Potential consequences of the red blood cell storage lesion on cardiac electrophysiology

Abstract

36The red blood cell (RBC) storage lesion is a series of morphological, functional and metabolic 37 changes that RBCs undergo following collection, processing and refrigerated storage for clinical 38 use. Since the biochemical attributes of the RBC unit shifts with time, transfusion of older blood 39 products may contribute to cardiac complications, including hyperkalemia and cardiac arrest. 40We measured the direct effect of storage age on cardiac electrophysiology and compared with 41 hyperkalemia, a prominent biomarker of storage lesion severity. Donor RBCs were processed 42 using standard blood banking techniques. The supernatant was collected from RBC units 43 (sRBC), 7-50 days post-donor collection, for evaluation using Langendorff-heart preparations 44 (rat) or human stem-cell derived cardiomyocytes. Cardiac parameters remained stable following 45 exposure to 'fresh' sRBC (day 7: 5.9+0.2 mM K + ), but older blood products (day 40: 9.7+0.4 mM 46 K + ) caused bradycardia (baseline: 279±5 vs day 40: 216±18 BPM), delayed sinus node 47 recovery (baseline: 243±8 vs day 40: 354±23 msec), and increased the effective refractory 48 period of the atrioventricular node (baseline: 77+2 vs day 40: 93+7 msec) and ventricle 49 (baseline: 50+3 vs day 40: 98+10 msec) in perfused hearts. Beating rate was also slowed in 50 human cardiomyocytes after exposure to older sRBC (-75+9%, day 40 vs control). Similar 51 effects on automaticity and electrical conduction were observed with hyperkalemia (10-12 mM 52 K + ). This is the first study to demonstrate that 'older' blood products directly impact cardiac 53 electrophysiology, using experimental models. These effects are likely due to biochemical 54 alterations in the sRBC that occur over time, including, but not limited to hyperkalemia. Patients 55 receiving large volume and/or rapid transfusions may be sensitive to these effects. 56 57New & noteworthy 58We demonstrate that red blood cell storage duration time can have downstream effects on 59 cardiac electrophysiology, likely due to biochemical alterations in the blood product. 60Hyperkalemia and cardiac arrest have been reported following blood transfusions, but this is the 61 first experimental study to show a direct correlation between storage duration and cardiac 62 function. Infant and pediatric patients, and those receiving large volume and/or rapid 63 transfusions may be sensitive to these effects. 64

Measuring potassium level in packed red blood cells before using: Word of caution for congenital cardiac surgery

“…Reilly et al 23 studied the electrophysiological effects of the transfusion done by older PRBCs with the effects of biochemical alterations in the stored blood including hyperpotassemia. They demonstrated that older blood products mostly affected cardiac electrophysiology due to the alterations in the electrolytes of the stored blood especially potassium.…”

Biochemical disturbance in damage control resuscitation: mechanisms, management and prognostic utility

“…Hyperkalaemia represents a key component of the pRBC storage lesion in which biochemical, metabolic and structural alterations occur within pRBCs in a time-dependent fashion, with a 3.76-fold increase in potassium concentration observed after three weeks [17 & ]. An in-vitro study demonstrated a direct link between supernatant from pRBCs stored for longer periods, hyperkalaemia and adverse electrocardiogram changes [18].…”

Preventing transfusion‐associated hyperkalemia in pediatric cardiac surgery: Measure the levels of potassium in packed red blood cells before using – Invited commentary

“…2 Potassium is a predominant intracellular cation, but an extracellular concentration greater than 5.5 mEq/L has significant effects on cardiac rhythm, which may lead to cardiac arrest. 7 Stored PRBCs are depleted of ATP, which alters the cell membrane, resulting in hemolysis and dysfunction of cation transporters, including impairment of Na + /K + ATPase, 8 which leads to a progressive increase in extracellular K + in the PRBC unit supernatant. 9 Furthermore, gamma irradiation, which is used to prevent graft-versus-host disease, increases hemolysis, resulting in potentiated K + leakage.…”