In vivo MRI and ex vivo histological assessment of the cardioprotection induced by ischemic preconditioning, postconditioning and remote conditioning in a closed-chest porcine model of reperfused acute myocardial infarction: importance of microvasculature

Abstract

BackgroundCardioprotective value of ischemic post- (IPostC), remote (RIC) conditioning in acute myocardial infarction (AMI) is unclear in clinical trials. To evaluate cardioprotection, most translational animal studies and clinical trials utilize necrotic tissue referred to the area at risk (AAR) by magnetic resonance imaging (MRI). However, determination of AAR by MRI‚ may not be accurate, since MRI-indices of microvascular damage, i.e., myocardial edema and microvascular obstruction (MVO), may be affected by cardioprotection independently from myocardial necrosis. Therefore, we assessed the effect of IPostC, RIC conditioning and ischemic preconditioning (IPreC; positive control) on myocardial necrosis, edema and MVO in a clinically relevant, closed-chest pig model of AMI.Methods and resultsAcute myocardial infarction was induced by a 90-min balloon occlusion of the left anterior descending coronary artery (LAD) in domestic juvenile female pigs. IPostC (6 × 30 s ischemia/reperfusion after 90-min occlusion) and RIC (4 × 5 min hind limb ischemia/reperfusion during 90-min LAD occlusion) did not reduce myocardial necrosis as assessed by late gadolinium enhancement 3 days after reperfusion and by ex vivo triphenyltetrazolium chloride staining 3 h after reperfusion, however, the positive control, IPreC (3 × 5 min ischemia/reperfusion before 90-min LAD occlusion) did. IPostC and RIC attenuated myocardial edema as measured by cardiac T2-weighted MRI 3 days after reperfusion, however, AAR measured by Evans blue staining was not different among groups, which confirms that myocardial edema is not a measure of AAR, IPostC and IPreC but not RIC decreased MVO.ConclusionWe conclude that IPostC and RIC interventions may protect the coronary microvasculature even without reducing myocardial necrosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1166-z) contains supplementary material, which is available to authorized users.

An hs-TNT Second Peak Associated with High CRP at Day 2 Appears as Potential Biomarkers of Micro-Vascular Occlusion on Magnetic Resonance Imaging after Reperfused ST-Segment Elevation Myocardial Infarction

“…This trend is consistent with data from the literature. Indeed, ischemic preconditioning could be responsible for vascular collateralisation, improving the myocardium perfusion [30]. While hs-TnT first peak correlated with the infarct size, it did not reflect the quality of the reperfusion in our study.…”

Remote ischemic conditioning protects against endothelial ischemia-reperfusion injury via a glucagon-like peptide-1 receptor-mediated mechanism in humans

“…However, none of the trials were pre-specified for this endpoint. Nonetheless, a subsequent study in pigs found that RIC attenuated the extent of myocardial edema as measured by T2-weighted CMR 168 . Evaluation of MaR through T2-weighted and T2-mapping as well as early contrast-enhanced steady state free precession CMR sequences are edemabased and it has therefore been suggested that intervention with RIC may reduce the extent of edema and thereby MaR determined with CMR 169,170 .…”

Cardioprotective Effect of Novel Matrix Metalloproteinase Inhibitors

“…Therefore, it is important to investigate MVO in preclinical studies, to gather information for a better understanding of the pathomechanism and to find possible therapeutic options. In a large animal model, late gadolinium-enhanced cardiac MRI was used to assess the myocardial MVO burden after different ischemic conditionings [ 50 ]. So far, several findings have shown that myocardial edema and MVO are altered independently of myocardial necrosis, which is in line with the findings of clinical trials [ 50 ].…”

“…In a large animal model, late gadolinium-enhanced cardiac MRI was used to assess the myocardial MVO burden after different ischemic conditionings [ 50 ]. So far, several findings have shown that myocardial edema and MVO are altered independently of myocardial necrosis, which is in line with the findings of clinical trials [ 50 ]. In the present model, we used thioflavine-S staining perfused through the whole heart and the heart slices were investigated under UV light to visualize the penetration of the dye into the tissue.…”