Mustafa Seren

Collaborative Therapy with Nebivalol and l-NAME for Spinal Cord Ischemia/Reperfusion Injury

Postoperative neurologic deficit is the most devastating complication after thoracoabdominal aortic aneurysm repair. Our aim was to investigate whether nebivolol has protective effects during ischemia or reperfusion and the most effective mechanism of protection via inhibiting nitric oxide (NO) release with an NO synthase inhibitor in an experimental model of spinal cord ischemia/reperfusion injury. Spinal cord ischemia was induced by occlusion of the infrarenal aorta for 30 min. Thirty-one rabbits were divided into five groups according to the administration period of nebivolol and/or N(G)-nitro-L-arginine methyl ester (L-NAME): control group; group NI, nebivolol during ischemic period; group NR, nebivolol during reperfusion period; group NILR, nebivolol during ischemic period and L-NAME during reperfusion period; and group LINR, L-NAME during ischemic period and nebivolol during reperfusion period. Blood samples were taken at both ischemia and reperfusion periods to obtain nitrite/nitrate levels. After neurologic evaluation at 24 hr of reperfusion, malondialdehyde (MDA) levels were measured. Neurologic impairment was significantly lower in group LINR (Tarlov score 3.4 +/- 0.6, p < 0.05). MDA levels were lower in nebivolol-treated animals, but the lowest value was achieved in the NR group, 35.6 +/- 2.7 nmol/g (p < 0.001). Nitrite levels were decreased significantly in all nebivolol-treated animals in the reperfusion period, but the lowest value was measured in the LINR group (455 +/- 137 vs. 1,760 +/- 522 nmol/mL, p < 0.001). Prophylactic use of nebivolol reduced neurologic injury, and combining with L-NAME provided the best clinical improvement by attenuating the inflammatory mileu in this experimental model. Combination of nebivolol and L-NAME appears to be an effective option for spinal cord protection against ischemia/reperfusion injury.

The Protective Effects of Resveratrol and L-NAME on Visceral Organs following Aortic Clamping

BACKGROUNDnThis study investigated the effect of temporary occlusion of the aorta on the development of ischemia-reperfusion (I/R) injury of the visceral organs, the optimal timing of administration of resveratrol, and its mechanism of protection via inhibiting nitric oxide (NO) release with an NO synthase inhibitor.nnnMETHODSnRabbits were divided into seven groups according to the administration period of resveratrol and/or N(G)-nitro-L-arginine methyl ester (L-NAME): control group; group 1, resveratrol during ischemic period; group 2, resveratrol during reperfusion period; group 3, L-NAME during ischemic period; group 4, L-NAME during reperfusion period; group 5, resveratrol during ischemic period and L-NAME during reperfusion period; group 6, L-NAME during ischemic period and resveratrol during reperfusion period. The infrarenal aorta was clamped for 30 min. Blood samples were taken for the biochemical assessment, and organ specimens were taken for pathological assessment at 24hr of reperfusion.nnnRESULTSnIn groups 5 and 6, the renal I/R injury was comparatively milder (I/R injury score 1.04+/-0.29 in control group, 0.25+/-0.17 in group 5, and 0.33+/-0.13 in group 6 [p<0.05]). The I/R injury of bowel was milder in group 5 (I/R injury score 1.8+/-0.80 in control group vs. 0.0+/-0.0 in group 5 [p<0.05]).nnnCONCLUSIONnThe protective effects of resveratrol on organs that have high metabolic rate like kidney and bowel was proven histopathologically. It may be beneficial to use different pharmacological medications in different periods of the I/R damage as they represent different characteristics with and without oxygen. The combination of resveratrol and L-NAME against I/R injury appears to be an effective option in the near future.