Faculty Collaboration Database

Cardiac Remodeling and Reversible Pulmonary Hypertension During Pneumonitis in Rats after 13-Gy Partial-Body Irradiation with Minimal Bone Marrow Sparing: Effect of Lisinopril. Health Phys 2019 Apr;116(4):558-565

Date

01/10/2019

Pubmed ID

30624347

Pubmed Central ID

PMC6384144

DOI

10.1097/HP.0000000000000919

Scopus ID

2-s2.0-85061215751 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

Total-body irradiation causes acute and delayed toxicity to hematopoietic, pulmonary, cardiac, gastrointestinal, renal, and other organ systems. Angiotensin-converting enzyme inhibitors mitigate many of the delayed injuries to these systems. The purpose of this study was to define echocardiographic features in rats at two times after irradiation, the first before lethal radiation pneumonitis (50 d) and the second after recovery from pneumonitis but before lethal radiation nephropathy (100 d), and to determine the actions of the angiotensin-converting enzyme inhibitor lisinopril. Four groups of female WAG/RijCmcr rats at 11-12 wk of age were studied: nonirradiated, nonirradiated plus lisinopril, 13-Gy partial-body irradiation sparing one hind leg (leg-out partial-body irradiation), and 13-Gy leg-out partial-body irradiation plus lisinopril. Lisinopril was started 7 d after radiation. Echocardiograms were obtained at 50 and 100 d, and cardiac histology was assessed after 100 d. Irradiation without lisinopril demonstrated echocardiographic transient pulmonary hypertension by 50 d which was largely resolved by 100 d in survivors. Irradiated rats given lisinopril showed no increase in pulmonary artery pressures at 50 d but exhibited left ventricular remodeling. By 100 d these rats showed some signs of pulmonary hypertension. Lisinopril alone had no impact on echocardiographic end points at either time point in nonirradiated rats. Mild increases in mast cells and fibrosis in the heart were observed after 100 d following 13-Gy leg-out partial-body irradiation. These data demonstrate irradiation-induced pulmonary hypertension which was reversed in survivors of pneumonitis. Lisinopril modified cardiovascular remodeling to enhance survival in this model from 41% to 86% (p = 0.0013).

Author List

Jacobs ER, Narayanan J, Fish BL, Gao F, Harmann LM, Bergom C, Gasperetti T, Strande JL, Medhora M

MESH terms used to index this publication - Major topics in bold

Angiotensin-Converting Enzyme Inhibitors
Animals
Echocardiography
Female
Hypertension, Pulmonary
Lisinopril
Myocardium
Radiation Injuries, Experimental
Radiation Pneumonitis
Rats
Ventricular Remodeling