[On-line HFR and removal of uremic toxins inducing the loss of phospholipidic asymmetry of the erythrocyte membrane]. / HFR on-line e rimozione di tossine uremiche inducenti la perdita dell'asimmetria fosfolipidica della membrana eritrocitaria.

The phospholipids of the erythrocyte membrane are normally distributed asymmetrically in the double layer with the aminophospholipid phosphatidylserine (PS) present only on the inside of the membrane, since its exposure on the outside has numerous physiopathological consequences. In previous studies we have observed that solutes retained in uremia cause increased exposure of PS on the outer surfaces of the erythrocyte membrane and that this phenomenon may be involved in the uremic physiopathology, reducing erythrocyte survival and encouraging abnormal erythrocyte-endothelium interactions. The capability of the extracorporeal blood clearance treatment in removing the circulating uremic factors, responsible for the increased exposure of PS in red blood cells (RBC), was evaluated in 6 chronic uremic patients treated with haemodialysis (HD) or with on-line HFR in a random cross-over perspective study. The PS removal was evaluated indirectly by measuring the expression of PS in normal RBC incubated with uremic plasma obtained at various moments of the clearance session. The capability of the uremic plasma to expose PS on the RBC of healthy subjects (n-times increase compared to incubation of normal RBC with autologous plasma) was essentially unmodified during HD (3.3 +/- 0.2 pre HD; 3.3 +/- 0.1 after 2 hours; 3.1 +/- 0.2 at the end of the session) but was reduced during HFR (3.1 +/- 0.2 pre HD; 2.3 +/- 0.1 after 2 hours; 1.6 +/- 0.1 at the end of dialysis; p<0.001 at the end of dialysis vs pre and after 2 hours and p<0.001 vs HD at 2 hours and at the end of the session). The reduced capability of the uremic plasma obtained during the HFR session to expose PS in normal RBC, proves removal of the plasmatic uremic factors able to externalize the PS. To assess whether this removal effect is linked to the cartridge containing styrene resin used in the treatment with HFR, samples of ultrafiltrate were taken before and after the cartridge and its capability to express PS on normal RBC was measured. The absolute RBC values expressing PS (%) were (pre-cartridge vs post-cartridge) 8.6 +/- 0.3 vs 3.8 +/- 0.2 after 5 minutes from the start of the session; 3.9 +0.1 vs 1.6 +0.2 halfway through the session; 3.1 +/- 0.1 vs 1.3 +/- 0.66 at the end of the session (p<0.005 pre vs post at all times). Our results show that uremic compounds able to cause increased exposure of PS in RBC can be removed during on-line HFR, mainly thanks to the adsorption properties of the cartridge containing resin. This removal might be of benefit to uremic patients, improving the anaemic condition and reducing abnormal RBC-endothelium interactions which may contribute to endothelial disorder during uremia.

First human experience with pulmonary vein isolation using a through-the-balloon circumferential ultrasound ablation system for recurrent atrial fibrillation.

BACKGROUND: Standard mapping and ablation of focal sources of atrial fibrillation are associated with very long procedure times and low efficacy. An anatomic approach to complete pulmonary vein isolation could overcome these limitations. METHODS AND RESULTS: Fifteen patients with atrial fibrillation refractory to medication underwent circumferential isolation of the pulmonary veins by using a novel catheter, with an ultrasound transducer (8-MHz) mounted near the tip, in a saline-filled balloon. Twelve atrial foci and/or atrial fibrillation triggers were identified in 9 patients (pulmonary vein locations: left upper, 3; right upper, 6; right middle, 1; right lower, 1; and left inferior, 1). In 5 patients, lesions were placed in the absence of any mapped triggers. Irrespective of trigger mapping, circumferential isolation of both upper pulmonary veins was attempted in all patients. The lower pulmonary veins were ablated when sinus rhythm activation mapping revealed evidence of a sleeve of atrial muscle in the vein. The median number of lesions per patient required to isolate 1 pulmonary vein was 4 (range, 1 to 29). After ablation, no evidence of narrowing was seen with repeat venography or follow-up computed tomography scan. After a mean follow-up of 35+/-6 weeks, 5 patients had recurrence of atrial fibrillation. Three responded to drugs that were previously ineffective, and 2 remained in atrial fibrillation. CONCLUSIONS: This novel ultrasound ablation system can successfully isolate multiple pulmonary veins. At early follow-up, this approach seems to be effective in preventing recurrent atrial fibrillation in a significant number of patients.

