Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-10T20:06:47.509Z Has data issue: false hasContentIssue false

Acute normovolaemic haemodilution with a novel hydroxyethyl starch (130/0.4) reduces focal cerebral ischaemic injury in rats

Published online by Cambridge University Press:  01 July 2008

L. Xiong*
Affiliation:
Fourth Military Medical University, Xijing Hospital, Department of Anesthesiology, Xi’an, Shaanxi, China
C. Lei
Affiliation:
Fourth Military Medical University, Xijing Hospital, Department of Anesthesiology, Xi’an, Shaanxi, China
Q. Wang
Affiliation:
Fourth Military Medical University, Xijing Hospital, Department of Anesthesiology, Xi’an, Shaanxi, China
W. Li
Affiliation:
Fourth Military Medical University, Xijing Hospital, Department of Anesthesiology, Xi’an, Shaanxi, China
*
Correspondence to: Lize Xiong, Department of Anesthesiology, Xijing Hospital, Xi’an, Shaanxi Province 710032, China. E-mail: mzkxlz@126.com; Tel: +86 29 84775337; Fax: +86 29 83244986
Get access

Summary

Background and objectives

This study investigated the neuroprotective effect of acute normovolaemic haemodilution with a novel hydroxyethyl starch (130/0.4, HES) on focal cerebral ischaemia-reperfusion injury and determined optimum degree for haemodilution in the rat.

Methods

Male Sprague-Dawley rats were randomly divided into three groups (n = 10 each): hydroxyethyl starch, saline and controls. Animals in the hydroxyethyl starch and saline groups were haemodiluted until haematocrit decreased to 30% of baseline. In another experiment male Sprague-Dawley rats were randomly assigned to four groups (n = 10 each): HES30, HES25 and HES20 and controls. Rats in the HES30, HES25 and HES20 groups were haemodiluted with hydroxyethyl starch until the haematocrit decreased to 30%, 25% and 20%, respectively. At 15 min after haemodilution, all the rats were subjected to a right middle cerebral artery occlusion for 120 min. Neurologic deficit scores and infarct volumes were assessed 24 h after reperfusion.

Results

Haemodilution with hydroxyethyl starch improved neurologic outcome (P < 0.01) and reduced infarct volume (P < 0.01) compared to saline and controls. Haemodilution with saline augmented infarct volume (P < 0.05 vs. controls). Neurologic deficit scores in HES30 and HES25 groups were significantly lower compared to controls (P < 0.05) while infarct volumes in controls and HES20 were significantly larger compared to HES30 and HES25 (P < 0.01).

Conclusions

This study demonstrates that acute normovolaemic haemodilution with a novel hydroxyethyl starch (130/0.4) reduces infarct volume and improves neurological outcome after focal cerebral ischaemia in a rat stroke model. Neuroprotection by haemodilution was highest at haematocrit dilution between 25% and 30%, while ischaemic injury was exacerbates when haematocrit was diluted to 20%.

