Development of a Novel Piglet Model to Simulate the Physiology of a Child with Hypoplastic Left Heart Syndrome during the First Interstage for Investigating Changes in Tricuspid Valve as it Adapts to a High-pressure and High-volume Stress Environment

• Author / Creator

  Lin, Lily

• INTRODUCTION:
  Tricuspid valve (TV) failure develops in 25-35% of children with hypoplastic left heart syndrome (HLHS) and is a risk factor for morbidity and mortality. The mechanisms underlying TV failure in HLHS are not well understood. There is no effective medical therapy and current surgical strategies for TV repair in HLHS are modest in success and durability. Innovative strategies require improved understanding into the adaptive abilities of the TV.

  PURPOSE:
  Through the development of a novel piglet model simulating HLHS first surgical interstage right ventricular (RV) physiology, we aim to study TV adaptive changes when exposed to chronic preload and afterload stressors. We hypothesize that TV competency is maintained by adaptive rapid leaflet expansion despite annular dilation.

  METHODS:
  Twenty piglets (4 - 5weeks) underwent left thoracotomy. Intervention piglets (IP, n = 10) had their pulmonary valve torn to produce moderate to severe pulmonary regurgitation (volume loading) and pulmonary artery band placed to increase RV pressure. Age and gender-matched control piglets (CP, n = 10) had sham surgery. Following 4-week recovery, we performed RV pressure measurements and three-dimensional echocardiography (3DE) of TV. TV annulus and leaflet geometry at mid and end-systole were measured using custom 3DE MATLAB software. Ex-vivo TV leaflet area was photographed and measured.

  RESULTS:
  All IP had severe pulmonary regurgitation, significantly elevated RV systolic pressure, thicker RV free wall and anterior papillary muscle, confirming an effective model. IP had larger and more circular annulus, but similar bending angle to CP. IP in-vivo 3DE TV leaflet surface area was 43% greater than CP, especially in the posterior leaflet. Coaptation surface area was similar while IP TV leaflet tethered volume and tricuspid regurgitation was greater. No difference in ex-vivo TV pathologic specimen (unstretched) area was detected, however correlation with 3DE TV leaflet area persisted (r = 0.60, p = 0.02).

  CONCLUSION:
  Exposure to chronic RV volume and pressure stressors, TV adapt by annular dilation while maintaining “saddle” shape and total coaptation surface area. This is mostly achieved through a process of rapid leaflet expansion. Further study of TV leaflet growth and its modulation may provide novel insights into the pathophysiology of TV failure in HLHS.

• Subjects / Keywords

  • Piglet model
  • Tricuspid valve
  • 3D Echocardiography
  • Hypoplastic left heart syndrome

• Graduation date

  Spring 2020

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-9tyj-kk96

• License

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