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Effects of hypertonic (3%) saline in rats with circulatory shock and cerebral ischemia after heatstroke

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Abstract

Objective

To evaluate the effects of hypertonic (3%) saline in heatstroke rats with circulatory shock, intracranial hypertension, and cerebral ischemia.

Design and setting

Urethane-anesthetized rats were exposed to a high ambient temperature of 42°C until mean arterial pressure and local cerebral blood flow (CBF) in the corpus striatum began to decrease from their peak levels, which was arbitrarily defined as the onset of heatstroke. Control rats were exposed to 24°C.

Measurements and results

Extracellular concentrations of glutamate and lactate/pyruvate ratio (cellular ischemia markers), and glycerol (a cellular injury marker) in the corpus striatum of rat brain were assessed by intracerebral microdialysis methods. Striatal PO2, temperature, and local CBF were measured with a combined OxyLite PO2, thermocouple, and OxyFlo LDF, respectively. The values of mean arterial pressure, cerebral perfusion pressure, and striatal CBF and PO2 in rats treated with 0.9% NaCl solution after the onset of heatstroke were all significantly lower than those in normothermic controls. In contrast, the values of intracranial pressure, brain temperature, and extracellular concentrations of glutamate, glycerol, and lactate/pyruvate in the corpus striatum were greater. Intravenous infusion of hypertonic (3%) saline solution either "0" time before the start of heat exposure or right after the onset of heatstroke significantly attenuated the heatstroke-induced arterial hypotension, intracranial hypertension, decreased cerebral perfusion, and cerebral ischemia and damage and resulted in prolongation of survival time.

Conclusions

Our results strongly suggest that the experimental heatstroke syndromes can be effectively prevented and treated by hypertonic saline.

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Reference

  1. Simon HB (1993) Hyperthermia. N Engl J Med 329:483–487

    Google Scholar 

  2. Bouchama A, Cafege A, Deval EB, Labdi O, el-Assil K, Seraj M (1991) Ineffectiveness of dantrolene sodium in the treatment of heatstroke. Crit Care Med 19:176–180

    Google Scholar 

  3. Knochel JP, Reed G (1994) Disorders of heat regulation. In: Narins RG (ed) Maxwell & Kleeman's clinical disorders of fluid and electrolyte metabolism, 5th edn. McGraw-Hill, New York, pp 1549–1590

  4. Dematte JE, O'Mara K, Buescher J, Dematte JE, O'Mara K, Buescher J, Whitney CG, Forsythe S, McNamee T, Adiga RB, Ndukwu IM (1998) Near-fatal heatstroke during the 1995 heat wave in Chicago. Ann Intern Med 129:173–181

    CAS  PubMed  Google Scholar 

  5. Easterling DR, Meehl GA, Parmescan C, Changnon SA, Karl TR, Mearns LO (2000) Climate extremes: observations, modeling, and impacts. Science 298:2068–2074

    Article  Google Scholar 

  6. Rooney C, McMichael AJ, Kovats RS, Coleman MP (1998) Excess mortality in England and Wales, and in Greater London, during the 1995 heatwave. J Epidemiol Community Health 52:482–486

    CAS  PubMed  Google Scholar 

  7. Sartor F, Snacken R, Demuth C, Walckiers D (1995) Temperature, ambient ozone levels, and mortality during summer 1994, in Belgium. Environ Res 70:105–113

    Article  CAS  PubMed  Google Scholar 

  8. Katsouyanni K, Trichopoulos D, Zavitsanos X, Touloumi G (1988) The 1987 Athens heatwave. Lancet II:573

    Google Scholar 

  9. Nakai S, Itoh T, Morimoto T (1999) Deaths from heatstroke in Japan: 1968–1994. Int J Biometerol 43:124–127

    Article  CAS  Google Scholar 

  10. Bynum GD, Pandolf KB, Schuette WH, Goldman RF, Lees DE, Whang-Peng J, Atkinson ER, Bull JM (1978) Induced hyperthermia in sedated human and the concept of critical thermal maximum. Am J Physiol 235:R228–R236

