Larger infarct size but equal protection by ischemic conditioning in septum and anterior free wall of pigs with LAD occlusion.

Andreas Skyschally,Gerd Heusch,Helene Hagelschuer,Petra Kleinbongard

doi:10.14814/phy2.14236

Andreas Skyschally, Gerd Heusch + Show 2 more

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https://doi.org/10.14814/phy2.14236

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Abstract

The ischemic area at risk (AAR) is one major determinant of infarct size (IS). In patients, the largest AAR is seen with a proximal occlusion of the left anterior descending (LAD) coronary artery, which serves parts of the septum and of the anterior free wall. It is not clear, whether regional differences in the perfusion territories also impact on IS and the magnitude of cardioprotection by ischemic conditioning. We have retrospectively analyzed 132 experiments in pigs, which have a similar LAD perfusion territory as humans. The LAD was occluded for 60 min with subsequent 180 min reperfusion. Cardioprotection by either local ischemic pre‐ or postconditioning or remote ischemic pre‐ or perconditioning was induced in 93 pigs. The AAR was demarcated by blue dye staining, and IS was assessed by triphenyltetrazolium chloride (TTC) staining. Using digital planimetry, the AAR was separated into sections unequivocally located in the septum (AARS) or the anterior free wall (AARAFW). Relative IS was calculated for AARS or AARAFW. AARAFW was larger than AARS (51 ± 9% vs. 34 ± 8% of total AAR; mean ± SD, P < 0.001). Regional myocardial blood flow (microspheres) was not different between septum and anterior free wall. IS without ischemic conditioning tended to be larger in AARS than in AARAFW (50 ± 17% vs. 44 ± 19%; % of AARAWF or AARS, respectively; P = 0.075). Also, with robust IS reduction by ischemic conditioning, the difference in relative IS remained (AARS: 27 ± 16%; AARAFW: 21 ± 16%; P = 0.01). There is a somewhat greater susceptibility for infarction in septal than anterior free wall myocardium. However, ischemic conditioning still reduces IS in both septal and anterior free wall myocardium.

Highlights

In patients surviving an acute myocardial infarction, infarct size (IS) is a major determinant of prognosis (Stone et al 2016; Heusch and Gersh, 2017)
From all experiments performed between November 2012 and November 2018 with one of the above described experimental protocols, 58 pigs were not included in the present analysis
Confirming the data of Schulz et al (2005), the IS within the left anterior descending (LAD) perfusion territory in the present study differed between the septal and anterior free wall perfusion territories

Summary

Introduction

In patients surviving an acute myocardial infarction, infarct size (IS) is a major determinant of prognosis (Stone et al 2016; Heusch and Gersh, 2017). Cardioprotection by ischemic conditioning can be induced prior to ischemia as local ischemic preconditioning (IPC) (Murry et al 1986) or as remote ischemic preconditioning (RIPC) (Przyklenk et al 1993; Heusch et al 2015), during ischemia as remote ischemic perconditioning (RPER) (Schmidt et al 2007; Kleinbongard et al 2018), and locally at the onset of reperfusion as ischemic postconditioning (POCO) (Zhao et al 2003). The cause of acute myocardial infarction is usually the thrombotic occlusion of a large epicardial coronary artery after rupture of an atherosclerotic plaque, and the site of such thrombotic occlusion largely determines the area at risk (AAR).

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