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
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.
Asunto(s)
Azepinas/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Glicoproteínas de Membrana Plaquetaria , Receptores de Superficie Celular/metabolismo , Receptores Acoplados a Proteínas G , Choque Traumático/tratamiento farmacológico , Triazoles/uso terapéutico , Animales , Azepinas/sangre , Presión Sanguínea/efectos de los fármacos , Catepsina D/sangre , Técnicas In Vitro , Masculino , Factor Depresor Miocardico/sangre , Nitrógeno/sangre , Inhibidores de Agregación Plaquetaria/sangre , Conejos , Ratas , Ratas Endogámicas , Choque Traumático/fisiopatología , Tromboxano B2/sangre , Triazoles/sangreRESUMEN
The effect of 4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl- 3(2H)- pyridazinone (pimobendan, UD-CG 115 BS), a novel positive inotropic and vasodilator agent, was studied in a severe model of murine traumatic shock. Noble-Collip drum trauma produced a shock state characterized by a significantly reduced mean arterial blood pressure (MABP), a 5-fold increase in plasma cathepsin D and myocardial depressant factor (MDF) activities, and a survival time of 80 +/- 12 min. Administration of pimobendan (100 micrograms/kg, i.v. bolus) significantly prolonged the survival time to 175 +/- 24 min (p less than 0.01). Although plasma cathepsin D was not affected by pimobendan, this agent significantly attenuated the accumulation of MDF activity in the plasma when compared to animals receiving only its vehicle (37 +/- 6 vs 61 +/- 9 U/ml, p less than 0.05). Additionally, pimobendan inhibited platelet aggregation in cat platelet rich plasma, but failed to have an antiproteolytic effect in cat pancreatic homogenates. These results suggest that cardiotonic and vasodilator activities combined with inhibition of platelet aggregation could mediate the beneficial effects of pimobendan in traumatic shock.