Upper arm intermittent ischaemia reduces exercise-related increase of platelet reactivity in patients with obstructive coronary artery disease

Objective To assess whether upper arm ischaemia influences exercise-induced myocardial ischaemia and platelet activation in patients with coronary artery disease (CAD). Design Crossover study. Setting University hospital. Patients Twenty patients (17 men) of mean±SD age 64±8 years with stable CAD. Interventions Patients underwent two exercise stress tests (ESTs) on two separate days in a randomised manner: (1) a maximal EST only (EST-1); (2) a maximal EST after intermittent upper arm ischaemia (cycles of alternating 5-min inflation and 5-min deflation of a standard blood pressure cuff) (EST-2). Blood samples were obtained to evaluate platelet reactivity. Main outcome measures Platelet reactivity was assessed by flow cytometry at rest and after EST, with and without ADP stimulation, by measuring the percentage of monocyte-platelet aggregates (MPAs) and CD41 platelet expression measured as mean fluorescence intensity. Results Remote ischaemia had no significant effect on EST-induced myocardial ischaemia. At rest there were no differences before EST-1 and EST-2 in basal MPA (20.7±2.3 vs 20.8±2.4, p=0.56) and CD41 (21.5±2.3 vs 21.3±2.3, p=0.39), and ADP stimulation induced a similar increase in both MPA (+15.2±8.2% vs +14.9±8.4%, p=0.71) and CD41 (+15.7±5.7% vs 13.37±6.9%, p=0.59). While no differences in the increase in MPA and CD41 expression were observed after EST-1 and EST-2, ADP stimulation after EST-2 induced a lower increase in MPA (+18.3±8.1% vs +27.9±9.7%, p<0.001) and CD41 (+18.3±9.2% vs +27.2±12.4%, p<0.001) than after EST-1. Conclusion These results show that, in patients with stable CAD, remote ischaemia induces protection against an exercise-related increase in platelet reactivity.

[1]  D. Newby,et al.  Remote ischemic preconditioning prevents systemic platelet activation associated with ischemia–reperfusion injury in humans , 2011, Journal of thrombosis and haemostasis : JTH.

[2]  Manjeet Singh,et al.  Possible involvement of α1-adrenergic receptor and KATP channels in cardioprotective effect of remote aortic preconditioning in isolated rat heart , 2010, Journal of cardiovascular disease research.

[3]  C. Terkelsen,et al.  Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial , 2010, The Lancet.

[4]  F. Crea,et al.  Predictors of exercise-induced platelet reactivity in patients with chronic stable angina , 2009, Journal of cardiovascular medicine.

[5]  F. Crea,et al.  Brief low-workload myocardial ischaemia induces protection against exercise-related increase of platelet reactivity in patients with coronary artery disease , 2009, Heart.

[6]  Elena Kuzmin,et al.  Transient limb ischaemia remotely preconditions through a humoral mechanism acting directly on the myocardium: evidence suggesting cross-species protection. , 2009, Clinical science.

[7]  A. Fattorossi,et al.  Adenosine inhibition of adenosine diphosphate and thrombin-induced monocyte-platelet aggregates in cardiac syndrome X. , 2009, Thrombosis research.

[8]  L. Sharples,et al.  Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: A Prospective, Randomized Control Trial , 2009, Circulation.

[9]  D. Yellon,et al.  Remote ischaemic preconditioning: underlying mechanisms and clinical application. , 2008, Cardiovascular research.

[10]  I. Konstantinov,et al.  Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning. , 2007, American journal of physiology. Heart and circulatory physiology.

[11]  A. Fattorossi,et al.  Relationship between changes in platelet reactivity and changes in platelet receptor expression induced by physical exercise. , 2007, Thrombosis research.

[12]  I. Konstantinov,et al.  Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans. , 2006, Journal of the American College of Cardiology.

[13]  J. Deanfield,et al.  Remote ischemic preconditioning provides early and late protection against endothelial ischemia-reperfusion injury in humans: role of the autonomic nervous system. , 2005, Journal of the American College of Cardiology.

[14]  R. Guyton,et al.  Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. , 2003, American journal of physiology. Heart and circulatory physiology.

[15]  D. Liem,et al.  Transient limb ischemia induces remote ischemic preconditioning in vivo. , 2003, Circulation.

