Upright posture and maximal exercise increase platelet aggregability and prostacyclin production in healthy male subjects.

Feng, Deng; Murillo, Jaime; Jadhav, P. V.; McKenna, Carol; Gebara, Otávio; Lipinska, Izabella; Muller, James E.; Tofler, Geoffrey H.

doi:10.1136/bjsm.33.6.401

Cited by 23 publications

(24 citation statements)

References 41 publications

(37 reference statements)

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“…The greater degree of hypovolemia induced by LBNP in this study also demonstrated coagulation activation by reducing PT and APTT. This is in line with the reported activation of coagulation during LBNP (38) and other orthostatic challenges (10,21,36). Because direct vascular damage due to arterial and venous catheter placement was likely minimal in our study, it is probable that other factors contributed to the coagulation response.…”

Section: Discussionsupporting

confidence: 76%

“…However, it is unclear if markers of coagulation system activation respond similarly during these protocols. Reductions in central blood volume by LBNP (38) or orthostatic stress (10,21,36) activate the coagulation cascade; therefore, it is likely that central hypovolemia during BL elicits comparable changes in coagulation when the degree of central hypovolemia is similar between LBNP and BL.…”

Section: Our Study Provides Noteworthy Data That Directly Compare Blomentioning

confidence: 99%

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Coagulation changes during lower body negative pressure and blood loss in humans

Helmond

Johnson

Curry

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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van Helmond N, Johnson BD, Curry TB, Cap AP, Convertino VA, Joyner MJ. Coagulation changes during lower body negative pressure and blood loss in humans. Am J Physiol Heart Circ Physiol 309: H1591-H1597, 2015. First published September 9, 2015; doi:10.1152/ajpheart.00435.2015.-We tested the hypothesis that markers of coagulation activation are greater during lower body negative pressure (LBNP) than those obtained during blood loss (BL). We assessed coagulation using both standard clinical tests and thrombelastography (TEG) in 12 men who performed a LBNP and BL protocol in a randomized order. LBNP consisted of 5-min stages at 0, Ϫ15, Ϫ30, and Ϫ45 mmHg of suction. BL included 5 min at baseline and following three stages of 333 ml of blood removal (up to 1,000 ml total). Arterial blood draws were performed at baseline and after the last stage of each protocol. We found that LBNP to Ϫ45 mmHg is a greater central hypovolemic stimulus versus BL; therefore, the coagulation markers were plotted against central venous pressure (CVP) to obtain stimulus-response relationships using the linear regression line slopes for both protocols. Paired t-tests were used to determine whether the slopes of these regression lines fell on similar trajectories for each protocol. Mean regression line slopes for coagulation markers versus CVP fell on similar trajectories during both protocols, except for TEG ␣°angle (Ϫ0.42 Ϯ 0.96 during LBNP vs. Ϫ2.41 Ϯ 1.13°/mmHg during BL; P Ͻ 0.05). During both LBNP and BL, coagulation was accelerated as evidenced by shortened R-times (LBNP, 9.9 Ϯ 2.4 to 6.2 Ϯ 1.1; BL, 8.7 Ϯ 1.3 to 6.4 Ϯ 0.4 min; both P Ͻ 0.05). Our results indicate that LBNP models the general changes in coagulation markers observed during BL. blood coagulation; hemorrhage; lower body negative pressure; blood coagulation tests; humans; central hypovolemia NEW & NOTEWORTHYOur study provides noteworthy data that directly compare blood coagulation activation induced by lower body negative pressure to those observed during blood loss in conscious humans.HEMORRHAGE IS ONE OF THE LEADING causes of accidental death (1) and is the leading cause of death on the battlefield (8, 9). Activation of the coagulation system is vital following a hemorrhagic injury to reduce the risk of exsanguination. Consequently, studying the activation of the coagulation system during blood loss (BL) is of upmost importance so new therapies and treatment algorithms, such as fluid resuscitation, can be developed. However, using invasive methods to experimentally induce BL is challenging to perform in humans.Lower body negative pressure (LBNP) is a technique that is used as a noninvasive surrogate to study many of the physiological responses to BL (4, 15, 18). LBNP sequesters circulating blood in the lower body, thereby reducing central blood volume and mimicking hemodynamic responses generated during BL (4,15,18). However, it is unclear if markers of coagulation system activation respond similarly during these protocols. Reductions in central blood volume by LBNP (38) ...

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Section: Discussionsupporting

confidence: 76%

Section: Our Study Provides Noteworthy Data That Directly Compare Blomentioning

confidence: 99%

Coagulation changes during lower body negative pressure and blood loss in humans

Helmond

Johnson

Curry

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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“…Thus, lipid mediators may play an important role in adaptive responses to exercise that are evoked not only with classic injury or damaging stimuli. Heightened circulating COX-1-and COX-2-derived PGE 2 (28,50,66,70,107), PGF 2␣ (28,30), and 6-keto-PGF 1␣ (18,28,33,50,58,62,76,108) have been observed during continuous submaximal exercise. These transient changes appear to play an important role in the regulation of circulatory system responses during exercise, as NSAID administration can block exercise-induced muscle hyperemia and the cardiovascular pressor reflex (22,25,79).…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, circulating PGs and LTs (with the exception of TXB 2 ) were unchanged immediately after resistance exercise, but exhibited a delayed peak elevation between ϳ1 and 2 h (PGD 2 , PGE 2 , PGF 2␣ , and LTB 4 ) and 24 h (6-keto-PGF 1␣ ) into recovery. That TXA 2 is the major product of platelet COX-1 and elevated TXB 2 immediately after exercise likely reflects an acute proaggregatory cardiovascular response, as has been observed during maximal, but not submaximal, aerobic exercise (33,50,58). PGs and LTs are classical proinflammatory lipid mediators, the physiological effects of which include vascular vasodilation, increased blood vessel permeability, and neutrophil chemotaxis/activation (57,75).…”

