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Remote ischaemic preconditioning suppresses endogenous plasma nitrite during ischaemia-reperfusion: a randomized
Ashok Nair1,2,3, Sitara Khan1,2, Sami Omar1,2
1King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, St. Thomas' Hospital, London, SE1 7EH, UK.
British Journal of Clinical Pharmacology
|January 12, 2017
Summary
Remote ischaemic preconditioning (RIPC) did not increase plasma nitrite levels. Instead, RIPC decreased nitrite during ischaemia-reperfusion, potentially explaining its lack of clinical efficacy. Further research combining RIPC with nitrite may be needed.
Area of Science:
- Physiology
- Biochemistry
Background:
- Remote ischaemic preconditioning (RIPC) is a potential strategy to mitigate ischaemia-reperfusion injury (IRI).
- The mechanism of RIPC's protective effect is not fully understood, with a hypothesis suggesting increased endogenous nitrite levels.
Purpose of the Study:
- To investigate whether RIPC increases circulating plasma nitrite levels during RIPC and subsequent ischaemia-reperfusion (IR).
- To assess the role of plasma nitrite as a potential protective mechanism against IRI.
Main Methods:
- A crossover study involving six healthy male volunteers.
- Participants underwent either RIPC or a control period, followed by an IR sequence to an arm.
- Plasma nitrite levels were measured locally and systemically during RIPC and IR.
Main Results:
- RIPC did not alter plasma nitrite levels during the RIPC phase.
- RIPC significantly decreased plasma nitrite levels by approximately 24-26% during the subsequent IR phase.
- This reduction was observed both locally in the preconditioned limb and systemically.
Conclusions:
- RIPC does not increase, but rather decreases, plasma nitrite during IR.
- The observed decrease in nitrite may counteract potential protective mechanisms of RIPC.
- This finding could contribute to the limited efficacy of RIPC in recent clinical trials, suggesting a potential need for combined RIPC and nitrite administration strategies.
