Electrogastrogrom Monitoring And Mechanism Of The Serve Cerebral Hemorrhage With Stress Ulcer

BackgroundStress ulcer (SU) is a common complication of severe cerebral hemorrhage (up to 91%) and the death rate can reach to 80%. Cerebral hemorrhage(CH)as a stress source results in acute erosive or ulcerative injury of gastroduodenal mucosal through complex action which many factors participated, so stress ulcer occurred afetr CH. Those mild cases have no apparent clinical manifestations whereas upper gastrointestinal bleeding even with life-threatening bleeding might happen within severe cases.Early diagnosis and proper treatment to intracerebral hemorrhage with stress ulcer cut down mortality and disability of CH. Through the large sample evidence-based controlled study, prophylactic medication cann't reduce the incidence of stress ulcer, but increase the economic and physical burden on patients. This requires clinicians to detect the presence of stress ulcer, and take appropriate action in time, as well as monitor changes in stress ulcer and drug efficacy of treatment.Diagnosis and monitoring of cerebral hemorrhage stress ulcer are very sluggish. To diagnose stress ulcer complicated with hemorrhage is based on clinical symptoms including hematemesis, black stools, persistent blood pressure being decreased while continuous infusion or blood and positive results of gastric occult blood test. So that the cases with negative clinical manifestations can not receive timely treatment and the treatment time is delayed. The SU cases with negative clinical manifestations can be diagnosed by gastroscope which improve the diagnosis rate and accuracy of SU. However, the anesthetic tolerance is poor in acute phase of severe intracerebral hemorrhage following disturbance of consciousness or other changes in vital signs, furthermore gastroscopy operation can induce nausea and vomiting which increase the possibility of re-bleeding. Endoscopy in the acute phase of cerebral hemorrhage limited and even painless gastroscopy. Stress ulcer be complicated by cerebral hemorrhage in r mostly occurs in 72h-14d Acute stage. To find a non-invasive, accurate, and constantly monitoring way is essential for estimating the development of stress ulcer after intracerebral hemorrhage.Gastric electrical activities response electrical activities of gastric smooth muscle cells. Through the analysis of EGG after cerebral hemorrhage stress ulcer might be diagnosed and useful information might be provided. EGG records the activities of gastric smooth muscle signals accurately being used for clinical diagnosis of gastric motility disorders. Some studies showed that the frequency was faster and the amplitude was higher in ulcer patients. It also showed that change of gastric electrical rhythm after intracerebral hemorrhage. But gastric electrical change has not been reported about the stress ulcer after intracerebral hemorrhage. The pathogenesis of stress ulcer is not clear. Studies showed that neuroendocrine disorders, defense function of gastric mucosal being decreased, injury factors of gastric mucosal being strengthened and imbalance of autonomic function and so on. This study was to observe gastric electrical activity changes in stress ulcer complicated by cerebral hemorrhage of clinical patients and to understand pathology between stress ulcer complicated by cerebral hemorrhage and gastric electrical changes by animal experiments. To explore clinical application of EGG monitoring happen and development of stress ulcer complicated by cerebral hemorrhage .Purpose1. Observing the gastric electrical changes of cerebral hemorrhage in patients with stress ulcer, the presence or absence of stress ulcer was determined by analyzing the parameters of EGG.2. Monitoring intracranial pressure of intracerebral hemorrhage patients with stress ulcer to explore the role of intracranial pressure in stress ulcer.3. Observing the incidence of stress ulcer at different intracerebral hemorrhage model, to establish intracerebral hemorrhage animal model with stress ulcer.4. Through observing EGG, intracranial pressure, efferent discharge of vagus nerve, expression