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Archives of cardiovascular diseases
Volume 106, n° 3
pages 169-177 (mars 2013)
Doi : 10.1016/j.acvd.2012.12.005
Received : 26 July 2012 ;  accepted : 11 December 2012
Pathophysiology of persistent pulmonary hypertension of the newborn: Impact of the perinatal environment
Physiopathologie de l’hypertension artérielle pulmonaire persistante du nouveau-né : rôle de l’environnement périnatal

Figure 1

Figure 1 : 

Schematic representation of the circulation in PPHN. Sustained elevation of PVR contributes to low pulmonary blood flow and high pulmonary pressure, causing extrapulmonary right-to-left shunting of blood across the ductus arteriosus and foramen ovale and severe hypoxaemia. LA: left atrium; LV: left ventricle; PPHN: persistent pulmonary hypertension of the newborn; PV: pulmonary vein; PVR: pulmonary vascular resistance; RA: right atrium; RV: right ventricle.

Figure 2

Figure 2 : 

NO/cGMP pathway. NO, produced by endothelial NOS, diffuses towards the smooth muscle cell in which it stimulates soluble guanylate cyclase to produce cGMP. The mechanism whereby increased cGMP regulates pulmonary vascular tone includes activation of K+ channels, causing smooth muscle cell membrane hyperpolarization and inactivation of VOCC. Closure of VOCC causes a decrease in cytosolic Ca++ concentration and vasorelaxation. Intracellular concentration of cGMP is downregulated by PDE5 activities. Ca++: calcium; cGMP: cyclic guanosine monophosphate; eNOS: endothelial nitric oxide synthase; GMP: guanosine monophosphate; K+: potassium; NO: nitric oxide; NOS: nitric oxide synthase; PDE 5: phosphodiesterase 5; SMC: smooth muscle cell; VOCC: voltage-operated calcium channels.

Figure 3

Figure 3 : 

Schematic representation of the circulation in PPHN. Because of elevated PVR, part of the right ventricular outflow is directed towards the systemic circulation through the ductus arteriosus, contributing to systemic blood flow. Despite a right-to-left ductus arteriosus shunting-mediating drop in postductal SpO2 , oxygen supply is usually adequate as long as the ductus arteriosus is widely patent. Both aortic and pulmonary artery pressures are closely related when the ductus arteriosus is patent (low ductal resistance). Thus, aortic pressure plays a critical role in pulmonary circulation. A drop in aortic pressure is associated with a decrease in pulmonary artery pressure, and since pulmonary artery pressure is the driving force for lung blood flow, a decrease in aortic pressure-induced drop in pulmonary artery pressure may worsen hypoxaemia and oxygen delivery. This electrical representation further highlights that a patent ductus arteriosus and normal right ventricle function are required for sustaining systemic blood flow and oxygen supply. F(PAP): proportional to pulmonary artery pressure; PA: pulmonary artery; PAP: pulmonary artery pressure; PPHN: persistent pulmonary hypertension of the newborn; PVR: pulmonary vascular resistance; SVR: systemic vascular resistance.

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