Liver transplantation in man: morphometric analysis of the parenchymal alterations following cold ischaemia and warm ischaemia/reperfusion

Ischaemia and reperfusion phases represent critical events during liver transplantation. The purpose of this study was to describe morphological alterations of both vascular and parenchymal compartments after ischaemia and reperfusion and to evaluate the possible relationship between morphometric parameters and biochemical/clinical data. Three needle biopsies were drawn from 20 patients who underwent orthotopic liver transplantation. The first biopsy was taken before flushing with preservation solution, and the second and the third to evaluate respectively the effects of cold ischaemia and of warm ischaemia/reperfusion. Biopsies were examined by an image analyser and morphometric parameters related to the liver parenchyma were evaluated. At the second biopsy we observed a decrease of the endothelium volume fraction while the same parameter referred to the sinusoidal lumen achieved a peak value. The hepatocytes showed a lower surface parenchymal/vascular sides ratio. This parameter was reversed at the end of the reperfusion phase; furthermore the third biopsy revealed endothelial swelling and a decreased volume fraction of the sinusoidal lumen. The results quantify the damage to the sinusoidal bed which, as already known, is one of the main targets of cold ischaemia; warm ischaemia and reperfusion accentuate endothelial damage. The end of transplantation is characterised by damage chiefly to parenchymal cells. Hepatocytes show a rearrangement of their surface sides, probably related to the alterations of the sinusoidal bed. In addition, the fluctuations of morphometric parameters during ischaemia/reperfusion correlate positively with biochemical data and clinical course of the patients.     

Hybrid Therapies for Ventricular Arrhythmias

In recent years several trials demonstrated the efficacy of implantable cardioverter-defibrillation (ICD) therapy in reducing cardiac and total mortality in patients affected by rapid ventricular tachycardia (VT) and/or ventricular fibrillation. Nevertheless, ICD do not prevent arrhythmia recurrences, thus being a palliative and not a curative treatment modality. The tolerance to ICD therapy varies greatly, and within individuals, this leading to a nonuniform acceptance of this form of therapy. The very frequent occurrence of VT, defined as an arrhythmic storm, may be a life threatening condition. The majority of ICD patients is under antiarrhythmic drug therapy, to reduce episodes of VT or to make antitachycardia pacing more effective by slowing the tachycardia rate. Drug therapy, however, may cause additional problems, and does not represent the optimal solution. The prevention of VT and/or ventricular fibrillation episodes and excessive ICD therapy, remains a worthwhile goal. Radiofrequency catheter ablation (RFCA) is a curative approach, and can be expected to reduce the frequency of recurrent VT episodes in the majority of patients. The combination of these treatment modalities (ICD and RFCA) is often described as hybrid therapy, implying that the two treatments act providing some form of synergism. In experienced centers, RFCA is now performed, regardless of whether the VT rate is rapid and/or is hemodynamically unstable. Newer mapping and ablation techniques are now available, enhancing the acute success rate of the procedure. In this review the most recent application of VT catheter ablation and the use of advanced mapping and ablation techniques will be discussed.     

Effects of Hydrophilic and Lipophilic β-Blockers on Heart Rate Variability and Baroreflex Sensitivity in Normal Subjects

To evaluate the effect of a hydrophilic and a lipophilic β- blocker on the autonomic nervous system, 20 normal subjects were studied under baseline conditions and 7 days after being randomly assigned to metoprolol (200 mg/day), nadolol (80 mg/day), and placebo. Under each condition, the time-domain parameters were analyzed by means of 24-hour ECG monitoring and the frequency-domain parameters by means of the autoregressive method using 10-minute ECGs during rest, controlled respiration, and after a head-up tilt test. The alpha index (the gain in the relationship between the RR period and systolic arterial pressure variability) was also calculated. Both nadolol and metoprolol significantly increased all of the time-domain parameters except the standard deviation of the RR intervals; they also modified the frequency-domain parameters. Both blunted the significant reduction in the high frequency (HF) component and alpha index during tilt. In normal subjects, hydrophilic and lipophilic β-blockers similarly modify the time- and frequency-domain parameters that are particularly evident when high sympathetic tone is present (during daytime and tilt). The value of the alpha index was increased by both β-blockers in the HF, but not in the low frequency band; this difference might be due to the fact that the former is a measure of the vagal component of the baroreflex control and the latter a measure of the sympathethic component. The effects of hydrophilic and lipophilic β-blockers on the time- and frequency-domain parameters of heart rate variability are similar.     

Right-sided Infective Endocarditis with Acquired Tricuspid Valve Stenosis Associated with Transvenous Pacemaker: A Case Report

Five years prior to presentation, a 29-year-old woman received a transvenous pacemaker (DDD) for sick sinus syndrome and nodo-hisian pathology. After pacemaker insertion, she complained of recurrent febrile episodes. Her pacemaker related endocarditis was quite unusual for the infecting organism (a micrococcus) and for an acquired tricuspid valve stenosis. The suspected cause was confirmed at surgery.     

