Digoxin-induced vasoconstriction of normal and atherosclerotic epicardial coronary arteries.

This study evaluated the effect of bolus infusion of digoxin (0.014 mg/kg in 10 minutes, intravenously) on large coronary arteries measured by quantitative digital angiography. Twenty-two patients (mean age +/- standard deviation 47 +/- 12 years) divided into 3 groups were studied. The effects of digoxin infusion (after 10 and 20 minutes) and sublingual administration of isosorbide dinitrate were investigated in group I (patients with angiographically normal coronary arteries, n = 9) and in group II (patients with atherosclerotic coronary arteries, n = 8). To determine whether the effects of digoxin were mediated by activation of alpha-adrenergic receptors, coronary angiography was performed in group III after alpha-adrenoceptor blockade (phentolamine 0.11 mg/kg, intravenously) (n = 5). Ten minutes after the end of digoxin infusion, the cross-sectional area decreased from 7.7 +/- 4.1 to 6.0 +/- 2.2 mm2, and after 20 minutes to 5.6 +/- 2.6 mm2 (p less than 0.05) in group I. Isosorbide dinitrate reverted digoxin-induced vasoconstriction as cross-sectional area increased to 8.5 +/- 3.4 mm2 (p = not significant versus baseline). Twenty minutes after digoxin infusion, heart rate significantly decreased from 79 +/- 16 to 74 +/- 13 beats/min (p less than 0.01). Ten minutes after digoxin infusion, peripheral vascular resistance increased significantly from 1,396 +/- 693 to 1,693 +/- 984 dynes.s.cm-5 (p less than 0.05), whereas cardiac output did not change. Twenty minutes after digoxin infusion, minimal stenosis diameter decreased significantly from 1.6 +/- 0.5 to 1.4 +/- 0.5 mm (p less than 0.05) in group II.(ABSTRACT TRUNCATED AT 250 WORDS)     

Failure of nitroglycerin and diltiazem to reduce platelet-mediated vasoconstriction in dogs with coronary artery stenosis and endothelial injury: further evidence for thromboxane A2 and serotonin as mediators of coronary artery vasoconstriction in vivo

This study was designed to test the efficacy of nitroglycerin and diltiazem in inhibiting in vivo platelet aggregation and reducing platelet-mediated vasoconstriction in a canine model of coronary artery stenosis and endothelial injury. Coronary artery diameter was measured in vivo by means of ultrasonic crystals sutured on the left anterior descending coronary artery (LAD) immediately distal to an external constrictor (LAD1), 1 cm below (LAD2), and on the left circumflex coronary artery. Coronary diameter was continuously measured before, during cyclic flow variations (progressive declines in blood flow followed by sudden restorations of flow due to recurrent intracoronary platelet aggregation), during cyclic flow variations and intravenous infusion of nitroglycerin (5 micrograms/kg per min) or diltiazem (15 micrograms/kg per min), and after cyclic flow variations were abolished by administration of LY53857, a serotonin receptor antagonist (n = 7), or SQ29548, a thromboxane A2 receptor antagonist (n = 7). During control cyclic flow variations, at the nadir of coronary flow (6% to 11% of the nonstenosed values), LAD1 cross-sectional area decreased by 43 +/- 8% and 44 +/- 3% in the two groups of dogs subsequently treated with LY53857 and SQ29548, respectively. Neither nitroglycerin nor diltiazem caused changes in cyclic flow variation frequency or severity. Furthermore, neither drug significantly reduced the vasoconstriction associated with cyclic flow variations, whereas they significantly increased circumflex artery cross-sectional area. In contrast, LY53857 and SQ29548 were very effective in abolishing cyclic flow variations and the coronary vasoconstriction related to them. Five additional dogs received an intracoronary infusion of nitroglycerin (21 +/- 5 micrograms/kg per min) and later diltiazem (15 micrograms/kg per min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Immediate and long-term outcome of recanalization of chronic total coronary occlusions