Serum levels of soluble adhesion molecules in chronic renal failure and dialysis patients.

Besides cell-bound adhesion molecules, which are of fundamental importance to a large number of physiological and pathological processes, soluble forms of adhesion molecules have been detected in the circulating blood in recent years. Circulating soluble adhesion molecules appear to be biologically active, and raised levels have been reported in a variety of disorders. In the present study, we used ELISA to measure the serum levels of four soluble adhesion molecules in 23 undialyzed patients with chronic renal failure (CRF), 13 patients on continuous ambulatory peritoneal dialysis (CAPD), 17 on chronic hemodialysis (HD) and 18 healthy controls having a similar mean and distribution of ages. The investigated soluble (s) molecules included intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), sE-selectin and sP-selectin. sICAM-1 was found to be elevated in patients with CRF (p < 0.05), on CAPD (p < 0.02) and HD (p < 0.0001) compared with the controls but levels did not differ between the three patient groups. The higher sVCAM-1 values found in CRF (p < 0.02), CAPD (p < 0.05) and HD (p < 0.0001) as compared to controls again failed to differentiate the three groups of patients. Soluble E-selectin was also raised in the three groups (p < 0.0001) with no difference between them. Increased sP-selectin was found in CRF (p < 0.05), CAPD (p < 0.02) and in HD patients (p < 0.0001) compared to controls, and levels in HD were significantly higher (p < 0.02) than in CRF patients. Predialysis serum molecule levels did not differ between HD patients treated with cuprophan or with polyacrylonitrile dialyzers. HD sessions with both dialyzers had no effect on sICAM-1, while a decrease (p < 0.02) in sP-selectin was found after dialysis with cuprophan. In undialyzed patients with CRF, regression analysis showed a strong linear correlation between serum creatinine and serum levels of each soluble molecule. These results demonstrate that serum levels of soluble adhesion molecules ICAM-1, VCAM-1, E-selectin and P-selectin are elevated in both undialyzed patients with CRF and patients on CAPD or HD. The elevated serum levels of these proteins probably reflect inadequate clearance as well as enhanced synthesis/release.

Palliative coronary artery surgery in patients with severe noncardiac diseases.

Eight patients with severe systemic pathologies and refractory angina unsuitable for angioplasty were submitted to palliative surgical revascularization without the use of cardiopulmonary bypass and limited to the culprit vessels. Complete relief from angina was achieved in all patients without postoperative mortality and morbidity.

Conventional left atrial versus superior septal approach for mitral valve replacement.

BACKGROUND: This study was designed to evaluate the safety and effectiveness of the superior septal approach for routine mitral valve replacement. METHODS: One hundred forty-six consecutive patients undergoing mitral valve replacement at our institution were randomly assigned to undergo the procedure using either the conventional left atriotomy or the superior septal approach. Postoperatively and during the follow-up, 12-lead electrocardiography, 24-hour Holter monitoring, and transthoracic and transesophageal echocardiography were performed in all patients. RESULTS: The cardiopulmonary bypass and cross-clamp times were significantly higher in the superior septal group. No significant difference in blood loss was found between the two groups, and no residual atrial septal defect was found in patients in whom we used the superior septal approach. The maintainance of sinus rhythm at late follow-up and the incidences of postoperative arrhythmias and newly developed atrioventricular block were not significantly different between the two groups. CONCLUSIONS: The use of the superior septal approach to the mitral valve is not associated with a greater incidence of rhythm disturbances or other complications. Because this approach provides optimal exposure of the valve and the subvalvular apparatus, it has been routinely adopted for use in patients undergoing mitral valve replacement at our institution.