    CAS  PubMed  Google Scholar 

  11. Pettigrew RT, Gait JM, Ludge CM, Horn DB, Smith AN (1974) Circulatory and biochemical effects of whole body hyperthermia. Br J Surg 61:727–730

    CAS  PubMed  Google Scholar 

  12. Lin MT (1997) Heatstroke-induced cerebral ischemia and neuronal damage: involvement of cytokines and monoamines. Ann NY Acad Sci 813:572–580

    CAS  PubMed  Google Scholar 

  13. Lin MT (1999) Pathogenesis of an experimental heatstroke model. Clin Exp Pharmacol Physiol 26:826–827

    Article  CAS  PubMed  Google Scholar 

  14. Qureshi AI, Suarez JI (2000) Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension. Crit Care Med 28:3301–3313

    CAS  PubMed  Google Scholar 

  15. Qureshi AI, Suarez JI, Bhardwaj A, Mirski M, Schnitzer MS, Hanley DF, Ulatowski JA (1998) Use of hypertonic (3%) saline/acetate infusion in the treatment of cerebral edema. Effect on intracranial pressure and lateral displacement of the brain. Crit Care Med 26:440–446

    CAS  PubMed  Google Scholar 

  16. Schatzmann C, Heissler HE, Konig K, Klinge-Xhemajli P, Rickels E, Muhling M, Borschel M (1998) Treatment of elevated intracranial pressure by infusions of 10% saline in severely head injured patients. Acta Neurochir Suppl (Wien) 71:31–33

    Google Scholar 

  17. Simma B, Burger R, Falk M, Sacher P, Fanconi S (1998) A prospective, randomized, and controlled study of fluid management in children with severe head injury: lactated ringer's solution versus hypertonic saline. Crit Care Med 26:1265–1270

    CAS  PubMed  Google Scholar 

  18. Shackford SR, Bourguignon RR, Wald SL, Rogers FB, Osler TM, Clark DE (1998) Hypertonic saline resuscitation of patients with head injury: a prospective, randomized clinical trial. J Trauma 44:50–58

    CAS  PubMed  Google Scholar 

  19. Peterson B, Khanna S, Fisher B, Marshall L (2000) Prolonged hypernatremia controls elevated intracranial pressure in head-injured pediatric patients. Crit Care Med 28:1136–1143

    CAS  PubMed  Google Scholar 

  20. Horn P, Munch E, Vajkoczy P, Herrmann P, Quintel M, Schilling L, Schmiedek P, Schurr L (1999) Hypertonic saline solution for control of elevated intracranial pressure in patients with exhausted response to mannitol and barbiturates. Neurol Res 21:758–764

    CAS  PubMed  Google Scholar 

  21. Khanna S, Davis D, Piterson B, Fisher B, Tung H, O'Quigley J, Deutsch R (2000) Use of hypertonic saline in the treatment of severe refractor posttraumatic intracranial hypertension in pediatric traumatic brain injury. Crit Care Med 28:1144–1151

    CAS  PubMed  Google Scholar 

  22. Vassar MJ, Fischer RP, O'Brien PE, Bachulis BL, Chambers JA, Hoyt DB, Holcroft JW (1993) A multicenter trial for resuscitation of injured patients with 7.5% sodium chloride: the effect of added dextran 70. Arch Surg 128:1003–1013

    CAS  PubMed  Google Scholar 

  23. Kramer GC, Perron PR, Lindsay DC, Ho HS, Gunter RA, Boyle WA, Holcroft JW (1986) Small-volume resuscitation with hypertonic saline dextran solution. Surgery 100:239–247

    CAS  PubMed  Google Scholar 

  24. Schwarz S, Georgiadis D, Aschoff A, Schwab S (2002) Effects of hypertonic (10%) saline in patients with raised intracranial pressure after stroke. Stroke 33:136–140

    Article  CAS  PubMed  Google Scholar 

  25. Liu CC, Chien CH, Lin MT (2000) Glucocorticoids reduce interleukin-1β concentration and result in neuroprotective effects in rat heatstroke. J Physiol (Lond) 527:333–343

