Table 10 Selected Studies of SAH in Dogs Examining Mortality and Neurological Endpoints
From: Neurological and neurobehavioral assessment of experimental subarachnoid hemorrhage
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 | Â | 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 |