Experimental And Clinical Study On Hyponatremia After Cervical Spinal Cord Injury

Objective Hyponatremia is a serious complication following cervical spinal cord injury(SCI).The mechanism of the hyponatremia caused by cervical SCI is still in dispute now.Basically there are two explanations:One is the syndrome of inappropriate secretion of antidiuretic hormone(SIADH).Another one is the cerebral salt wasting syndrome(CSWS).Initially these two theories try to explain the blood sodium loss after the craniocerebral injury.Later they were also used to explain the hyponatremia after cervical SCI.The precise mechanisms underlying hyponatremia induced by cervical SCI is not clear.Somebody reported:The high plasma concentration atrial natriuretic factor(ANP) responded to excessive water and salt excretion in SCI patients.Many clinic cases were reported every year,there is no experimental detail reported to study hyponatremia after cervical SCI.So we decided to establish a novel rat model for mechanism investigation of hyponatremia following cervical spinal cord injury(SCI),Method.Experimental study:1.Preparation phase of the experiment:Retrospective analysis of clinical reports of hyponatremia after cervical SCI.Some feature can be found.The incidence of hyponatremia was related to the degree of the spinal cord injury.So the Frankle A type spinal cord injury was used in the study.Hyponatremia is highly related with the metabolism of water and sodium.Precisely measuring the input-output amounts of water and sodium is the key of the experiment.Using gastrostomy feeding and urethral catheterization can resolve the problems.2.Test experiments:The rat has similar serum sodium(SNa) concentration with human being and has widely accepted as the experimental animal.All the experimental techniques, such as SCI surgery gastrostomy and Urethral catheterization,have successfully performed in rat formerly.Rat is omnivorous animal and very economy.Subsequently, we established the rat model for studying the hyponatremia following cervical SCI. Healthy adult Wistar Rats(16 rats,half male,half female with average body weight of 290±10g).The rats were self-fed with enteral nutritional emulsion(TP).The daily quantities of intake TP,the feces,as well as the changes of weight behavior and SNa concentration were recorded.The anatomy of spine and ventriculus of the rats were studied.The rat spinal cord can be experimentally transected,contused or compressed to produce a lesion.After comparison of the length of surgery,the quantity of bleeding,as well as the survival rate of various procedures to cause the cervical SCI, it was decided to use the rat SCT model was used in our study.The spinous process of T2 can reach a length of 7mm,longest of all vertebrae.According to the spinous process of T2,the 6th cervical vertebra(C6) can be exposed easily.Through the opened interval between the C6,7 spinous process,spinal cord can be intersected.The stomach capacity of the rats was measured after the gastrostomy.The TP was injected into the stomach gently and slowly through the catheter by syringe.The rat feces,as well as the changes of weight behavior and SNa concentration were recorded after gastrostomy feeding.Urethral catheterization was done with a catheter through the urethra..As male rat,its anatomy of the urethra structure is more complicated than female rat.We recommend female rat as experimental animal.3.Experiment: Forty-five female adult Wistar rats,were divided into three groups randomly,group A were fed with normal rodent food and had no surgery(control group),group B were fed with enteral nutritional emulsion(TP) through gastrostomy after lesions of paravertebral muscles(sham group),group C were fed with TP through gastrostomy after cervical spinal cord transaction(SCT) and urethral catheterization(SCI group). Before done the operation,each rat both in group B and group C were fed with TP(60ml/day) for 1 week.The TP was in little battles,and the rats could catch the TP by themselves.Before operation,the blood samples were collected in group B and C, and the samples were also collected in group A at same time.After surgery,the blood samples were collected every 24 hours in group B and C.All the blood samples were collected from the tail veins and were analyzed by the electrolyte analyzer(Chiron 348,Chiron Diagnostics Corp.,MA,USA).The urine volumes were collected every 24 hours in group C after surgery.The same thing did in group B by using metabolic cage.The dally average urinary sodium concentration was checked by the electrolyte analyzer.At the 4th day,the rats in group B and C were put to death by CO2 after blood and urine samples were collected.Autopsies were done to observe the locations with surgeries.The blood sodium concentrations of prior operation in three groups and the differences of blood sodium concentration between prior and post operation in group B and C were analyzed by one or two way ANOVA,with P＜0.05 considered significant.All data are presented as the means±S.E.M.Clinical study:54 patients admitted to the Orthopedic Department of Jinan central Hospital between 2005 and 2008 were studied.Group A:32 cases,6 were female and 26 were male,with a mean age of 42.5 years(range 18 to 63 years);All patients suffered cervical injury and admitted in the same day of the injury,2 patients suffered only cervical fracture,30 patients of them suffered acute cervical spinal cord injury;Frankel classification: Grade-A 6 cases,Grade-B 9 cases,Grade-C 11 cases,Grade-D 4 cases,Grade-E 2 cases.Group B(control group):22 cases,4 were female and 18 were male,with a mean age of 43.3 years(range 20 to 65 years);4 patients