Development of an experimental model to study the pathophysiology of cerebral salt wasting following subarachnoid hemorrhage.
Hyponatremia is frequent following cranial -neurosurgery or acute brain injury like subarachnoid hemorrhage (SAH), and increases mortality by 30%. The patho-physiology is not understood nor does a causal therapy exist. Since clinical trials are potentially dangerous in this very ill population, we examined whether an established rat model allows studying cerebral salt wasting (CSW) following SAH. The daily urine sodium excretion as well as plasma sodium, osmolality and antidiuretic hormone (ADH) levels were measured for 10 days. Following the injection of 300 μl of blood into the great cistern (SAH(severe)), natriuresis peaked twice (days 1 and 3-5, p < 0.05) resulting in a plasma sodium nadir (day 1 - 133.9 mmol/L, day 5 - 132.6 mmol/L), while following the injection of 300 μL saline (ICP(control)), natriuresis occurred delayed on days 4-5 (p < 0.05). Following double SAH (200 μL twice, 24 h apart), a natriuresis on day 4 resulted in a hyponatremia (131.7 mmol/L, p = 0.025). Neither SAH(mild) (100 μL), the injection of hemolyzed blood (100 μL) or hypertonic saline (200 μL) replicated the effect. The immediate release of ADH (32.23 ± 34.87 pg/mL) following SAH(severe) normalized over the next few days. We conclude that first, the rat model of SAH is suitable for studying CSW, second the increase in intracranial pressure generates the delayed hyponatremia, and third, the ADH release does not mediate natriuresis.
Department of Neurosurgery, University Erlangen-Nuremberg, Erlangen, Germany. andrea.kleindienst@uk-erlangen.de
Andrea
A
Kleindienst
Sven M
SM
Schlaffer
Nikhil
N
Sharma
Lisa
L
Linde
Michael
M
Buchfelder
Joseph G
JG
Verbalis
D000704:Analysis of Variance; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000652:urine; D001835:Body Weight / Q000502:physiology; D002540:Cerebral Cortex / Q000503:physiopathology*; D004195:Disease Models, Animal; D004326:Drinking / Q000502:physiology; D004435:Eating / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D007010:Hyponatremia / Q000097:blood / Q000209:etiology* / Q000473:pathology* / Q000652:urine; D008297:Male; D009318:Natriuresis / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D013997:Time Factors
D001127:Arginine Vasopressin