Eighty-three consecutive patients with 85 coronary total occlusions undergoing coronary angioplasty were retrospectively studied. Patients were divided into two groups according to the occlusion age that was < 30 days (subacute total occlusion [STO]: 25 patients; range 1-30 days) or > 30 days (chronic total occlusion [CTO]: 58 patients; range 3-144 months). All procedures were carried out using a hydrophilic guidewire. Clinical success, consisting of crossing the lesion, balloon dilatation, stent deployment without complications, was 96% in STO and 81% in CTO. Multiple stepwise logistic regression analysis identified a family history of coronary artery disease (CAD), left anterior descending and right coronary artery occlusions as independent predictors of a successful procedure. No major events occurred during or immediately after the angioplasty. After a mean follow-up of 24 +/- 2 months, no difference was found in survival or freedom from myocardial infarction or target vessel revascularization among the STO and CTO patients. Successful recanalization by using a hydrophilic guidewire was achieved in a high percentage of chronic total occlusions with a low incidence of complications and a satisfactory late clinical outcome. Family history of CAD and occlusion of left anterior descending or right coronary arteries are independent predictors of procedural success.     

Adipose tissue and vascular inflammation in coronary artery disease

Obesity has become an important public health issue in Western and developing countries,with well known metabolic and cardiovascular complications.In the last decades,evidence have been growing about the active role of adipose tissue as an endocrine organ in determining these pathological consequences.As a consequence of the expansion of fat depots,in obese subjects,adipose tissue cells develope a phenotypic modification,which turns into a change of the secretory output.Adipocytokines produced by both adipocytes and adipose stromal cells are involved in the modulation of glucose and lipid handling,vascular biology and,moreover,participate to the systemic inflammatory response,which characterizes obesity and metabolic syndrome.This might represent an important pathophysiological link with atherosclerotic complications and cardiovascular events.A great number of adipocytokines have been described recently,linking inflammatory mileu and vascular pathology.The understanding of these pathways is crucial not only from a pathophysiological point of view,but also to a better cardiovascular disease risk stratification and to the identification of possible therapeutic targets.The aim of this paper is to review the role of Adipocytokines as a possible link between obesity and vascular disease.     

Increased heterogenity of ventricular repolarization in obese nonhypertensive children

Objective: Obese children, without arterial hypertension, may be a unique clinical opportunity to evaluate the effect of obesity, per se, on ventricular repolarization, excluding the influence of possible comorbidities. The QTc dispersion (QTc‐d), JTc dispersion (JTc‐d), and transmural dispersion of repolarization (TDR) have been suggested to be electrocardiographic indexes reflecting the physiological variability of regional ventricular repolarization. The aim of our study is to define the effects of obesity on the ventricular repolarization in obese children who have no other clinically appreciable cause of heart disease. Methods: The study involved 70 subjects (48 male, 22 female), with a mean age (± standard deviation) of 13 ± 2 years. A total of 35 individuals were obese (Group A: 24 male, 11 female, mean body mass index [BMI] of 38.2 ± 5.8 kg/m²), and 35 participants were healthy lean children (Group C: 24 male, 11 female, mean BMI of 22.3 ± 0.3 kg/m²). Heart rate; QRS duration; maximum and minimum QT interval; and QTc‐d, JTc‐d, and TDR measurement were performed. Results: Compared with the healthy control group, obese children presented increased values of the QTc‐d, JTc‐d, and TDR (31.1 ± 10.6 vs 46.2 ± 15.3 ms, P < 0.003; 29.8 ± 8.5 vs 40.1 ± 10.3 ms, P < 0.04; 83.2 ± 13.5 vs 100.7 ± 16.3 ms, P < 0.05). A statistically significant correlation was found between the values of QTc‐d, insulin serum concentration (r = 0.46, P = 0.04), and homeostasis model assessment of insulin resistance (r = 0.34, P = 0.03). Conclusions: Our data suggest that obese nonhypertensive children have an increased ventricular repolarization heterogeneity in relation to controls. (PACE 2010; 33:1533–1539)     

Activated platelets and leucocytes cooperatively stimulate smooth muscle cell proliferation and proto-oncogene expression via release of soluble growth factors.

