“…The present study confirms our previous findings in sheep: pneumonectomy followed by one-lung ventilation with excessive tidal volumes and zero end-expiratory pressure promotes lung injury, as characterized by increased pulmonary vascular pressure and permeability, and accumulation of extravascular lung water in concert with derangements of gas exchange [4,12]. Continuous infusion of the inhibitor of nNOS, 7-nitroindazole (NI), from two hours after the start of injurious ventilation dampened the decrease in oxygenation and the respiratory acidosis.…”
Section: Discussionsupporting
confidence: 92%
“…The absence of changes in PBVI in the early postpneumonectomy period confirmed our previous finding that ovine ventilator-induced lung injury after pneumonectomy is not a result of cardiac failure or fluid volume overload [4,12]. This notion is also supported by the observation of no significant differences in GEDVI, which is another marker of preload, between injuriously and protectively ventilated animals [19].…”
Section: Discussionsupporting
confidence: 85%
“…The introducer was also used for infusion of Ringer’s acetate at a rate of 10 ml/kg/h throughout the experiment. Additionally, a 4 F fiberoptic thermistor catheter (PV PV2024L, Pulsion Medical Systems) was placed in the descending thoracic aorta via an introducer in a femoral artery, and a right-sided pneumonectomy was performed, as previously reported [4,12]. …”
Section: Methodsmentioning
confidence: 99%
“…Systemic vascular resistance index (SVRI) and pulmonary vascular resistance index (PVRI) were calculated by the Cold Z-021. All the thermodilution variables were computed as a mean of three measurements, as previously described from our laboratory [4,12]. …”
Section: Methodsmentioning
confidence: 99%
“…The cytotoxic effect of NO, most likely, increases after combining with highly reactive oxygen species to form peroxynitrite, which supposedly plays an important role in the pathogenesis of MODS [5]. In a previous study, we found that infusion of methylene blue, an unspecific inhibitor of eNOS and iNOS, did not attenuate the emergence of ovine PPE [12]. This motivated us to a search for other inhibitors of NOS that could potentially protect against VILI.…”
BackgroundMechanical ventilation with high tidal volumes may cause ventilator-induced lung injury (VILI) and enhanced generation of nitric oxide (NO). We demonstrated in sheep that pneumonectomy followed by injurious ventilation promotes pulmonary edema. We wished both to test the hypothesis that neuronal NOS (nNOS), which is distributed in airway epithelial and neuronal tissues, could be involved in the pathogenesis of VILI and we also aimed at investigating the influence of an inhibitor of nNOS on the course of VILI after pneumonectomy.MethodsAnesthetized sheep underwent right pneumonectomy, mechanical ventilation with tidal volumes (VT) of 6 mL/kg and FiO2 0.5, and were subsequently randomized to a protectively ventilated group (PROTV; n = 8) keeping VT and FiO2 unchanged, respiratory rate (RR) 25 inflations/min and PEEP 4 cm H2O for the following 8 hrs; an injuriously ventilated group with VT of 12 mL/kg, zero end-expiratory pressure, and FiO2 and RR unchanged (INJV; n = 8) and a group, which additionally received the inhibitor of nNOS, 7-nitroindazole (NI) 1.0 mg/kg/h intravenously from 2 hours after the commencement of injurious ventilation (INJV + NI; n = 8). We assessed respiratory, hemodynamic and volumetric variables, including both the extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI). We measured plasma nitrite/nitrate (NOx) levels and examined lung biopsies for lung injury score (LIS).ResultsBoth the injuriously ventilated groups demonstrated a 2–3-fold rise in EVLWI and PVPI, with no significant effects of NI. In the INJV group, gas exchange deteriorated in parallel with emerging respiratory acidosis, but administration of NI antagonized the derangement of oxygenation and the respiratory acidosis significantly. NOx displayed no significant changes and NI exerted no significant effect on LIS in the INJV group.ConclusionInhibition of nNOS improved gas exchange, but did not reduce lung water extravasation following injurious ventilation after pneumonectomy in sheep.
