The pulmonary vasculature in a neonatal porcine model with increased pulmonary blood flow and pressure

2001 ◽  
Vol 11 (4) ◽  
pp. 420-430 ◽  
Author(s):  
Elisabeth V. Stenbøg ◽  
Daniel A. Steinbrüchel ◽  
Anne Bloch Thomsen ◽  
Ulrik Baandrup ◽  
Lene Heickendorff ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Vascular Disease ◽  
Pulmonary Blood Flow ◽  
Left Pulmonary Artery ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Systolic Pulmonary Arterial Pressure ◽  
Pulmonary Arterial ◽  
Circulating Levels

Introduction: Hypertension and hyperperfusion of the pulmonary vascular bed in the setting of congenital cardiac malformations may lead to progressive pulmonary vascular disease. To improve the understanding of the basic mechanisms of this disease, there is a need for clinically relevant animal models which reflect the disease process. Material and Results: We randomly allocated 45 newborn pigs, at the age of 48 hrs, to groups in which there was either construction of a 3 mm central aorto-pulmonary shunt, undertaken in 9, or ligation of the left pulmonary artery, achieved in 13. Controls included sham operations in 13, or no operations in 10 pigs. Follow-up was continued for three months. The interventions were compatible with survival in most pigs. The shunts resulted in an acute 85% increase in systolic pulmonary arterial pressure, and a more than twofold increase in pulmonary blood flow. By three months of age, nearly all shunts had closed spontaneously, and haemodynamics were normal. Ligation of the left pulmonary artery resulted in a normal total pulmonary blood flow, despite only the right lung being perfused, and a 33% increase in systolic pulmonary arterial pressure. These haemodynamic changes were maintained throughout the period of study. In both groups, histomorphometry revealed markedly increased muscularity of the intra-acinar pulmonary arteries. Circulating levels of endothelin were normal in the shunted animals, and elevated in those with ligation of the left pulmonary artery. Conclusion: In neonatal porcine models of pulmonary vascular disease, created by construction of 3 mm central aorto-pulmonary shunts and ligation of one pulmonary artery, we observed histopathological changes of the pulmonary vasculature similar to early hypertensive pulmonary vascular disease in humans. Elevated circulating levels of endothelin were associated with abnormal haemodynamics rather than abnormal pathology. These findings could be valuable for future studies on the pathogenesis of hypertensive pulmonary vascular disease associated with congenital cardiac malformations.

DIAGNOSIS AND TREATMENT: MANAGEMENT OF VENTRICULAR SEPTAL DEFECT

PEDIATRICS ◽  
1964 ◽  
Vol 34 (2) ◽  
pp. 271-273
Author(s):  
Alexander S. Nadas
Keyword(s):  
Blood Flow ◽  
Ventricular Septal Defect ◽  
Vascular Disease ◽  
Pulmonary Blood Flow ◽  
Septal Defect ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
The Status ◽  
Full Analysis ◽  
Intelligent Management

Intelligent management of a ventricular septal defect necessitates full analysis of the size of the defect, the shunt across it and the status of the pulmonary vasculature. Only patients with moderate or large defects with appreciably increased pulmonary blood flow deserve surgery. Those with small left-to-right shunts, with or without pulmonary vascular disease, should be managed medically.

scholarly journals Mechanical forces alter endothelin-1 signaling: comparative ovine models of congenital heart disease

2020 ◽  
Vol 10 (2) ◽  
pp. 204589402092211
Author(s):  
Terry Zhu ◽  
Samuel Chiacchia ◽  
Rebecca J. Kameny ◽  
Antoni Garcia De Herreros ◽  
Wenhui Gong ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Pulmonary Artery ◽  
Vascular Disease ◽  
Congenital Heart ◽  
Left Pulmonary Artery ◽  
Pulmonary Vascular Disease ◽  
Endothelin 1 ◽  
Pulmonary Arterial ◽  
The Right

The risk and progression of pulmonary vascular disease in patients with congenital heart disease is dependent on the hemodynamics associated with different lesions. However, the underlying mechanisms are not understood. Endothelin-1 is a potent vasoconstrictor that plays a key role in the pathology of pulmonary vascular disease. We utilized two ovine models of congenital heart disease: (1) fetal aortopulmonary graft placement (shunt), resulting in increased flow and pressure; and (2) fetal ligation of the left pulmonary artery resulting in increased flow and normal pressure to the right lung, to investigate the hypothesis that high pressure and flow, but not flow alone, upregulates endothelin-1 signaling. Lung tissue and pulmonary arterial endothelial cells were harvested from control, shunt, and the right lung of left pulmonary artery lambs at 3–7 weeks of age. We found that lung preproendothelin-1 mRNA and protein expression were increased in shunt lambs compared to controls. Preproendothelin-1 mRNA expression was modestly increased, and protein was unchanged in left pulmonary artery lambs. These changes resulted in increased lung endothelin-1 levels in shunt lambs, while left pulmonary artery levels were similar to controls. Pulmonary arterial endothelial cells exposed to increased shear stress decreased endothelin-1 levels by five-fold, while cyclic stretch increased levels by 1.5-fold. These data suggest that pressure or an additive effect of pressure and flow, rather than increased flow alone, is the principal driver of increased endothelin signaling in congenital heart disease. Defining the molecular drivers of the pathobiology of pulmonary vascular disease due to differing mechanical forces will allow for a more targeted therapeutic approach.

