Polyamines stimulate superoxide production in human neutrophils activated by N-fMet-Leu-Phe but not by phorbol myristate acetate.

The polyamines putrescine, spermidine and spermine, at concentrations of 10 microM, stimulated superoxide generation by human polymorphonuclear leukocytes induced by fMet-Leu-Phe in the presence of Ca2+. This positive effect was not evident in the absence of Ca2+ or when the polymorphonuclear leukocytes were stimulated by phorbol myristate acetate. Spermidine in the range of 10-100 microM showed a dose-dependent stimulatory effect on the superoxide generation induced by fMet-Leu-Phe, whilst at doses above 25 mM it produced an inhibitory effect. At this concentration, spermidine did not reduce the phorbol myristate acetate-neutrophil-induced O2-. generation, while an inhibitory effect by the polyamine was evident at concentrations above 50 mM. In addition, 100 microM spermidine increased the amount of superoxide generated and enhanced the ability of the chemotactic peptide to stimulate superoxide generation. The polyamines in the range of 10 microM-25 mM did not modify the activity of purified NADPH oxidase, nor the rate of reduction of cytochrome c as supported by the xanthine/xanthine oxidase reaction. These results indicate that physiological concentrations of polyamines can stimulate superoxide formation by polymorphonuclear leukocyte cells produced by the chemotactic peptide fMet-Leu-Phe, probably by increasing the availability of external calcium.

Usefulness of transesophageal echocardiographic monitoring to improve the outcome of stent-graft treatment of thoracic aortic aneurysms.

The stent-graft procedure is becoming an alternative to surgery for treatment of many diseases of the descending thoracic aorta. This study evaluated the role of transesophageal echocardiography (TEE), used in combination with fluoroscopy and angiography, in monitoring the outcome of stent-graft placement. Twenty-two consecutive patients were submitted to stent-graft positioning in the descending aorta for various pathologies (7 patients had type B aortic dissections, 6 had thoracic aneurysms, 2 had thoraco-abdominal aneurysms, and 7 had post-traumatic aortic aneurysms). Before stent-graft deployment, TEE changed the proximal site of stent positioning initially identified by angiography in 33% of patients (5 of 15) with aortic aneurysms because of calcifications or atheromas that could interfere with stent adhesion to the aortic wall and that were not seen on angiography. In 28% of patients (2 of 7) with aortic dissection, TEE showed the guidewire in the false lumen, allowing an immediate repositioning. After stent-graft deployment, color Doppler TEE showed a perigraft leak in 7 patients, whereas angiography detected a perigraft leak in only 2 patients (p = 0.02). In 4 of these patients, further balloon expansions resulted in resolution of the leak. In the remaining 3 patients, additional stent-graft positioning was necessary. Considering the total patient cohort, TEE yielded relevant information, resulting in procedure changes in 59% (13 of 22). In conclusion, TEE provided additional information with respect to angiography in all phases of stent-graft treatment, improving immediate outcome and reducing complications.

Primary endoleakage in endovascular treatment of the thoracic aorta: importance of intraoperative transesophageal echocardiography.

OBJECTIVES: Endovascular treatment of the thoracic aorta has developed as an efficacious alternative to open surgical repair. However, despite the high primary success rate, perigraft leakage constitutes the major concern in long-term follow-up. Endoleaks are widely reported both in abdominal and thoracic endovascular series and are usually identified by intraoperative angiography. Transesophageal echocardiography is a sensitive imaging technique in the evaluation of aortic diseases, widely used to monitor cardiac surgery. The aim of this study was to evaluate the efficacy of transesophageal echocardiography in leakage detection during endovascular stent procedures of the thoracic aorta. METHODS: Intraoperative transesophageal echocardiography was used in conjunction with angiography in 25 patients subjected to endovascular stent treatment of the descending thoracic aorta. Spiral computed tomographic scanning was performed before discharge and 3, 6, and 12 months after treatment. RESULTS: Information from transesophageal echocardiography was relevant in the selection of the landing zone in 62% of cases. In 8 patients, transesophageal echocardiography with color Doppler sonography showed a perigraft leak, 6 of which were not visible on angiography, suggesting the need for further balloon expansion or graft extension. Postoperative computed tomographic scanning in the 25 patients showed 1 endoleak, which sealed spontaneously. At 3 months, computed tomographic examination confirmed the absence of perigraft leakage in all patients. CONCLUSIONS: During implantation of a stent-graft in the descending thoracic aorta, transesophageal echocardiography provides information in addition to that provided by angiography, improving immediate and late procedural results.

