Temporal hemodynamic and histological progression in Sugen5416/hypoxia/ normoxia-exposed pulmonary arterial hypertensive rats

Michie Toba, Abdallah Alzoubi, Kealan D. O'Neill, Salina Gairhe, Yuri Matsumoto, Kaori Oshima, Kohtaro Abe, Masahiko Oka, Ivan F. McMurtry

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

We have investigated the temporal relationship between the hemodynamic and histological/morphological progression in a rat model of pulmonary arterial hypertension that develops pulmonary arterial lesions morphologically indistinguishable from those in human pulmonary arterial hypertension. Adult male rats were injected with Sugen5416 and exposed to hypoxia for 3 wk followed by a return to normoxia for various additional weeks. At 1, 3, 5, 8, and 13 wk after the Sugen5416 injection, hemodynamic and histological examinations were performed. Right ventricular systolic pressure reached its maximum 5 wk after Sugen5416 injection and plateaued thereafter. Cardiac index decreased at the 3~5-wk time point, and tended to further decline at later time points. Reflecting these changes, calculated total pulmonary resistance showed a pattern of progressive worsening. Acute intravenous fasudil markedly reduced the elevated pressure and resistance at all time points tested. The percentage of severely occluded small pulmonary arteries showed a similar pattern of progression to that of right ventricular systolic pressure. These small vessels were occluded predominantly with nonplexiform-type neointimal formation except for the 13-wk time point. There was no severe occlusion in larger arteries until the 13-wk time point, when significant numbers of vessels were occluded with plexiform-type neointima. The Sugen5416/hypoxia/normoxia-exposed rat shows a pattern of chronic hemodynamic progression similar to that observed in pulmonary arterial hypertension patients. In addition to vasoconstriction, nonplexiform-type neointimal occlusion of small arteries appears to contribute significantly to the early phase of pulmonary arterial hypertension development, and plexiform-type larger vessel occlusion may play a role in the late deterioration.

Original languageEnglish
Pages (from-to)H243-H250
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume306
Issue number2
DOIs
Publication statusPublished - Jan 15 2014

Fingerprint

Hemodynamics
Pulmonary Hypertension
Lung
Ventricular Pressure
Arteries
Blood Pressure
Neointima
Injections
Vasoconstriction
Pulmonary Artery
Hypoxia
Pressure

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Temporal hemodynamic and histological progression in Sugen5416/hypoxia/ normoxia-exposed pulmonary arterial hypertensive rats. / Toba, Michie; Alzoubi, Abdallah; O'Neill, Kealan D.; Gairhe, Salina; Matsumoto, Yuri; Oshima, Kaori; Abe, Kohtaro; Oka, Masahiko; McMurtry, Ivan F.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 306, No. 2, 15.01.2014, p. H243-H250.

Research output: Contribution to journalArticle

Toba, Michie ; Alzoubi, Abdallah ; O'Neill, Kealan D. ; Gairhe, Salina ; Matsumoto, Yuri ; Oshima, Kaori ; Abe, Kohtaro ; Oka, Masahiko ; McMurtry, Ivan F. / Temporal hemodynamic and histological progression in Sugen5416/hypoxia/ normoxia-exposed pulmonary arterial hypertensive rats. In: American Journal of Physiology - Heart and Circulatory Physiology. 2014 ; Vol. 306, No. 2. pp. H243-H250.
@article{cd2cabcdd99246e0932796dd3d8ec046,
title = "Temporal hemodynamic and histological progression in Sugen5416/hypoxia/ normoxia-exposed pulmonary arterial hypertensive rats",
abstract = "We have investigated the temporal relationship between the hemodynamic and histological/morphological progression in a rat model of pulmonary arterial hypertension that develops pulmonary arterial lesions morphologically indistinguishable from those in human pulmonary arterial hypertension. Adult male rats were injected with Sugen5416 and exposed to hypoxia for 3 wk followed by a return to normoxia for various additional weeks. At 1, 3, 5, 8, and 13 wk after the Sugen5416 injection, hemodynamic and histological examinations were performed. Right ventricular systolic pressure reached its maximum 5 wk after Sugen5416 injection and plateaued thereafter. Cardiac index decreased at the 3~5-wk time point, and tended to further decline at later time points. Reflecting these changes, calculated total pulmonary resistance showed a pattern of progressive worsening. Acute intravenous fasudil markedly reduced the elevated pressure and resistance at all time points tested. The percentage of severely occluded small pulmonary arteries showed a similar pattern of progression to that of right ventricular systolic pressure. These small vessels were occluded predominantly with nonplexiform-type neointimal formation except for the 13-wk time point. There was no severe occlusion in larger arteries until the 13-wk time point, when significant numbers of vessels were occluded with plexiform-type neointima. The Sugen5416/hypoxia/normoxia-exposed rat shows a pattern of chronic hemodynamic progression similar to that observed in pulmonary arterial hypertension patients. In addition to vasoconstriction, nonplexiform-type neointimal occlusion of small arteries appears to contribute significantly to the early phase of pulmonary arterial hypertension development, and plexiform-type larger vessel occlusion may play a role in the late deterioration.",
author = "Michie Toba and Abdallah Alzoubi and O'Neill, {Kealan D.} and Salina Gairhe and Yuri Matsumoto and Kaori Oshima and Kohtaro Abe and Masahiko Oka and McMurtry, {Ivan F.}",
year = "2014",
month = "1",
day = "15",
doi = "10.1152/ajpheart.00728.2013",
language = "English",
volume = "306",
pages = "H243--H250",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "2",

