A Randomized Comparison of Alternative Techniques to Achieve Coronary Sinus Cannulation During Biventricular Implantation Procedures

INTRODUCTION: Biventricular pacing system implantation is a time-consuming and challenging procedure. A critical step in biventricular pacemaker implantation is coronary sinus (CS) cannulation. CS cannulation can be achieved either using dedicated guiding catheters (guiding catheter alone positioning strategy, GCA) or with the aid of an electrophysiology catheter advanced inside the guiding catheter (electrophysiology catheter aided positioning strategy, EPA). AIM OF THE STUDY: To evaluate whether the EPA technique is useful for reducing CS cannulation time compared to a conventional GCA technique. METHODS: Thirty-four consecutive patients were randomly assigned to the GCA (18 patients) or EPA (16 patients) CS cannulation strategy. RESULTS: Time to successful catheterization of CS was 5.0 +/- 2.4 min in the EPA group versus 10.1 +/- 5.4 min in the GCA group p = 0.004. Fluoroscopy time was 4.6 +/- 2.3 min in the EPA group versus 9.2 +/- 4.9 min in the GCA group p = 0.004. Total contrast dye volume to search and engage the CS ostium was 0.0 ml in the EPA group versus 14.3 +/- 3.4 ml in the GCA group p < 0.001. CONCLUSIONS: Cannulation of CS with the adjunct of an electrophysiology catheter to dedicated delivery systems significantly reduces procedural time, fluoroscopy time and contrast dye volume compared to a conventional strategy.     

High Ascitic Fluid Leptin Levels in Patients with Decompensated Liver Cirrhosis and Sterile Ascites: Relationship with TNF-α Levels

Leptin is an adipocyte-derived hormone involved in the homeostasis of body composition. An imbalance in leptin regulation has been observed in patients with liver cirrhosis. We aimed to assess serum and ascitic leptin levels in a group of patients with decompensated liver cirrhosis and to evaluate the relationship of these levels with tumor necrosis factor alpha (TNF-alpha). We assessed both serum and ascitic fluid leptin levels in a series of 16 consecutive patients with liver cirrhosis. We calculated the body mass index (BMI) and assessed body fat (BF) of all patients by means of bioelectric impedence analysis. Leptin levels were analyzed in relationship to biochemical indexes, TNF-alpha levels, and body composition. None of the patients had spontaneous bacterial peritonitis. Both serum and ascites leptin levels were correlated with BMI and BF. On average, ascitic fluid leptin levels (13.1 +/- 10.9 ng/ml) were twice as high as serum levels (7.0 +/- 6.4 ng/ml), and the ascitic fluid/serum ratio of leptin was > 1 in all patients. Serum and ascites leptin levels were positively correlated (rS = 0.675, P = 0.009), while no correlation was observed between leptin and TNF-alpha levels, both in serum and in ascites. Serum and ascites TNF-alpha were not correlated. The ascitic fluid leptin levels of cirrhotic patients with sterile ascites are on average two times higher than circulating levels of this hormone. Noteworthily, they correlate significantly with body composition. These findings seem to suggest that in patients with decompensated liver cirrhosis, intraabdominal production of leptin may contribute to the metabolic picture.     

Radiofrequency ablation of hepatic tissue: a new experimental animal model

BACKGROUND/AIMS: Experimental radiofrequency ablation has already been performed in healthy livers of porcine models, but not in less expensive and easy-to-manage rats, with devices capable of delivering radiofrequency ablation in the 20-30 g liver of such small animals being so far unavailable. METHODOLOGY: We experimented with a modified system of radiofrequency ablation of liver tissue in rat models developing a custom-made needle-microelectrode of very small dimensions (0.3x2 mm) and an electrode-tip cooling technique, based on saline solution infusion. We adjusted duration (seconds) and power (watts) of radiofrequency ablation letting them range between 5-50 seconds and 5-25 W, respectively, to obtain the greatest lesions with the least side effects. After sacrificing the animals, an accurate histological examination of the liver was made. RESULTS: It is possible to establish beforehand the diameter of thermal liver lesion on the basis of joules of applied energy. The greatest increase of liver thermal lesion diameter (8 mm) is obtained with a 250-joule (10 W for 25 seconds) thermal energy cooling the electrode-tissue interface. CONCLUSIONS: Experimental radiofrequency ablation in rat liver is an effective and cheap way to study its effects on healthy hepatic tissues. It might be the first step to treat experimentally caused liver tumors.     