BACKGROUND: Previous studies indicate that platelets and leucocytes might contribute to the development of neointimal hyperplasia following arterial injury. The present study was aimed at further investigating the role of platelets and leucocytes, alone or in combination, in promoting vascular smooth muscle cell (SMC) proliferation in vitro, focusing on the relative contribution of different soluble growth factors released by these cells, and on the ability to induce proto-oncogene expression, such as c-fos. METHODS: SMCs from rabbit aortas, made quiescent by serum deprivation, were stimulated with either activated platelets, leucocytes, or both, separated from SMCs by a membrane insert. SMC proliferation was evaluated by measuring the incorporation of 3H-thymidine. The relative contribution of different platelet-derived mediators to SMC growth was evaluated by adding either ketanserin, a 5-HT2 receptor antagonist, R68070, a TxA2 receptor antagonist, BN52021, a platelet activating factor (PAF) receptor antagonist, and trapidil, a platelet derived growth factor (PDGF) receptor antagonist. The role of different leucocyte sub-populations (neutrophils and monocytes + lymphocytes) was also determined in additional experiments. RESULTS: SMC proliferation was significantly increased by activated platelets to 360 +/- 9% of control values (P < 0.05). This effect was reduced by ketanserin, R68070, BN 52021 or trapidil. Whole leucocytes, neutrophils or lymphocytes + monocytes also increased SMC proliferation with respect to control experiments. Simultaneous stimulation of SMCs by platelets and whole leucocytes was associated with a significant greater increase in SMC proliferation as compared to SMC stimulated with platelets or leucocytes alone. c-fos expression, almost undetectable in unstimulated SMCs, was markedly increased by activated platelets or leucocytes. CONCLUSIONS: Activated platelets promote SMC proliferation in vitro via release of soluble mediators, including serotonin, thromboxane A2 PAF and PDGF; activated leucocytes also induce a significant SMC proliferation and exert an additive effect when activated together with platelets; SMCs stimulated with activated platelets and leucocytes show an early expression of the proto-oncogene c-fos.     

A putative new ampelovirus associated with grapevine leafroll disease

A putative new ampelovirus was detected in Vitis vinifera cv. Carnelian showing mild leafroll symptoms and molecularly characterized. The complete genome consisted of 13,625 nt and had a structure similar to that of members of subgroup I in the genus Ampelovirus (fam. Closteroviridae). In-depth analyses showed that the virus from cv. Carnelian is the most distinct member of the “GLRaV-4 lineage” of ampeloviruses, which comprises GLRaV-4, -5, -6, -9, and the recently characterized GLRaV-Pr, and GLRaV-De. This virus appears to be a new member of the family Closteroviridae, for which the provisional name grapevine leafroll-associated Carnelian virus is proposed.     

Adipose tissue-mediated inflammation: the missing link between obesity and cardiovascular disease?

Until relatively recently, the role of adipose tissue in the development of obesity and its consequences was considered to be a passive one. Mounting evidence highlights the role of adipose tissue in the development of a systemic inflammatory state that contributes to obesity-associated vasculopathy and cardiovascular risk. It is now clear that, in addition to storing calories as triglycerides, adipocytes secrete a large variety of cytokines, chemokines and hormone-like factors, such as leptin, resistin, and acute-phase proteins. In addition, insulin resistance, both in nondiabetic and diabetic subjects, is frequently associated with obesity, particularly with an excess of intraabdominal fat. This production of pro-atherogenic substances is of particular interest since an increase in the plasma levels of these mediators may provide a novel mechanistic link between obesity and its vascular complications.