Effects of warm ischemia following harvesting of allograft cardiac valves

Abstract

The clinical use of cryopreserved allograft valves is rapidlyincreasing. Viability of valve leaflet fibroblasts has been proposed to becritical to durability. Harvesting of allograft valves involves variablewarm ischemia times, defined as the time from cessation of donor heart beatto initial cooling for transport. This ischemic period has been implicatedas one of the more critical periods of injury to leaflet cell, even thoughadequate characterization of this potentially injurious phase has neverbeen accomplished. The present study was undertaken to characterize themetabolic response to warm ischemia in a porcine valve leaflet model. Valvehandling was similar to clinical valve harvest and transport protocols.Injury was assessed by protein (1H) and phosphorus (31P) magnetic resonancespectroscopy of 224 porcine semilunar valves. Leaflets were analyzed overtime for lactate accumulation and ATP degradation. A radiolabelledincubation assay (48 valves) was used to measure proline accumulation byfibroblasts. Electron microscopy was performed on 36 valves with varyingwarm ischemia times. ATP stores were entirely depleted after 2 h hypoxia (pless than 0.05). However, lactate continued to accumulate over 24 h.Although aerobic metabolism ceased after 2 h warm ischemia, anaerobicmetabolism continued for up to 24 h, which may represent an extended windowfor harvesting fresh tissue for allograft valve implantation.