Mechanisms of inducible nitric oxide synthase (iNOS) inhibition-related improvement of gut mucosal acidosis during hyperdynamic porcine endotoxemia

Abstract

Given the uninfluenced parameters of the ileal mucosal microcirculation in our model of long-term porcine endotoxemia, selective iNOS inhibition probably improved the PCO(2) gap due to a redistribution of the microvascular perfusion within the gut wall and/or an amelioration of the cellular respiration.

Vascular biology in sepsis: pathophysiological and therapeutic significance of vascular dysfunction

“…Interestingly, microvascular perfusion has been shown to be restored by a redistribution within the gut wall and/or an amelioration of the cellular respiration after application of 1,400 W, an inhibitor that has partial iNOS selectivity, in pig endotoxemia model (Pittner et al, 2003). Furthermore, it has been reported that, in a rat CLP model of sepsis, microvascular reactivity to acetylcholine quantified as changes in arteriolar diameter and downstream capillary red blood cell velocity, is impaired in skeletal muscle by NO and restored by neuronal NOS (nNOS) inhibition (Gocan et al, 2000).…”

Untitled

“…Nevertheless, this technique reflected the effect of iloprost on microcirculation by showing significant differences between treatment groups and the control group and between the different treatment groups. This method has not been used in pig IECR thus far, but measurements in mouse livers 13 and pig 15 and human 29 intestinal mucosa during sepsis episodes have been performed, providing evidence that microcirculatory disturbances can be measured. Ischemia-reperfusion, reflected by compromised nutritional perfusion and leukocyte adherence, can be decreased significantly by prostacyclin donor bolus pretreatment, as shown previously in a rat liver transplant model using intravital microscopy for microcirculatory measurements.…”

“…The technique and reliability testing were described previously. [13][14][15][16][17] Microvascular blood flow (recorded in arbitrary units [AU]) was derived from the power spectra of back scattered laser light representing the distribution of Doppler shifts of the erythrocyte velocities. The rHb and SO 2 values were derived from light spectra detected after tissue illumination and back scattering.…”

Modulação do óxido nítrico no choque séptico: estudo experimental dos efeitos hemodinâmicos e inflamatórios do tratamento com doador de óxido nítrico (nitroprussiato) e inibidor da enzima óxido nítrico sintase induzida (1400W) em suínos submetidos ao choque séptico

“…Num estudo em um modelo de endotoxemia em porcos, a perfusão microvascular foi restabelecida pela redistribuição do fluxo dentro da parede intestinal, com a utilização do 1400W (PITTNER et al, 2003;SPRONK et al, 2004 …”

“…Tabela 10 -Médias e desvios padrão dos parâmetros acessórios de todos os animais dos grupos Sham, Choque e NO/iNOs, nos tempos experimentais avaliados -São Paulo -2010 Tbasal T0 T60 T120 T180 T240 Sham 36,7 ± 0,2 36,9 ± 0,3 37,3 ± 0,5 37,7 ± 0,4 37,9 ± 0,4 38 ± 0,5 Temp Choque 37,2 ± 0,7 37,7 ± 0,8 37,5 ± 0,7 37,9 ± 0,8 38 ± 0,5 37,9 ± 0,5 (oC) NO/iNOs 37,2 ± 0,9 37,7 ± 0,7 37,2 ± 0,5 37,5 ± 0,5 37,6 ± 0,6 37,5 ± 0,5 Alguns autores propõem inclusive, outros parâmetros para classificação e estratificação dos pacientes sépticos, quando da realização de testes para novos tratamentos (ABRAHAM et al, 2000;VINCENT;BYL, 2000;CARLET et al, 2001;LEVY et al, 2003;MARSHALL et al, 2003;VENTETUOLO;VINCENT;MARTINEZ; ter sido efetiva em não provocar nenhum efeito negativo, ao menos no período de duração do tratamento específico, que foi de 2 horas (PASTOR et al, 1995;ZHANG et al, 1997;GROVER et al, 2000;PITTNER et al, 2003;SIEGEMUND et al, 2005SIEGEMUND et al, , 2007ASSADI et al, 2008;KLIJN et al, 2008).…”