AbstractThe red blood cell (RBC) storage lesion is a series of morphological, functional and metabolic changes that RBCs undergo following collection, processing and refrigerated storage for clinical use. Since the biochemical attributes of the RBC unit shifts with time, transfusion of older blood products may contribute to cardiac complications, including hyperkalemia and cardiac arrest. We measured the direct effect of storage age on cardiac electrophysiology and compared with hyperkalemia, a prominent biomarker of storage lesion severity. Donor RBCs were processed using standard blood banking techniques. The supernatant was collected from RBC units (sRBC), 7-50 days post-donor collection, for evaluation using Langendorff-heart preparations (rat) or human stem-cell derived cardiomyocytes. Cardiac parameters remained stable following exposure to ‘fresh’ sRBC (day 7: 5.9+0.2 mM K+), but older blood products (day 40: 9.7+0.4 mM K+) caused bradycardia (baseline: 279±5 vs day 40: 216±18 BPM), delayed sinus node recovery (baseline: 243±8 vs day 40: 354±23 msec), and increased the effective refractory period of the atrioventricular node (baseline: 77+2 vs day 40: 93+7 msec) and ventricle (baseline: 50+3 vs day 40: 98+10 msec) in perfused hearts. Beating rate was also slowed in human cardiomyocytes after exposure to older sRBC (−75+9%, day 40 vs control). Similar effects on automaticity and electrical conduction were observed with hyperkalemia (10-12 mM K+). This is the first study to demonstrate that ‘older’ blood products directly impact cardiac electrophysiology, using experimental models. These effects are likely due to biochemical alterations in the sRBC that occur over time, including, but not limited to hyperkalemia. Patients receiving large volume and/or rapid transfusions may be sensitive to these effects.New & noteworthyWe demonstrate that red blood cell storage duration time can have downstream effects on cardiac electrophysiology, likely due to biochemical alterations in the blood product. Hyperkalemia and cardiac arrest have been reported following blood transfusions, but this is the first experimental study to show a direct correlation between storage duration and cardiac function. Infant and pediatric patients, and those receiving large volume and/or rapid transfusions may be sensitive to these effects.