Effect of vardenafil on cerebral vasospasm following experimental subarachnoid hemorrhage in rats |
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| Authors: | Sanser Gul Burak Bahadir Volkan Hanci Sibel Bektas Murat Can Murat Kalayci Serefden Acikgoz Bektaş Acikgoz |
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| Affiliation: | 1. Department of Neurosurgery, School of Medicine, Zonguldak Karaelmas University, Kozlu, Zonguldak 67600, Turkey;2. Department of Pathology, School of Medicine, Zonguldak Karaelmas University, Zonguldak, Turkey;3. Department of Anesthesiology, School of Medicine, Zonguldak Karaelmas University, Zonguldak, Turkey;4. Department of Biochemistry, School of Medicine, Zonguldak Karaelmas University, Zonguldak, Turkey;1. Laboratory for Molecular and Psychiatric Neuroscience, McLean Hospital, Belmont, MA 02478, USA;2. Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA;3. Department of Psychology, College of the Holy Cross, Worcester, MA 01610, USA;1. Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-751 24 Uppsala, Sweden;2. Department of Medicinal Chemistry, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden;3. AstraZeneca, CNSP iMed Södertälje, Research & Development Innovative Medicines, SE-151 85 Södertälje, Sweden;1. Department of Oral and Maxillofacial Surgery, University Hospital Freiburg, Freiburg, Germany;2. Department of Oral and Maxillofacial Surgery/Clinical Navigation, Campus Virchow-Clinic, Charité University Hospital, Berlin, Germany;3. Department of Oral and Maxillofacial Surgery, Ev. Jung-Stilling-Hospital, Siegen, Germany;1. Specialist and Master of Oral and Maxillofacial Surgery, PhD Candidate in Oral and Maxillofacial Surgery, Department of Oral and Maxillofacial Surgery, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil;2. Specialist and Master Candidate in Oral and Maxillofacial Surgery, Department of Oral and Maxillofacial Surgery, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil;3. Mechanical Engineer, Three-Dimensional Technologies Division, Renato Archer Center for Information Technology, Brazilian Ministry of Science and Technology, Campinas, Brazil;4. Chemical Engineer, Three-Dimensional Technologies Division, Renato Archer Center for Information Technology, Brazilian Ministry of Science and Technology, Campinas, Brazil;6. Professor, Department of Oral and Maxillofacial Surgery, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil;5. Professor, Department of Oral and Maxillofacial Surgery, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil;1. Post Doctoral Fellow, Department of Periodontology and Oral Implantology, Dental Research Division, University of Guarulhos, Guarulhos, SP, Brazil;2. Ph.D. Graduate Student, Department of Pharmacology, Anesthesiology and Therapeutics, São Leopoldo Mandic Dental School, Campinas, SP, Brazil;3. Ph.D. Graduate Student, School of Chemical Engineering, Oklahoma State University, Stillwater, OK;4. Professor, Postgraduate Program in Dentistry, School of Health Sciences, Unigranrio University, Duque de Caxias, RJ, Brazil;6. Professor, Postgraduate Program in Dentistry, School of Health Sciences, Unigranrio University, Duque de Caxias, RJ, Brazil;5. Director for Research, Department of Periodontology and Implant Dentistry; Assistant Professor of Biomaterials and Biomimetics, New York University College of Dentistry, New York, New York;7. Professor, Department of Pharmacology, Anesthesiology and Therapeutics, São Leopoldo Mandic Dental School, Campinas, SP, Brazil |
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| Abstract: | ![]()
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. |
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