Influence of vasostatins, the chromogranin A-derived peptides, on the working heart of the eel (Anguilla anguilla): negative inotropy and mechanism of action

We have studied the effects of exogenous human recombinant Vasostatin-1 (VS-1), Vasostatin-2 (VS-2) and the human Chromogranin A (CGA) 7-57 synthetic peptides on the mechanical performance of the isolated and perfused working eel (Anguilla anguilla) heart. Under basal conditions, the three peptides decreased stroke volume (SV) and stroke work (SW), thus exerting negative inotropism. The VS-1-mediated negative inotropism was abolished by exposure to inhibitors of either Gi/o protein (pertussis toxin; PTx) or M1 muscarinic receptors (Pirenzepine) or calcium (Lantanum and Diltiazem) and potassium (Ba2+, 4-aminopyridine, tetraethylammonium, glibenclamide) channels, while it required an intact endocardial endothelium (EE). Using NG-monomethyl-L-arginine (L-NMMA) as an inhibitor of nitric oxide (NO) synthase (NOS), and hemoglobin as a NO scavenger, we demonstrated the obligatory role of NO signaling in mediating the vasostatin response. Pretreatment with either a specific inhibitor of soluble guanylate cyclase (GC) 1H-(1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ), or the inhibitor of the cGMP-activated protein kinase (PKG) KT5823, abolished the VS-1-mediated inotropism, indicating the cGMP-PKG component as a crucial target of NO signaling. Of note, VS-1 was effective in counteracting the adrenergic (Isoproterenol and Phenylephrine)-mediated positive inotropism. These findings provide the first evidence that vasostatins exert cardiotropic action in fish, thus suggesting their long evolutionary history as well as their species-specific mechanisms of action.     

The antihypertensive chromogranin a peptide catestatin acts as a novel endocrine/paracrine modulator of cardiac inotropism and lusitropism

Circulating levels of catestatin (Cts; human chromogranin A352-372) decrease in the plasma of patients with essential hypertension. Genetic ablation of the chromogranin A (Chga) gene in mice increases blood pressure and pretreatment of Chga-null mice with Cts prevents blood pressure elevation, indicating a direct role of Cts in preventing hypertension. This notable vasoreactivity prompted us to test the direct cardiovascular effects and mechanisms of action of wild-type (WT) Cts and naturally occurring human variants (G364S-Cts and P370L-Cts) on myocardial and coronary functions. The direct cardiovascular actions of WT-Cts and human variants were determined using the Langendorff-perfused rat heart. WT-Cts dose-dependently increased heart rate and coronary pressure and decreased left ventricular pressure, rate pressure product and both positive and negative LVdP/dt. WT-Cts not only inhibited phospholamban phosphorylation, but also the inotropic and lusitropic effects of WT-Cts were abolished by chemical inhibition of beta2-adrenergic receptors, Gi/o protein, nitric oxide or cGMP, indicating involvement of beta2-adrenergic receptors-Gi/o protein-nitric oxide-cGMP signaling mechanisms. In contrast, G364S-Cts did not affect basal cardiac performance but abolished isoproterenol-induced positive inotropism and lusitropism. P370L-Cts decreased rate pressure product and inhibited only isoproterenol-induced positive inotropism and lusitropism by 70%. Cts also inhibited endothelin-1-induced positive inotropism and coronary constriction. Taken together, the cardioinhibitory influence exerted on basal mechanical performance and the counterregulatory action against beta-adrenergic and endothelin-1 stimulations point to Cts as a novel cardiac modulator, able to protect the heart against excessive sympathochromaffin overactivation, e.g. hypertensive cardiomyopathy.     

Homozygosity for human leucocyte antigen-C ligands of KIR2DL1 is associated with increased risk of relapse after human leucocyte antigen-C-matched unrelated donor haematopoietic stem cell transplantation

Human leucocyte antigen (HLA)-C molecules regulate the function of natural killer cells and may be subdivided into two groups, C(1) and C(2), based on their specificity for inhibitory killer immunoglobulin-like receptors. We analysed the impact of the HLA-C genotype on outcome of HLA-C-matched unrelated donor haematopoietic stem cell transplantation (URD-HSCT) recipients. HLA-C(2) homozygous patients (n = 18) had lower probability of overall survival (P = 0.01) and disease-free survival (P = 0.02), resulting from increased relapse rate (P = 0.02) when compared with both HLA-C(1) homozygous (n = 43) and HLA-C(1),C(2) heterozygous (n = 50) subgroups. Patients lacking HLA-C(1) should, therefore, be considered at increased risk of relapse following HLA-C-matched URD-HSCT.     