Type
Original Article
Copyright
Copyright © European Society of Anaesthesiology 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Tu, YK, Heros, RC, Karacostas, D et al. Isovolemic hemodilution in experimental focal cerebral ischemia. Part 2: effect on regional cerebral blood flow and size of infarction. J Neurosurg 1988; 69: 8291.CrossRefGoogle ScholarPubMed
2.Chang, CK, Chien, CH, Chou, HL, Lin, MT. The protective effect of hypervolemic hemodilution in experimental heat stroke. Shock 2001; 16: 153158.CrossRefGoogle Scholar
3.Cole, DJ, Reynolds, LW, Nary, JC, Drummond, JC, Patel, PM, Jacobsen, WK. Subarachnoid hemorrhage in rats: effect of singular or sustained hemodilution with alpha-alpha diaspirin crosslinked hemoglobin on cerebral hypoperfusion. Crit Care Med 1999; 27: 972977.CrossRefGoogle ScholarPubMed
4.Lin, SZ, Chiou, TL, Song, WS, Chiang, YH. Isovolemic hemodilution normalizes the prolonged passage of red cells and plasma through cerebral microvessels in the partially ischemic forebrain of rats. J Cereb Blood Flow Metab 1996; 16: 280289.Google Scholar
5.Rebel, A, Ulatowski, JA, Joung, K, Bucci, E, Traystman, RJ, Koehler, RC. Regional cerebral blood flow in cats with cross-linked hemoglobin transfusion during focal cerebral ischemia. Am J Physiol Heart Circ Physiol 2002; 282: H832H841.CrossRefGoogle ScholarPubMed
6.Schell, RM, Cole, DJ, Schultz, RL, Osborne, TN. Temporary cerebral ischemia effects of pentastarch or albumin on reperfusion injury. Anesthesiology 1992; 77: 8692.Google Scholar
7.Perez-Trepichio, AD, Furlan, AJ, Little, JR, Jones, SC. Hydroxyethyl starch 200/0.5 reduces infarct volume after embolic stroke in rats. Stroke 1992; 23: 17821790.CrossRefGoogle Scholar
8.Langeron, O, Doelberg, M, Ang, ET, Bonnet, F, Capdevila, X, Coriat, P. Voluven, a lower substituted novel hydroxyethyl starch (HES 130/0.4), causes fewer effects on coagulation in major orthopedic surgery than HES 200/0.5. Anesth Analg 2001; 92: 855862.CrossRefGoogle Scholar
9.Jungheinrich, C, Neff, TA. Pharmacokinetics of hydroxyethyl starch. Clin Pharmacokinet 2005; 44: 681699.CrossRefGoogle ScholarPubMed
10.Ickx, BE, Bepperling, F, Melot, C, Schulman, C, Van der Linden, PJ. Plasma substitution effects of a new hydroxyethyl starch HES 130/0.4 compared with HES 200/0.5 during and after extended acute normovolemic haemodilution. Br J Anaesth 2003; 91: 196202.CrossRefGoogle Scholar
11.Gallandat Huet, RC, Siemons, AW, Baus, D et al. A novel hydroxyethyl starch (Voluven®) for effective perioperative plasma volume substitution in cardiac surgery. Can J Anesth 2000; 47: 12071215.Google Scholar
12.Xiong, L, Zheng, Y, Wu, M et al. Preconditioning with isoflurane produces dose-dependent neuroprotection via activation of adenosine triphosphate-regulated potassium channels after focal cerebral ischemia in rats. Anesth Analg 2003; 96: 233237.CrossRefGoogle ScholarPubMed
13.Wang, Q, Xiong, L, Chen, S, Liu, Y, Zhu, X. Rapid tolerance to focal cerebral ischemia in rats is induced by preconditioning with electroacupuncture: window of protection and the role of adenosine. Neurosci Lett 2005; 381: 158162.CrossRefGoogle ScholarPubMed
14.Longa, EZ, Weinstein, PR, Carlson, S, Cummins, R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 1989; 20: 8491.Google Scholar
15.Swanson, RA, Morton, MT, Tsao-Wu, G, Savalos, RA, Davidson, C, Sharp, FR. A semiautomated method for measuring brain infarct volume. J Cereb Blood Flow Metab 1990; 10: 290293.Google Scholar
