Quercetin glucuronide improves cardiac function in an ex vivo model of xenogeneic porcine heart transplantation

Objectives: Unmodified solid organs from pigs perfused with human blood undergo hyperacte rejection within minutes to hours. This reaction is mainly triggered by preformed anti-pig-antibodies binding to endothelial cell structures. Subsequent activation of the complement system causes endothelial cell damage, edema and venulothrombosis. Quercetin glucuronide (QG) was reported to stabilize cultured endothelial cells of venular origin in presence of inflammatory mediators and blood cells. We now investigated an assumed protective action of this substance in isolated hearts.

Methods: Twelve hearts of non-transgenic landrace pigs were perfused for 180 minutes in an ex vivo working-mode with human blood in the absence (control group, n=6) or presence of 50µM QG (added to the perfusion blood and organ preservation solution=HTK, n=6). Hemodynamic organ function was evaluated and immunological and inflammatory reaction was assessed with histological methods.

Results: All hearts maintained mandatory perfusion pressure of >55mmHg throughout the whole study period. Cardiac function was significantly improved in the GC-group. Stroke work index (mean±SEM) was 4272±434 in the QC-group vs. 2790±558 ergs/g in controls (P<0.05) after 30min and was still significantly higher at the end of the perfusion period (QC: 3145±160 vs. control: 1570±300 ergs/g; P<0.05). Microscopic examination of the myocardium revealed no venulothrombosis in the QC-group.

Conclusion: QG improved cardiac function and protected the xenogeneic perfused organ from microvascular damage. Thus, this flavonoid appears to be a promising additive to organ preservation solutions in cardiac xenotransplantation.