Development of a Selective Aortic Arch Perfusion System in a Porcine Model of Exsanguination Cardiac Arrest

Summary

The goal of this protocol is to demonstrate a porcine exsanguination cardiac arrest model and a specifically built selective aortic arch perfusion circuit for translational research.

Abstract

Hemorrhage constitutes the majority of potentially preventable deaths from trauma. There is growing interest in endovascular resuscitation techniques such as selective aortic arch perfusion (SAAP) for patients in cardiac arrest. This involves active perfusion of the coronary circulation via a thoracic aortic balloon catheter and is approaching clinical application. However, the technique is complex and requires refinement in animal models before human use can be considered. This paper describes a large animal model of exsanguination cardiac arrest treated with a bespoke SAAP system.

Swine were anesthetized, instrumented and a splenectomy was performed before a controlled, logarithmic exsanguination was initiated. Animals were heparinized and the shed blood collected in a reservoir. Once cardiac arrest was observed, the blood was pumped through an extra-corporeal circuit into an oxygenator and then delivered through a 10 Fr balloon catheter placed in the thoracic aorta.

This resulted in the return of a spontaneous circulation (ROSC) as demonstrated by ECG and aortic root pressure waveform. This model and accompanying SAAP system allow for standardized and reproducible recovery from exsanguination cardiac arrest.

Introduction

Hemorrhage accounts for the majority of potentially preventable trauma deaths¹. In the terminal stages of exsanguination, coronary perfusion is reduced, leading to cardiac arrest and death. Current strategies – intravenous transfusion and cardiac massage – are ineffective as they do not address the failure of coronary perfusion.

SAAP is a catheter-based resuscitation technique that aims to address this problem by the infusion of oxygenated resuscitation fluid and drugs directly to proximal aorta, perfusing the coronary and cerebral circulation. Limited swine studies have demonstrated promising outcomes in restoring cardiac activity following ventricular fibrillation and hemorrhagic cardiac arrest^2,3,4. However, SAAP research is ongoing and the technique remains in the pre-clinical phases.

There are several technical challenges with SAAP. It is critical that a certain volume of perfusate be delivered via the catheter at a precise infusion rate, and currently there is no commercially available, FDA approved catheter for use in SAAP. The technique requires a specific circuit which is capable of efficiently storing, oxygenating and delivering perfusate during SAAP. The aim of this study is to present a traumatic pulseless electrical activity (PEA) cardiac arrest animal model and custom built, reliable SAAP system for use in exploring this tool in exsanguination animal research.

Protocol

This study was conducted at the Medical School Teaching Facility (MSTF, University of Maryland, Baltimore, MD, USA), which is accredited by the American Association for Laboratory Animal Science. The study protocol was approved by the local Institutional Animal Care and Use Committee. 1. Animal selection and housing Use adult male swine (Sus Scrofa) weighing 60-80 kg. Following arrival to the animal facility, house the animals one per cage but with ability to interact wit…

Representative Results

Aortic root blood pressure was 83/58 mmHg at baseline and gradually decreased to 0-10 mmHg during the exsanguination. Following onset of pulseless electrical activity (PEA), SAAP was performed, during which, the systolic blood pressure rapidly increased to 120 mmHg for the duration of SAAP (Figure 4). Following cessation of SAAP and aortic balloon deflation BSP dropped to about 60 mmHg however it gradually increased again during the post- SAAP period to baseline levels with a couple of spike…

Discussion

Adequate perfusate oxygenation is a critical capability of SAAP¹². We use a filter that is integrated with a reservoir. The filter is connected to an oxygen cylinder via standard oxygen tubing. The oxygen flow is delivered to the oxygenator at 6 L/min. The centrifugal pump incorporated in the circuit propels the blood, which is filtered through the oxygenator. Adequate oxygenation can be confirmed by performing a blood gas analysis of a sample from the perfusion limb of the circuit. A blood gas sa…

Materials

3/8” ID tubing	Saint-Gobain	E-3603	This tubing is used throughout the circuit.
1/4" Tubing	Tygon	E-3603	2" segment for a connector between Exsanguination tubing and ECMO cannula
2-way stopcocks	Harvard Apparatus	72-2650	standard stopcock
3-way	Harvard Apparatus	72-2658	Standard stopcock
Barbed Connectors	Harvard Apparatus	72-1587	Y connectors
Barbed Connectors	Harvard Apparatus	72-1575	Straight connectors
Blood Reservoir	LivaNova	50715	This is sold together with the oxygenator
Cable ties	Commercial Electric	GT-200ST	Standard cable ties.
Centrifugal pump BVP-Z	ISMATEC	ISM 446	Centrifugal Pump used for recirculation of blood
Controlled Peristaltic Dispensing Pump	New Era Pump Systems	NE-9000B	Peristaltic pump for Exsanguination
ECMO Cannula	Medtronic	96570-015	Exsanguination cannula
Gas tubing	AirLife	1302	Standard oxygen tubing
Oxygen source	AirGas	OX USP300	Standard oxygen tank with flowmeter
Oxygenator	LivaNova	50715	This is sold together with the reservoir
Peristaltic pump 1 MCP	ISMATEC	ISM 405	SAAP peristaltic pump
SAAP catheter	n/a	n/a	Proprietary catheter designed by Dr. Manning
Venous catheter	Teleflex	CDC-29903-1A	9 French single lumen catheter