Ashok Nair1,2,3, Sitara Khan1,2, Sami Omar1,2, Xiao-Qing Pei1,2,4, Karen McNeill1,2, Phil Chowienczyk1,2, Andrew James Webb1,2. 1. King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, St. Thomas' Hospital, London, SE1 7EH, UK. 2. Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust, London, UK. 3. Department of Anaesthetics, Guy's & St. Thomas' NHS Foundation Trust, London, UK. 4. Ultrasound Department, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China.
Abstract
AIM: The aim of this article is 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 randomized in a crossover study to initially receive either RIPC (4 × 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 vs. 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-1 ) locally in the left arm (P = 0.008) overall, with an independent effect of -58.70 nmol l-1 (95% confidence intervals -116.1 to -1.33) at 15 min reperfusion, and by ~24% (from 109 ± 9 to 83 ± 7 nmol l-1 ) 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.
AIM: The aim of this article is 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 randomized in a crossover study to initially receive either RIPC (4 × 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 vs. 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-1 ) locally in the left arm (P = 0.008) overall, with an independent effect of -58.70 nmol l-1 (95% confidence intervals -116.1 to -1.33) at 15 min reperfusion, and by ~24% (from 109 ± 9 to 83 ± 7 nmol l-1 ) 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.
Authors: Stephen P Hoole; Patrick M Heck; Linda Sharples; Sadia N Khan; Rudolf Duehmke; Cameron G Densem; Sarah C Clarke; Leonard M Shapiro; Peter M Schofield; Michael O'Sullivan; David P Dutka Journal: Circulation Date: 2009-02-02 Impact factor: 29.690
Authors: M Kume; Y Yamamoto; S Saad; T Gomi; S Kimoto; T Shimabukuro; T Yagi; M Nakagami; Y Takada; T Morimoto; Y Yamaoka Journal: J Lab Clin Med Date: 1996-09
Authors: Derek J Hausenloy; Peter K Mwamure; Vinod Venugopal; Joanne Harris; Matthew Barnard; Ernie Grundy; Elizabeth Ashley; Sanjeev Vichare; Carmelo Di Salvo; Shyam Kolvekar; Martin Hayward; Bruce Keogh; Raymond J MacAllister; Derek M Yellon Journal: Lancet Date: 2007-08-18 Impact factor: 79.321
Authors: Jibran Khatri; Charlotte Elizabeth Mills; Perry Maskell; Chimed Odongerel; Andrew James Webb Journal: Br J Clin Pharmacol Date: 2016-05-06 Impact factor: 4.335
Authors: Derek J Hausenloy; Luciano Candilio; Richard Evans; Cono Ariti; David P Jenkins; Shyam Kolvekar; Rosemary Knight; Gudrun Kunst; Christopher Laing; Jennifer Nicholas; John Pepper; Steven Robertson; Maria Xenou; Tim Clayton; Derek M Yellon Journal: N Engl J Med Date: 2015-10-05 Impact factor: 91.245
Authors: Luca Faconti; Charlotte Elizabeth Mills; Virginia Govoni; Haotian Gu; Steven Morant; Benju Jiang; J Kennedy Cruickshank; Andrew James Webb Journal: Br J Clin Pharmacol Date: 2018-11-13 Impact factor: 4.335