suffered lateral meniscus injury,4 patients suffered medial collateral ligament injury,8 patients suffered chronically low back pain,6 patients suffered osteoarthritis of knees.All patient s had measurement including blood press(BP),pulse,sodium,potassium,chlorine of blood and urine,blood urine nitrogen(BUN),input-output amounts of water,ALD,ANP, ADH.All the data were analyzed by one or two way ANOVA,with P＜0.05 considered significant.All data are presented as the mean±S.E.M.Result.Experimental results:There were no changes in weights,behavior and activity after feeding with TP before surgery.At the 1st day after surgery,three rats undergone SCT were excluded from experiment because Cheyne-Stokes breathing was observed. In these three rats,the SNa concentration between prior and post of surgery had not changed much.All the other rats were in good condition during experiment. Compared to normal diet,the SNa was not changed much by TP feeding.After normal or TP feeding one week,all rats were collected blood sample before surgery.In group A,the average of SNa concentration is 140.27mmol/l;and the average of SNa concentration is 141.67mmol/1 in group B and C.There is no significant difference (P=0.185＞0.05) between these two feeding.At the fourth day after surgery,the SNa concentration loss or change was observed in group C and B.In rats undergone SCT injury,the average of SNa concentration decreased from 141.417 mmol/1 to 123.083mmol/1.In group B,the average of SNa concentration changed from141.867mmol/1 to141.333mmol/1.After surgery,the decreases of SNa concentration in group C and B was shown significant difference(P=0.000＜0.05). The rats in group C developed hyponatremia four days after surgery.In group C,the urine was collected daily after surgery.The daily average urine volumes got obvious increase in group C since the 2nd day after operation.And the daily average urinary sodium concentrations got obvious increase since the 3rd day after operation.The urine volumes were collected every day in group B by using metabolic cage.The urine contaminated by pasty feces frequently.The differences of daily average urinal sodium between group B and C after surgery could be acquired obviously.Over natriuresis could be observed in group C compared with group B.At the 4th day,all the rats in group B and C were sacrificed by CO₂.Then autopsies were shown that there was no TP or urine leakage and infection of the gastric fistula or Urethral catheter.In the lesion area of cervical spinal cords of rats in group C,the complete ruptures of the spinal cords were observed,and hematomases were formation in the interspaces of lesion spinal cords.Clinical result:Comparison of group B that group A is correlated with a low blood pressure(BP),high urine output,and low serum sodium, high urine sodium,low serum chlorine,high plasma ALD and ANP.There were no obvious serum potassium,urine nitrogen and plasma ADH changes in group A compared with group B.Orthostatic hypotension was observed in the patients of group A.All the cases of hyponatremia in group A was corrected during hospitalization. Conclusion:The hyponatremia induced by cervical SCI can be related to four factors. First,renal conservation of sodium may be impaired owing to the renin-angiotensin-aldosterone system(RAS) lost normal level cause by sympathetic denervation of the kidney or impaired renal blood flow.Second,The hypotension of cervical SCI is related to the disability of both the sympathetic and the somatic nervous systems in these subjects.The somatic nervous system lesion impairs breathing ability,manifested by decreasing vital capacity with progressively higher levels of paralysis.Breathing is the pulmonary pump that determines venous return and cardiac output and supports BP.The lowering of BP coincides with the loss of vital capacity as the level of paralysis becomes higher.This somatic disability also inactivates the assistance of leg muscle contraction in the return of venous blood from the lower extremities.Although the centrally disabled sympathetic system reacts by reflex to noxious stimuli with autonomic dysreflexia,it fails to respond to orthostasis with vasoconstriction to protect the circulation against gravity.ADH is secreted to exceptionally high concentrations in response to the reduced blood pressure.The stimulating effect of hypotension overcomes the inhibitory effect of hypotonicity. Thus,water is conserved despite serum hyponatremia.Third,The high plasma concentration ANP responded to excessive water and salt excretion in SCI patients. Fourth,the augmented water intake,evidenced by polyuria,provides ample substrate for the expression of ADH.In summary,the hyponatremia of SCI can be related to the effects of partially blocked sodium conservation,enhanced water conservation,and increased fluid intake.We used gastrostomy to feed the rats with TP.Urethral catheterization was used to collect the urine.The quantity of the input-output water and the sodium were precisely measured.After SCT,the changes of the urine volume, urinal sodium as well as SNa were recorded.Comparing with the data of groupB,we got the positive results,we primarily established the rat model of hyponatremia following cervical SCI.Next study also should be focused on the long term investigation and the continue change of the blood sodium concentration by this model.We will test more electrolytes and hormone changes in hyponatremia following cervical SCI by this model.Electrophysiologic and therapeutics study on hyponatremia of SCI will be done by this model.Hopefully,it will be helpful to study the mechanism and therapeutic approaches for SCI-associated hyponatremia.