    Google Scholar 

  26. Yang CY, Lin MT (2002) Oxidative stress in rats with heatstroke-induced cerebral ischemia. Stroke 33:790–794

    Article  PubMed  Google Scholar 

  27. Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic, New York

  28. Berger C, Schäbitz WR, Georgiadis D, Steiner T, Aschoff A, Schwab S (2002) Effects of hypothermia on excitatory amino acids and metabolism in stroke patients. A microdialysis study. Stroke 33:519–524

    Article  CAS  PubMed  Google Scholar 

  29. Hillered L, Persson L (1999) Neurochemical monitoring of the acutely injured human brain. Scand J Clin Lab Invest Suppl 229:9–18

    CAS  PubMed  Google Scholar 

  30. Hillered L, Persson L, Ponten U, Ungerstedt U (1990) Neurometabolic monitoring of the ischemic human brain using microdialysis. Acta Neurochir (Wien) 102:91–97

    Google Scholar 

  31. Ungerstedt U (1997) Microdialysis-a new technique for monitoring local tissue events in the clinic. Acta Anaesthesiol Scand Suppl 110:123

    CAS  PubMed  Google Scholar 

  32. Hillered L, Valtysson J, Enblad P, Person L (1998) Interstial glycerol as a marker for membrane phospholipid degradation in acutely injured human brain. J Neurol Neurosurg Psychiatry 64:486–491

    CAS  PubMed  Google Scholar 

  33. Bullock R, Zauner A, Woodward J, Young MF (1995) Massive persistent release of excitatory amino acids following human occlusive stroke. Stroke 26:2187–2189

    CAS  PubMed  Google Scholar 

  34. Persson L, Hillered L (1992) Chemical monitoring of neurosurgical intensive care patients using intra-cerebral microdialysis. J Neurosurg 76:72–80

    CAS  PubMed  Google Scholar 

  35. Nilsson OG, Saveland H, Boris-Moller F, Brandt L, Wieloch T (1996) Increased levels of glutamate in patients with subarachnoid haemorrhage as measured by intracerebral microdialysis. Acta Neurochir Suppl (Wien) 67:45–47

    Google Scholar 

  36. Kao TY, Chio CC, Lin MT (1994) Hypothalamic dopamine release and local cerebral blood flow during onset of heatstroke in rats. Stroke 25:2483–2487

    CAS  PubMed  Google Scholar 

  37. Chang CK, Chien CH, Chou HL, Lin MT (2001) The protective effect of hypervolemic hemodilution in experimental heatstroke. Shock 16:153–158

    CAS  PubMed  Google Scholar 

  38. Lin MT, Kao TY, Chio CC, Jin YT (1995) Dopamine depletion protects striatal neuron from heatstroke induced ischemia and cell death in rats. Am J Physiol 269:H487–H490

    CAS  PubMed  Google Scholar 

  39. Lin MT, Kao TY, Su CF, Hsu SSF (1994) Interleukin-1β production during the onset of heatstroke in rabbits. Neurosci Lett 174:17–20

    CAS  PubMed  Google Scholar 

  40. Keller TS, MsGillicudy JF, LaBond VA, Kindt GW (1982) Volume expansion in focal cerebral ischemia: the effect of cardiac output on local cerebral blood flow. Clin Neurosurg 29:40–50

    CAS  PubMed  Google Scholar 

  41. Muizelaar JP, Lutz HA 3rd, Becker DP (1984) Effect of mannitol on ICP and CBF and correlation with pressure autoregulation in severely head-injured patients, J Neurosurg 61:700–706

    Google Scholar 

  42. Kirkpatrick PJ, Smielewski P, Piechnik S, Pickard JD, Czosnyka M (1996) Early effects of mannitol in patients with head injuries assessed during bedside multimodality monitoring. Neurosurgery 39:714–720

    CAS  PubMed  Google Scholar 

  43. Schwarz S, Schwab S, Bertram M, Aschoff A, Hacke W (1998) Effects of hypertonic saline hydroxyethyl starch solution and mannitol in patients with increased intracranial pressure after stroke. Stroke 29:1550–1555