of acetylcholine receptor (M1, M2 and M3) and COX-2 in stomach mucosa, pH of gastric fluid, gastric acid secretion volume and tension of pylorus changes of intracerebral hemorrhage, to explore relationship between changes of EGG and stress ulcer and pathogenesis of stress ulcer after cerebral hemorrhage.MethodsPart I: clinical trials1. The parameters of EGG were analyzed in the normal group , primary ulcer group, SU after CH group and CH group through monitoring the gastric electrical activity 15 days. The accuracy to judge the occuring of SU after CH was analyzed by discriminant analysis.2. The relationship between the genesis of stress ulcer and the level of ICP was analyzed by monitoring intracranial pressure in patients with severe cerebral hemorrhage through lateral ventricle catheter .Part II: animal experiments1. 150μl, 100μl, 150μl of autologous blood and 0.3U, 0.6U, 0.9U, 1.2UⅦcollagenase were injected into the right side basal ganglia of SD rat brain respectively. HE staining of brain and stomach, brain water content and ulcer index were undergone at 72h after CH.2. The healthy SD rats meeting with the requirements were randomly divided into normal control group (15), acetic acid ulcer control group (20) and brain basal ganglia hemorrhage model group, being setted up time for the 12h, 1d, 2d, 3d, 5d, 7d , 14d, 30 rats at each time point. The vagus nerves of 60 rats were transected at 12h and 24h after the brain basal ganglia hemorrhage. EGG, vagus nerve efferent discharge, intracranial pressure and pyloric pressure were recorded, acetylcholine receptor (M1, M2, M3) and COX-2 in gastric mucosa were measured by immunohistochemical method at each time in each group. Gastric acid secretion in 4h and gastric pH were measured at same time.ResultsPart I: Dynamic changes of EGG of Severe cerebral hemorrhage patients with stress ulcer and relationship between intracranial pressure and stress ulcer (clinical trials)1. EGG of intracerebral hemorrhage patients with stress ulcerEGG showed smooth sine wave transferred from the irregular curve of the original wave form through the filter in normal control group. In ulcer control group, Vpp, AF, DF, RA increased (P<0.01), DPR and the NSW decreased (P<0.01). In intracerebral hemorrhage with no complication of stress ulcer group, the wave type varied greatly, Vpp, ARI, CVf, ICF and RA increased (P< 0.01), AF remained unchanged (P> 0.05), NSW decreased (P<0.01) being compared with the normal control group. Differences in waveform morphology were more in cerebral hemorrhage complicated stress ulcer group. Compared the EGG between intracerebral hemorrhage with stress ulcer group and CH without stress ulcer group, Vpp, ARI, DF, CVv, CVf, ICF, AF and RA increased (P<0.05, P<0.01), DPR and NSW decreased (P<0.05). while compared with ulcer control group, Vpp, AF, ARI, CVv, DF, CVf, ICF and RA increased (P<0.05, P<0.01), NSW decreased (P<0.05).2. Discriminant analysis of EGG parametersThe significant parameters of EGG were achieved through discriminant analysis to diagnose SU, including Vpp, RA, ICF, NSW, AF, ARI and the DPR. Fisher discriminant function was setted up which EGG was applied to discriminate normal healthy people, patients with ulcer, patients with CH, patients with CH complicated with SU. The discriminant accuracy rate was 87.9%.3. The relationship between Intracranial pressure and EGG of patients with intracerebral hemorrhageIntracranial pressure(5.69±0.53kPa) was higher in intracerebral hemorrhage with stress ulcer than that of those without stress ulcer (4.22±1.14kPa, P<0.01). Along with increased intracranial pressure, Vpp, DF, ARI, CVf, CVv, ICF, and RA increased, NSW and C decreased (P<0.05, P<0.01).Part II: Rearch to cerebral hemorrhage with stress ulcer in rats and related mechanism (animal experiments) Experiment one Construction of cerebral hemorrhage stress ulcer models in rats1. Hematoma volume changes in different basal ganglia hemorrhage modelsHematoma volume of 50μl autologous blood group was similar to 0.3U collagenase group by HE stainning measurement of brain slices (P>0.05), so as to 100μl autologous blood group and 0.6U collagenase