Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction

Guilielmus H.J.M. Ellenbroek; Gerardus P.J. van Hout; Leo Timmers; Pieter A. Doevendans; Gerard Pasterkamp; Imo E. Hoefer

doi:10.3791/54021

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Method Article

Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction

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DOI:

10.3791/54021

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October 14th, 2016

Guilielmus H.J.M. Ellenbroek¹ , Gerardus P.J. van Hout¹^,² , Leo Timmers¹^,² , Pieter A. Doevendans²^,⁴ , Gerard Pasterkamp¹^,³ , Imo E. Hoefer¹^,³

¹Department of Experimental Cardiology, University Medical Center Utrecht, ²Department of Cardiology, University Medical Center Utrecht, ³Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, ⁴Interuniversity Cardiology Institutes of the Netherlands (ICIN)

Summary

Reliable and accurate outcome assessment is the key for translation of preclinical therapies into clinical treatment. The current paper describes how to assess three clinically relevant primary outcome parameters of cardiac performance and damage in a pig acute myocardial infarction model.

Abstract

Mortality after acute myocardial infarction remains substantial and is associated with significant morbidity, like heart failure. Novel therapeutics are therefore required to confine cardiac damage, promote survival and reduce the disease burden of heart failure. Large animal experiments are an essential part in the translational process from experimental to clinical therapies. To optimize clinical translation, robust and representative outcome measures are mandatory. The present manuscript aims to address this need by describing the assessment of three clinically relevant outcome modalities in a pig acute myocardial infarction (AMI) model: infarct size in relation to area at risk (IS/AAR) staining, 3-dimensional transesophageal echocardiography (TEE) and admittance-based pressure-volume (PV) loops. Infarct size is the main determinant driving the transition from AMI to heart failure and can be quantified by IS/AAR staining. Echocardiography is a reliable and robust tool in the assessment of global and regional cardiac function in clinical cardiology. Here, a method for three-dimensional transesophageal echocardiography (3D-TEE) in pigs is provided. Extensive insight into cardiac performance can be obtained by admittance-based pressure-volume (PV) loops, including intrinsic parameters of myocardial function that are pre- and afterload independent. Combined with a clinically feasible experimental study protocol, these outcome measures provide researchers with essential information to determine whether novel therapeutic strategies could yield promising targets for future testing in clinical studies.

Introduction

Heart failure with reduced ejection fraction (HFrEF) accounts for about 50% of all heart failure cases, affecting an estimated 1 - 2% of people in the western world¹. Its most prevalent cause is acute myocardial infarction (AMI). As acute mortality after AMI has declined significantly due to increased awareness and improved treatment options, emphasis has shifted towards its chronic sequelae; the most prominent being HFrEF^2,3. Together with increasing health care costs⁴, the growing epidemic of heart failure stresses the need for novel diagnostics and therapies, which can be studied in a highly translational porcine model of adverse re....