Clinical evaluation of St Jude Medical Hemodynamic Plus versus standard aortic valve prostheses: The Italian multicenter, prospective, randomized study.

OBJECTIVE: Hemodynamic and clinical performances of 21-mm and 23-mm St Jude Medical Hemodynamic Plus aortic valves (St Jude Medical, Inc, St Paul, Minn) were compared with those of 21-mm and 23-mm St Jude Medical standard cuff aortic valves in the first such multicenter, prospective, randomized study. Hemodynamic Plus valves are mechanical, bileaflet prostheses suitable for the small aortic anulus. METHODS: Patients with 21-mm and 23-mm anulus diameters were randomized to receive either a Hemodynamic Plus or a standard cuff valve. Postoperatively and at 6 months after the operation, patients underwent 2-dimensional Doppler echocardiography. Ejection fraction, cardiac output, peak gradient, mean gradient, effective orifice area, effective area index, and performance index were calculated. Postoperative and 6-month echocardiographic measurements and their variations across observation times were analyzed statistically. RESULTS: Of the 140 patients enrolled, 5 died at operation and 1 died of aortic dissection during the follow-up period. Eight patients were lost to follow-up. A total of 125 patients completed the study. In 1 patient a sewing cuff escaped intraoperatively. At 6 months the 21-mm and 23-mm Hemodynamic Plus valves showed significantly lower peak gradients and mean gradients than those of the 21-mm and 23-mm standard cuff valves. The 21-mm Hemodynamic Plus valves had gradients similar to those of the 23-mm Hemodynamic Plus valves. The effective orifice area did not differ significantly between the Hemodynamic Plus and standard cuff valves at either measurement. No valve mismatch was found in the 4 groups of patients. A more enhanced decrease of peak gradients and mean gradients and a more enhanced increase of effective orifice areas, effective area indices, and performance indices were found across observation times for patients with Hemodynamic Plus valves compared with those with standard cuff valves. CONCLUSIONS: Clinical hemodynamic performances of 21-mm and 23-mm St Jude Medical Hemodynamic Plus valves correspond closely with those of standard cuff valves, and gradients are substantially better than those of standard cuff valves of the same diameter. Therefore, use of this valve may minimize the need for aortic anulus enlargement. Early follow-up results with the Hemodynamic Plus valves were excellent, although more time is required to confirm this outcome.

Spontaneous superoxide generation by polymorphonuclear leukocytes isolated from patients with stable angina after physical exercise.

The activation of circulating polymorphonuclear leukocytes was determined in terms of O2.- generation and elastase release in patients with stable angina (n = 12) and in control subjects (n = 8) after maximal physical exercise and after a 15-min recovery. There was no spontaneous O2.- formation under basal conditions in both groups of patients. On the contrary, there was significant formation of O2.- (p < 0.001) from patients with stable angina measured directly after exercise, along with a slight spontaneous O2.- formation in control subjects (p < 0.05). After recovery, the spontaneous polymorphonuclear leukocyte-O2.- formation decreased but was still present in the patients with stable angina, while in the healthy subjects these values returned to resting levels. The activation of polymorphonuclear leukocytes with phorbol 12-myristate 13-acetate enhanced O2.- formation both in healthy subjects and in patients with stable angina, with a lesser effect in the latter. Moreover, no differences were observed in polymorphonuclear leukocyte-stimulated O2.- formation during the protocol, both in the angina stable patients and healthy subjects. No changes were found in plasma elastase levels among stable angina patients nor in control subjects as a consequence of exercise or recovery. This study indicates there is an early activation of circulating polymorphonuclear leukocytes in terms of O2.- production in stable angina patients during maximal exercise, which is still present after a 15-min recovery. Such activation occurs without elastase release. However, in healthy subjects maximal exercise resulted in very little increase in neutrophil activation.

Biochemical correlates with myocardial aging.

