Objective To investigate the effects of hypertonic saline mannitol (HSM), hypertonic saline dextran(HSD) and hypertonic acetate mannitol (HAM) to reverse severe hemorrhagic shock in rabbits.
Methods Eighteen male rabbits were divided into 3 groups (n=6): HSM group, HSD group and HAM group, and hemorrhaged to mean blood pressure of 5.3kPa in 10 minutes. After stabilization for 30 minutes, the rabbits were infused with the solution at the dose of 4ml/kg, then infused with normal saline at the same speed until the death of the animals. The changes of arterial blood pressure, mean arterial pressure, pulse pressure and blood electrolytes were observed before and after treatment.
Results The small volume of hypertonic-hyperoncotic solution could raise systolic blood pressure, mean arterial pressure and pulse pressure, and stabilize them for a period of time. The systolic blood pressure, mean arterial pressure and pulse pressure in the HSM group were higher than those in the HSD and HAM groups; HAM raised pH, while HSD and HSM decreased it, and HAM could better stabilize serum sodium concentration and chloride concentration. The surviving time of using the three kinds of solution was 205±11 min in the HSM group, 162±31 min in the HSD group and 155±22 min in the HAM group.
Conclusion HSM, HSD and HAM can reverse hemorrhagic shock and HSM has better effect than HSD and HAM, HAM can maintain hemeostasis in rabbits with hemorrhagic shock.

Since 1980, Velasco, et al found that hypertonic saline solution rapidly reversed the blood pressure of hemorrhagic shock animals,¹ the research has been paid widespread attention by basic scientists and clinicians. For controlled bleeding animals and human, the research results indicate that hypertonic saline has better effect than normal salt on elevation of the blood pressure of hemorrhagic shock. If hypertonic saline combines with dextran, the effect would be much better. But hypertonic saline solution may induce hyperchloremic acidosis,² while dextran may impair the blood coagulation mechanism and cause allergic reaction. Using 7.5% sodium chloride/mannitol and hypertonic sodium acetate/mannitol to make new hypertonic-hyperoncotic solutions, we compared their resuscitation effect with that of 7.5% sodium chloride/dextran on animal model.

MATERIALS AND METHODS
Hypertonic saline dextran (HSD) was prepared by putting sodium chloride (NaCl) 7.5g and dextran₇₀ 6g in 100 ml distilled water to make 7.5% sodium chloride / 6% dextran solution.

RESULTS
The changes of mean arterial pressure of the animals in the three groups before and after treatment are shown in Table 1, and the comparison of pulse pressure before and after treatment shown in Table 2. The changes of serum sodium concentration before and after treatment are shown in Fig 1, and the changes of serum chloride concentration before and after treatment shown in Fig 2. The surviving time was 205±11 minutes in the HSM group, 162±31 minutes in the HSD group and 155±21 minutes in the HAM group, the HSD and HAM groups vs. the HSM group (P<0.05).

Table 2 The changes of pulse pressure before and after treatment (kPa)(±s)

Fig 1 The changes of serum sodium concentration before and after treatment

Fig 2 The changes of serum chloride concentration before and after treatment

DISCUSSION
The present experiment indicated that in all the three groups a small dose of hypertonic-hyperoncotic solutions (4ml/kg) could raise blood pressure and reversed hemorrhagic shock in 10 minutes, but SBP and PBP were higher and the surviving time was longer in the HSM group than in the HSD and HAM groups. The effect of mannitol in HSM differs from that of dextran. The molecular weight of mannitol is 188.2, so it does not easily leak from the capillaries into the interstitial space after infusion. This may be the reason that HSM raises serum osmotic pressure by. Furthermore, during ischemia and reperfusion of hemorrhagic shock, a great deal of OH free radicals are produced. Mannitol can inactivate OH free radicals.⁵ This may explain the machanism that HSM stabilize blood pressure longer. The serum Na⁺ concentration after infusion of HSM.³ increases, which stimulates vagus nerve more, so the blood pressure is restored more quickly and stabilize longer. So HSM has better effect to restore and stabilized blood pressure than HAM.

Hypertonic sodium chloride has the side effect of causing hyperchloremic acidosis.² Many studies have been done to replace hypertonic sodium chloride with hypertonic sodium acetate. Hypertonic sodium lactate then is combined with dextran. The combination is thought to raise blood pressure quickly and to decrease the side effect of hyperchloremic acidosis. We combined hypertonic sodium acetate with mannitol. The result showed HAM could raise blood pressure quickly in some degree, did not increase serum chloride concentration, improved blood pH in the rabbits after infusion with it compared with the rabbits in shock and also maintained the acid-base balance.

The animals infused with HSM can live longer than those infused with HSD and HAM, for HSM restores and stabilizes blood pressure longer, provides the vital organs with adequate blood supply, in addition, mannitol can inactivate OH free radicals, reduce the injury of ischemia and reperfusion, and protect organs.⁴

REFERENCES
[1] Velasco IT, Pontieri V, Roocha C, et al. Hyperosmotic NaCl and severe hemorrhagic shock. Am J Physiol 1980; 239∶664.
[2] Hannou JP, Wade CE, Bossone CA, et al. Blood Gas and Acid-base status of conscious pigs subjected to fixed volume hemorrhage and resuscitated with hypertonic saline dextran. Circ shock 1990; 32∶19.
[3] Modig J. Effevtiveness of dextran 70 versus Ringer's acetate in traumatic shock and adult respiratory distress syndrome. Crit Care Med 1986; 14∶454.
[4] Marti-Cabrera M, Ortiz JL, Dura JM, et al. Hemodynamic effects of hyperosmotic mannitol infusion in anesthetized open-chest dogs: modification by cyclo oxygenase inhibition. Research in surgery 1991; 3∶29.