RESUMEN
Myocardial depression and heart failure are frequent complications in critically ill burn patients. The physiopathology is complex and involves the activation of inflammatory pathways, ischemia-reperfusion, oxidative stress and endothelial lesion. Diagnosis should be made early by means of hemodynamic monitoring. Treatment is accomplished by inotropics that act on different pathways of the contractile function and immune response associated with antioxidants and allopurinol.
Asunto(s)
Quemaduras/complicaciones , Gasto Cardíaco Bajo/etiología , Choque Traumático/etiología , Adulto , Quemaduras/tratamiento farmacológico , Quemaduras/fisiopatología , Gasto Cardíaco Bajo/tratamiento farmacológico , Gasto Cardíaco Bajo/fisiopatología , Cardiotónicos/uso terapéutico , Humanos , Masculino , Estrés Oxidativo/fisiología , Choque Traumático/tratamiento farmacológico , Choque Traumático/fisiopatología , Resultado del TratamientoRESUMEN
The role of nitric oxide (NO) on liver oxidative stress and tissue injury in rats subjected to tourniquet shock was investigated. This shock model differs from others in that injury is a consequence of remote organ damage. Liver oxidative stress becomes evident after hind limb reperfusion, as evidenced by the loss of total tissue thiols; by increases in tissue oxidized glutathione (GSSG), lipid peroxidation (LPO), plasma aminotransferases (alanine aminotransferase (ALT) and (aspartate aminotransferase (AST)), and plasma nitrites; and by a 36% loss in total superoxide dismutase (SOD) activity. Portal blood flow is reduced by 54.1% after 2 h of hind limb reperfusion. Inhibition of NO synthesis with Nomega-nitro-L-arginine methyl ester or L-arginine methyl ester increased mean arterial blood pressure; further reduced portal blood flow; and aggravated liver injury as assessed by further loss in total thiols, increased LPO and GSSG content, and further increases in plasma ALT and AST. Total plasma nitrites were lower than in control animals, and total tissue SOD activity decreased by more than 80%. Treatment with the NO donor sodium nitroprusside reverted the decrease in portal blood flow and also reverted tissue thiol loss, LPO, and GSSG increases, as well as the loss of ALT and AST to plasma and of SOD activity to levels comparable to untreated control shock animals. As expected, plasma nitrites were greater than in tourniquet control animals. These data support the hypothesis that endogenous NO formation protects the rat liver from the consequences of oxidative stress elicited by hind limb reperfusion in rats subjected to tourniquet shock.
Asunto(s)
Glutatión/metabolismo , Hígado/fisiopatología , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Estrés Oxidativo , Choque Traumático/fisiopatología , Superóxido Dismutasa/metabolismo , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Presión Sanguínea , Cisteína/metabolismo , Femenino , Disulfuro de Glutatión/metabolismo , Peroxidación de Lípido , Hígado/efectos de los fármacos , Hígado/metabolismo , Malondialdehído/análisis , Nitroprusiato/farmacología , Ratas , Ratas Sprague-Dawley , Reperfusión , Choque Traumático/metabolismo , Superóxido Dismutasa/antagonistas & inhibidores , TorniquetesRESUMEN
We studied the effects of BN 50739, a novel PAF antagonist, in a rat model of traumatic shock. Pentobarbital anesthetized rats subjected to Noble-Collip drum trauma developed a shock state characterized by marked hypotension, significant increases in plasma cathepsin D (4.2-fold), free amino-nitrogen (2.8-fold) and myocardial depressant factor (4.7-fold) activities and a survival time of 1.62 +/- 0.16 h. Treatment with BN 50739 (10 mg/kg, i.v.) 10 min post-trauma prolonged survival time to 3.14 +/- 0.44 h (p less than 0.01) and attenuated the accumulations of cathepsin D (5.8 vs. 12.5 U/ml, p less than 0.01), free amino-nitrogen (4.6 vs. 12.5 U/ml, p less than 0.001) and myocardial depressant factor (19.4 vs. 65.1 U/ml, p less than 0.001). Moreover, in washed rabbit platelets, BN 50739 inhibited PAF (1.85 nM)-induced aggregation (IC50: 50 nM) without affecting ADP (5 microM)-induced aggregation. In anesthetized rats, BN 50739 (10 mg/kg, i.v.) attenuated PAF (10-30 ng/kg, i.v.)-induced hypotension for longer than 5 h, without influencing acetylcholine (10 micrograms/kg, i.v.)-induced hypotension. These findings indicate that BN 50739 is a specific PAF receptor antagonist with a long duration of action in vivo. The beneficial effects of PAF antagonism on traumatic shock are significant in the present study, and are consistent with the concept that PAF is involved in the pathogenesis of traumatic shock.