Document Type
Article
Publication Date
5-1-2025
Abstract
Background: Severe pulmonary embolism (PE) with right heart failure (RHF) has high mortality. To more fully understand PE progression, we evaluated the right ventricle (RV) and pulmonary circulation response to graded PE in an acute PE sheep model.
Methods: Polydextran beads were intravenously administered every 15 minutes in 250 mg doses to adult female sheep (n = 8) until death. Concurrent pulmonary artery (PA) blood flow/pressure was measured. RV pressure-volume (P-V) loops were generated with a conductance catheter. Pulmonary vascular resistance was used to stage PE severity into mild, moderate, and severe groups.
Results: All sheep developed graded RHF. For mild, moderate, and severe PE, 3, 6, and 9 doses were needed, respectively. Only 1 additional dose triggered death. In severe PE, mean PA pressure reached 42 ± 6 mm Hg with significantly decreased cardiac output (CO). Pulmonary impedance spectra showed significantly increased Z0 (RV static load) and Z1 (RV pulsatile load). PE shifted the RV P-V loop from lower left triangular to upper right rectangular shape. PA elastance (Ea, RV afterload) and end-systolic elastance (Ees, RV contractility) progressively increased. Ees/Ea (RV-PA coupling) was initially maintained but became uncoupled in severe PE, causing RHF.
Conclusions: Compensatory increases in RV contractility initially maintain CO in PE despite RV afterload elevation. Increased RV contractility eventually fails to compensate for elevated RV afterload, causing RV-PA uncoupling in severe PE with RHF. Severe PE rapidly progresses to lethal RHF and will likely require immediate intervention to prevent death.
© 2025 International Society for Heart and Lung Transplantation
Recommended Citation
Zhou, Cheng; Li, Yuman; Polley, Kyle; Ballard-Croft, Cherry; Kawabori, Masashi; Rajagopal, Keshava; Zwischenberger, Joseph B.; and Wang, Dongfang, "Graded Response of the Pulmonary Circulation to Progressive Pulmonary Embolism in Sheep: From Compensation to Lethal Right Heart Failure" (2025). Department of Surgery Faculty Papers. Paper 298.
https://jdc.jefferson.edu/surgeryfp/298
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
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PubMed ID
40276320
Language
English
Comments
This article is the author's final published version in JHLT Open, Volume 8, May 2025, Article number 100260.
The published version is available at https://doi.org/10.1016/j.jhlto.2025.100260.
Copyright 2950-1334/© 2025 The Authors.