Both contraction and relaxation times are prolonged in cardiac muscle of senescent animals. This is in part explained by an alteration of excitation-contraction coupling due to an increased duration of the action potential, reduced biosynthesis of the Ca(2+)-stimulated ATPase pump of sarcoplasmic reticulum, and prevalence of the V3 isoform of myosin with slow ATPase activity. The response to catecholamine decreases with aging because of a defective transmission of alpha and beta adrenergic stimulation mediated respectively by phosphoinositide hydrolysis and adenylate cyclase. Cardiac energetics is also impaired in the aged myocardium, since ATP and creatine phosphate levels are reduced by about 20%. This reduction seems in part the consequence of defective mitochondrial function, especially in fatty acid oxidation and ATP translocation to the cytoplasm. In this paper we have discussed the possibility that oxygen free radicals may be a cause of myocardial senescence, by damaging the nuclear and mitochondrial genomes as well as membranes and other cellular components.

The effect of treatment with coenzyme Q10 on the mitochondrial function and superoxide radical formation in cardiac muscle hypertrophied by mild aortic stenosis.

A 40% reduction of the diameter of the ascending aorta maintained for 60 days induced the formation of a compensate cardiac hypertrophy in rabbits without changing the value of the azide insensitive Ca2+-ATPase activity in comparison to control hearts. The cardiac mitochondria isolated from constricted animals assayed in presence of glutamate and succinate did not show a change in the R.C.I. and ADP/O values in comparison to the controls, whilst the QO2 value enhanced or decreased respectively when determined with glutamate or succinate. The intramuscular injections of CoQ10 (12 mg/kg body weight/48 h) enhanced the mitochondrial CoQ10 concentrations both in the control and in the constricted animals and further increased the QO2 value determined in both groups of animals when glutamate was used as the substrate. The production of O2.- radicals by the level of the complexes I and III of the respiratory chain, did not change in the constricted animals, nor in the animals administered with CoQ10 in comparison to the control. CoQ10 augmented the rate of oxygen consumption by the submitochondrial particles only in the constricted animals. Moreover, the treatment with the coenzyme or the constriction of the aorta, did not modify the cardiac superoxide dismutase activity, but increased the glutathione peroxidase activity only in the banded animals. In addition, in the CoQ10 treated animals there was a reduction of NADH-diaphorase activity both in the control and constricted animals, while the malondialdehyde, generated during the thiobarbituric acid test, and the cardiac content of lipofuscin were decreased.

[Brucella endocarditis: role of drug treatment associated with surgery]. / Endocardite da brucella: ruolo del trattamento medico associato a quello chirurgico.

Brucella infective endocarditis is an uncommon, but serious complication of brucellosis. The aortic valve is the most commonly affected cardiac valve, and a fearful complication is the formation of aortic root abscess. Due to the characteristics of the infection, medical therapy alone is not sufficient in treating the disease and best results are achieved in combination with surgery. We describe 2 cases of brucella endocarditis involving the aortic valve. Aggressive treatment, with surgery performed during a period of active infection, produced good results in eradication of infection and in preventing fatal complications such as rupture of aortic root abscesses.

[An echocardiographic analysis of the insufficient mitral valve: its intraoperative functional anatomy in relation to valvular reconstruction]. / Analisi ecocardiografica della valvola mitrale insufficiente: anatomia funzionale intraoperatoria in relazione alla ricostruzione valvolare.

Mitral valve repair in patients with mitral regurgitation requires a precise evaluation of the mechanism of valvular pathology before surgery. Transesophageal echocardiography has become the principal method for imaging valvular pathology, especially with the latest introduction of multiplanar transesophageal technology. Traditionally, echocardiographic analysis of regurgitant mitral valves has concentrated on the description of abnormalities of leaflet motion such as prolapse, while surgical correction aims at restoring the coaptation of the edges of the leaflets. To reconcile these different approaches, the echocardiographic features the findings on direct inspection, and the types of repair performed were analyzed in 37 incompetent mitral valves. The zone of coaptation of the mitral valve was studied in a series of left ventricular long-axis views obtained with a transesophageal multiplanar echo-transducer from the anterolateral via the central, to the posteromedial segment. Four patterns of leaflet closure were found: normal apart from a dilated annulus (24%), normal apposition but absent coaptation (8%); asymmetrical apposition but intact coaptation (16%); and abnormal apposition and absent coaptation (52%). In addition leaflet motion was described (prolapse, retraction, normal), and the anteroposterior dimension of the mitral annulus was measured. There was a direct relationship between these echocardiographic findings and the types of reconstructive techniques used. The echocardiographic analysis offers a logical approach to the preoperative diagnosis of regurgitant mitral valves, with the possibility to predict the feasibility and the type of mitral repair.