Neutrophil reactive oxygen species production during hemodialysis: role of activated platelet adhesion to neutrophils through P-selectin.

Platelet interaction with leukocytes can occur to a significant degree during hemodialysis, but it remains to be determined what pathophysiological consequences stem from the intradialytic formation of platelet-leukocyte coaggregates. By the use of flow cytometry techniques, this study was set out to analyze intradialytic platelet-neutrophil coaggregate formation and neutrophil hydrogen peroxide production from 10 end-stage renal disease patients each dialyzed with cuprophane and polyacrylonitrile membranes. Platelet-neutrophil coaggregates increased during dialysis with cuprophane, whereas no changes occurred with polyacrylonitrile membranes. Dialysis with cuprophane, unlike that with polyacrylonitrile, also resulted in a significant increase in neutrophil hydrogen peroxide production 10 min after dialysis initiation which persisted at significantly higher levels than predialysis values through the first 20 min. We found that the increased hydrogen peroxide production by neutrophils essentially occurred in concomitance with neutrophil-platelet coaggregation. Intracellular fluorescence representing hydrogen peroxide formation significantly increased through the first 20 min of cuprophane dialysis in neutrophils aggregated to platelets. By contrast, no change occurred in neutrophils not aggregated to platelets. Neutrophils which had formed aggregates with platelets produced higher hydrogen peroxide levels, as assessed by significantly higher fluorescence values, than non-aggregate-forming neutrophils at all time points tested. The phenomenon was duplicated in vitro when ADP-activated normal platelets were incubated with neutrophil cells but was largely inhibited when ADP-activated platelets were treated with anti-P-selectin antibody before incubation with neutrophils. These results strongly suggest that platelet-neutrophil aggregates occurring during hemodialysis, representing cell-cell interactions with pathophysiological effects, may serve as a new parameter to assess biocompatibility.

Use of [123I]MIBG to assess cardiac adrenergic innervation: experience in hypertensive cardiopathy and left ventricular aneurysms.

[123I]MIBG has been proposed as a suitable tracer of the adrenergic system of the heart. The aims of this study was to investigate the adrenergic functional status of the heart in hypertensive patients with left ventricular hypertrophy (LVH), and to evaluate the distribution of neuroadrenergic terminals in patients with left ventricular aneurysms (LVA) presenting complex arrhythmias. We studied 21 patients (4 normals, 11 with LVH and hypertension, and 6 with previous myocardial infarction, LVA and complex arrhythmias) who underwent series of [123I]MIBG planar scans (from 0.5 to 24 hours p.i.) and SPECT scans using both [123I]MIBG and 201Tl. Data quantification was performed by calculating the heart/mediastinum ratio (planar scan) and the percent uptake in 5 myocardial regions (SPECT scan). No significant differences between normals and hypertensive patients were found either in the heart/mediastinum ratio or in the regional distribution of [123I]MIBG and 201Tl. In hypertensive patients the uptake of [123I]MIBG was significantly higher than that of 201Tl in the septal wall while in the lateral and inferior walls it was significantly lower. In patients with anteroapical myocardial infarction (MI), the size of the [123I]MIBG defect was slightly smaller than the 201Tl defect; moreover a constant, severe [123I]MIBG defect was observed in the inferior walls whereas 201Tl uptake was normal. We conclude that while in hypertensive patients adrenergic innervation seems to be slightly impaired as compared to myocardial perfusion, in patients with MI a large area of functional or anatomical denervation may be detected despite the preserved perfusion and viability; this mismatch may be the trigger of complex arrhythmias.

Immunohistochemical evidence for sympathetic denervation and reinnervation after necrotic injury in rat myocardium.