group(P>0.05). With the dose of autologous blood and collagenase increased, the hematoma volume of right basal ganglia was enlarged.2. Incidence of SU after different doses of autologous blood and the collagenase intracerebral hemorrhage modelMost of the rats in 1.2U collagenase group died at 72h after different dose autologous blood and collagnase injected into the cerebral basal ganglia. Hematoma volume and brain water content increased with the dose increase of blood and collagnanse being injected, so as to the incidence of SU and ulcer index. The incidence of SU was greater in collagenase group than in autologous blood group at the equal hematoma volume.Experiment two EGG changes of cerebral hemorrhage stress ulcer and mechanism of the relationship between EGG and stress ulcer1. Gastric wall of rats with SUThe gastric ulcer mostly occured in arcus minor ventriculi at the junction of proventriculus and stomach in which the vagus nerve distributed. Gastric mucosa showed a single or sporadic bleeding or ulcers of different sizes, depth up to muscle, or even perforation. HE staining showed crater-like ulcer, involving the mucosa to the submucosa, partial to muscularis and serosa. It could be seen that accumulation of inflammatory cells, vascular occlusion and bleeding in the ulcer margin. Typical ulceration was more ofen occurred at 2d and 3d.2. EGG recording, evaluation of ulcer index and relationship between themSlow wave of EGG showed sine wave, in which some had notch and bimodal in normal group. Compared to the sham-operated group, Amp increased at 12h, 1d, 2d, 3d, 5d in acetic acid ulcer control group (P<0.01). Amp became larger at 12h, 1d, 2d in intracerebral hemorrhage without stress ulcer group (P<0.05, P<0.01). Amp was higher than all other groups in intracerebral hemorrhage with SU(P<0.05, P<0.01). Compared with the sham-operated group, F increased at 12h, 1d, 2d, 3d in acetic acid ulcer control group (P<0.05, P<0.01), at 12h, 1d, 2d, 3d, 5d, 7d in intracerebral hemorrhage without stress ulcer group(P<0.01). F was faster than all other groups in intracerebral hemorrhage with SU (P<0.05, P<0.01). ARI and CV had no difference between the acetic acid ulcers control group and sham-operated group at each time point. Except for intracerebral hemorrhage without SU group at 14d, ARI and CV were higher than sham-operated group in all intracerebral hemorrhage group at each time points (P<0.01); in which ARI and CV were higher in intracerebral hemorrhage with SU than that of CH with non-ulcer group (P<0.05, P<0.01).At experimental different time points, under a dissecting microscope counted UI of occurred ulcers in rats, UI is small at 24h and 48h, to 72h the peak reached, then reduced. All EGG parameters associated with UI by the correlation analysis (P<0.01).3. Intracranial pressure recording and correlation with other parameters in experimental ratsIntracranial pressure elevated significantly at 12h, then to the peak at 2d and returned to nomal at 7d after intracerebral hemorrhage in rats. Intracranial pressure of intracerebral hemorrhage modules was higher significantly than sham-operated group at 12h, 1d, 2d, 3d and 5d (P<0.01). At same time, intracranial pressure was higher in CH with SU group than those without ulcers groups (P<0.01). The level of intracranial pressure correlated positively with ulcer index (P<0.01, R=0.732). F, Amp, ARI and CV of EGG parameters correlated with intracranial pressure (P<0.01).4. Intracranial hypertension effects to cell apoptosis and tissue injury of hypothalamus and brainstem in experimental ratsNecrosis and hemorrhage could be seen in the hypothalamus and brainstem of CH rats through HE staining. Tunnel positive staining apoptotic cells were located in the hypothalamus and midline structures of brainstem.5. Vagus nerve efferent discharge records and correlation with other parameters in experimental ratsVF and VA of vagus nerve efferent discharge was higher in basal ganglia hemorrhage rats than sham-operated group at 12h, 1d, 2d, 3d (P<0.05, P<0.01). Within CH groups, VF and VA were higher in CH with SU group than those without ulcer group(P<0.05, P<0.01). PCV in