Atrasentan Treatment of Pulmonary Vascular Disease in Piglets With Increased Pulmonary Blood Flow

2007 ◽  
Vol 50 (3) ◽  
pp. 286-292 ◽  
Author(s):  
Matthias Gorenflo ◽  
Michael V Ullmann ◽  
Esther Herpel ◽  
Stephan Neumayer ◽  
Ralf Dieckmann ◽  
...  
Keyword(s):  
Blood Flow ◽  
Vascular Disease ◽  
Pulmonary Blood Flow ◽  
Pulmonary Vascular Disease

scholarly journals Computational haemodynamic analysis of left pulmonary artery angulation effects on pulmonary blood flow

2016 ◽  
Vol 23 (4) ◽  
pp. 519-525 ◽  
Author(s):  
Weimin Zhang ◽  
Jinlong Liu ◽  
Qin Yan ◽  
Jinfen Liu ◽  
Haifa Hong ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Pulmonary Blood Flow ◽  
Left Pulmonary Artery

scholarly journals Pulmonary Pulse Wave Transit Time is Associated with Right Ventricular–Pulmonary Artery Coupling in Pulmonary Arterial Hypertension

2016 ◽  
Vol 6 (4) ◽  
pp. 576-585 ◽  
Author(s):  
Kurt W. Prins ◽  
E. Kenneth Weir ◽  
Stephen L. Archer ◽  
Jeremy Markowitz ◽  
Lauren Rose ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Transit Time ◽  
Pulse Wave ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Pulse Wave Transit Time ◽  
Pulmonary Arterial

Pulmonary pulse wave transit time (pPTT), defined as the time for the systolic pressure pulse wave to travel from the pulmonary valve to the pulmonary veins, has been reported to be reduced in pulmonary arterial hypertension (PAH); however, the underlying mechanism of reduced pPTT is unknown. Here, we investigate the hypothesis that abbreviated pPTT in PAH results from impaired right ventricular–pulmonary artery (RV-PA) coupling. We quantified pPTT using pulsed-wave Doppler ultrasound from 10 healthy age- and sex-matched controls and 36 patients with PAH. pPTT was reduced in patients with PAH compared with controls. Univariate analysis revealed the following significant predictors of reduced pPTT: age, right ventricular fractional area change (RV FAC), tricuspid annular plane excursion (TAPSE), pulmonary arterial pressures (PAP), diastolic pulmonary gradient, transpulmonary gradient, pulmonary vascular resistance, and RV-PA coupling (defined as RV FAC/mean PAP or TAPSE/mean PAP). Although the correlations between pPTT and invasive markers of pulmonary vascular disease were modest, RV FAC ( r = 0.64, P < 0.0001), TAPSE ( r = 0.67, P < 0.0001), and RV-PA coupling (RV FAC/mean PAP: r = 0.72, P < 0.0001; TAPSE/mean PAP: r = 0.74, P < 0.0001) had the strongest relationships with pPTT. On multivariable analysis, only RV FAC, TAPSE, and RV-PA coupling were independent predictors of pPTT. We conclude that shortening of pPTT in patients with PAH results from altered RV-PA coupling, probably occurring as a result of reduced pulmonary arterial compliance. Thus, pPTT allows noninvasive determination of the status of both the pulmonary vasculature and the response of the RV in patients with PAH, thereby allowing monitoring of disease progression and regression.