To study the short and long term effects of myocardial injury on sympathetic nerve fibers, a necrotizing lesion was performed on the diaphragmatic side of rat myocardium by freeze-thawing. Animals were sacrificed at 2, 6, 18, 28 and 105 days after the surgical procedure and paraffin-embedded hearts were subjected to peroxidase immunohistochemistry. According to previous studies cardiac nerves were visualized by staining their surrounding Schwann cells with an anti-S100 protein antibody. Catecholaminergic axons were specifically identified by an anti-tyrosine hydroxylase antibody. No S-100 positive structures were found in 2-day lesions (denervation). Starting from day 6,S-100 positive structures became progressively more evident (reinnervation) and persisted up to day 105. Many of these newly formed nerve fibers were positive for tyrosine hydroxylase, indicating that a necrotic injury of rat myocardium causes a disappearance of sympathetic innervation which is followed by a phase of sympathetic reinnervation.

Electrophysiologic effects of amlodipine vs. diltiazem in patients with coronary artery disease and beta-blocking therapy.

This study compares the electrophysiologic effects of amlodipine and diltiazem in patients with coronary artery disease concomitantly treated with background beta-blocking therapy. Thirty patients were included in an open-label parallel study in two phases. During phase 1, patients were screened and placed on maintenance atenolol therapy at 50 or 100 mg/day, while phase 2 consisted of right-sided catheterization and randomization of patients to either amlodipine (10 mg i.v.) or diltiazem (10 mg i.v.). Following treatment with amlodipine, no significant alteration in markers of electrophysiological activity was observed. Treatment with diltiazem resulted in a significant lengthening of sinus cycle length (SCL, p < 0.04), AH interval (p < 0.02), and Wenckebach CL (WCL, p < 0.001), and a trend towards an increase in sinus node recovery time (SNRT, p = 0.057). No effects were observed with regard to HV interval and corrected SNRT. The results of this study indicate that 10 mg intravenous amlodipine has no significant electrophysiological action on sinus or AV node function in patients receiving beta-blocker therapy with atenolol, suggesting that amlodipine can be added to beta-blockers to treat patients with myocardial ischemia and/or hypertension without any significant increase in the risk of bradyarrhythmias.

Effects of thrombolysis and atenolol or metoprolol on the signal-averaged electrocardiogram after acute myocardial infarction. Late Potentials Italian Study (LAPIS).

Late potentials (LPs) detected on the signal-averaged (SA) electrocardiogram (ECG) predict arrhythmic events after acute myocardial infarction (AMI). The effect of thrombolysis on the incidence of LPs after AMI is controversial and its impact on subsequent arrhythmic events is not known. Moreover, the effects of beta blockers on the SAECG have not been studied. Six hundred eighteen patients with AMI were studied; thrombolysis was given to 228 (37%). In comparison with patients treated conventionally, those receiving thrombolysis were significantly younger and more frequently male, had higher peak values of creatine kinase, a lower prevalence of non-Q-wave AMI, and a higher incidence of ventricular fibrillation in the acute phase, and more frequently received beta blockers. An SAECG obtained 6 to 8 days after AMI showed LPs in 24% of patients receiving and in 25% not receiving thrombolysis (p = NS). On admission, intravenous beta blockers were administered to 110 patients (18%); those receiving beta blockers were younger, had lower peak values of creatine kinase and more frequently received thrombolysis. LPs were less frequently found in patients treated than in those not treated with beta blockers (15 vs 27%; p = 0.007); however, this effect was found only in those with an ejection fraction > or = 40%. Independent predictors of LPs by multivariate analysis were an ejection fraction < 40% (p = 0.007), ventricular fibrillation in the acute phase (p = 0.02), and absence of beta-blocking therapy (p = 0.03). During a mean follow-up of 12 +/- 7 months, there were 39 cardiac deaths (6%), 13 of which were sudden (2%), and 9 sustained ventricular tachycardias.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial antioxidant defenses during cardiopulmonary bypass.