16.Shichinohe, H, Kuroda, S, Abumiya, T et al. FK506 reduces infarct volume due to permanent focal cerebral ischemia by maintaining BAD turnover and inhibiting cytochrome c release. Brain Res 2004; 1001: 5159.Google Scholar
17.Belayev, L, Khoutorova, L, Belayev, A et al. Delayed post-ischemic albumin treatment neither improves nor worsens the outcome of transient focal cerebral ischemia in rats. Brain Res 2004; 998: 243246.Google Scholar
18.Licker, M, Mariethoz, E, Costa, MJ, Morel, D. Cardioprotective effects of acute isovolemic hemodilution in a rat model of transient coronary occlusion. Crit Care Med 2005; 33: 23022308.Google Scholar
19.Fenger-Eriksen, C, Hartig Rasmussen, C, Kappel Jensen, T et al. Renal effects of hypotensive anaesthesia in combination with acute normovolaemic haemodilution with hydroxyethyl starch 130/0.4 or isotonic saline. Acta Anaesthesiol Scand 2005; 49: 969974.CrossRefGoogle ScholarPubMed
20.Homi, HM, Yang, H, Pearlstein, RD, Grocott, HP. Hemodilution during cardiopulmonary bypass increases cerebral infarct volume after middle cerebral artery occlusion in rats. Anesth Analg 2004; 99: 974981.Google Scholar
21.Rudolf, J. HES in Acute Stroke Study Group. Hydroxyethyl starch for hypervolemic hemodilution in patients with acute ischemic stroke: a randomized, placebo-controlled phase II safety study. Cerebrovasc Dis 2002; 14: 3341.Google Scholar
22.Gow, KW, Phang, PT, Tebbutt-Speirs, SM et al. Effect of crystalloid administration on oxygen extraction in endotoxemic pigs. J Appl Physiol 1998; 85: 16671675.CrossRefGoogle ScholarPubMed
23.Wisselink, W, Nguyen, JH, Becker, MO, Money, SR, Hollier, LH. Ischemia-reperfusion injury of the spinal cord: the influence of normovolemic hemodilution and gradual reperfusion. Cardiovasc Surg 1995; 3: 399404.Google Scholar
24.Jones, SB, Whitten, CW, Monk, TG. Influence of crystalloid and colloid replacement solutions on hemodynamic variables during acute normovolemic hemodilution. J Clin Anesth 2004; 16: 1117.Google Scholar
25.Hitomi, A, Satoh, S, Ikegaki, I, Suzuki, Y, Shibuya, M, Asano, T. Hemorheological abnormalities in experimental cerebral ischemia and effects of protein kinase inhibitor on blood fluidity. Life Sci 2000; 67: 19291939.CrossRefGoogle ScholarPubMed
26.Forconi, S, Turchetti, V, Cappelli, R, Guerrini, M, Bicchi, M. Haemorheological disturbances and possibility of their correction in cerebrovascular diseases. J Mal Vasc 1999; 24: 110116.Google ScholarPubMed
27.Chang, CK, Chiu, WT, Chang, CP, Lin, MT. Effect of hypervolaemic haemodilution on cerebral glutamate, glycerol, lactate and free radicals in heatstroke rats. Clin Sci 2004; 106: 501509.Google Scholar
28.Kaplan, SS, Park, TS, Gonzales, ER, Gidday, JM. Hydroxyethyl starch reduces leukocyte adherence and vascular injury in the newborn pig cerebral circulation after asphyxia. Stroke 2000; 1: 22182223.CrossRefGoogle Scholar
29.Wu, Z, Tian, YK, Zhang, CH, Wang, P. Effect of hemodilution with different plasma substitutes on expression of tumor necrosis factor-α and intertenkinL-1 in brain after global cerebral ischemia-reperfusion in rats. Chin J Anesthesiol 2005; 25: 151153.Google Scholar
30.Miroslava, N, Burda, J, Danielisova, V, Marala, J. The effect of normovolemic hemodilution on c-Fos protein immunoreactivity in the postischemic rat brain cortex. Int J Neurosci 2005; 115: 523536.Google Scholar
31.Oda, T, Nakajima, Y, Kimura, T, Ogata, Y, Fujise, Y. Hemodilution with liposome-encapsulated low-oxygen-affinity hemoglobin facilitates rapid recovery from ischemic acidosis after cerebral ischemia in rats. J Artif Organs 2004; 7: 101106.Google Scholar