Molecular and pharmacological approaches to inhibiting XXXX after burn @entity130 .

@entity6708 @entity5118 @entity12874 @entity19 @entity409 @entity842 @entity13633 @entity6710 @entity299 @entity130
Whereas controversial, several studies have suggested that @entity842 (NO) alters cardiac contractility via @entity6708 , @entity6710 , or @entity12874 synthetase (PARS) activation. This study determined whether burn-related upregulation of myocardial inducible NO synthase ( @entity13633 ) and NO generation contributes to burn-mediated cardiac @entity409 . @entity19 homozygous null for the @entity13633 gene ( @entity13633 knockouts) were obtained from Jackson Laboratory. @entity13633 knockouts (KO) as well as wild-type @entity19 were given a cutaneous burn over 40% of the total body surface area by the application of brass probes (1 x 2 x 0.3 cm) heated to 100 degrees C to the animals' sides and back for 5 s ( @entity13633 /KO burn and wild-type burn). Additional groups of @entity13633 KO and wild-type @entity19 served as appropriate sham burn groups ( @entity13633 /KO sham and wild-type sham). Cardiac function was assessed 24 h postburn by perfusing hearts (n = 7-10 @entity19 /group). @entity130 in wild-type @entity19 @entity299 as indicated by the lower left ventricular pressure (LVP, 67 +/- 2 mmHg) compared with that measured in wild-type shams (94 +/- 2 mmHg, P < 0.001), a lower rate of LVP rise (+dP/dtmax, 1,620 +/- 94 vs. 2,240 +/- 58 mmHg/s, P < 0.001), and a lower rate of LVP fall (-dP/dtmax, 1,200 +/- 84 vs. 1,800 +/- 42 mmHg/s, P < 0.001). Ventricular function curves confirmed significant @entity409 after burn @entity130 in wild-type @entity19 . @entity130 in @entity13633 KO @entity19 produced fewer @entity299 compared with those observed in wild-type burns (LVP: 78 +/- 5 mmHg; +dP/dt: 1,889 +/- 160 mmHg/s; -dP/dt: 1,480 +/- 154 mmHg/s). The use of a pharmacological approach to inhibit @entity13633 ( @entity5118 , given ip) in additional wild-type shams and burns confirmed the @entity13633 KO data. Whereas the absence of @entity13633 attenuated burn-mediated cardiac @entity409 , these experiments did not determine the contribution of cardiac-derived NO versus NO generated by immune cells. However, our data indicate a role for NO in @entity299 after major @entity130 .
