Atherosclerosis is a process with inflammatory features and selective
cyclooxygenase 2 (COX-2) inhibitors may potentially have antiatherogenic effects
by virtue of inhibiting inflammation. However, by decreasing vasodilatory
and antiaggregatory prostacyclin production, COX-2 antagonists may lead to
increased prothrombotic activity. To define the cardiovascular effects of
COX-2 inhibitors when used for arthritis and musculoskeletal pain in patients
without coronary artery disease, we performed a MEDLINE search to identify
all English-language articles on use of COX-2 inhibitors published between
1998 and February 2001. We also reviewed relevant submissions to the US Food
and Drug Administration by pharmaceutical companies.Our search yielded 2 major randomized trials, the Vioxx Gastrointestinal
Outcomes Research Study (VIGOR; 8076 patients) and the Celecoxib Long-term
Arthritis Safety Study (CLASS; 8059 patients), as well as 2 smaller trials
with approximately 1000 patients each. The results from VIGOR showed that
the relative risk of developing a confirmed adjudicated thrombotic cardiovascular
event (myocardial infarction, unstable angina, cardiac thrombus, resuscitated
cardiac arrest, sudden or unexplained death, ischemic stroke, and transient
ischemic attacks) with rofecoxib treatment compared with naproxen was 2.38
(95% confidence interval, 1.39-4.00; P = .002). There
was no significant difference in cardiovascular event (myocardial infarction,
stroke, and death) rates between celecoxib and nonsteroidal anti-inflammatory
agents in CLASS. The annualized myocardial infarction rates for COX-2 inhibitors
in both VIGOR and CLASS were significantly higher than that in the placebo
group of a recent meta-analysis of 23 407 patients in primary prevention
trials (0.52%): 0.74% with rofecoxib (P = .04 compared
with the placebo group of the meta-analysis) and 0.80% with celecoxib (P = .02 compared with the placebo group of the meta-analysis).The available data raise a cautionary flag about the risk of cardiovascular
events with COX-2 inhibitors. Further prospective trial evaluation may characterize
and determine the magnitude of the risk.

/pdf/risk-of-cardiovascular-events-associated-with-selective-cox-1b98pd2lb1.pdf

Risk of cardiovascular events associated with selective COX-2 inhibitors.

Acute lung injury in humans is characterized histopathologically by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Most are based on reproducing in animals known risk factors for ARDS, such as sepsis, lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion of pulmonary or distal vascular beds, and other clinical risks. However, none of these models fully reproduces the features of human lung injury. The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury. We review the specific features of human ARDS that should be modeled in experimental lung injury and then discuss specific characteristics of animal species that may affect the pulmonary host response to noxious stimuli. We emphasize those models of lung injury that are based on reproducing risk factors for human ARDS in animals and discuss the advantages and disadvantages of each model and the extent to which each model reproduces human ARDS. The present review will help guide investigators in the design and interpretation of animal studies of acute lung injury.

Animal models of acute lung injury.

https://www.srcv.ro/ghiduri/Managementul%20pacientilor%20cu%20boala%20venoasa%20cronica%20-%20Ghidurile%20SVS%20-%20American%20Venous%20Forum.pdf

The care of patients with varicose veins and associated chronic venous diseases: Clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum

This review considers the role of low-dose aspirin for the prevention of atherothrombosis, discussing the molecular mechanism of action of aspirin as well as clinical and epidemiologic studies of aspirin as an antiplatelet agent, with special emphasis on the benefits and risks in different patient populations.

http://departamentos.cardiol.br/DECAGE/esquina/superligado/aspirina.pdf

Low-Dose Aspirin for the Prevention of Atherothrombosis

Background— We studied whether aspirin resistance, defined as failure of suppression of thromboxane generation, increases the risk of cardiovascular events in a high-risk population. Methods and Results— Baseline urine samples were obtained from 5529 Canadian patients enrolled in the Heart Outcomes Prevention Evaluation (HOPE) Study. Using a nested case-control design, we measured urinary 11-dehydro thromboxane B2 levels, a marker of in vivo thromboxane generation, in 488 cases treated with aspirin who had myocardial infarction, stroke, or cardiovascular death during 5 years of follow-up and in 488 sex- and age-matched control subjects also receiving aspirin who did not have an event. After adjustment for baseline differences, the odds for the composite outcome of myocardial infarction, stroke, or cardiovascular death increased with each increasing quartile of 11-dehydro thromboxane B2, with patients in the upper quartile having a 1.8-times-higher risk than those in the lower quartile (OR, 1.8; 95% CI, 1....

