Effect of vardenafil on cerebral vasospasm following experimental subarachnoid hemorrhage in rats.
We examined the effects of the phosphodiesterase 5 (PDE-5) inhibitor vardenafil on cerebral vasospasm in an experimental rat subarachnoid hemorrhage (SAH) model. Thirty-two albino Wistar rats were divided into five groups: G1, no experimental intervention; G2, administered subarachnoid physiological saline after sham surgery; G3, subjected to SAH; G4, subjected to SAH and administered low-dose (0.5 mg/kg) vardenafil treatment; and G5, subjected to SAH and administered high-dose (5 mg/kg) vardenafil treatment. For animals in G3, G4 and G5, SAH was induced by an injection of autologous non-heparinized blood into the cisterna magna. Immediately after SAH, for animals in G4 and G5, vardenafil was administered by gavage at intervals of 8 hours for 2 days. The rats were then decapitated, and basilar arteries and blood samples were taken for biochemical and histopathological examination. Malonyldialdehyde values in G2 (p = 0.004) and G3 (p = 0.002) were significantly higher than those in G1. G4 and G5 had significantly lower values than G2 and G3 (p = 0.014, G4 v. G2; p = 0.005, G4 v. G3; p = 0.005, G5 v. G2; p = 0.002, G5 v. G3). Total antioxidant capacity (TAC) values in G3 were significantly lower than those in G1 (p = 0.041). TAC values in G4 and G5 were significantly higher than those in G3 (p = 0.043). Mean luminal diameter in G3 was significantly smaller compared with G1 and G2 (p = 0.002), but larger in G4 (p = 0.002) and G5 (p = 0.001) compared with G3. Mean luminal diameter was also significantly larger in G5 than in G2 (p = 0.008) and G4 (p = 0.038). Mean wall thickness in G2 (p = 0.015) and G3 (p = 0.002) was significantly thicker compared with G1. Wall thickness was significantly thinner in G4 and G5 compared with G2 and G3 (p = 0.008, G4 v. G2; p = 0.001, G4 v. G3; p = 0.005, G5 v. G2; p = 0.001, G5 v. G3). Our results confirm that vardenafil may induce vasodilatation and provide potential benefits in SAH therapy by preventing vasospasm.
Gul
Sanser
S
Department of Neurosurgery, School of Medicine, Zonguldak Karaelmas University, Kozlu, Zonguldak 67600, Turkey. drsanser@yahoo.com
Bahadir
Burak
B
Hanci
Volkan
V
Bektas
Sibel
S
Can
Murat
M
Kalayci
Murat
M
Acikgoz
Serefden
S
Acikgoz
Bektaş
B
D000818:Animals; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008315:Malondialdehyde / Q000032:analysis; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D013450:Sulfones / Q000008:administration & dosage / Q000627:therapeutic use; D014227:Triazines / Q000008:administration & dosage / Q000627:therapeutic use; D000069058:Vardenafil Dihydrochloride; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology
D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D008315:Malondialdehyde; D000069058:Vardenafil Dihydrochloride