Repeated lung injury due to alpha-naphthylthiourea causes right ventricular hypertrophy in rats

1984 ◽  
Vol 56 (2) ◽  
pp. 388-396 ◽  
Author(s):  
N. S. Hill ◽  
R. F. O'Brien ◽  
S. Rounds
Keyword(s):  
Pulmonary Hypertension ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Vascular Reactivity ◽  
Tween 80 ◽  
Left Ventricular ◽  
Right Ventricular Hypertrophy ◽  
Arterial Blood

Acute lung injury due to alpha-naphthylthiourea (ANTU) is associated with increased permeability edema, transient pulmonary hypertension, and increased vascular reactivity. We sought to determine whether repeated administration of ANTU caused right ventricular hypertrophy. Rats were injected weekly for 4 wk with ANTU or an equivalent volume of the vehicle Tween 80. Rats injected repeatedly with ANTU in doses of 5–10 mg/kg body wt had increased ratios of right ventricular to left ventricular plus septal weights. The right ventricular hypertrophy in ANTU-treated rats was associated with right ventricular systolic hypertension. Repeated injections of ANTU also caused transient pulmonary edema after each dose, as evidenced by increased wet-to-dry lung weight ratios after 4 h, which returned to normal by 24 h. Lungs isolated from ANTU-injected rats had greater pressor responses to hypoxia and to angiotensin II than lungs from Tween 80-injected rats. Pressure-flow curves of isolated lungs, arterial blood gases, and hematocrits were similar in rats treated repetitively with ANTU or Tween alone. Lung histology was also similar in ANTU and control lungs, as were measurements of arterial medial thickness and ratios of numbers of arteries/100 alveoli, indicating that substantial vascular remodeling had not occurred. Thus, four weekly ANTU injections in rats caused right ventricular hypertrophy, probably due to pulmonary hypertension. We speculate that the pulmonary hypertension was due, at least in part, to sustained vasoconstriction, which somehow resulted from repeated acute lung injury.

Effects of thrombocytopenia on monocrotaline pyrrole-induced pulmonary hypertension

1984 ◽  
Vol 246 (6) ◽  
pp. H747-H753 ◽  
Author(s):  
K. S. Hilliker ◽  
T. G. Bell ◽  
D. Lorimer ◽  
R. A. Roth
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Injury ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Blood Platelet ◽  
Lavage Fluid ◽  
Right Ventricular Hypertrophy ◽  
Lactate Dehydrogenase Activity ◽  
Hypertrophic Response ◽  
Monocrotaline Pyrrole

Monocrotaline pyrrole (MCTP) causes lung injury, pulmonary hypertension, and right ventricular hypertrophy in rats. To determine if platelets are involved in the cardiopulmonary effects of MCTP, the response to MCTP was determined in thrombocytopenic rats. Blood platelet count was reduced to 10–20% of normal for 48 h by ip administration of an antirat platelet serum (PAS) prepared in the goat. Rats were treated iv with either MCTP 5 mg/kg or dimethylformamide vehicle and with either PAS or preimmune serum. Fourteen days after MCTP, right ventricular hypertrophy and several indexes of lung injury were measured. MCTP treatment produced right ventricular hypertrophy, increased lactate dehydrogenase activity and protein concentration in bronchopulmonary lavage fluid, increased perfusion pressure in isolated lungs, and decreased pulmonary clearance and metabolism of perfused 5-hydroxytryptamine. Thrombocytopenia did not influence the changes in these indexes of lung injury produced by MCTP in this protocol. When PAS was given 12 h before MCTP, it did not affect right ventricular hypertrophy, but when PAS treatment was begun 3 or 6 days after MCTP, right ventricular hypertrophy was decreased by 19 or 41%, respectively. These results suggest that platelets help to mediate the development of pulmonary hypertension and the hypertrophic response of the right heart following MCTP administration.

PAF antagonists inhibit monocrotaline-induced lung injury and pulmonary hypertension

1991 ◽  
Vol 71 (6) ◽  
pp. 2483-2492 ◽  
Author(s):  
S. Ono ◽  
N. F. Voelkel
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Injury ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Platelet Activating Factor ◽  
Lipid Mediators ◽  
Right Ventricular Hypertrophy ◽  
Vascular Leak ◽  
Paf Antagonists ◽  
Web 2086

Lung platelet-activating factor (PAF) levels increased in some rats at 1–3 wk after subcutaneous injection of monocrotaline (MCT). We tested the effect of specific PAF antagonists, WEB 2086 and WEB 2170, on MCT-induced lung injury and subsequent pulmonary hypertension and right ventricular hypertrophy. Treatment with either agent decreased MCT-induced pulmonary hypertension and right ventricular hypertrophy at 3 wk after injection. Treatment with WEB 2170 reduced MCT-induced pulmonary vascular leak at 1 wk after injection, and WEB 2086-treatment exclusively during the early leak phase also decreased MCT-induced right ventricular hypertrophy at 3 wk. Treatment with WEB 2170 between the 3rd and 4th wk after MCT injection inhibited the progression of right ventricular hypertrophy at 4 wk. These results suggest that PAF contributes to the early pulmonary vascular leak, and this leak phase is important for the development of pulmonary hypertension and right ventricular hypertrophy in MCT-treated rats. Furthermore, it appears that PAF action contributes to the maintenance of a chronic inflammatory process that involves the synthesis of other lipid mediators (prostaglandins and leukotrienes) and leads to pulmonary hypertension. We conclude that PAF has a role in the MCT-induced inflammatory lung injury and pulmonary hypertension.