https://www.aspirinworks.com/wp-content/uploads/2012/09/Aspirin-ResistantThromboxane.pdf

Aspirin-Resistant Thromboxane Biosynthesis and the Risk of Myocardial Infarction, Stroke, or Cardiovascular Death in Patients at High Risk for Cardiovascular Events

Background—The formation of prostacyclin (PGI2), thromboxane (TX) A2, and isoprostanes is markedly enhanced in atherosclerosis. We examined the relative contribution of cyclooxygenase (COX)-1 and -2 to the generation of these eicosanoids in patients with atherosclerosis. Methods and Results—The study population consisted of 42 patients with atherosclerosis who were undergoing surgical revascularization. COX-2 mRNA was detected in areas of atherosclerosis but not in normal blood vessel walls, and there was evidence of COX-1 induction. The use of immunohistochemical studies localized the COX-2 to proliferating vascular smooth muscle cells and macrophages. Twenty-four patients who did not previously receive aspirin were randomized to receive either no treatment or nimesulide at 24 hours before surgery and then for 3 days. Eighteen patients who were receiving aspirin were continued on a protocol of either aspirin alone or a combination of aspirin and nimesulide. Urinary levels of 11-dehydro-TXB2 and 2,3-dinor...

Cyclooxygenase-1 and -2–Dependent Prostacyclin Formation in Patients With Atherosclerosis

Pravastatin, A 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor, Attenuates Renal Injury in an Experimental Model of Ischemia-Reperfusion

Powered phlebectomy (TriVex) in treatment of varicose veins.

Background

Ischaemia–reperfusion injury is mediated by neutrophil–endothelial interaction. Induction of heat shock proteins attenuates neutrophil–endothelial interactions. The aim of this study was to determine whether thermal preconditioning could have a protective effect on neutrophil-mediated lung injury in an animal model of lower torso ischaemia–reperfusion.



Methods

Sprague-Dawley rats were randomized into: control, ischaemia–reperfusion, and ischaemia–reperfusion preconditioned with hyperthermia groups. Ischaemia–reperfusion injury was induced by infrarenal aortic clamping for 30 min and reperfusion for 120 min. Thermotolerance was induced by raising the core body temperature to 40·5–41·5°C for 15 min, 18 h before ischaemia–reperfusion. Wet:dry lung (W:D) weight ratio, bronchoalveolar lavage protein (BALprot) concentration, tissue myeloperoxidase (MPO) activity and bronchoalveolar lavage polymorphonuclear neutrophil (BAL PMN) count were measured. Heat shock protein 72 (hsp72) expression in lung, intestine and mesentery was measured using Western immunoblotting.



Results

Ischaemia–reperfusion resulted in a significant increase in tissue oedema (W:D weight ratio) and BALprot concentration. In addition there was a marked increase in tissue neutrophil infiltration (MPO activity, BAL PMN concentration). Preconditioning with hyperthemia resulted in increased expression of hsp72 and significantly reduced tissue oedema and neutrophil infiltration.



Conclusion

Thermal preconditioning protects against neutrophil-mediated ischaemia–reperfusion-induced lung injury, possibly by increasing the expression of heat shock proteins. © 1998 British Journal of Surgery Society Ltd

Thermotolerance induces heat shock protein 72 expression and protects against ischaemia–reperfusion‐induced lung injury

Increasing numbers of patients are being diagnosed with end-stage renal disease (ESRD), and the demand for on haemodialysis (HD) is rising. Arteriovenous fistulae (AVFs) remain the best conduit for adequate HD, with fewer complications associated with long-term use compared to bypass grafts and central venous catheters. However, it is known that many newly formed fistulae do not mature to provide useful HD access. The paper provides a narrative overview of factors influencing the process of AVF maturation failure.

Austin Leahy

Papers

Cyclooxygenase-1 and -2–Dependent Prostacyclin Formation in Patients With Atherosclerosis

Pravastatin, A 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor, Attenuates Renal Injury in an Experimental Model of Ischemia-Reperfusion

Powered phlebectomy (TriVex) in treatment of varicose veins.

Thermotolerance induces heat shock protein 72 expression and protects against ischaemia–reperfusion‐induced lung injury

Arteriovenous fistula in dialysis patients: Factors implicated in early and late AVF maturation failure.