“…The present study confirms our previous findings in sheep: pneumonectomy followed by one-lung ventilation with excessive tidal volumes and zero end-expiratory pressure promotes lung injury, as characterized by increased pulmonary vascular pressure and permeability, and accumulation of extravascular lung water in concert with derangements of gas exchange [4,12]. Continuous infusion of the inhibitor of nNOS, 7-nitroindazole (NI), from two hours after the start of injurious ventilation dampened the decrease in oxygenation and the respiratory acidosis.…”
Section: Discussionsupporting
confidence: 92%
“…The absence of changes in PBVI in the early postpneumonectomy period confirmed our previous finding that ovine ventilator-induced lung injury after pneumonectomy is not a result of cardiac failure or fluid volume overload [4,12]. This notion is also supported by the observation of no significant differences in GEDVI, which is another marker of preload, between injuriously and protectively ventilated animals [19].…”
Section: Discussionsupporting
confidence: 85%
“…The introducer was also used for infusion of Ringer’s acetate at a rate of 10 ml/kg/h throughout the experiment. Additionally, a 4 F fiberoptic thermistor catheter (PV PV2024L, Pulsion Medical Systems) was placed in the descending thoracic aorta via an introducer in a femoral artery, and a right-sided pneumonectomy was performed, as previously reported [4,12]. …”
Section: Methodsmentioning
confidence: 99%
“…Systemic vascular resistance index (SVRI) and pulmonary vascular resistance index (PVRI) were calculated by the Cold Z-021. All the thermodilution variables were computed as a mean of three measurements, as previously described from our laboratory [4,12]. …”
Section: Methodsmentioning
confidence: 99%
“…The cytotoxic effect of NO, most likely, increases after combining with highly reactive oxygen species to form peroxynitrite, which supposedly plays an important role in the pathogenesis of MODS [5]. In a previous study, we found that infusion of methylene blue, an unspecific inhibitor of eNOS and iNOS, did not attenuate the emergence of ovine PPE [12]. This motivated us to a search for other inhibitors of NOS that could potentially protect against VILI.…”
BackgroundMechanical ventilation with high tidal volumes may cause ventilator-induced lung injury (VILI) and enhanced generation of nitric oxide (NO). We demonstrated in sheep that pneumonectomy followed by injurious ventilation promotes pulmonary edema. We wished both to test the hypothesis that neuronal NOS (nNOS), which is distributed in airway epithelial and neuronal tissues, could be involved in the pathogenesis of VILI and we also aimed at investigating the influence of an inhibitor of nNOS on the course of VILI after pneumonectomy.MethodsAnesthetized sheep underwent right pneumonectomy, mechanical ventilation with tidal volumes (VT) of 6 mL/kg and FiO2 0.5, and were subsequently randomized to a protectively ventilated group (PROTV; n = 8) keeping VT and FiO2 unchanged, respiratory rate (RR) 25 inflations/min and PEEP 4 cm H2O for the following 8 hrs; an injuriously ventilated group with VT of 12 mL/kg, zero end-expiratory pressure, and FiO2 and RR unchanged (INJV; n = 8) and a group, which additionally received the inhibitor of nNOS, 7-nitroindazole (NI) 1.0 mg/kg/h intravenously from 2 hours after the commencement of injurious ventilation (INJV + NI; n = 8). We assessed respiratory, hemodynamic and volumetric variables, including both the extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI). We measured plasma nitrite/nitrate (NOx) levels and examined lung biopsies for lung injury score (LIS).ResultsBoth the injuriously ventilated groups demonstrated a 2–3-fold rise in EVLWI and PVPI, with no significant effects of NI. In the INJV group, gas exchange deteriorated in parallel with emerging respiratory acidosis, but administration of NI antagonized the derangement of oxygenation and the respiratory acidosis significantly. NOx displayed no significant changes and NI exerted no significant effect on LIS in the INJV group.ConclusionInhibition of nNOS improved gas exchange, but did not reduce lung water extravasation following injurious ventilation after pneumonectomy in sheep.
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