In 31 male patients undergoing coronary bypass surgery who underwent different periods of cardioplegic hypothermic arrest, the activities of glutathione peroxidase, glutathione reductase, glutathione transferase, copper/zinc-containing and manganese-containing superoxide dismutases, and catalase were studied in the right atrial myocardium, before and 5 minutes after aortic cross-clamping. The levels of thiobarbituric acid reactive substances (TBARS) and nonproteic thiol compounds (NP-SH) were also assessed. Prolonged ischemia followed by reperfusion induced activation of the major myocardial antioxidant enzymes with marked NP-SH depression and TBARS increase, despite cold crystalloid cardioplegic protection. These changes were significantly related to the duration of the ischemic arrest, suggesting: (1) that reperfusion free radical generation is dependent on the severity of the previous ischemic period; and (2) the occurrence of myocardial oxidative stress during cardiopulmonary bypass.

Effects of subcutaneous recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis.

The use of recombinant human erythropoietin (rHuEPO) has revolutionized the treatment of renal anemia, but the dose regimens, the optimal frequency, and the effects on other target organs like the central nervous systems (CNS) are still under discussion. We designed a prospective, ongoing study with 10 stable continuous ambulatory peritoneal dialysis (CAPD) patients (6 males, 4 females; mean age 64.4 +/- 7.8 years), with a pretreatment hemoglobin (Hb) < 7.0 g% and requiring regular blood transfusions. Seven patients were treated with 4000 U rHuEPO once weekly (Eritrogen, Boehringer Mannheim), 2 patients received 4000 U every 5 and 8 days, and the last one 4000 U every 10 days. The target hematocrit was 33% and Hb 10.0 g%. The CNS activity was recorded as visual (VEP), brainstem (BAER), and somatosensory (SEP)-evoked potentials. The mean Hb concentration increased from 6.9 +/- 1.2 g% to 10.3 +/- 1.6 g% (p < 0.001) over 8 weeks. There were no significant changes in urea, creatinine, and potassium levels, and urine output. rHuEPO induced a decrease in latency of P100 VEP, in the four main components of BAER, and in the P27-N35 intertime of SEP. Parallel to the improvement of red cell indices, patients experienced a dramatic improvement in well-being. The subcutaneous administration of a single vial of rHuEPO is safe, convenient, and inexpensive in CAPD. The role of rHuEPO treatment in improving the electrophysiological brain function in uremic and anemic patients remains to be studied and may not necessarily be based on improved cerebral oxygenation.

[Results of surgical treatment in supraventricular tachycardias]. / Risultati del trattamento chirurgico delle tachicardie sopraventricolari.

From May 1989 to May 1992, 44 patients (mean age 41 years, range 15-66) underwent surgery for supraventricular tachycardias: in 35 patients with atrioventricular reentrant tachycardia or atrial fibrillation associated with accessory pathway and refractory to medical treatment, the epicardial approach was used; in 8 with atrioventricular nodal reentrant tachycardia, a perinodal cryosurgery of the atrioventricular node was used, and in 1 patient with atrial flutter a cryosurgical ablation around the orifice of the coronary sinus and surrounding tissues was performed. All 38 accessory pathways were successfully ablated in 35 patients and no recurrences of delta wave or tachycardia were observed during a mean follow-up of 17 +/- 10 months. Atrial perforation during surgery and pericarditis were the only complications observed. All 8 patients with atrioventricular nodal reentrant tachycardia were successfully treated: in 2 patients dual pathways persisted after surgery but tachycardia was no longer inducible. No recurrences were observed during a mean follow-up of 15 +/- 4 months. Since surgery (15 months), the patient with atrial flutter has been free of recurrent episodes of atrial flutter. In conclusion, surgical treatment of supraventricular tachycardias is highly successful, with no mortality and very low morbidity. Should transcatheter ablation fail, surgery should be the treatment of choice in patients with frequent and symptomatic supraventricular tachycardias.

