thromboxane-a2 and Atrial-Fibrillation

Cardioplegia and cardiopulmonary bypass (CP/CPB) alters coronary arteriolar response to thromboxane A2 (TXA2) in patients undergoing cardiac surgery. Comorbidities, including hypertension (HTN), can further alter coronary vasomotor tone. This study investigates the effects of HTN on coronary arteriolar response to TXA2 pre and post-CP/CPB and cardiac surgery.. Coronary arterioles pre and post-CP/CPB were dissected from atrial tissue samples in patients with no HTN (NH, n = 9), well-controlled HTN (WC, n = 12), or uncontrolled HTN (UC, n = 12). In-vitro coronary microvascular reactivity was examined in the presence of TXA2 analog U46619 (10. TXA2 analog U46619 induced dose-dependent contractile responses of coronary arterioles in all groups. Pre-CPB contractile responses to U46619 were significantly increased in microvessels in the UC group compared to the NH group (P < 0.05). The pre-CP/CPB contractile responses of coronary arterioles were significantly diminished post-CP/CPB among the three groups (P < 0.05), but there remained an increased contractile response in the microvessels of the UC group compared to the WC and NH groups (P < 0.05). There were no significant differences in U46619-induced vasomotor tone between patients in the NH and WC groups (P > 0.05). There were no differences in expression of TXA2R among groups.. Poorly controlled HTN is associated with increased contractile response of coronary arterioles to TXA2. This alteration may contribute to worsened recovery of coronary microvascular function in patients with poorly controlled HTN after CP/CPB and cardiac surgery.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Atrial Fibrillation; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Coronary Vessels; Humans; Hypertension; Thromboxane A2

Platelet activation plays a major role in cardiovascular events (CVEs). Mediterranean diet (Med-Diet) reduces the incidence of stroke and myocardial infarction but it is still unclear if it affects platelet activation. Aim of the study was to evaluate the effect of Med-Diet on the urinary excretion of 11-dehydro-thromboxane (Tx) B2, a marker of in vivo platelet activation, in patients with atrial fibrillation (AF).. Prospective observational cohort study including 801 non-valvular AF patients on chronic treatment with warfarin/acenocumarol referring to I Medical Clinic - Atherothrombosis Center of Sapienza University of Rome, Italy, from February 2008 to December 2013. Adherence to Med-Diet was evaluated by a short nine-items dietary questionnaire. Urinary excretion of 11-dehydro-TxB2 was measured in all patients.. Mean follow-up was 33.9 (±19.8) months, yielding 2223 patient/year of observation. Mean age of patients was 73.3 (±8.9) years, 43.7% were female. Median value of urinary TxB2 was 105.5 [60.0-190.0] ng/mg creatinine. We found a significant inverse correlation between total Med-Diet score and 11-dehydro-TxB2 values (Rs: -0.356, p < 0.001). In a multivariable stepwise linear regression analysis, history of stroke/TIA (β = 0.146, p = 0.003), olive oil (β = -0.130, p = 0.007), wine (β = -0.102, p = 0.036) and antiplatelet drugs (β = -0.098, p = 0.045) were independently associated to 11-dehydro-TxB2. We found no differences in the rate of ischemic or bleeding events across tertiles of Med-Diet score during follow-up.. Med-Diet adherence is inversely associated to urinary excretion of 11-dehydro-TxB2, suggesting that Med-Diet may favorably affect platelet function in AF patients. Clinical Trial Registration: ClinicalTrials.gov NCT01882114.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Diet, Mediterranean; Female; Follow-Up Studies; Humans; Italy; Linear Models; Male; Middle Aged; Multivariate Analysis; Olive Oil; Patient Compliance; Platelet Activation; Platelet Aggregation Inhibitors; Prospective Studies; Surveys and Questionnaires; Thromboxane A2; Thromboxane B2; Warfarin; Wine