Obese related effects of inflammatory markers and insulin resistance on increased carotid intima media thickness in pre-pubertal children

Obesity in children appears to be associated with increased risk of cardiovascular and metabolic diseases later in life. Early development of insulin resistance and impaired oxidant-antioxidant status may lead to endothelial dysfunction and increased carotid intima media thickness (IMT) even in childhood. The aim of this study was to measure IMT and the relationship between IMT, insulin resistance and oxidant status in obese pre-pubertal children. In 53 obese pre-pubertal children (27M/26F, mean age 8+/-2 years), anthropometric measurements and inflammatory markers (hs-CRP and PGF-2 alpha), were evaluated compared with 41 healthy pre-pubertal subjects (21M/20F, mean age 7+/-2 years). OGTT was performed and insulin resistance (IR) indices (HOMA-IR, WBISI, G/I and QUICKI) were calculated in all patients. High-resolution ultrasound techniques were used to evaluate IMT. Obese children had higher levels of PGF-2 alpha and hs-CRP compared to healthy subjects (p=0.001 and p=0.005). Furthermore, fasting insulin levels and HOMA-IR were higher in obese children than in controls (p=0.001 and p=0.001) while WBISI was significantly lower (p=0.002). In addition, obeses had an increased IMT (p=0.001). In obese children there was a significant correlation between IMT and indices of IR (HOMA-IR: beta=-1.233, p=0.002; WBISI: beta=-0.921, p=0.008; G/I: beta=-0.811, p=0.003) and between IMT and PGF-2 alpha (beta=0.505, p=0.004). After categorizing subjects according to tertiles of body mass index (BMI) (or=26.23 kg/m(2)) and to waist circumference (WC) (or=79.04 cm), no influence of BMI or WC on IMT were found in the three groups. In conclusion, early changes in glucose metabolism and an alteration of oxidant-antioxidant status may be present in obese pre-pubertal children; this could lead to increase IMT and early cardiovascular disease.     

Effects of nitroglycerin treatment on baroreflex sensitivity and short-term heart rate variability in humans

OBJECTIVES: We set out to determine the effect of sustained treatment with nitroglycerin (GTN) on neural modulation of heart rate in humans. BACKGROUND: Acutely, exogenous and endogenous nitric oxide reduces sympathetic, while increasing vagal, outflow. An animal study showed loss of these effects during nitrate tolerance. METHODS: A total of 29 healthy men (age range, 18 to 32 years) received transdermal GTN (0.6 mg/h/24 h) or no therapy for six days in a parallel controlled trial. The reflex regulation of heart rate was assessed with the spontaneous baroreflex sensitivity (BRS) method. Heart rate variability was calculated both in time (standard deviation of mean RR interval [RRSD]) and frequency domains (Fast Fourier Transformation) over 10-min intervals. RESULTS: Systolic blood pressure was unchanged after continuous GTN, whereas mean RR interval decreased significantly (from 839 to 781 ms, p < 0.05). Nitroglycerin blunted BRS (p < 0.05). When compared with untreated subjects, RRSD was significantly lower after GTN, whereas the ratio of low to high frequencies was increased (all p < 0.05). CONCLUSIONS: Chronic GTN reduces tonic and reflex vagal heart rate modulation, resulting in greater relative sympathetic influence. Importantly, such changes in the regulation of chronotropic oscillations might have negative prognostic implications in both heart failure and coronary artery disease. Furthermore, because chronic GTN alters the blood pressure/heart rate relationship, our data suggest caution when using these variables as pharmacodynamic markers for the development of nitrate tolerance.     

Detection of myocardial iron overload by two-dimensional speckle tracking in patients with beta-thalassaemia major: a combined echocardiographic and T2* segmental CMR study

We aimed to evaluate the role of two-dimensional speckle tracking imaging (2DSTI) in detecting early changes of myocardial deformation in patients affected by thalassemia major (TM) and its relation with myocardial iron overload (MIO) detected by T2* cardiovascular magnetic resonance (CMR). We studied 28 TM patients (15 males, 37.4?±?10 years). All patients underwent CMR and echocardiography in the same day. Segmental and global T2* values were measured. Values of global longitudinal strain (GLS) were derived from the three apical views, while radial and circumferential strain were obtained as average strain from the short axis views at basal, mid and apical level. Six patients (21.4%) showed significant MIO (global heart T2*?<?20 ms). GLS showed a significant correlation with T2* values (R?=??0.49; P?=?0.001) and it was significantly lower in patients with a significant MIO than in those with no significant MIO (?18.3?±?2 vs. ?21.3?±?2.7, P?=?0.02). No significant difference was found for radial and circumferential strain in relation to the severity of MIO. Patients with impaired GLS (<?19.5%) had a significant higher risk of showing significant MIO (Odds-ratio-OR?=?17; 95%). GLS is related with global T2* in TM patients. Moreover, GLS can identify TM patients with severe MIO detected by CMR.