Cardiac Catheterization for Assessment of Pulmonary Hypertension in Preterm Lambs

Summary

Here, we present a protocol to assess pulmonary hypertension by cardiac catheterization in a preterm lamb model of evolving bronchopulmonary dysplasia-associated pulmonary hypertension. The described method enables direct measurement of mean pulmonary artery and pulmonary capillary wedge pressures and calculation of pulmonary vascular resistance.

Abstract

Bronchopulmonary dysplasia with pulmonary hypertension (BPD-PH) is a devastating complication of preterm birth that is associated with increased morbidity and mortality. Preterm birth disrupts normal lung and vascular development, and postnatal exposures such as mechanical ventilation and oxygen therapy can further impair lung and pulmonary vascular growth, contributing to the development of BPD-PH. In the preterm lamb model of evolving BPD, lambs are delivered preterm and mechanically ventilated for up to 21 days, incorporating interrupted lung development along with injury from mechanical ventilation and oxidative stress to recapitulate key features of evolving BPD-PH.

The goal of the cardiac catheterization protocol is to directly assess pulmonary hemodynamics in preterm and term neonatal lambs. Lambs are intubated, mechanically ventilated, and sedated throughout the study. At the time of cardiac catheterization, a Swan-Ganz catheter is advanced through the external jugular vein to the superior vena cava and then through the right atrium, right ventricle, and main pulmonary artery. Cather position is confirmed by identification of characteristic pressure waveforms obtained during advancement through the right-sided cardiac chambers. Mean pulmonary artery pressure and pulmonary capillary wedge pressure are measured via pressure transduction, and cardiac output is determined by thermodilution to enable calculation of pulmonary vascular resistance.

The protocol provides reproducible measurements of pulmonary hemodynamics that parallel those obtained during clinical cardiac catheterization in human neonates. By enabling direct assessment of pulmonary vascular pressures and resistance, this method enhances the translational utility of the preterm lamb model for mechanistic evaluation of potential therapies for BPD-PH.

Introduction

Bronchopulmonary dysplasia (BPD) occurs in up to 45% of preterm infants born before 28 weeks of gestation, is increasing in the United States, and can be complicated by pulmonary hypertension (PH, BPD-PH)^1,2,3. The chronic cardiopulmonary disease process begins when normal lung maturation is interrupted by preterm birth and is exacerbated by postnatal injury from mechanical ventilation and oxidative stress. Ongoing lung injury leads to pulmonary vascular remodeling and the development of PH^4,5.

Protocol

All experimental procedures were prospectively approved and done in compliance with the animal handling and training standards of the University of Utah Institutional Animal Care and Use Committee.

1. Position setup

1. Position the lamb prone in a sling and ensure that previously placed vascular access is functioning (umbilical or jugular central venous catheter).
2. Maintain dexmedetomidine infusion at 0.2 to 1.0 mcg/kg/h for sedation and adjust the infusion rate to achieve the desired sedation depth.
3. Provide additional faster-acting sedation and analgesia with pentobarbital (1 mg/kg/dose IV push)....

Results

Expected pressure tracings from the right atrium, right ventricle, pulmonary artery and pulmonary capillary wedge locations are illustrated in Figure 1. Upon entry into a central vein, the pressure tracing should show a very low-pressure undulating waveform (not pictured). Respiratory variation may be present. No sharp upstrokes should be present (characteristic of arterial tracing). Upon entry to the right atrium, the waveform becomes organized and rhythmic with two small peaks per cycle (a.......

Discussion

Cardiac catheterization provides direct measurement of mPAP and calculation of CO in the preterm lamb model of evolving BPD-PH. The procedure is technical and requires specialized equipment, but it provides accurate and reproducible measurements, which is why it is the preferred diagnostic procedure in humans and is considered a superior clinical trial endpoint. When cardiac catheterization is done in the preterm lamb model, the critical steps of the procedure are successful advancement of the catheter to the right heart.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
0.45% Sodium Chloride Injection USP	Baxter	2B1313
3-Way Stopcock w/ Swivel Male Luer Lock	Medex	MX5311L
48 in (121.9 cm) Extension Set	Medex	MX048
5 mL Syringe	Terumo	SS-05L
Bridge Amp	ADInstruments	FE221/CS
CONTINU-FLO Solution Set with CONTROL-A-FLOW Regulator	Baxter	2C6895
DB9M - DB9F Cable (400 mm)	ADInstruments	MLAC02
DIN(8) to MLT0699 or MLT0670 Cable (3.9 m)	ADInstruments	MLAC06
Disposable BP Transducer (Stopcock)	ADInstruments	MLT0670
Injectate Temperature Probe	Edwards Lifesciences	9850A
LabChart 8.1.30 for Windows	ADInstruments		Pro Upgrade
Patient CCO Cable	Edwards Lifesciences	70CC2
Percutaneous Sheath Introducer Kit with Integral Hemostasis Valve/Side Port for use with 4 - 6 Fr. Catheters	Arrow	AK-09601
Power Lab C	ADInstruments	PLC01
Swan-Ganz True Size Thermodilution Catheter	Edwards Lifesciences	132F5	6 Fr, 10 cm, Ballon Volume 0.7 mL
Vigilance II Monitor	Edwards Lifesciences	VIG2