Preliminary report on endothelial functional injury in brain arterioles of diabetic rats:In vivo observation of macromolecular transit across the vascular wall

Summary The coloring of longitudinal nuclei, resembling a convoy, was observedin vivo in the terminal arterioles of diabetic rat brain by means of a microcirculatory experimental model and Evans blue/albumin tracer. This emergency transit could confirm other well known passages across the vessel wall, or be considered as ‘functional injury’ of the diabetic endothelium. especially in case of the so-called brain-blood barrier. Communication presented to the meeting of theSezione Lombardia della Società Italiana di Diabetologia, Pavia, 22 June 1985.     

Effects of AT1 Receptor Antagonism With Candesartan on Endothelial Function in Patients With Hypertension and Coronary Artery Disease

Endothelial dysfunction is a major determinant of atherosclerosis and a negative prognostic factor in patients with coronary artery disease and hypertension. Recovery of endothelial dysfunction has been associated with improved prognosis in these patients. The aim of the present study was to verify whether antagonism of angiotensin II AT1 receptors with an angiotensin receptor blocker, candesartan, improved endothelial function in patients with hypertension, stable coronary artery disease, and endothelial dysfunction. We studied 26 patients who were receiving β-blockers with optimal blood pressure control, in a randomized, double blind study. Patients were randomized to placebo (n=13) or to candesartan 16 mg/d (n=13) for 2 months. Endothelial function was assessed by ultrasound using hyperemic flow-mediated dilation of the brachial artery. Mean arterial blood pressure was unchanged in both groups (from 93.3±9.2 to 93.2±17.3 mm Hg in the candesartan group and from 101.3±14.2 to 102.3±13.9 mm Hg in the placebo group; both P =ns). Maximal blood flow was similar between placebo and candesartan groups at baseline and at the end of the study, whereas flow-mediated dilation significantly increased in the candesartan group (from 5.27%±1.69% to 7.15%±2.67%; P =0.01) but remained unchanged in the placebo group (from 4.49%±1.97% to 5.88%±2.30%; P =ns). AT1 receptor antagonism with candesartan, in addition to β-blocker therapy, improves endothelial function in high-risk hypertensive patients.     

Coronary stenting and abciximab in primary angioplasty for ST-segment-elevation myocardial infarction

Advances in anti-platelet therapy and improvement of stent deployment techniques have improved the safety and efficacy of stenting in the setting of ST-segment-elevation myocardial infarction (STEMI). However, in randomized trials, routine coronary stenting does not reduce mortality and re-infarction, compared to balloon angioplasty. Further, the benefits in target vessel revascularization seem to be reduced when applied to unselected patients with STEMI. Direct stenting represents an attractive strategy with potential benefits in terms of myocardial perfusion. Future large randomized trials are needed to evaluate whether this strategy has a significant impact on outcome, and to provide a cost-benefit analysis of the unrestricted use of drug-eluting stents in this high-risk subset of patients. The additional use of abciximab reduces mortality in primary angioplasty. Since the feasibility of long-distance transportation has been shown in several randomized trials, early pharmacological pre-treatment may confer further advantages by early recanalization and shorter ischaemic time, particularly in high-risk patients. Further randomized trials are needed to clarify the potential benefits from early abciximab administration and the potential role of small molecules in primary angioplasty for STEMI.