Randomized evaluation of comparative effects of optimized static cold storage, hypothermic and normothermic machine perfusion, and colchicine pretreatment on ischemia-reperfusion injury in a porcine model.

Abstract

BACKGROUND: Heart transplantation remains limited by ischemia-reperfusion injury (IRI). Optimizing graft preservation and modulating inflammation may improve early graft quality. We compared optimized static cold storage (SCS), hypothermic machine perfusion (HMP), and normothermic machine perfusion (NMP), and evaluated colchicine pretreatment as an adjunct anti-inflammatory strategy. METHODS: Thirty-six pigs were randomized to colchicine or placebo (n=18 each) and subsequently assigned to SCS, HMP, or NMP (n=12 per group). After 4&#xa0;h of preservation, all hearts underwent 1&#xa0;h of normothermic reperfusion. Myocardial injury, lactate extraction, systemic cytokines, and histological assessments were performed. Mixed-effects models accounting for repeated measures and treatment-preservation interactions were used for all longitudinal analyses. RESULTS: HMP was associated with lower H-FABP levels than SCS (&#x3b2; -92.6; 95% CI -183 to -2.6; p=0.04), while NMP showed no difference. Troponin I release was significantly higher in NMP versus SCS (&#x3b2; 97.9; 95% CI 63.4-132; p<0.001). Lactate extraction was greater with HMP compared with SCS (&#x3b2; 10.2; 95% CI -0.2 to 20.6; p=0.05), with no difference for NMP. Preservation modality strongly influenced inflammation: IL-6 (&#x3b2; 3.72; p<0.001) and TNF-&#x3b1; (&#x3b2; 0.25; p=0.003) were markedly increased in NMP, whereas IL-10 was reduced in HMP versus SCS (&#x3b2; -0.38; p<0.001). Colchicine had no significant effect on any biomarker. Oxidative stress proteins, apoptosis markers, and histological injury scores did not differ across preservation modalities or treatment groups. CONCLUSIONS: In this randomized large-animal model, hypothermic preservation (SCS, HMP) provides superior metabolic and inflammatory profiles compared with NMP. Colchicine did not confer additional benefit under these conditions.