Ischemia Minimization Reduces Cardiac Xenograft Injury

Abstract

<h3>Purpose</h3> Previous work has shown the benefit of ischemia minimization (IM) to reduce initial xenograft dysfunction. We examined cardiac injury in an <i>ex vivo</i> xenoperfusion model comparing IM with cold storage (CS). <h3>Methods</h3> Hearts from pigs expressing TKO.GHRKO (QKO) were compared to wild-type (WT) using an <i>ex vivo</i> model. Three QKO and 1 WT hearts were treated with IM for 2.5 hours following procurement. IM consisted of continuous cold cardioplegia. Two QKO and 2 WT hearts were placed in iced saline for the same time period. Following IM or CS hearts were Langendorff perfused with warm human blood then converted to working heart mode (WHM) if able. Total perfusion time was 4 hours. Troponin levels and physiologic function were periodically observed. <h3>Results</h3> Release of troponin was significantly reduced in the WT IM group (IM 185, CS>1000; p=0.02). A similar yet non-significant observation was noted in the QKO IM hearts (IM 750, CS>1000; p=0.37) (Fig.1). Two WT hearts (1 CS and 1 IM) were physiologically unable to reach WHM. One WT CS heart achieved WHM though failed at 3 hours (Fig.2F). Physiologic function was maintained in 2 of 3 QKO IM hearts (Fig 2A, B), and 1 of 2 QKO CS hearts (Fig. 2E). All WT hearts (2 CS and 1 IM (Fig. 2F)) and 2 of 5 QKO hearts (1 CS (Fig. 2D) and 1 IM (Fig. 2C)) failed within 4 hours. The 4 hour survival rate was not significantly improved by IM. <h3>Conclusion</h3> IM was shown to reduce cardiac injury in WT hearts and promote an increase in functional outcomes. This was a limited pilot study, however, the results were consistent with prior reported observations showing that IM reduced heart xenograft injury and dysfunction and support further evaluation of IM in <i>ex vivo</i> and <i>in vivo</i> models.