Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, PC216

Poster Communications

Exercising Arterial Oxygenation Oxidative Stress and NO: Impact on the Regulation of Blood Coagulation in Man

K. J. New1, L. Fall1, C. Templeton2, G. Ellis2, D. Hullin3, J. McEneny4, P. E. James5, B. Davies1, D. M. Bailey1

1. Neurovascular Research Laboratory, University Of Glamorgan, Pontypridd, United Kingdom. 2. Cardiology, Royal Glamorgan Hospital, Llantrisant, United Kingdom. 3. Pathology, Royal Glamorgan Hosptial, Llantrisant, United Kingdom. 4. Centre for Public Health, Queens University, Belfast, United Kingdom. 5. Wales Heart Research Institute, Cardiff University, Cardiff, United Kingdom.


Patients with peripheral arterial occlusive disease undertake prescribed exercise experiencing hypoxaemia with periods of ischaemia-reperfusion. Hence this population regularly encounters sinusoidal changes in arterial oxygen tension. Whilst hypoxia and exercise have been independently associated with activation of blood coagulation in humans (Weiss et al, 1998; 2002) our laboratory recently reported the significance of plasma volume correction for the interpretive analysis of haemostasis (Fall et al, 2011). We have also documented redox regulation of blood coagulation following exercise (New et al, 2011). The additional effect of hyperoxic exercise on the coagulation cascade is not known. The current study tested the hypothesis that an acute bout of mild hypoxic and hyperoxic exercise would not lead to a hypercoagulable state. 9 males, MAP = 106 ± 5 mmHg were studied for 2-hours following 30-minutes of cycle exercise at 75% maximal oxygen consumption in hypoxia (16% O2), normoxia (21% O2) and hyperoxia (50% O2). Subjects were followed post-exercise for 2-hours on return back to normoxia. Echocardiography assessed cardiac output (Q) determined systemic vascular resistance (SVR) [MAP/Q] and vascular conductance (SVC) [Q/MAP]. Blood was sampled from an antecubital vein pre-, immediately post-, 1-hour (P1) and 2-hours post- (P2) exercise and corrected for haemoconcentration/dilution. Plasma was assayed for fibrinogen, international normalized ratio (INR), activated partial thromboplastin time (aPTT), activated partial thromboplastin time ratio (aPTTr), and prothrombin time (PT) parameters utilising coagulometric analysis. Plasma nitrate and nitrite (NOx) was determined fluorometrically and S-Nitrosothiol (RSNO) concentrations by the Saville reaction. Lipid hydroperoxides (LOOH) were determined spectrophotometrically and selective antioxidants by HPLC. Following confirmation of distribution normality using Shapiro-Wilk W tests, data were analysed using repeated measures ANOVA and Bonferonni corrected paired samples t-tests. Hyperoxic exercise significantly attenuated the reductions in SVR and MAP (P<0.05; paired t-test) compared to normoxic and hypoxic exercise across the post-exercise period. Fibrinogen, INR, aPTT, aPTTr, PT, RSNO and NOx were unmodified by the acute exercise bout or oxygen tension. Exercise per se increased LOOH concentration by P1 (P<0.05; paired t-test) and LOOH concentration post exercise (Δ) inversely correlated with ΔINR (r = -0.50; P<0.01; pearson correlation). The current data support our previous findings and indicate that in this population acute hypoxic and hyperoxic exercise are not associated with activation of clotting when corrected for plasma volume changes. However, in this in vivo model it appears that systemic oxidative stress is associated with activation of clotting following exercise per se.

Where applicable, experiments conform with Society ethical requirements