Endogenous Hydrogen Sulfide Regulates Pulmonary Artery Collagen Remodeling in Rats with High Pulmonary Blood Flow

2009 ◽  
Vol 234 (5) ◽  
pp. 504-512 ◽  
Author(s):  
Xiaohui Li ◽  
Hongfang Jin ◽  
Geng Bin ◽  
Li Wang ◽  
Chaoshu Tang ◽  
...  
Keyword(s):  
Blood Flow ◽  
Hydrogen Sulfide ◽  
Pulmonary Artery ◽  
Lung Tissue ◽  
Pulmonary Blood Flow ◽  
Pulmonary Arteries ◽  
Tissue Growth ◽  
Pulmonary Vasculature ◽  
Collagen Remodeling ◽  
Collagen Iii

The mechanisms responsible for the structural remodeling of pulmonary vasculature induced by increased pulmonary blood flow are not fully understood. This study explores the effect of endogenous hydrogen sulfide (H2S), a novel gasotransmitter, on collagen remodeling of the pulmonary artery in rats with high pulmonary blood flow. Thirty-two Sprague-Dawley rats were randomly divided into sham, shunt, sham+PPG (D,L-propargylglycine, an inhibitor of cystathionine-γ-lyase), and shunt+PPG groups. After 4 weeks of shunting, the relative medial thickness (RMT) of pulmonary arteries and H2S concentration in lung tissues were investigated. Collagen I and collagen III were evaluated by hydroxyproline assay, sirius-red staining, and immunohistochemistry. Pulmonary artery matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and connective tissue growth factor (CTGF) were evaluated by immunohistochemistry. After 4 weeks of aortocaval shunting, resulting in an elevation of lung tissue H2S to 116.4%, rats exhibited collagen remodeling and increased CTGF expression in the pulmonary arteries. Compared with those of the shunt group, lung tissue H2S production was lowered by 23.4%, RMT of the pulmonary artery further increased by 39.5%, pulmonary artery collagen accumulation became obvious, and pulmonary artery CTGF expression elevated ( P < 0.01) in the shunted rats treated with PPG. However, pulmonary artery MMP-13 and TIMP-1 expressions decreased significantly in rats of shunt+PPG group ( P < 0.01). This study suggests that endogenous H2S exerts an important regulatory effect on pulmonary collagen remodeling induced by high pulmonary blood flow.

scholarly journals Anomalous Origin of the Left Pulmonary Artery: Hemi-Truncus Arteriosus

2017 ◽  
Vol 8 (2) ◽  
pp. 9 ◽  
Author(s):  
Ali Shabbir Hussain ◽  
Mariam Shakir ◽  
Shabina Ariff ◽  
Rehan Ali ◽  
Babar Hassan
Keyword(s):  
Heart Failure ◽  
Pulmonary Artery ◽  
Vascular Disease ◽  
Left Pulmonary Artery ◽  
Truncus Arteriosus ◽  
Anomalous Origin ◽  
Pulmonary Vascular Disease ◽  
Cardiovascular Malformation

Hemi-truncus arteriosus is a rare congenital cardiovascular malformation. It usually presents in infancy and leads to development of progressive pulmonary vascular disease, heart failure, and death. We report a case of hemi truncus arteriosus in a 12-day-old neonate who was successfully managed at our institute.

scholarly journals Pulmonary Hypertension in Children with Congenital Left to Right Cardiac Shunt Anomalies

2015 ◽  
Vol 14 (2) ◽  
pp. 31-37
Author(s):  
Chaity Barua ◽  
Sunam Kumar Barua ◽  
Md Zahid Hossain ◽  
Tahmina Karim
Keyword(s):  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Pulmonary Blood Flow ◽  
Congenital Heart ◽  
Heart Diseases ◽  
Congenital Heart Diseases ◽  
Age Group ◽  
Cardiac Defects ◽  
Pulmonary Arterial

The Normal Pulmonary Artery (PA) systolic pressure of children and adults is < 30 mm Hg and the mean PA pressure is < 25 mm Hg at sea level. Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure > 25 mm Hg at rest or > 30 mm Hg during exercise. An increase in pulmonary flow, vascular resistance, or both can result in pulmonary hypertension. Pulmonary Arterial Hypertension (PAH) commonly arises in patients with Congenital Heart Diseases (CHD) are usually associated with increased pulmonary blood flow. Greater number of patients with Pulmonary Arterial Hypertension (PAH), associated with congenital heart disease, are now surviving into adulthood, many with increasingly complex cardiac defects. Patients with cardiac defects which result in left-to-right shunting tend to develop PAH, owing to the increased shear stress and circumferential stretch induced by pulmonary blood flow, which leads to endothelial dysfunction and progressive vascular remodeling followed by vascular resistance. Pulmonary hypertension in association with congenital heart diseases is seen in large systemicto- pulmonary communications such as Ventricular Septal Defect (VSD), Patent Ductus Arteriosus (PDA) atrioventricular septal defects, aorticopulmonary window defect etc. Pulmonary hypertension associated with large L-R shunt lesions (e.g. VSD, PDA) is called Hyperkinetic Pulmonary Hypertension (PH). It is the result of an increase in pulmonary blood flow, a direct transmission of the systemic pressure to the pulmonary artery, and compensatory pulmonary vasoconstriction. Hyperkinetic PH is usually reversible if the cause is eliminated before permanent changes occur in the pulmonary arterioles. If large L-R shunt lesions are left untreated, irreversible changes take place in the pulmonary vascular bed, with severe pulmonary hypertension and cyanosis due to a reversal of the L-R shunt. This stage is called Eisenmenger syndrome or Pulmonary Vascular Obstructive Disease (PVOD). Surgical correction is not possible at this stage. Due to lack of formal study which of the L-R congenital shunt is more commonly associated with the development of pulmonary hypertension is not known the cross-sectional study therefore intends to find the pattern of congenital L-R heart diseases commonly attributed to the development pulmonary hypertension. The diagnosis of the abovementioned congenital heart disease will be made by echocardiography. In this study, most of the participant [22 (44.0%)] were in the ‘< 1 years’ age group, female were proportionately higher, most patients presented with cough and difficulty in breathing, dyspnoea and tachycardia were the most common clinical findings, murmur mostly systolic were found, Eisenmenger syndrome was not found in any child, ASD was the most common congenital anomaly. About four-fifth of the participants had single congenital anomaly. Two-fifth of the participant was found having severe PAH. Significant correlation were revealed between age group and Pulmonary arterial pressure (R= 0.775), Status of PAH was found significantly different (p< 0.05) in age groups and presence of number of anomalies.Chatt Maa Shi Hosp Med Coll J; Vol.14 (2); Jul 2015; Page 31-37