Difference in QT Interval Measurement on Ambulatory ECG Compared with Standard ECG

Measurement of the QT interval on standard ECG has diagnostic importance in the congenital long QT syndrome, in pharmacological therapy of arrhythmias, as well as in ischemic heart disease. It has been suggested that QT prolongation on ambulatory ECG (Holter) may have similar importance. To assess agreement between methods, QT interval measurement on standard ECG was compared to that on Holter. Simultaneously obtained ECG and Holter tracings (25 mm/s) of the same complexes in leads V₁ and V₅ were studied in 14 patients (age range 4–36 years). ECG pairs (n = 100, 49 V₁ and 51 V₅) were compared over a range of QT interval from 300–620 ms, as determined with the use of calipers by two observers blinded to pairing relationship. Correlation between methods was high for both observers (observer 1: r[V₁] = 0.872, r[V₅] = 0.973; observer 2: r[V₁] = 0.972, r[V₅] = 0.988), and interobserver variability was small (> 85% of measurements within 20 ms). As compared to ECG, Holter underestimated QT interval in V₁ mean difference (QT [Holter]—QT [ECG]) observer 1 (-23 ms, P < 0.001), observer 2 (-7 ms, P < 0.05), and overestimated QT in V5, mean difference observer 1 (+ 13 ms, P < 0.001), observer 2 (+13 ms, P < 0.001). However, individual variation between methods was wide, as expressed by the difference between individual measurements (95% confidence interval [V₁]: observer 1 [-99 to +53 ms] observer 2 [-47 to +33 ms]; [V₅]: observer 1 [-33 to +59 ms] observer 2 [-17 to +43 ms]). Furthermore, when using the QTA (interval from onset of Q wave to apex of T wave) similar variability was observed. In the assessment of QT interval, potential sources of error of this magnitude could limit the clinical utility of ambulatory monitoring in detecting prolongation of the QT interval for diagnostic purposes.     

Focal Atrial Tachycardia Originating from the Donor Superior Vena Cava after Bicaval Orthotopic Heart Transplantation

An 11‐year‐old boy, who underwent bicaval orthotopic heart transplantation for idiopathic dilated cardiomyopathy, had a focal atrial tachycardia originating from the donor superior vena cava. The pathogenesis of this tachycardia may be related to transplant rejection or transplant vasculopathy. Radiofrequency catheter ablation can eliminate this unique tachycardia and result in hemodynamic improvement. (PACE 2010; e68–e71)     

A CD strategy for the study of polypeptide folding/unfolding

The circular dichroism spectrum of the 20-residue immunogenic peptide from the foot-and-mouth disease virus (VP1; 141-160 of serotype A, subtype 12) was solvent- and temperature-dependent. Careful solvent titration revealed two isodichroic points and plateaux consistent with stepwise unfolding of specific stable conformations. Variable temperature studies in cryogenic solvents and urea perturbation were consistent with the existence of three conformational moieties, the left-handed extended helix, the a-helix, and the α-helix. The number of residues in each helix was confirmed by CD spectral simulations. The strategy described here can be used to determine the components of a conformational equilibrium and their statistical weights, to study peptide folding and unfolding and to determine the bioactive conformation(s) of linear peptides. The conclusions were supported by 2D-NMR studies. A new mechanism for the stabilization of left-handed extended helices and destabilization of a-helices by urea is proposed. The structure of the peptide as resolved by CD spectroscopy is of particular significance since the conformation of this antigenic sequence in situ has so far not been solved by X-ray crystallography.     

Hemodynamics of Idiopathic Paroxysmal Atrial Fibrillation

The hemodynamics of induced atrial fibrillation (AF) was investigated in 15 patients (ages 58 ± 11 years) with paroxysmal AF presenting without organic heart disease or hypertension. A hemodynamic study was performed both during sinus rhythm and after the induction of AF. The mean heart rate increased from 73 ± 11 to 128 ± 18 beats/min (P < 0.001) after AF. Systolic and mean aortic pressures did not significantly change, and diastolic aortic pressure increased (78 ± 11 vs 89 ± 12 mmHg, P < 0.01). Left ventricular enddiastolic pressure decreased during AF (9 ± 3 vs 6 ± 2.6 mmHg, P < 0.005), whereas mean pulmonary wedge pressure increased (8 ± 2 vs 12 ± 4 mmHg, P < 0.001). Systolic pulmonary arterial pressure did not show significant variations, and there was a slight but statistically significant increase in the diastolic and mean pulmonary arterial pressures (P < 0.01). The right ventricular end-diastolic pressure decreased during AF (5.6 ± 2 vs 3.8 ± 2 mmHg, P < 0.01 j, whereas mean right atrial pressure showed a trend toward an increase. Stroke volume markedly decreased (P < 0.001) while the cardiac index did not significantly change. Systemic vascular resistance, pulmonary arteriolar resistance, and the arteriovenous O₂ difference showed no significant variations after the induction of AF. These results suggest that in subjects without organic heart disease, paroxysmal AF is well tolerated hemodynamicaily, and the rise in the atrial pressures during AF is not related to an increase in the ventricular end-diastolic pressure.