing was not significantly different during eating, but during stimulation of the solitary nucleus the timing was significantly shorter than in the dogs with intact nerves. It was concluded that superior laryngeal nerve transection modulates the central pattern generator for pharyngeal swallowing in dogs.     

The effects of neuronal uptake blockade on the cardiac responses to sympathetic nerve stimulation and norepinephrine infusion in anesthetized dogs

In anesthetized dogs, cocaine (COC) was administered intravenously in order to block the neuronal uptake of norepinephrine (NE) by the heart. COC had relatively little effect on the magnitudes of the inotropic and chronotropic responses to sympathetic stimulation, but it did prolong the decay times, especially those of the chronotropic responses. The marked prolongation of the decay times of the chronotropic responses indicates that neuronal uptake must be the main mechanism for dissipating the adrenergic transmitter in the sinus node. However, this mechanism appears to be less important in the ventricular myocardium. At all dosage levels, COC increased the overflow of NE into the coronary sinus blood during cardiac sympathetic stimulation. The extraction of exogenously infused norepinephrine by heart tissue varied inversely with the dose of COC, indicating that the extent of neuronal uptake blockade increased with the dose. Nevertheless, NE overflow into the coronary sinus blood after a relatively large dose (5.7 mg/kg) of COC was less than that observed after a much smaller dose (0.5 mg/kg), suggesting that relatively large doses of COC also tend to inhibit the neuronal release of NE. These results indicate that the effects of COC on the cardiac responses to sympathetic stimulation depend on the balance between its influences on the release and dissipation of neurotransmitter in the neuroeffector gap.     

Intracellular activity of superior laryngeal nerve motoneurons during fictive swallowing in decerebrate rats

We examined the swallowing-related intracellular activity of motoneurons of the superior laryngeal nerve (SLN) in decerebrate, paralyzed and artificially-ventilated rats, to elucidate the neuronal mechanism of the pharyngo-esophageal and laryngo-esophageal coordination during swallowing. The majority of the SLN motoneurons exhibited respiratory rhythm (n=16; 13 inspiratory, one expiratory and two non-respiratory neurons). During fictive swallowing evoked by electrical stimulation of the SLN, all these motoneurons showed a hyperpolarization-depolarization sequence in their membrane potentials. The hyperpolarization, which was shown to consist of inhibitory postsynaptic potentials, started at the onset of the hypoglossal swallowing burst, lasted during the burst, and was followed by a depolarization at the end of the burst. This hyperpolarization-depolarization pattern implies that the SLN motoneurons may be involved in the 'inhibitory chain' within the swallowing pattern generator, which may be cardinal in the sequential activation of different populations of motoneurons innervating the swallowing-related muscles.     

Inhibition of renal sympathetic nerve activity by electrical stimulation of the hypothalamic paraventricular nucleus in anesthetized rats

In an attempt to obtain direct evidence for involvement of sympathetic outflow in paraventricular nucleus (PVN)-induced depressor response, effects of electrical stimulation of the PVN on renal sympathetic nerve activity were examined in urethane-chloralose anesthetized rats. Low intensity stimulation of the PVN inhibited renal sympathetic nerve activity, whereas the high intensity stimulation evoked an excitation followed by long-lasting inhibition in renal sympathetic nerve activity. Latencies of the inhibitory and the excitatory responses were about 200 ms and 50-100 ms, respectively. The result suggests that a decrease in blood pressure induced by low intensity stimulation of the PVN is due to inhibiting the sympathetic outflow.     

Long-term effects of preganglionic nerve stimulation on tyrosine hydroxylase activity in the rat superior cervical ganglion

The effects of increased synaptic stimulation of sympathetic neurons on the tyrosine hydroxylase activity of these cells were studied. Seventy-two hours after unilateral stimulation of the preganglionic cervical sympathetic trunk at 10 Hz for 30 min tyrosine hydroxylase activity was 32% higher in stimulated than in control superior cervical ganglia. Stimulation at 10 Hz for only 10 min increased enzyme activity by 25% when measured 72 h later, while stimulation for 60 min increased activity by 73%. No further change in enzyme activity was found after 90 min of stimulation although electrophysiological recordings from the ganglion demonstrated that synaptic transmission was maintained throughout the period of stimulation.Ganglionic neurons also follow high frequency trains of stimuli when they are interrupted by silent periods. Stimulation with 40 Hz trains (250 msec on/500 msec off) for 30 min and 90 min produced a 50% and a 92% increase in tyrosine hydroxylase activity, respectively. Stimulation of ganglia with the same number of pulses administered stered either continuously or in trains produced the same size increase in enzyme activity.The relationship between preganglionic nerve activity and tyrosine hydroxylase activity may represent an adaption of sympathetic neurons to situations requiring increased transmitter release.     

Age-related effects on superior temporal gyrus activity during an auditory oddball task

We used magnetoencephalography in combination with magnetic resonance imaging to investigate the effects of aging on the temporal dynamics of activity localized to several brain regions during an auditory oddball task. The most interesting effects were noted in the superior temporal gyrus as follows: (1) responses were generally stronger to rare than to frequent tones throughout the entire 600-ms time interval, and (2) increases in the amplitude of the 40-ms peak and the latency of the maximum late response were evident in the elderly. Although superior temporal gyrus activity has traditionally been associated with early sensory processing, these results suggest that superior temporal gyrus activity is also important for later decision-related processing.     

Effects of vascular constriction on occlusive thrombus formation of rat mesenteric artery

Effects of vascular constriction on thrombotic occlusion was evaluated using rat mesenteric arteries and video-recording system attached to the microscope. Topical application of norepinephrine of 1, 10 and 100 micrograms/ml reduced the arterial diameter dose dependently from 297 +/- 41 mu to 166 +/- 50, 87 +/- 18 and 84 +/- 11 mu (mean +/- SD, n = 7), respectively. The diameter reduction by the higher 2 doses persisted for more than 30 minutes until the wash out of the agent. But, no thrombus formation was observed. A reproducible thrombus formation was induced by inserting a glass micropipette into the vascular lumen. The maximal percent occlusion by the thrombus was 80 +/- 11% (range; 67 to 95%, n = 7). The topical application of 10 micrograms/ml norepinephrine induced vasoconstriction and increased the percent occlusion significantly to 97 +/- 8% (p less than 0.05). Complete occlusion of the lumen developed in 6 of 7 rats after the agent and in 2 rats it was not released until the wash out of the agent for more than 30 minutes. Thrombus formation itself did not change the arterial diameter at the site of thrombus formation as well as at sites of 300 and 600 mu down stream. It is suggested that the vascular constriction alone does not necessarily cause thrombus formation but may aggravate the arterial flow reduction induced by thrombosis.