scholarly journals Pulmonary artery size is associated with functional clinical status in the Fontan circulation

Heart ◽  
2019 ◽  
pp. heartjnl-2019-314972 ◽  
Author(s):  
Floris-Jan S Ridderbos ◽  
Bregje E Bonenkamp ◽  
Sophie L Meyer ◽  
Graziella Eshuis ◽  
Tjark Ebels ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Pulmonary Blood Flow ◽  
Independent Predictor ◽  
Clinical Status ◽  
Fontan Circulation ◽  
Pulmonary Vasculature ◽  
Cross Sectional ◽  
Fontan Patients

ObjectiveIn the Fontan circulation, non-pulsatile pulmonary blood flow is suggested to negatively affect pulmonary artery growth. The pulmonary vasculature is regarded a key determinant of outcome after Fontan completion. We hypothesised that in Fontan patients pulmonary artery size correlates with follow-up and functional clinical status.MethodsThis is a single-centre, cross-sectional cohort study. Thirty-nine paediatric and adult Fontan patients with a concomitant cardiac magnetic resonance (CMR) scan and a cardiopulmonary exercise test between 2012 and 2013 were included. CMR-derived left and right pulmonary artery cross-sectional areas were expressed as Nakata index. Functional status was defined as peak oxygen consumption (pVO2) indexed for weight, as percentage of predicted (pred) and as New York Heart Association Functional Class (NYHA-FC).ResultsAge at CMR was 18±7.2 years. Time since Fontan completion was 11.9±7.4 years. Nakata index was lower versus the reference values (238.6±78.5 vs 330±30 mm2/m2, p<0.001). Nakata index correlated negatively with age at CMR (r=−0.393, p=0.013) and time since Fontan completion (r=−0.341, p=0.034). pVO2 was 27.9±8.9 mL/min/kg and pVO2pred was 58.1%±14.1%. Nakata index correlated positively with pVO2 (r=0.468, p=0.003) and pVO2pred (r=0.353, p=0.028). Nakata index correlated negatively with NYHA-FC (r=−0.450, p=0.004). Nakata index was an independent predictor (β=0.359, p=0.007) for pVO2 (adjusted R2=0.442, with maximum heart rate and oxygen pulse at peak exercise).ConclusionsPulmonary artery size expressed as Nakata index is a novel independent predictor for functional clinical status. Nakata index negatively correlated with follow-up duration, suggesting that chronic abnormal non-pulsatile pulmonary blood flow plays a role in lagging pulmonary arterial growth in the Fontan circulation.

Transposition of the great arteries {S,D,D} and absent proximal left pulmonary artery

1995 ◽  
Vol 5 (2) ◽  
pp. 199-201
Author(s):  
Dipak Kholwadwala ◽  
Vincent A. Parnell ◽  
Rubin S. Cooper
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Pulmonary Blood Flow ◽  
Left Ventricular Outflow Tract ◽  
Pulmonary Arteries ◽  
Left Pulmonary Artery ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Left Ventricular Outflow ◽  
The Right

while preferential blood flow to the rightpulmonary artery has been described in transposition of the great arteries with or without obstruction of the left ventricular outflow tract, this disparity of pulmonary blood flow is not present in newborns.1We report a newborn with transposition in whom there was discontinuity of the pulmonary arteries and ductal blood supply to the left pulmonary artery. To our knowledge, this entity has not been described in newborns with transposition of the great arteries {S,D,D}.

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