Research flock at US

Sheep Experiment Station

Research conducted in sheep indicates that pretreating red blood cells (RBCs) with nitric oxide (NO) may make it safer to transfuse blood nearing its expiration date.

Past studies have suggested that RBCs stored for more than 30 days are less likely than “fresher” RBCs to survive after transfusion, and receiving a transfusion of RBCs nearing their expiration date of 42 days may increase the risk of pulmonary hypertension.

However, a new study published in Anesthesiology suggests that pretreating older RBCs with NO may increase their likelihood of survival after transfusion and reduce the risk of pulmonary hypertension in the recipient.

“Extended storage of RBCs makes them rigid and decreases their ability to change shape, which is necessary as they travel through small blood vessels,” said study author Warren M. Zapol, MD, of Massachusetts General Hospital in Boston.

“We found that pretreatment with nitric oxide actually rejuvenates RBCs, making them more flexible so they can more easily travel through blood vessels. This can further reduce the risk of pulmonary hypertension.”

Dr Zapol and his colleagues performed their experiments on RBCs derived from lambs. The team treated RBCs with NO gas, a short-lived NO donor, or gas without NO (control).

The RBCs were then stored for either 2 days (hereafter referred to as “fresh” RBCs) or 40 days (referred to as “stored” RBCs) and transfused back into the original lambs.

RBC survival

The researchers found that treatment with NO gas improved the early post-transfusion survival of stored RBCs.

At 1 hour after transfusion, 75.3 ± 5.8% of the control-treated stored RBCs remained in the circulation, compared to 86.8 ± 8.1% of the NO-treated stored RBCs and 94.2 ± 4.6% of the fresh RBCs.

At 24 hours after transfusion, 73.4 ± 3.8% of the control-treated stored RBCs remained in the circulation, compared to 78.3 ± 6.3% of the NO-treated stored RBCs, 90.8 ± 4.1% of control-treated fresh RBCs, and 91.4 ± 1.4% of NO-treated fresh RBCs.

The differences between stored RBCs that were treated with NO gas and stored control RBCs was statistically significant at both 1 hour and 24 hours, with P values of 0.002 and 0.046, respectively.

Seven days after transfusion, there was no significant difference in the percentage of NO-treated and control-treated RBCs in the circulation.

Pulmonary hypertension

The researchers found that pretreating RBCs with NO prevented transfusion-associated pulmonary hypertension in the lambs.

Lambs that received control-treated stored RBCs had an increase in pulmonary arterial pressure (PAP) during and after transfusion—from 13.4 ± 0.8 mmHg at baseline to a maximum of 22.7 ± 2.2 mmHg.

However, lambs that received stored RBCs treated with NO gas did not have an increase in PAP when compared to lambs that received fresh RBCs.

At 20 minutes, PAP was 14.5 ± 1.4 mmHg for NO-treated stored RBCs, 13.9 ± 0.6 mmHg for control-treated fresh RBCs, and 14 ± 1.2 mmHg for NO-treated fresh RBCs.

The researchers also found that transfusion of stored RBCs caused a transient increase in the pulmonary vascular resistance index (PVRI) from 10 minutes to 30 minutes after transfusion, but pretreatment with NO gas prevented this increase.

At 20 minutes, the PVRI was 211.1 ± 44.4 dyn·sec·cm⁻⁵·m⁻² for control-treated stored RBCs and 114.6 ± 18.9 dyn·sec·cm⁻⁵·m⁻² for NO-treated stored RBCs (P<0.0001).

Transfusion of fresh RBCs, with or without prior NO exposure, did not alter the PVRI.

Finally, the researchers found that treating stored RBCs with the NO donor compound MAHMA NONOate prevented transfusion-associated pulmonary hypertension and pulmonary vasoconstriction in awake lambs.

The team said studies with human RBCs are required to confirm the beneficial effects of NO exposure observed in this study.

Treating RBCs with NO may make them safer