The interaction of vasoactive substances during exercise modulates platelet aggregation in hypertension and coronary artery disease

<p>Abstract</p> <p>Background</p> <p>Acute vigorous exercise, associated with increased release of plasma catecholamines, transiently increases the risk of primary cardiac arrest. We tested the effect of acute submaximal exercise on vasoactive substances and their combined result on platelet function.</p> <p>Methods</p> <p>Healthy volunteers, hypertensive patients and patients with coronary artery disease (CAD) performed a modified treadmill exercise test. We determined plasma catecholamines, thromboxane A₂, prostacyclin, endothelin-1 and platelet aggregation induced by adenosine diphosphate (ADP) and collagen at rest and during exercise.</p> <p>Results</p> <p>Our results during exercise showed a) platelet activation (increased thromboxane B₂, TXB₂), b) increased prostacyclin release from endothelium and c) decreased platelet aggregation in all groups, significantly more in healthy volunteers than in patients with CAD (with hypertensives lying in between these two groups).</p> <p>Conclusion</p> <p>Despite the pronounced activation of Sympathetic Nervous System (SNS) and increased TXB₂levels during acute exercise platelet aggregation decreases, possibly to counterbalance the prothrombotic state. Since this effect seems to be mediated by the normal endothelium (through prostacyclin and nitric oxide), in conditions characterized by endothelial dysfunction (hypertension, CAD) reduced platelet aggregation is attenuated, thus posing such patients in increased risk for thrombotic complications.</p

The Human Endogenous Circadian System Causes Greatest Platelet Activation during the Biological Morning Independent of Behaviors

Platelets are involved in the thromboses that are central to myocardial infarctions and ischemic strokes. Such adverse cardiovascular events have day/night patterns with peaks in the morning (~9 AM), potentially related to endogenous circadian clock control of platelet activation. The objective was to test if the human endogenous circadian system influences (1) platelet function and (2) platelet response to standardized behavioral stressors. We also aimed to compare the magnitude of any effects on platelet function caused by the circadian system with that caused by varied standardized behavioral stressors, including mental arithmetic, passive postural tilt and mild cycling exercise.We studied 12 healthy adults (6 female) who lived in individual laboratory suites in dim light for 240 h, with all behaviors scheduled on a 20-h recurring cycle to permit assessment of endogenous circadian function independent from environmental and behavioral effects including the sleep/wake cycle. Circadian phase was assessed from core body temperature. There were highly significant endogenous circadian rhythms in platelet surface activated glycoprotein (GP) IIb-IIIa, GPIb and P-selectin (6-17% peak-trough amplitudes; p ≤ 0.01). These circadian peaks occurred at a circadian phase corresponding to 8-9 AM. Platelet count, ATP release, aggregability, and plasma epinephrine also had significant circadian rhythms but with later peaks (corresponding to 3-8 PM). The circadian effects on the platelet activation markers were always larger than that of any of the three behavioral stressors.These data demonstrate robust effects of the endogenous circadian system on platelet activation in humans--independent of the sleep/wake cycle, other behavioral influences and the environment. The 9 AM timing of the circadian peaks of the three platelet surface markers, including platelet surface activated GPIIb-IIIa, the final common pathway of platelet aggregation, suggests that endogenous circadian influences on platelet function could contribute to the morning peak in adverse cardiovascular events as seen in many epidemiological studies

Aprotinin and Epsilon Aminocaproic Acid are Effective in Reducing Blood Loss After Primary Total Hip Arthroplasty - A Prospective Randomized Double-Blind Placebo-Controlled Study

Summary. A prospective randomized double-blind placebo-controlled study was undertaken to determine the efficacy and mechanism of action of two antifibrinolytic drugs aprotinin and epsilon aminocaproic acid (EACA) in reducing blood loss in primary unilateral total hip arthroplasty (THA). Aprotinin was administered as a bolus of 2 × 106 kallikrein inhibitor units (KIU) followed by 0.5 × 106 KIU h1 for 3 h, EACA was given as 10 g over 30 min followed by 5 g over 3 h. The median postoperative blood loss 24 h postoperatively was reduced from 450 mL in the placebo group to 180 mL for aprotinin (60% reduction, P < 0.001) and to 210 mL for EACA (53% reduction, P < 0.01). In this population, there was no reduction in the perioperative transfusion requirements. The mechanism of both drugs was independent of platelets as indicated by flow cytometric measurement of change of their expression of P-selectin, platelet–monocyte aggregates, V/Va and CD40 ligand. There were no thrombotic or infective complications and no adverse events were attributable to use of either drug. Infusion of either aprotinin or EACA at the doses described is a safe and effective means of reducing blood loss after THA. These therapies provide a means of reducing blood loss in THA patients