}

TY - JOUR

T1 - Temporal hemodynamic and histological progression in Sugen5416/hypoxia/ normoxia-exposed pulmonary arterial hypertensive rats

AU - Toba, Michie

AU - Alzoubi, Abdallah

AU - O'Neill, Kealan D.

AU - Gairhe, Salina

AU - Matsumoto, Yuri

AU - Oshima, Kaori

AU - Abe, Kohtaro

AU - Oka, Masahiko

AU - McMurtry, Ivan F.

PY - 2014/1/15

Y1 - 2014/1/15

N2 - We have investigated the temporal relationship between the hemodynamic and histological/morphological progression in a rat model of pulmonary arterial hypertension that develops pulmonary arterial lesions morphologically indistinguishable from those in human pulmonary arterial hypertension. Adult male rats were injected with Sugen5416 and exposed to hypoxia for 3 wk followed by a return to normoxia for various additional weeks. At 1, 3, 5, 8, and 13 wk after the Sugen5416 injection, hemodynamic and histological examinations were performed. Right ventricular systolic pressure reached its maximum 5 wk after Sugen5416 injection and plateaued thereafter. Cardiac index decreased at the 3~5-wk time point, and tended to further decline at later time points. Reflecting these changes, calculated total pulmonary resistance showed a pattern of progressive worsening. Acute intravenous fasudil markedly reduced the elevated pressure and resistance at all time points tested. The percentage of severely occluded small pulmonary arteries showed a similar pattern of progression to that of right ventricular systolic pressure. These small vessels were occluded predominantly with nonplexiform-type neointimal formation except for the 13-wk time point. There was no severe occlusion in larger arteries until the 13-wk time point, when significant numbers of vessels were occluded with plexiform-type neointima. The Sugen5416/hypoxia/normoxia-exposed rat shows a pattern of chronic hemodynamic progression similar to that observed in pulmonary arterial hypertension patients. In addition to vasoconstriction, nonplexiform-type neointimal occlusion of small arteries appears to contribute significantly to the early phase of pulmonary arterial hypertension development, and plexiform-type larger vessel occlusion may play a role in the late deterioration.

AB - We have investigated the temporal relationship between the hemodynamic and histological/morphological progression in a rat model of pulmonary arterial hypertension that develops pulmonary arterial lesions morphologically indistinguishable from those in human pulmonary arterial hypertension. Adult male rats were injected with Sugen5416 and exposed to hypoxia for 3 wk followed by a return to normoxia for various additional weeks. At 1, 3, 5, 8, and 13 wk after the Sugen5416 injection, hemodynamic and histological examinations were performed. Right ventricular systolic pressure reached its maximum 5 wk after Sugen5416 injection and plateaued thereafter. Cardiac index decreased at the 3~5-wk time point, and tended to further decline at later time points. Reflecting these changes, calculated total pulmonary resistance showed a pattern of progressive worsening. Acute intravenous fasudil markedly reduced the elevated pressure and resistance at all time points tested. The percentage of severely occluded small pulmonary arteries showed a similar pattern of progression to that of right ventricular systolic pressure. These small vessels were occluded predominantly with nonplexiform-type neointimal formation except for the 13-wk time point. There was no severe occlusion in larger arteries until the 13-wk time point, when significant numbers of vessels were occluded with plexiform-type neointima. The Sugen5416/hypoxia/normoxia-exposed rat shows a pattern of chronic hemodynamic progression similar to that observed in pulmonary arterial hypertension patients. In addition to vasoconstriction, nonplexiform-type neointimal occlusion of small arteries appears to contribute significantly to the early phase of pulmonary arterial hypertension development, and plexiform-type larger vessel occlusion may play a role in the late deterioration.

UR - http://www.scopus.com/inward/record.url?scp=84892624282&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892624282&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00728.2013

DO - 10.1152/ajpheart.00728.2013

M3 - Article

C2 - 24240870

AN - SCOPUS:84892624282

VL - 306

SP - H243-H250

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 2

ER -