Abstract 19156: Gene Expression Profiles Underlying the Cardioprotective Effects of Mechanical Primary Unloading of the Left Ventricle Before Reperfusion in Acute Myocardial Infarction
We recently reported that compared to Primary Reperfusion (PR), first unloading the left ventricle (LV) by activating an mechanical circulatory support pump while delaying coronary reperfusion (Primary Unloading; PU) reduces myocardial damage in models of acute myocardial infarction (AMI). We now employed a transcriptomics-directed approach to identify the underlying mechanisms by which PU reduces myocardial infarct size.
Methods: AMI was induced by occlusion of the left anterior descending artery (LAD) for 90 min in male swine. In the PR group, the LAD was reperfused for 120 min. In the PU group, after 90 min of ischemia a pump was activated and the LAD left occluded for an additional 30 min, followed by 120 min of reperfusion. Myocardial infarct size was quantified by TTC staining. Whole-transcript expression analysis was performed on RNA from the infarct zone using Porcine 1.0 ST microarrays and ConsensusPathDB pathway programs. Quantitative PCR confirmed expression of select genes from regulated pathways. Scanning electron microscopy (SEM) evaluated mitochondrial integrity within infarct zones. Sham operated LV samples served as controls.
Results: Compared to PR, PU reduced myocardial infarct size (65% vs 34%, P<0.01). Principle component analysis showed that infarct tissue from the PU group clustered separately from the PR and Sham groups. Pathway analysis indicated that, compared to PR, PU triggered changes in several processes including reduced inflammation, reduced fibrosis, and increased metabolic enzyme expression and cellular respiration (Fig. A). SEM showed a higher ratio of intact mitochondria/cardiomyocyte area within the infarct zone after PU (Fig. B).
Conclusions: We identified for the first time that Primary LV Unloading triggers a global shift in gene expression and preserves mitochondrial integrity within the infarct zone during the acute phase of AMI. Further studies exploring the clinical utility of PU are required.
Author Disclosures: Y. Zhang: None. G. Schnitzler: None. M. Esposito: None. X. Qiao: None. S. Annamalai: None. E. Mackey: None. K. Morine: None. A. Mullin: None. R. Pedicini: None. C. Breton: None. R. Karas: None. N.K. Kapur: Research Grant; Significant; Abiomed.
- © 2016 by American Heart Association, Inc.