Leukotrienes, products of the 5-lipoxygenase pathway in the metabolism of arachidonic acid, are potent mediators of airway microvascular leakage and smooth muscle contraction in guinea pigs. We studied the effect of a specific 5-lipoxygenase inhibitor, A-63162, on airway microvascular leakage and airflow obstruction following inhaled ovalbumin in actively sensitized guinea pigs. Airway microvascular leakage was assessed by extravasation of Evans blue dye Into airway tissues. Inhaled ovalbumin caused increased lung resistance (Rl) with decreased dynamic compliance (Cl) and increased extravasation of Evans blue dye at all airway levels. A-63162 reduced the changes in Rl and Cl at 1.0 µmol/kg (p < 0.05) but not at lower doses of 0.1 and 0.3 µmol/kg. A-63162 reduced Evans blue dye extravasation in airway tissues at all three doses, however, being most effective in the distal airways (p < 0.01), and these reductions were greater than those in Rl and Cl. A 5-lipoxygenase inhibitor thus reduced airway microvascular leakage to a greater extent than airflow obstruction, suggesting that leukotrienes have a larger contribution to changes in airway microvascular permeability than smooth muscle contraction following inhaled allergen challenge in actively sensitized guinea pigs in vivo.
Angina pectoris is chest pain caused by ischemia of the myocardium secondary to a supply/demand mismatch. Myocardial ischemia is caused by one or more flow-limiting stenoses in one or more of the epicardial coronary arteries, while in a minority it is caused by coronary vasospasms or microvascular dysfunction. Historically, clinical research evaluating percutaneous coronary intervention (PCI) treatment is mostly focused on the quantification of the failure of the treatment including (cardiac) death, myocardial infarctions (MIs), repeat revascularizations, and stent thrombosis (ST). A patient-reported outcome (PRO) instrument quantifies the status of a patient's health condition in which the information comes directly from the patient. The most widely used PRO to assess angina is the Seattle Angina Questionnaire (SAQ). The SAQ has five domains, including "physical limitation", "angina stability", "angina frequency", "treatment satisfaction", and "disease perception". Angina can be assessed using PRO or site-reported outcomes, both with their own strengths and weaknesses.
The value of exercise testing and thallium scintigraphy in predicting recurrence of angina pectoris and restenosis after a primary successful transluminal coronary angioplasty (PTCA) was prospectively evaluated. In 89 patients, a symptom-limited exercise electrocardiogram (ECG) and thallium scintigraphy were performed 4 weeks after they had undergone successful PTCA. Thereafter, the patients were followed for 6.4 ± 2.5 months (mean ± standard deviation) or until recurrence of angina. They all underwent a repeat coronary angiography at 6 months or earlier if symptoms recurred. PTCA was considered successful if the patients had no symptoms and if the stenosis was reduced to less than 50% of the luminal diameter. Restenosis was defined as an increase of the stenosis to more than 50% luminal diameter. The ability of the thallium scintigram (presence of a reversible defect) to predict recurrence of angina was 66%, vs 38% for the exercise ECG (ST-segment depression or angina at peak workload). Restenosis was predicted in 74% of patients by thallium scintigraphy, but only in 50% of patients by the exercise ECG. Thus, thallium scintigraphy was highly predictive but the exercise ECG was not (p < 0.005). These results suggest that restenosis had occurred to some extent already at 4 weeks after the PTCA in most patients in whom it was going to occur.
In chronic inflammatory diseases, such as asthma, rheumatoid arthritis, inflammatory bowel disease, and psoriasis, several cytokines recruit activated immune and inflammatory cells to the site of lesions, thereby amplifying and perpetuating the inflammatory state.1 These activated cells produce many other mediators of inflammation.What causes these diseases is still a mystery, but the disease process results from an interplay of genetic and environmental factors. Genes, such as those for atopy in asthma and for HLA antigens in rheumatoid arthritis and inflammatory bowel disease, may determine a patient's susceptibility to the disease and the disease's severity, but environmental factors, often unknown, . . .
