L-arginine and substance P reverse the pulmonary endothelial dysfunction caused by congenital heart surgery

Schulze‐Neick, Ingram; Penny, DJ; Rigby, ML; Morgan, Cliff; Kelleher, Andrea; Collins, Peter; Li, J; Bush, A; Shinebourne, E A; Redington, A.

doi:10.1186/cc325

Cited by 14 publications

(16 citation statements)

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“…While in a previous study, we demonstrated in preoperative children with congenital heart disease an almost complete fall of mildly increased PVRI to normal with hyperoxia alone, 5 in other studies with more severely diseased and older patients, PVRI fell with oxygen and again with 50 to 80 ppm NO. 16,17 Our patients had moderately increased PVRI which failed to respond to 20 ppm of NO.…”

Section: Intravenous Sildenafil Compared With Inhaled No As a Specifimentioning

confidence: 95%

“…Endtidal CO 2 (etCO 2 ) and systemic oxygen consumption {O [mL/(kg⅐min)]} were continuously determined using respiratory mass spectrometry by the mixed expirate inert gas dilution method 11 with our previously described modification 5 for use in ventilated patients. Special care was taken to detect and exclude any air leaks or carbon dioxide contamination of the monitoring and ventilatory circuits.…”

Section: Hemodynamic Measurements and Determinatin Of Oxygen Consumptionmentioning

confidence: 99%

“…3 Alternatively, responders to longterm NO therapy may develop severe, life-threatening, rebound pulmonary hypertension on withdrawal of nitric oxide. 4 We have recently shown 5 that by enhancement of the NO-arginine pathway, ie, by providing the substrate for NO-production (L-arginine) and stimulating the enzyme responsible for NO-formation (substance P), that there is almost no PED in preoperative patients, and that it is possible to restore the pulmonary endothelial vasodilating function to a large degree in most postoperative patients.…”

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confidence: 99%

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Intravenous Sildenafil Is a Potent Pulmonary Vasodilator in Children With Congenital Heart Disease

et al. 2003

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Background-Increased pulmonary vascular resistance (PVR) because of congenital heart disease (CHD) may be caused by a dysfunction in endogenous pulmonary endothelial nitric oxide (NO) production. In other forms of pulmonary vascular disease with increased PVR, an elevated activity of a phosphodiesterase type 5 (PDE-5), responsible for the degradation of cyclic guanidine monophosphate (cGMP), the second messenger of endothelially produced NO, has been demonstrated. This study compares the effects of inhaled NO before and after the specific inhibition of the PDE-5 by intravenous sildenafil (Viagra™) in pre-and postoperative children with increased PVR because of CHD. Methods and Results-12 children with congenital heart disease (age 0.2 to 15.7 years, median 2.4 years) and increased mean pulmonary arterial pressure, and 12 postoperative children (age 0.11 to 0.65 years, median 0.32 years) with increased PVR (8.3Ϯ1.0 Wood Units*m 2 ) were studied during cardiac catheterization ("cath laboratory"), or within 2 hours after return from cardiac surgery ("post op"), respectively. All were sedated, tracheally intubated and paralyzed. During alveolar hyperoxygenation (F i O 2 ϭ0.65), the effects of inhaled NO (20 ppm) were compared before and after the stepwise infusion of sildenafil ("cath laboratory", 1 mg/kg; post op, 0.25 mg/kg). Intravenous sildenafil more effectively reduced PVR than NO (11.5% versus 4.3% in the "cath laboratory" patient group, PϽ0.05, and 25.8% versus 14.6% in the post op patient group, Pϭ0.09. The increase in cGMP in response to NO was potentiated (2-to 2.4-fold) by PDE-5 inhibition. While the vasodilating effects of sildenafil showed pulmonary selectivity, its infusion was associated with increased intrapulmonary shunting in the postoperative patients (Q s / Q t ϭ16.5Ϯ4.7% to 25.5Ϯ18.2% Pϭ0.04). Conclusions-Intravenous sildenafil is as effective as inhaled NO as a pulmonary vasodilator in children with congenital heart disease. Although clinically insignificant in this study, increased intrapulmonary shunting with sildenafil may be disadvantageous in some patients after CHD surgery.

