Protective Effect of Sildenafil (Viagra) in Transient Spinal Cord Ischemia

Abstract

Prospective study of the neuroprotective activity of sildenafil in a rat spinal ischemia model. The present study involved 21 male Sprague-Dawley rats. The animals were divided into 3 groups. Physiological serum was administered intraperitoneally to the 8 rats in the control group at the beginning of reperfusion for a period of 20 min after abdominal aortal occlusion. Sildenafil (Viagra®) was administered as a single 10-mg/kg/day intraperitoneal dose to the 8 rats in the sildenafil group at the beginning of reperfusion after 20 min of abdominal aortal occlusion. No occlusion was performed and no agent was administered to the 5 rats in the sham group, but the abdominal aorta was reached by means of surgical intervention. Before the animals were sacrificed, several physiological and biochemical parameters were investigated, preoperative and postoperative motor functions were also assessed, and somatosensory evoked potential (SEP) monitoring and histopathological examinations were carried out. No differences were found between the physiological and biochemical parameters in each of the 3 groups. Neurological scoring performed after reperfusion demonstrated a significant improvement in the neurological results relative to those of the control group over 48 h in subjects that received sildenafil. These animals also showed better 24-hour SEP results, measured in terms of extended latency and decreased amplitude, than the control animals. A histopathological study showed reduced ischemic symptoms in rats that received sildenafil compared with those in the control group. However, no anomalies were observed in the sham group with respect to the histopathological and neurological findings. These results indicate that neurological damage due to spinal-cord ischemia-reperfusion injury can be reduced by sildenafil.

Sildenafil Improves Epicenter Vascular Perfusion but not Hindlimb Functional Recovery after Contusive Spinal Cord Injury in Mice

“…These studies differ substantially in methodology. For example, the models of ischemic injury, spinal ischemia (Kiymaz et al, 2008), focal cerebral ischemia (Zhang et al, 2006), and middle cerebral artery occlusion (MCAO; Menniti et al, 2009) all differed. The phosphodiesterase antagonist investigated also differed: sildenafil (Kiymaz et al, 2008;Zhang et al, 2006) or PF-5 (Menniti et al, 2009).…”

“…For example, the models of ischemic injury, spinal ischemia (Kiymaz et al, 2008), focal cerebral ischemia (Zhang et al, 2006), and middle cerebral artery occlusion (MCAO; Menniti et al, 2009) all differed. The phosphodiesterase antagonist investigated also differed: sildenafil (Kiymaz et al, 2008;Zhang et al, 2006) or PF-5 (Menniti et al, 2009). The duration and route of drug administration varied: 1 day, IP (Kiymaz et al, 2008), 6 days, oral (Zhang et al, 2006), or 7 days, subcutaneous (Menniti et al, 2009).…”

“…The duration and route of drug administration varied: 1 day, IP (Kiymaz et al, 2008), 6 days, oral (Zhang et al, 2006), or 7 days, subcutaneous (Menniti et al, 2009). Finally, different methods of neurological assessment were utilized: the Tarlov classification (Kiymaz et al, 2008), body-swing and limb-placement tests (Menniti et al, 2009), or foot-fault and adhesive removal tests (Zhang et al, 2006).…”

“…Indeed, while acute neurological improvements following sildenafil administration have been reported in a spinal ischemia model (Kiymaz et al, 2008), no significant acute functional improvements following tadalafil administration could be found acutely after trauma in a weight drop model of SCI (Serarslan et al, 2010). Additionally, our rationale for a more chronic duration of treatment was to assess the potential benefits of improving angiogenesis after injury, as observed after embolic stroke (Ding et al, 2008;Li et al, 2007;Zhang et al, 2006), in addition to the potential vasodilatory protective effects of a more acute administration.…”

The Sildenafil Citrate Does Not Prevent Tissue Damage On Early Period in Rat Kidney Ischemia Reperfusion Model

“…Bununla birlikte yeniden kanlanma sı-rasında oluşan çeşitli faktörlere bağlı olarak hücresel hasar oluşmaktadır. Böbrek iskemi yeniden kanlanma hasarının patofizyolojisinde, tübüler apoptozis gelişimi, serbest oksijen radikalleri formasyonu, mitokondriyal disfonksiyon, inflamatuar sitokin oluşumu ve nötrofil salınımının neden olduğu bildirilmiştir (1)(2)(3) .…”