    CAS  PubMed  Google Scholar 

  44. Kaufmann AM, Cardoso ER (1992) Aggravation of vasogenic cerebral edema by multiple-dose mannitol. J Neurosurg 77:584–589

    CAS  PubMed  Google Scholar 

  45. Bereczki D, Liu M, Prado GF, Fekete I (2000) Cochrane report: a systematic review of mannitol therapy for acute ischemic stroke and cerebral parenchymal hemorrhage. Stroke 31:2719–2722

    CAS  PubMed  Google Scholar 

  46. Kregel KC, Gisolfi CV (1990) Circulatory response to vasoconstrictor agents during passive heating in the rat. Am J Physiol 68:1220–1227

    CAS  Google Scholar 

  47. Hammami MM, Bouchama A, Al-Sedairy S, Shail E, Alohaly Y, Mohamed GE (1997) Concentrations of soluble tumor necrosis factor and interleukin-6 receptors in heatstroke and heat stress. Crit Care Med 25:1314–1319

    CAS  PubMed  Google Scholar 

  48. Bouchama A, Al-Sedairy S, Siddiqui S, Shail E, Rezeig M (1993) Elevated pyrogenic cytokines in heatstroke. Chest 104:1498–1502

    CAS  PubMed  Google Scholar 

  49. Chang DM (1993) The role of cytokines in heatstroke. Immunol Invest 22:553–561

    CAS  PubMed  Google Scholar 

  50. Bouchama A, Parhar RS, el-Yazigi A, Sheth K, al-Sedairy S (1991) Endotoxin and release of tumor necrosis factor and interleukin 1 alpha in acute heatstroke. J Appl Physiol 70:2640–2644

    CAS  PubMed  Google Scholar 

  51. Lin MT, Liu HH, Yang YL (1997) Involvement of interleukin-1 receptor mechanisms in development of arterial hypotension in rat heatstroke. Am J Physiol 273:H2072–H2077

    CAS  PubMed  Google Scholar 

  52. Bouchama A, Hammani MM, Haq A, Jackson J, al-Sedairy S (1996) Evidence for endothelial cell activation/injury in heatstroke. Crit Care Med 24:1173–1178

    CAS  PubMed  Google Scholar 

  53. Shieh SD, Shiang JC, Lin YF, Shiao WY, Wang JY (1995) Circulating angiotensin-converting enzyme, von Willebrand factor antigen and thrombomodulin in exertional heatstroke. Clin Sci (Colch) 89:261–265

    Google Scholar 

  54. Bouchama A, Bridey F, Hammani MM, Lacombe C, al-Shail E, al-Ohali Y, Combe F, al-Sedairy S, de Prost D (1996) Activation of coagulation and fibrinolysis in heatstroke. Thromb Haemost 76:909–915

    CAS  PubMed  Google Scholar 

  55. al-Mashhadani SA, Gader AG, al Harthi SS, Kanger D, Shaheen FA, Bogus F (1994) The coagulopathy of heatstroke: alterations in coagulation and fibrinolysis in heatstroke patients during the pilgrimage (Haj) to Makkah. Blood Coagul Fibrinolysis 5:731–736

    CAS  PubMed  Google Scholar 

  56. el-Kassimi FA, Al-Mashhadani S, Abdullah AK, Akhtar J (1986) Adult respiratory distress syndrome and disseminated intravascular coagulation complicating heatstroke. Chest 90:571–574

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by research funding from the National Science Council of Republic of China (Taipei, Taiwan): NSC 91-2320-B-384-001.

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Correspondence to Mao-Tsun Lin.

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An editorial regarding this article can be found in the same issue (http://dx.doi.org/10.1007/s00134-003-1882-0)

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Kuo, JR., Lin, CL., Chio, CC. et al. Effects of hypertonic (3%) saline in rats with circulatory shock and cerebral ischemia after heatstroke. Intensive Care Med 29, 1567–1573 (2003). https://doi.org/10.1007/s00134-003-1854-4

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  • DOI: https://doi.org/10.1007/s00134-003-1854-4

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