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Section: Intravenous Sildenafil Compared With Inhaled No As a Specifimentioning

confidence: 95%

Section: Hemodynamic Measurements and Determinatin Of Oxygen Consumptionmentioning

confidence: 99%

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confidence: 99%

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Intravenous Sildenafil Is a Potent Pulmonary Vasodilator in Children With Congenital Heart Disease

et al. 2003

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“…Ischemia-reperfusion injury and the CPB-induced inflammatory response lead to pulmonary endothelial injury, including decreased production of nitric oxide [35]. Nitric oxide production is also impaired due to decreased availability of nitric oxide precursors such as L-arginine [36]. Pulmonary vasodilators are effective at reducing post-operative elevations in PVR resulting from the adverse affects of CPB.…”

Section: Pulmonary Arterial Hypertensionmentioning

confidence: 98%

Perioperative Management of Pulmonary Hypertension in Children with Critical Heart Disease

Bronicki

2011

Curr Treat Options Cardio Med

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Pulmonary hypertension (PHTN) is common to a variety of conditions occurring in infants and children presenting to the intensive care unit. A fundamental understanding of the response of the right ventricle to an increase in afterload and the clinical syndromes responsible for PHTN is essential for managing patients with PHTN and critical heart disease. There are important distinguishing features between PHTN syndromes, and although one form of PHTN may predominate, often more than one mechanism of PHTN is contributing to the pathophysiologic state. Thus, it is imperative to tailor therapies accordingly in order to optimize outcomes.

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“…134 A study that included 20 infants with PH related to cardiac defects with increased pulmonary blood flow examined the effects of an infusion of intravenous L-arginine on hemodynamic variables. 135 Ten patients were studied preoperatively and another 10 were studied 2 hours after separating from cardiopulmonary bypass in the postoperative period. PVR decreased in both groups in response to oxygen.…”

Section: Nitric Oxide-cgmp Cascade: Inhaled Nitric Oxidementioning

confidence: 99%

Advances in the Management of Pediatric Pulmonary Hypertension

2011

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Pulmonary hypertension is a rare disease in neonates, infants, and children, and is associated with substantial morbidity and mortality. An adequate understanding of the controlling pathophysiologic mechanisms is lacking. Moreover, a minority of research is focused specifically on neonatal and pediatric populations. Although therapeutic options have increased over the past several decades, they remain limited. In advanced pulmonary hypertension, progressive pulmonary vascular functional and structural changes ultimately cause increased pulmonary vascular impedance, rightventricular failure, and death. Management includes the prevention and/or treatment of active pulmonary vasoconstriction, the support of right-ventricle function, treatment of the underlying disease (if possible), and the promotion of regressive remodeling of structural pulmonary vascular changes. Most currently available therapies augment or inhibit factors, or mediators of their downstream signaling cascades, that originate in the pulmonary vascular endothelium. These pathways include nitric-oxide/cyclic guanosine monophosphate (cGMP), prostacyclin, and endothelin-1. The ability to reverse advanced structural changes remains an as yet unattained goal. This paper reviews the epidemiology, pathophysiology, current treatments, and emerging therapies related to neonatal and pediatric pulmonary hypertension.

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L-arginine and substance P reverse the pulmonary endothelial dysfunction caused by congenital heart surgery

Cited by 14 publications

References 0 publications

Intravenous Sildenafil Is a Potent Pulmonary Vasodilator in Children With Congenital Heart Disease

Intravenous Sildenafil Is a Potent Pulmonary Vasodilator in Children With Congenital Heart Disease

Perioperative Management of Pulmonary Hypertension in Children with Critical Heart Disease

Advances in the Management of Pediatric Pulmonary Hypertension

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