Therapeutic hypercapnia prevents inhaled nitric oxide-induced right-ventricular systolic dysfunction in juvenile rats

Tumour necrosis factor‐α contributes to improved cardiac ischaemic tolerance in rats adapted to chronic continuous hypoxia

“…However, chronic infliximab treatment had no effect on COX-2 level and only slightly reduced iNOS expression in CNH rat hearts. Similarly, the blockade of TNF-a signalling by other TNF-a inhibitor etanercept did not prevent the increased expression of iNOS in RV of chronically hypoxic juvenile rats (Dunlop et al 2014). These findings suggest that CNH-induced cardiac overexpression of iNOS and COX-2, respectively, is related to TNF-a-mediated cell signalling.…”

“…Similarly, the blockade of TNF‐ α signalling by other TNF‐ α inhibitor etanercept did not prevent the increased expression of iNOS in RV of chronically hypoxic juvenile rats (Dunlop et al . ). These findings suggest that CNH‐induced cardiac overexpression of iNOS and COX‐2, respectively, is related to TNF‐ α ‐mediated cell signalling.…”

Sodium nitrite augments lungS-nitrosylation and reverses chronic hypoxic pulmonary hypertension in juvenile rats

“…Two-dimensional echocardiography and pulsed wave Doppler ultrasound. Two-dimensional echocardiography and pulsed wave Doppler ultrasound was performed as a noninvasive method to assess pulmonary hemodynamics as previously described (15), using a Philips Affiniti 50 cardiac ultrasound system with a small high frequency linear probe (L15-7io, Philips Healthcare, Richmond Hill, Ontario, Canada). The right ventricular ejection time (RVET) and pulmonary arterial acceleration time (PAAT) were measured using the pulmonary Doppler profile obtained from the parasternal short axis; RVET is the time from onset of systolic flow to completion of systolic flow and PAAT is from onset to peak pulmonary outflow velocity.…”

“…A biochemical obstacle to effective NO-based therapy relates to the high potential for NO to be diverted to produce reactive nitrogen species such as peroxynitrite (31); particularly in the lung, which is directly exposed. Reactive nitrogen species cause irreversible oxidation and tyrosine nitration (51), which permanently alters protein function (6,23,59) and directly contributes to pulmonary vascular disease in neonatal rats (7,15,31,35).…”

Hypercapnia

“…In an infant rat model of right ventricular dysfunction induced by inhaled nitric oxide and hypoxia, hypercapnia was shown to normalize ventricular function by modulating interleukin-1 [12].…”