[Right accessory pathway simulating a nodo-ventricular pathway: an electrophysiologic study and intraoperative mapping]. / Via accessoria destra che simula una via nodo-ventricolare: studio elettrofisiologico e mappaggio intraoperatorio.

We report a case of a patient with episodes of wide QRS tachycardia and syncope. During the electrophysiologic study, a wide QRS tachycardia (200 b/m) with left bundle branch block morphology was reproducibly induced by incremental atrial pacing with progressive shortening of the HV interval and lengthening of the AV interval, suggesting the presence of a nodoventricular accessory pathway (Mahaim fiber). The intraoperative mapping performed during tachycardia showed the earliest ventricular activation to be over the right antero-lateral AV groove, different from the usual epicardial activation previously described. According to the earliest epicardial breakthrough point, we performed an epicardial AV fat pad dissection which produced irreversible disappearance of preexcitation, confirmed at the postoperative electrophysiologic study. No recurrence of tachycardia was observed during a follow-up of 11 months. This case further confirms previous data that the "so-called" Mahaim fibers could be a right accessory pathway with decremental properties.

Comparison between two versus three patches single pulse shock defibrillation in pigs.

The aim of the study was to test the hypothesis that defibrillation with a single pulse shock can be obtained at lower energy using three epicardial patches configuration (one cathode and two anodes) instead of the conventional two patches. The total surface area of the two- and three-patches configuration was the same (10 cm2 vs 9.9 cm2). Epicardial spatial configuration was planned by using a computerized heart model. In ten anesthetized open-chest pigs, ventricular fibrillation was induced by using AC current through the mesh plaque epicardial custom-designed electrodes, and the minimum energy requirement for defibrillation was determined 15 seconds after the onset of stable ventricular fibrillation. Results were as follows (mean +/- standard deviation): Defibrillation Threshold 16 +/- 9 J 9 +/- 5 J P less than 0.01 CONCLUSIONS: three epicardial patches configuration significantly reduces energy requirements for defibrillation compared with two patches when single pulse shock is used.

Surgical treatment of cardiac arrhythmias.

This report describes 20 consecutive patients who underwent surgical procedures for treatment of cardiac arrhythmias. 16 patients have been operated for WPW syndrome, always using the epicardial approach, without extracorporeal circulation. Three patients underwent surgery for atrio-ventricular nodal reentrant tachycardia, using a discrete perinodal cryotreatment, during normothermic extracorporeal circulation. In one case we used cryoablation of the atrial myocardium below the coronary sinus to treat atrial flutter. This operation was performed under normothermic extracorporeal circulation. In our observations, there was no early or late death; postoperative complications developed in 1 patient (5%) due to pericarditis. Ablation of the AP was completely successful in all the cases (100%) operated for WPW as well as for AVNRT syndromes and atrial flutter.

[Myocardial revascularization with the internal mammary artery. The indications, technics and results]. / La rivascolarizzazione miocardica con arteria mammaria interna. Indicazioni, tecniche e risultati.

This report reviews 218 patients who underwent internal mammary artery (IMA) grafting alone or with vein graft between 1986-1989. Our experience with IMA started with a single attached graft for proximal left anterior descending lesions in young patients affected from stable angina. After that our indications became more extensive. One IMA was utilized in 209 cases, both two IMAs in the remaining 9. Sequential IMA graft was performed in 16 patients and free IMA graft in 8. There were 242 IMA anastomosis and 295 associated vein by-passes. The overall operative mortality was 2.3%. Perioperative complications include myocardial infarction in 3 (1.4%), reoperation for bleeding in 4 (1.8%) and sternal wound complication in 4 (1.8%). These results are comparable to those of patients having only saphenous vein by-pass during the same period. At the follow-up actuarial survival rate at 42 months was 94 1.8% and 90% of these patients were completely asymptomatic. We include that IMA grafting shows low operative risk and provide excellent short term results. Our findings and the high long term patency rate of this conduit encourage us to extend the indication to IMA and to perform those surgical techniques that make possible multiple mammary coronary anastomosis.