Pharmacological Conditioning Reduces Damage from Ischemia-Reperfusion Injury in Porcine Skeletal Muscle and Ex-Vivo Functional Hearts

D. A. Ramirez, W. Upchurch, M. Uchenik, K. Ziegler, T. Iles, P. A. Iaizzo

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: Heart transplantation is commonly considered to be the only option available for patients with congenital heart defects and/or individuals with terminal heart failure. Myocardial ischemia-reperfusion injury (IRI) can damage the heart and prolong recovery. Common complications of IRI include graft rejection, cardiac allograft vasculopathy, graft dysfunction, and chronic kidney disease. Solutions of omega-3/omega-6 fatty acids and bear bile acids have been found to attenuate IRI. This study observes the protection conferred by these agents in isolated muscle bundles as well as on ex-vivo perfused hearts METHODS: Diaphragm skeletal muscle bundles are harvested from swine. Each individual bundle is placed in an isolated tissue bath measuring twitch force. Muscle bundles are stimulated and the force of contraction is recorded. Baseline and pretreatment data is collected for 1 hour each. Following pretreatment nitrogen gas is bubbled to induce hypoxia. Recovery force data is collected for 5 hours. Recorded data is normalized to baseline and analyzed.Additionally, swine hearts were pretreated for 1 hour before explant and subsequent reanimation on the Visible Heart Apparatus. Left ventricular pressure was collected for 2 hours post-reanimation. RESULTS: Preliminary results indicate pretreatment protects and increases muscle contractile function compared to controls. Increased function was observed in bundles that received omega-3 and omega-6 treatment before hypoxia and improved recovery was observed when combined with bear bile acids. Reanimated hearts show an increased left ventricular pressure differential after pretreatment CONCLUSION: The preliminary investigations in diminishing IRI suggest there are promising applications of omega-3, omega-6, and bear bile acid treatments, specifically in heart transplantation.

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