Hypertonic fluid resuscitation from subarachnoid hemorrhage in rats: a comparison between small volume resuscitation and mannitol.
OBJECTIVE
Death and severe morbidity after subarachnoid hemorrhage (SAH) are mainly caused by global cerebral ischemia through increased intracranial pressure (ICP) and decreased cerebral blood flow (CBF). We have recently demonstrated neuroprotective effects of small volume resuscitation (7.5% saline in combination with 6% dextran 70) in an animal model of SAH, leading to normalization of increased ICP, reduced morphological damage and improved neurological recovery. In the present study, we compared the concept of small volume resuscitation represented by two clinically licenced hypertonic-hyperoncotic saline solutions with the routinely used hyperosmotic agent-mannitol-and investigated their effects on ICP, CBF, neurological recovery and morphological damage after SAH in rats.


METHODS
60 dextran-resistant Wistar rats were subjected to SAH by an endovascular filament. ICP, MABP (mean arterial blood pressure) and bilateral local CBF were continuously recorded. All animals were randomly assigned to four groups: (I) NaCl 0.9% (4 ml/kg bw), (II) 7.5% NaCl+6% dextran 70 (4 ml/kg bw), (III) 7.2% NaCl+HES 200,000 (4 ml/kg bw) and (IV) 20% mannitol (9.33 ml/kg bw) given 30 min after SAH. Neurological deficits were assessed on days 1, 3 and 7 after SAH. The morphological damage was evaluated on day 7 after SAH.


RESULTS
The induction of SAH resulted in an immediate ICP increase to 46.6+/-3.2 mm Hg (mean+/-S.E.M.) and 29.6+/-1.3 (mean+/-S.E.M.) mm Hg 90 min post-SAH. While a treatment with both hypertonic saline solutions (II, III) decreased ICP as well as the 20% mannitol solution, only the group treated with hypertonic saline and dextran 70 (II) showed an increase of ipsilateral CBF for 20 min after the infusion and significantly more surviving neurons in the motorcortex and caudoputamen. Mortality was reduced from 60% (I) and 73% (III and IV), respectively, to 40% in group II.


CONCLUSIONS
Of all hypertonic solutions investigated, small volume resuscitation with NaCl 7.5% in combination with 6% dextran 70 evolved to be most effective in terms of reducing the initial harmful sequelae of SAH, leading to lowered ICP and less morphological damage after SAH in the rat.
Bermueller
Christian
C
Department of Otorhinolaryngology-Head and Neck Surgery, University of Ulm, D-89070 Ulm, Germany. christian.bermueller@uniklinik-ulm.de
Thal
Serge C
SC
Plesnila
Nikolaus
N
Schmid-Elsaesser
Robert
R
Kreimeier
Uwe
U
Zausinger
Stefan
S
D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003911:Dextrans / Q000627:therapeutic use; D004195:Disease Models, Animal; D007839:Functional Laterality; D006982:Hypertonic Solutions / Q000627:therapeutic use*; D007427:Intracranial Pressure / Q000187:drug effects; D008297:Male; D008353:Mannitol / Q000627:therapeutic use*; D009460:Neurologic Examination; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012151:Resuscitation / Q000379:methods*; D013345:Subarachnoid Hemorrhage / Q000401:mortality / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D013997:Time Factors
D003911:Dextrans; D006982:Hypertonic Solutions; D008353:Mannitol