Section: Discussionmentioning

confidence: 99%

Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

Markworth

Vella

Lingard

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

133

153

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Classical proinflammatory eicosanoids, and more recently discovered lipid mediators with anti-inflammatory and proresolving bioactivity, exert a complex role in the initiation, control, and resolution of inflammation. Using a targeted lipidomics approach, we investigated circulating lipid mediator responses to resistance exercise and treatment with the NSAID ibuprofen. Human subjects undertook a single bout of unaccustomed resistance exercise (80% of one repetition maximum) following oral ingestion of ibuprofen (400 mg) or placebo control. Venous blood was collected during early recovery (0 -3 h and 24 h postexercise), and serum lipid mediator composition was analyzed by LC-MS-based targeted lipidomics. Postexercise recovery was characterized by elevated levels of cyclooxygenase (COX)-1 and 2-derived prostanoids (TXB2, PGE2, PGD2, PGF2␣, and PGI2), lipooxygenase (5-LOX, 12-LOX, and 15-LOX)-derived hydroxyeicosatetraenoic acids (HETEs), and leukotrienes (e.g., LTB4), and epoxygenase (CYP)-derived epoxy/dihydroxy eicosatrienoic acids (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of bioactive lipid mediators with anti-inflammatory and proresolving properties, including arachidonic acid-derived lipoxins (LXA4 and LXB4), and the EPA (E-series) and DHA (D-series)-derived resolvins (RvD1 and RvE1), and protectins (PD1 isomer 10S, 17S-diHDoHE). Ibuprofen treatment blocked exercise-induced increases in COX-1 and COX-2-derived prostanoids but also resulted in off-target reductions in leukotriene biosynthesis, and a diminished proresolving lipid mediator response. CYP pathway product metabolism was also altered by ibuprofen treatment, as indicated by elevated postexercise serum 5,6-DiHETrE and 8,9-DiHETrE only in those receiving ibuprofen. These findings characterize the blood inflammatory lipid mediator response to unaccustomed resistance exercise in humans and show that acute proinflammatory signals are mechanistically linked to the induction of a biological active inflammatory resolution program, regulated by proresolving lipid mediators during postexercise recovery. eicosanoid; exercise; inflammation; nonsteroidal anti-inflammatory drug; resolution LIPID MEDIATORS ARE A DIVERSE class of bioactive autocrine/ paracrine signaling molecules that are synthesized endogenously from essential omega-6 and omega-3 fatty acids. Oxidation of free fatty acid substrates via cyclooxygenase (COX-1 and COX-2), lipoxygenase (5-LOX, 12-LOX, and 15-LOX), epoxygenase (CYP), and nonenzymatic pathways, produces a potential array of more than 100 distinct lipid mediators. Bioactive lipid mediators are involved in a wide range of physiological and pathological processes, one of the best characterized of which is their key role in the inflammatory response (reviewed in Ref. 91). Classical eicosanoids derived from omega-6 arachidonic acid (AA, -6 20:4), including prostaglandins (PGs; synthesized via COX-1 and COX-2) and leukotrienes (LTs, synthesized via 5-LOX), are well established proinflammatory signaling molecules that stimul...

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“…14,15 Once exposed to injuries, such as, high blood pressure or increased shear stress, their procoagulant activity prevails. 16,17 Although intensive exercise was shown to be associated with increased coagulability through a mechanism involving endothelial activation, 18 virtually no data are available regarding the effect of still standing on the coagulation cascade.…”

mentioning

confidence: 99%

Orthostatic Hypercoagulability

et al. 2008

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Abstract-Orthostatic stress causes significant plasma shift and raises transmural pressure in lower extremities, resulting in an increase in endothelial activation and plasma proteins concentrations, possibly including coagulation factors. This may lead to activation of the coagulation system during standing. To test this hypothesis, we recruited 18 healthy volunteers (9 females and 9 males; mean age: 25Ϯ1.2 years; body mass index: 21.7Ϯ0.5 kg/m 2 ). Hemodynamics, plasma shift (extrapolated from sequential hematocrit concentration), plasma proteins, and coagulation tests, including procoagulants; fibrinogen, factor V, and factor VIII activity; prothrombin fragments 1 and 2; and endothelial activation-related factors (tissue factor and von Willebrand factor), as well as protein C global pathway, were determined at rest supine and at 15 minutes, 30 minutes, and 60 minutes of still standing. Thirty minutes of standing caused a decrease in plasma volume by 12.0Ϯ0.5% and an increase in plasma protein by 13.0Ϯ0.7%. Fibrinogen, factor V, and factor VIII activity rose by 12.0Ϯ1.2%, 13.0Ϯ1.0%, and 40.0Ϯ6.0% (PϽ0.002 for all), respectively. Prothrombin fragments 1 and 2 were elevated by 150.0Ϯ30.0%. Tissue factor and von Willebrand factor increased by 30.0Ϯ9.0% and 17.4Ϯ51.0% (PϽ0.02 for both), respectively. However, protein C assay results decreased from 0.95Ϯ0.20 to 0.83Ϯ0.16 (PϽ0.001). We hereby introduce a novel physiological mechanism, "orthostatic procoagulation," that should be considered during coagulation tests. Furthermore, it could be extrapolated to the pathophysiology of stasis and venous thromboembolism.

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Upright posture and maximal exercise increase platelet aggregability and prostacyclin production in healthy male subjects.

Cited by 23 publications

References 41 publications

Coagulation changes during lower body negative pressure and blood loss in humans

Coagulation changes during lower body negative pressure and blood loss in humans

Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

Orthostatic Hypercoagulability

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