Paroxysmal atrial fibrillation might be a risk factor for stroke such as chronic atrial fibrillation. We examined the relation between mean platelet volume and paroxysmal atrial fibrillation to determine the effect of paroxysmal atrial fibrillation on the thrombotic state via elevated mean platelet volume. Mean platelet volume is a marker of platelet size, function, and activation. Increased mean platelet volume reflects active and large platelets that release more thromboxane A2 than smaller ones. We hypothesized that mean platelet volume is elevated in patients with paroxysmal atrial fibrillation. The study population comprised 103 consecutive patients who were detected to have paroxysmal atrial fibrillation by 24-h Holter monitoring and 87 control individuals with normal Holter monitoring. Mean platelet volume and inflammatory parameters were measured. Comprehensive clinical and echocardiographic data were collected. Patients with aortic and mitral stenosis, hyperthyroidism, hypothyroidism, malignancy, infection, and pregnancy were excluded from the study. Mean age of the patients was 63 +/- 11 vs. 45 +/- 14 years (P < 0.001) in paroxysmal atrial fibrillation and control groups, respectively. Fifty-seven patients (55%) in paroxysmal atrial fibrillation and 19 (21%) (P < 0.001) patients in control group were men. Mean platelet volume was significantly higher in the paroxysmal atrial fibrillation group when compared with control group (10.0 +/- 2.0 vs. 8.3 +/- 1.5 fl, respectively; P < 0.001). C-reactive protein (18.5 +/- 28 vs. 3.8 +/- 2 mg/l, respectively; P = 0.004) and erythrocyte sedimentation rate (21 +/- 21 vs. 12 +/- 7 mm/h, respectively; P = 0.01) were also higher in the paroxysmal atrial fibrillation group. There was no difference in white blood cell and platelet counts between groups. In a multivariate analysis, elevated mean platelet volume was associated with the occurrence of paroxysmal atrial fibrillation before and after adjustment for age and sex. Our results indicate that inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate and the marker of platelet size and activity mean platelet volume are elevated in patients with paroxysmal atrial fibrillation.

Topics: Adult; Atrial Fibrillation; Biomarkers; Blood Platelets; Blood Sedimentation; C-Reactive Protein; Cell Size; Female; Humans; Inflammation; Inflammation Mediators; Male; Middle Aged; Platelet Activation; Thromboxane A2

Thromboxane A2 (TXA2) biosynthesis was studied in healthy subjects, patients with chronic cerebral infarction, patients under chronic aspirin treatment and patients with atrial fibrillation. Urinary 11-dehydro-TXB2, as a major metabolite of TXA2, was measured by radioimmunoassay. The extent of carotid atherosclerosis was determined by B-mode ultrasonography. The mean +/- SD urinary excretion in patients with cerebral infarction and distinct carotid-atherosclerotic lesions (1,725 +/- 239 ng/g creatinine, n = 6) was significantly higher (p less than 0.01) than in healthy subjects (911 +/- 239 ng/g creatinine, n = 44) and patients with cerebral infarction who had no distinct carotid lesion (1,050 +/- 191 ng/g creatinine, n = 6). The urinary excretion of healthy subjects was higher (p less than 0.01) in smokers (1,063 +/- 244 ng/g creatinine, n = 17) than in non-smokers (815 +/- 183 ng/g creatinine, n = 27). Aspirin largely suppressed 11-dehydro-TXB2 excretion (266 +/- 114 ng/g creatinine, n = 7). Three of 5 patients with atrial fibrillation showed very high values. Our results indicated that platelet activation occurs in the atherosclerotic lesions, and that urinary 11-dehydro-TXB2 is the appropriate analytic target for detecting platelet activation.

Topics: Adult; Aged; Arteriosclerosis; Aspirin; Atrial Fibrillation; Carotid Artery Diseases; Cerebral Infarction; Female; Humans; Male; Middle Aged; Platelet Activation; Thromboxane A2; Thromboxane B2

The variations in the content of endogenic prostanoids and cyclic nucleotides in the blood plasma of the coronary sinus and ascending aorta were studied in patients with the idiopathic stable form of atrial fibrillation before and after sinus rhythm recovery effected by electroimpulse therapy. Changes in the levels and ratios of these compounds in the coronary venous and arterial blood were found to be opposite in their trends. A significant elevation in TxB2 levels and the TxB2/6-keto-PGF1 ratio as well as increased cGMP concentrations in the plasma of the coronary venous blood appear to be suggestive of an unfavourable prognosis because patients with such changes developed atrial fibrillation recurrences soon after electroimpulse therapy.

Topics: Adult; Aorta, Thoracic; Atrial Fibrillation; Coronary Vessels; Cyclic AMP; Cyclic GMP; Dinoprost; Epoprostenol; Female; Humans; Male; Middle Aged; Prostaglandins; Prostaglandins E; Prostaglandins F; Thromboxane A2; Thromboxanes