[16]  A. Hsu,et al.  Cardioprotection at a distance: mesenteric artery occlusion protects the myocardium via an opioid sensitive mechanism. , 2002, Journal of molecular and cellular cardiology.

[17]  F. Tomai,et al.  Warm up phenomenon and preconditioning in clinical practice , 2002, Heart.

[18]  M. Furman,et al.  Circulating Monocyte-Platelet Aggregates Are a More Sensitive Marker of In Vivo Platelet Activation Than Platelet Surface P-Selectin: Studies in Baboons, Human Coronary Intervention, and Human Acute Myocardial Infarction , 2001, Circulation.

[19]  M. Sans,et al.  Preconditioning protects against systemic disorders associated with hepatic ischemia‐reperfusion through blockade of tumor necrosis factor–induced P‐selectin up‐regulation in the rat , 2001, Hepatology.

[20]  A. Maseri,et al.  Low-grade exercise enhances platelet aggregability in patients with obstructive coronary disease independently of myocardial ischemia. , 2001, The American journal of cardiology.

[21]  R. Schoemaker,et al.  Bradykinin mediates cardiac preconditioning at a distance. , 2000, American journal of physiology. Heart and circulatory physiology.

[22]  P. Capecchi,et al.  SYSTEMIC ADENOSINE INCREASE DURING COLD PRESSOR TEST IS DEPENDENT ON SYMPATHETIC ACTIVATION , 1999, Clinical and experimental pharmacology & physiology.

[23]  F. Crea,et al.  Exercise-induced myocardial ischemia triggers the early phase of preconditioning but not the late phase. , 1999, The American journal of cardiology.

[24]  S. Morikawa,et al.  Renal ischemia/reperfusion remotely improves myocardial energy metabolism during myocardial ischemia via adenosine receptors in rabbits: effects of "remote preconditioning". , 1999, Journal of the American College of Cardiology.

[25]  D. Yellon,et al.  Renal ischemia preconditions myocardium: role of adenosine receptors and ATP-sensitive potassium channels. , 1998, The American journal of physiology.

[26]  Y. Matsuzawa,et al.  Endogenous adenosine inhibits P-selectin-dependent formation of coronary thromboemboli during hypoperfusion in dogs. , 1998, The Journal of clinical investigation.

[27]  P Hjemdahl,et al.  Effects of mental and physical stress on platelet function in patients with stable angina pectoris and healthy controls. , 1997, European heart journal.

[28]  F. Crea,et al.  Mechanisms of the warm-up phenomenon. , 1996, European heart journal.

[29]  Y. Ikeda,et al.  Enhanced Platelet Aggregability under High Shear Stress after Treadmill Exercise in Patients with Effort Angina , 1996, Thrombosis and Haemostasis.

[30]  K. Mullane,et al.  Adenosine-mediated inhibition of platelet aggregation by acadesine. A novel antithrombotic mechanism in vitro and in vivo. , 1994, The Journal of clinical investigation.

[31]  R. Kloner,et al.  Regional Ischemic 'Preconditioning' Protects Remote Virgin Myocardium From Subsequent Sustained Coronary Occlusion , 1993, Circulation.

[32]  M. Hori,et al.  Endogenous adenosine inhibits platelet aggregation during myocardial ischemia in dogs. , 1991, Circulation research.

[33]  R. Jennings,et al.  Cardiac adaptation to ischemia. Ischemic preconditioning increases myocardial tolerance to subsequent ischemic episodes. , 1990, Circulation.

[34]  K. Winther,et al.  Exercise-induced platelet aggregation in angina and its possible prevention by beta 1-selective blockade. , 1990, European heart journal.

[35]  D. Seals.  Sympathetic activation during the cold pressor test: influence of stimulus area. , 1990, Clinical physiology.

[36]  J. Fagius,et al.  The cold pressor test: effects on sympathetic nerve activity in human muscle and skin nerve fascicles. , 1989, Acta physiologica Scandinavica.

[37]  A. Mark,et al.  Effects of the cold pressor test on muscle sympathetic nerve activity in humans. , 1987, Hypertension.

[38]  R. Berne,et al.  Adenosine and Adenine Nucleotides as Possible Mediators of Cardiac and Skeletal Muscle Blood Flow Regulation , 1971, Circulation research.