the CH group was higher than that of sham-operated group at each time point. Within CH groups, PCV was higher in CH with SU group than those without ulcer group(P<0.05, P<0.01). There was positive relationship between intracranial pressure and efferent discharge of vagus nerve after CH (P<0.01). VF, VA and PCV of vagus nerve efferent discharge were related to F, Amp, ARI and CV of EGG (P<0.01). VF, VA, and PCV of vagus nerve efferent discharge related to the ulcer index (P<0.01). F, Amp, CV decreased after vagus nerve being transected in CH rats compared with before(P<0.01).6. Changes of the expression of M1 receptors in gastric muscoa, volume of gastric acid secretion and pH value of gastric wall and their correlation with other parametersIOD value of the expression of M1 receptors was higher at 12h, 1d, 2d and 3d in CH groups compared with the sham-operated group (P<0.01). Within which IOD value of the CH with SU was higher than those without SU (P<0.01). 4h volume of gastric acid secretion was greater at 12h in CH groups than that of sham-operated group (P<0.01), while there has no difference at the other times(P<0.05). Within CH groups which SU occurred, the volume of gastric acid secretion was higher at 12h, 1d, 2d,3d than that of those with no SU (P<0.01). pH value of gastric wall descended at each time after basal ganglia hemorrhage in rats (P<0.05, P<0.01)except for 14d(P>0.05). It was lower in CH with SU groups compared with the CH with no SU group(P<0.05, P<0.01). The vagus nerve efferent discharge had positive relationship with the expression of M1 receptor in gastric muscoa and acid secretion, negative correlated with the pH value. The expressions of M1 receptor and ulcer index were positively related. pH value and the ulcer index was negatively correlated. The expression of M1 receptor was decreased and gastric acid secretion reduced and pH value increased after the vagotomy at 12h in CH rats(P<0.05).7. Expressions of M2, M3 receptor in gastric muscoa and their correlation with other parameters in experimental ratsExpressions of M2, M3 receptor in gastric muscoa was up-regulation at 12h after CH (P<0.01), up to peak level at 24h, being stated until 5d and decreased at 7d (P<0.05). It was expressed intensivly in CH with SU rats than that of the CH rats which SU not occurred (P<0.01, P<0.05). M2 and M3 receptors in the stomach wall in rats the expression of basal ganglia hemorrhage and vagus nerve efferent discharge has a good correlation (P<0.01). The expression of M2, M3 receptor had relationship with EGG and the efferent discharge of vagus nerve.8. Expression of COX-2 in gastric muscoa and changes of pyloric tension in experimental ratsThe IOD of COX-2 expression was significantly higher at 12h in basal ganglia hemorrhage groups than sham-operated group (P<0.01), up to peak at 2d, there was no significant difference at 14d compared with the sham-operated group (P>0.05). It was higher in CH with SU group than that of CH without SU (P<0.01). The frequency of pyloric contraction slowed and its amplitude decreased at 12h, 1d, and 2d after CH significantly (P<0.01), This change was more obvious in the CH rats which SU occured(P<0.01).9. Discriminant analysis of EGG judge the experimental basal ganglia intracerebral hemorrhage compicated with stress ulcer in ratsThe discriminat function was achieved about the four parameters of EGG including F, Amp, ARI and CV. Its accuracy rate was 90.8% to discriminate the CH complicated with SU rats and no SU, rats with ulcer induced by acetic acid and noamal rats.ConclusionsEGG had diagnostic value to stress ulcer after intracerebral hemorrhage and could be a reliable method to monitor the pathogenetic condition mobility. EGG instructions on the role of stress ulcer is one possible mechanism of cerebral hemorrhage due to increased intracranial pressure effects on the autonomic nerve center, so that autonomic dysfunction occurs, vagus nerve efferent impulses and gastric acid secretion increase, pH value decreases. Acute gastric mucosa is injuried while increased vagal efferent impulses are also involved in regulating gastric motility and affect changes of EGG.