Effects Of Pentoxifylline On Cardiac Dysfunctions Following High Level Spinal Cordinjury In Rats

Objective: To investigate the effects of pentoxifylline (PTX) on cardiacdysfunctions after high level spinal cord injury (SCI) in rats and to study the potentialmechanism．Methods:90adult male Sprague-Dawley rats weighing between260and300gwere carried out as experiments animals which were approved by the ExperimentalAnimal Center of Binzhou Medical University.60rats were subjuceted into C7injuryto induce the moderate high level SCI animal models using an improved Allensweight-drop device as SCI group．Rats in SCI group were then randomly divided intoPTX intraperitoneal treatment rats called PTX subgroup (SCI-PTX group) or Normalsaline intraperitoneal treatment rats called normal saline subgroup (SCI-NS group),30rats for each subgroup. In addition, the other30rats were subjected into the Sham group.The PTX or normal saline was administered intraperitoneally (30mg/kg) immediatelyafter surgery, and then once every12hours. At4h,12h,24h,48h and72h time pointevery6rats for each group were used for acute researches. Arterial pressure (AP), meanarterial pressure (MAP) and heart rate (HR) were determined with a catheter placed intothe carotid artery. And then LV systolic pressure (LVSP) and LV peak velocities ofcontraction (LVdP/dtmax) were measured with a catheter placed into left ventricle.After that, blood samples were collected from carotid artery into a tube and hearts aswell as injured spinal cord tissues were removed. Serum creatine kinase (CK), CK-MBand lactate dehydrogenase(LDH) were measured using automatic chemical analyzer.Superoxide dismutase(SOD) activity and malondialdehyde(MDA) level in themyocardium and injured spinal cord tissures were determined by ultravioletspectrophotometry method. In addition, tumor necrosis factor(TNF)-α andinterleukin(IL）-1β level in the injured spinal cord tissures were measured by enzyme-linked immunosorbent assay(ELISA) method.Results:1. hemodynamics variables changesThe SCI-NS rats exhibited significantly lower MAP, HR, LVSP and LVdP/dtmaxcompared with Sham rats at4,12,24,48and72h after surgery, reaching peak at12h.The SCI-PTX rats exhibited significantly higher MAP, HR, LVSP and LVdP/dtmaxcompared with SCI-NS rats at4,12,24,48and72h after surgery.2. cardiac enzymes changesThe SCI-NS rats exhibited significantly higher serum CK and CK-MB levelcompared with Sham rats at4,12,24,48and72h after surgery, reaching peak at24h.Although there was no significant serum LDH changes at4h after surgery, the SCI-NSrats exhibited significantly higher serum LDH level compared with Sham rats at12,24,48and72h after surgery, reaching peak at48h. The SCI-PTX rats exhibitedsignificantly lower serum CK and CK-MB level compared with SCI-NS rats at4,12,24,48and72h after surgery and significantly lower serum LDH level compared withSCI-NS rats at12,24,48and72h after surgery.3. oxidative stress in myocardiumThe SCI-NS rats exhibited significantly lower SOD activity and higher MDAlevel in the myocardium compared with Sham rats at4,12,24,48and72h after surgery,reaching peak at48h. The SCI-PTX rats exhibited significantly higher SOD activityand lower MDA level in the myocardium compared with SCI-NS rats at12,24,48and72h after surgery.4. TNF-α、IL-1βlevel and oxidative stress in the injured spinal cord tissuresThe SCI-NS rats exhibited significantly higher TNF-α、IL-1βlevel in the injuredspinal cord tissures compared with Sham rats at4,12and24h after surgery, reachingpeak at12h. The SCI-NS rats also exhibited significantly persistent lower SOD activityand higher MDA level in the injured spinal cord tissures compared with Sham rats. TheSCI-PTX rats exhibited significantly lower TNF-α、IL-1βlevel in the injured spinalcord tissures compared with SCI-NS rats at4,12and24h after surgery andsignificantly higher SOD activity and lower MDA level in the injured spinal cordtissures at4,12,24,48and72h after surgery.Conclusions: PTX have protective effects on heart function in high level SCI rats,and its mechanism may involve reduced inflammatory responses and oxidative stress ofthe injured spinal cord tissures.