Remote ischaemic preconditioning suppresses endogenous plasma nitrite during ischaemia-reperfusion: a randomised controlled crossover pilot study

AIM: To test the hypothesis that remote ischaemic preconditioning (RIPC) increases circulating endogenous local and systemic plasma [nitrite] during RIPC and ischaemia-reperfusion (IR) as a potential protective mechanism against ischaemia-reperfusion injury (IRI).

METHODS: Six healthy male volunteers (mean age 29.5 ± 7.6 years) were randomised in a cross-over study to initially receive either RIPC (4 x 5 min cycles) to the left arm, or no RIPC (Control), both followed by an ischaemia-reperfusion (IR) sequence (20 min cuff inflation to 200 mmHg, 20 min reperfusion) to the right arm. The volunteers returned at least 7 days later for the alternate intervention. The primary outcome was the effect of RIPC versus control on local and systemic plasma [nitrite].

RESULTS: RIPC did not significantly change plasma [nitrite] in either the left or the right arm during the RIPC sequence. However, compared to control, RIPC decreased plasma [nitrite] during the subsequent IR sequence by ~26% (from 118 ± 9 to 87 ± 5 nmol/L) locally in the left arm (P = 0.008) overall, with an independent effect of -58.70 nmol/L (95% Confidence Intervals -116.1 to -1.33) at 15 min reperfusion, and by ~24% (from 109 ± 9 to 83 ± 7 nmol/L) systemically in the right arm (P = 0.03).

CONCLUSIONS: RIPC had no effect on plasma [nitrite] during the RIPC sequence, but instead decreased plasma [nitrite] by ~25% during IR. This would likely counteract the protective mechanisms of RIPC, and contribute to RIPC's lack of efficacy, as observed in recent clinical trials. A combined approach of RIPC with nitrite administration may be required.