The role of increased pulmonary blood flow in pulmonary arterial hypertension.
Chronic increased pulmonary blood flow is considered a pre-requisite for the induction of advanced vascular lesions in pulmonary arterial hypertension in congenital heart defects. The aim of the present study was to characterise the effects of increased pulmonary flow induced by an aortocaval shunt in the monocrotaline rat model for pulmonary hypertension in terms of survival, haemodynamics, pathology and histology. Male Wistar rats were injected with monocrotaline followed by the creation of an abdominal aortocaval shunt. Animals were sacrificed when displaying symptoms of weight loss or dyspnoea, 4-5 weeks after the creation of the shunt. Echocardiography identified increased ventricular dimensions in shunted rats and right ventricular hypertrophy in monocrotaline-treated rats. At similar pulmonary artery pressures, shunted monocrotaline rats displayed higher morbidity and mortality, increased pulmonary-to-systemic artery pressure ratios and increased right ventricular hypertrophy compared with nonshunted monocrotaline rats. Histological assessment demonstrated increased number and diameter of pre-acinar pulmonary arteries. Intra-acinar vessel remodelling and occlusion occurred to a similar extent in shunted and nonshunted monocrotaline rats. In conclusion, increased pulmonary blood flow in monocrotaline-induced pulmonary hypertension is associated with increased morbidity, mortality, and unfavourable haemodynamic and cardiac effects. These effects could be attributed to more pronounced right heart failure rather than to altered intra-acinar pulmonary vessel remodelling.
van Albada
M E
ME
Dept of Experimental Cardiology, University Medical Centre Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. m.e.van.albada@med.umcg.nl
Schoemaker
R G
RG
Kemna
M S
MS
Cromme-Dijkhuis
A H
AH
van Veghel
R
R
Berger
R M F
RM
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D006325:Heart Atria / Q000473:pathology; D018610:Heart Bypass, Right; D006351:Heart Valves / Q000000981:diagnostic imaging / Q000473:pathology; D006976:Hypertension, Pulmonary / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology*; D008168:Lung / Q000473:pathology; D008297:Male; D016686:Monocrotaline; D011651:Pulmonary Artery / Q000473:pathology; D011652:Pulmonary Circulation / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014463:Ultrasonography
D016686:Monocrotaline