Table 10

Selected Studies of SAH in Dogs Examining Mortality and Neurological Endpoints

    Author

    Model

    Mortality

    Neurological and Neurobehavioral Tests

    Controls

    Experimental findings

    Disconnect between vasospasm and outcomes


White1979

Single cisterna magna injection of 2-4 ml without ICP monitoring

None reported

Whether the animal ate, neurological deficits and change in demeanor

None

Saline treatment for vasospasm gave 46% behavior abnormalities, versus 11% for sudoxicam treatment

Some relation between behavior and vasospasm but authors reported that there was no absolute correlation.

White1979A

Single cisterna magna injection of 2-4 ml without ICP monitoring

None reported

Whether the animal ate, stood up, central nervous system depression, paresis and ataxia

Some animals assessed after angiography only

SAH produced more behavior change than angiography alone

Phenoxybenzamine treatment did not decrease vasospasm, no correlation between vasospasm and behavior

Chyatte1983

Double hemorrhage model, ICP not measured

11/36 (31%) eliminated from study, including 5 deaths as result of initial anesthesia, 3 after injection of blood and 3 angiographic complications

Brief qualitative mention of meningeal signs and neurological deficits

None

9/9 with SAH had meningeal signs and this was significantly less with drug treatment (2/8 treated with ibuprofen and 2/8 treated with methylprednisolone). Neurological deficits in all groups but seemed to improve faster with drug treatment, no statistical analysis

Vasospasm correlated with meningeal signs and behavior

Varsos1983

Double hemorrhage model, ICP not measured

None reported

Brief mention that no dogs developed hemiparsis, some were drowsy and had staggering gait on day 5

None

Aminophylline, nifedipine and papaverine at single tested doses did not reverse vasospasm

Not assessable

White1983

Single cisterna magna injection of 2-4 ml without ICP monitoring

None reported

6 level scale of no neurological deficit (0), lethargic/decreased motor activity (1), paresis/staggering gait (2), failure to eat (3), failure to walk (4), failure to stand (5)

None

Some benefit of nonsteroidal antiinflammatory drugs for early vasospasm 1 and 24 hours after SAH

No relationship between behavioral abnormalities and vasospasm 24 hours after blood injection altthough the average vasoconstriction increased with increased behavior abnormality (r = 0.44, p < 0.01)

Alexander1985

Double hemorrhage model, ICP not measured

The neurological findings were graded from 0 to 5, based on meningismus, ataxia, paresis, and cranial nerve deficits. No significant differences in neurological grade were found on any day between the two groups.

None

No effect of lavage on vasospasm or behavior

No correlation between neurological findings and vasospasm

Diringer1991

4-5 ml blood or saline injected 2 to 3 times into cisterna magna, ICP not measured

None reported

Brief description of behavior

SAH, saline injected and controls

General observations that SAH was associated with animals being less alert and having decreased appetite

Not assessable

Kaoutzanis1993

Single and double hemorrhage models, ICP not measured

None reported

11-point coma scale assessing motor response, eye movements and food intake

None

All dogs had normal consciousness regardless of degree of vasospasm

Not assessable

Tibbs2000

Double hemorrhage model, ICP not measured

1 of 22 (5%)

3 categories - 1. dog active with normal appetite and no focal neurological deficits, 2. not active, poor appetite or somnolent or 3. focal neurological changes such as ataxia or hemiparesis

None

PD-98059, a mitogen-activated protein kinase inhibitor, decreased vasospasm and improved behavior compared to dimethyl sulfoxide and controls. U-0126 was not effective against vasospasm but did improve behavior.

U-0126 did not prevent vasospasm but improved behavior

Zhou2004

Double hemorrhage model, ICP not measured

None reported

6 point neurological grading based on appetite, activity and neurological deficits

None

Caspase inhibitors Ac-DEVD-CHO and Z-VAD-FMK prevented vasospasm and improved appetite and activity. SAH had almost no effect on neurological function

By day 7 behaviour was similar among groups despite decreased vasospasm with caspase inhibitors

Yamaguchi2004B

Double hemorrhage model, ICP not measured

None reported

6 point neurological grading scale based on appetite, activity and neurological deficits

None

Ras farnsyl transferase (FTAse) inhibitor (FTI-277) and FTAse inhibitor 1 prevented vasospasm and improved activity and appetite but had no effect on neurological function which was normal in most animals

They correlated

Yamaguchi2004A

Double hemorrhage model, ICP not measured

None reported

6 point neurological grading scale based on appetite, activity and neurological deficits

None

Adenovirus expressing superoxide dismutase or lac Z did not prevent vasospasm and was associated with no effect on neurological and neurobehavioral ouotcome expect for worse appetite score with superoxide dismutase treatment 1 day after SAH

They correlated

Yatsushige2005

Double hemorrhage model, ICP not measured

None reported

6 point neurological grading scale based on appetite, activity and neurological deficits

None

C-jun N-terminal kinase (JNK) inhibitor SP600125 improved behavior and reduced vasospasm in dose-dependent manner

They correlated

Zhou2005

Double hemorrhage model, ICP not measured

None reported

6 point neurological grading scale based on appetite, activity and neurological deficits

None

Intracisternal p53 inhibitor, pifithrin alpha, improved appetite and activity several days after SAH, no effect on neurological deficits (most dogs were normal), less apoptosis and decrease in vasospasm

They correlated


Jeon et al. BMC Neuroscience 2009 10:103   doi:10.1186/1471-2202-10-103

Open Data