scholarly journals The Roles of S100A4 and the EGF/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular Hypertrophy

Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 118
Author(s):  
Maria Laggner ◽  
Philipp Hacker ◽  
Felicitas Oberndorfer ◽  
Jonas Bauer ◽  
Thomas Raunegger ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Tissue Expression ◽  
Left Ventricular ◽  
Right Ventricular Hypertrophy ◽  
Pulmonary Vasculature ◽  
Mesenchymal Transition ◽  
Pulmonary Arterial

Pulmonary hypertension (PH) is characterized by increased pulmonary arterial pressure caused by the accumulation of mesenchymal-like cells in the pulmonary vasculature. PH can lead to right ventricular hypertrophy (RVH) and, ultimately, heart failure and death. In PH etiology, endothelial-to-mesenchymal transition (EndMT) has emerged as a critical process governing the conversion of endothelial cells into mesenchymal cells, and S100A4, EGF, and EGFR are implicated in EndMT. However, a potential role of S100A4, EGF, and EGFR in PH has to date not been elucidated. We therefore quantified S100A4, EGF, and EGFR in patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH). To determine specificity for unilateral heart disease, the EndMT biomarker signature was further compared between PH patients presenting with RVH and patients suffering from aortic valve stenosis (AVS) with left ventricular hypertrophy. Reduced S100A4 concentrations were found in CTEPH and iPAH patients with RVH. Systemic EGF was increased in CTEPH but not in iPAH, while AVS patients displayed slightly diminished EGF levels. EGFR was downregulated in all patient groups when compared to healthy controls. Longitudinal data analysis revealed no effect of surgical therapies on EndMT markers. Pulmonary thrombo-endarterectomized samples were devoid of S100A4, while S100A4 tissue expression positively correlated with higher grades of Heath–Edwards histopathological lesions of iPAH-derived lung tissue. Histologically, EGFR was not detectable in CTEPH lungs or in iPAH lesions. Together, our data suggest an intricate role for S100A4 and EGF/EGFR in PH with right heart pathology.

Neither anticoagulant nor nonanticoagulant heparin affects monocrotaline lung injury

1987 ◽  
Vol 62 (2) ◽  
pp. 816-820 ◽  
Author(s):  
J. W. Fasules ◽  
K. R. Stenmark ◽  
P. M. Henson ◽  
N. F. Voelkel ◽  
J. T. Reeves
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Injury ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Vascular Leak ◽  
Hypoxic Pulmonary Hypertension ◽  
Antiproliferative Agent ◽  
The Right ◽  
Insight Into

The administration of monocrotaline to rats causes pulmonary vascular leak within 1 wk followed in 2–3 wk by perivascular proliferation and fatal pulmonary hypertension. Possibly blocking the proliferation might block the pulmonary hypertension, providing insight into its mechanism. Because heparin, given as an antiproliferative agent, reduced hypoxic pulmonary hypertension in mice, it might also block monocrotaline-induced pulmonary hypertension. Alternatively, anticoagulation could worsen the lung injury. We found that heparin (300 and 600 U/kg sc twice daily) inhibited clotting in rats given monocrotaline but did not change the vascular leak, the right ventricular pressure, the right ventricular hypertrophy, the increased medial thickness of the pulmonary arterioles, or the production of a slow-reacting substance of anaphylaxis-like material by the lungs. A nonanticoagulant heparin fragment (2 mg/kg sc twice daily), given to avoid anticoagulation also did not influence the monocrotaline injury. Thus neither anticoagulant nor nonanticoagulant heparin either attenuated or worsened the measured effects of monocrotaline.

Transient severe isolated right ventricular hypertrophy in neonates

2003 ◽  
Vol 13 (4) ◽  
pp. 384-386 ◽  
Author(s):  
Munesh Tomar ◽  
Sitaraman Radhakrishnan ◽  
Savitri Shrivastava
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Ventricular Function ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Posterior Wall ◽  
Right Ventricular Hypertrophy ◽  
Pulmonary Vasculature ◽  
Normal Thickness ◽  
The Right

We report two instances of transient isolated right-sided myocardial hypertrophy in patients with an intact ventricular septum, normal thickness of the posterior wall of the left ventricle, and normal ventricular function, diagnosed by echocardiography on the third day of life. The two neonates, born at 36 and 38 weeks gestation respectively, had perinatal distress. Both were diagnosed as having isolated right ventricular hypertrophy with mild pulmonary hypertension, which disappeared in both cases within 8 weeks without any specific therapy. Though the cause of the ventricular hypertrophy remains unclear, we believe that it is the consequence of remodeling of pulmonary vasculature secondary to acute perinatal distress, resulting in persistent pulmonary hypertension and producing pressure overload on the right ventricle, and hence right ventricular hypertrophy. The finding of early and transient right ventricular hypertrophy, with normal left-sided structures and normal ventricular function, has thus far failed to gain attention in the paediatric cardiologic literature.

scholarly journals Bosentan attenuates right ventricular hypertrophy and fibrosis in normobaric hypoxia model of pulmonary hypertension

2011 ◽  
Vol 30 (7) ◽  
pp. 827-833 ◽  
Author(s):  
Gaurav Choudhary ◽  
Frederick Troncales ◽  
Douglas Martin ◽  
Elizabeth O. Harrington ◽  
James R. Klinger
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Normobaric Hypoxia
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