Pulmonary Arterial Hypertension

 

Scientific Updates – December 2004

 

 

Compiled by

United Therapeutics Corporation     


Gene transfer of hepatocyte growth factor with prostacyclin synthase in severe pulmonary hypertension of rats.

Eur J Cardiothorac Surg. 2004 Dec;26(6):1092-7

Ono M, Sawa Y, Fukushima N, Suhara H, Nakamura T, Yokoyama C, Tanabe T, Matsuda H.

Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.

Objective: Hepatocyte growth factor (HGF) is a multi-potent growth factor, which has anti-fibrotic effects for lung injuries. In this study, we investigated whether human HGF gene transfer may attenuate the medial hypertrophy of pulmonary arteries and enhance the ameliorating effect of prostacyclin in monocrotaline (MCT)-induced pulmonary hypertension in rats. Methods and results: The day before MCT injection, HVJ-liposome complex with the cDNA encoding HGF gene (H group), PGIS gene (P group), and both HGF and PGIS gene (HP group) were transfected to the liver of rats as drug delivery system for the lung. Rats transfected with control vector served as controls (C group). Twenty-eight days after MCT injection, histological examination showed marked thickening of medial wall of pulmonary arteries and right ventricular hypertrophy. Percent medial wall thickness (%WT) of peripheral pulmonary arteries, pressure ratio of the right ventricle (RV) to the left ventricle (LV), and weight ratio of the RV to the LV plus septum were significantly increased in the control. Percent medial wall thickness was significantly ameliorated in H group and HP group in comparison with C group. Pressure and weight ratio of RV to LV was significantly ameliorated in P group and HP group in comparison with C group, and was significantly ameliorated in HP group than P group. Conclusions: In vivo gene transfection with HGF gene attenuated the medial hypertrophy of pulmonary arteries and enhanced the ameliorating effect of prostacyclin for pulmonary hypertension in MCT rats. Thus, gene therapy with HGF and PGIS may be a promising strategy for severe pulmonary hypertension.

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Risk factors of meconium aspiration syndrome developing into persistent pulmonary hypertension of newborn.

Acta Paediatr Taiwan. 2004 Jul-Aug;45(4):203-7


Hsieh TK, Su BH, Chen AC, Lin TW, Tsai CH, Lin HC.

Department of Pediatrics, Hsin Chu General Hospital, Hsinchu, Taiwan.

Clinical experience indicates that persistent pulmonary hypertension of the newborn (PPHN) is one of the major causes of death in infants with meconium aspiration syndrome (MAS). We aimed to investigate the risk factors associated with MAS which lead to PPHN in order to search for ways to reduce the mortality associated with MAS. From 1995 to 2003, we conducted a retrospective study of infants with MAS at the China Medical University Hospital. We compared the risk factors associated with MAS, including pattern of fetal heart beat, mode of delivery, apgar score, sex, gestational age, birth body weight, in born or out born infants, resuscitation before admission, first pH at admission, asphyxia, surfactant usage, pneumothorax, pulmonary hemorrhage and shock before the diagnosis of PPHN between PPHN and non PPHN infants. During the nine-year study, 362 infants with MAS were enrolled. There were 64 infants with (17.7%) PPHN and 298 infants without PPHN. According to univariant analysis, the significant risk factors associated with MAS which lead to PPHN were out born infant (p=0.007), change of fetal heart beat pattern (p=0.0001), resuscitation before admission (p=0.0001), low pH (p=0.002), asphyxia (p<0.0001), shock (p<0.0001), pneumothorax (p=0.0004), and pulmonary hemorrhage (p<0.0002). Based on the results of logistic regression analysis, the risk factors were pneumothorax (p=0.04, odds ratio: 2.34), change of fetal heart beat pattern (p=0.02, odds ratio: 2.37) and asphyxia (p=0.001, odds ratio: 5.48). We conclude that pneumothorax, change of fetal heart beat pattern and asphyxia are the most important risk factors associated with MAS which lead to the development of PPHN. Avoidance of asphyxia and pneumothorax might be the key to reduce the incidence of PPNH and mortality rate of MAS.

 

 

 

Meconium-stained amniotic fluid, meconium aspiration syndrome, and persistent pulmonary hypertension of the newborn.

Acta Paediatr Taiwan. 2004 Jul-Aug;45(4):197-9


Hsieh WS.

Publication Types:

·                     Comment

·                     Editorial

 

 

Hepatic cirrhosis associated with arterial pulmonary hypertension.

Rom J Gastroenterol. 2004 Dec;13(4):341-3

 

Radulescu D, Duncea C, Donca V.

5th Medical Clinic, University of Medicine and Pharmacy, Str. Tabacarilor 11, Cluj-Napoca, Romania.

The association between hepatic cirrhosis and arterial pulmonary hypertension is mentioned in the literature. The authors report the case of a patient with hepatic cirrhosis, who developed in time an arterial pulmonary hypertension with a fatal outcome. They discuss the pathogenesis of arterial pulmonary hypertension in patients with hepatic diseases, and the therapeutic options in these patients.