Composite graft replacement of the ascending aorta: leakage detection with gadolinium-enhanced MR imaging.

PURPOSE: To assess the value of magnetic resonance (MR) imaging in the detection of postoperative complications after composite valve graft replacement. MATERIALS AND METHODS: Spin-echo and gradient-echo MR imaging was performed in 52 patients 1/2 to 200 months after composite graft replacement of the ascending aorta (22 for dissection, 30 for aneurysm). The prosthetic aortic segment, distal and proximal anastomoses, general morphologic characteristics, and diameter of the reimplanted coronary arteries were evaluated. In patients with abnormal perigraft thickening, additional spin-echo imaging was performed after injection of gadopentetate dimeglumine. RESULTS: Normal postoperative perigraft thickening (< or = 10 mm) was observed in 42 patients. Ten patients had abnormal periprosthetic thickening of 15-52 mm. Gadolinium-enhanced MR imaging demonstrated leakage in five of those 10 patients. The lack of enhancement excluded the presence of bleeding in the remaining five patients (three with chronic hematomas, one with infection, and one with granulation tissue). These findings were confirmed at surgery or with subsequent follow-up MR examinations. CONCLUSION: MR imaging was an optimal imaging modality for evaluating the morphologic characteristics of composite grafts and reimplanted coronary arteries. Gadolinium-enhanced MR imaging is a simple, accurate, and noninvasive method for detecting a leak, which necessitates urgent repeat surgery.

Reduced oxidative activity of circulating neutrophils in patients after myocardial infarction.

Circulating neutrophils isolated from patients 3-4 h after a myocardial infarction produced less O2-. compared with controls, when stimulated with phorbol myristate acetate or formyl-methionine-leucine-phenylalanine. Three days after the infarction the O2-. generation elicited by both stimuli further decreased markedly. Seven and 15 days after infarction the O2-. stimulated production was only slightly lower than or similar to the control values. The neutrophils of infarcted patients showed an augmented latency period before O2-. production compared with controls in response to exogenous stimuli, particularly three days after infarction. Electron microscopy revealed that the neutrophils isolated from the infarcted patients displayed signs of cell exhaustion with few alterations of the plasma membranes when stimulated with phorbol ester. In contrast, control neutrophils displayed alterations of the plasma membranes characteristic of active neutrophils. The results of this study indicate that the circulating neutrophils appear exhausted and functionally inhibited immediately after myocardial infarction.

Multiplane transoesophageal echocardiography and morphology of regurgitant mitral valves in surgical repair.

BACKGROUND: An essential step in the surgical management of patients with mitral regurgitation, is a thorough understanding of the pathophysiological mechanism. This information can be obtained by multiplane transoesophageal echocardiography which displays all the components of the incompetent valve. METHODS AND RESULTS: Forty-nine patients were scanned intra-operatively by multiplane transoesophageal echocardiography, and findings compared with those at visual inspection during surgery. The pre-operative diagnosis was prolapse of the anterior mitral leaflet in nine patients (sensitivity 100%, specificity 95%), prolapse of the posterior leaflet in 17 patients (sensitivity 100%, specificity 94%) and prolapse of both leaflets in eight patients (sensitivity 87%, specificity 100%). In 11 patients annular dilatation with no abnormalities in mitral leaflet closure or motion was diagnosed (sensitivity 73%, specificity 100%). Two patients had a false-positive diagnosis of prolapse of the anterior leaflet, two others on the posterior leaflet. A prolapse of both leaflets was overlooked in one patient. Multiplane transoesophageal echocardiography scanned the mitral valve, disclosing the extent of pathology along the closure line of leaflets in 88% of patients with mitral valve prolapse. The antero-posterior diameter of the mitral annulus was measured: a diameter over 35 mm indicated annular dilatation. Using this criterion, sensitivity was 89% and specificity 100%. CONCLUSIONS: Multiplane transoesophageal echocardiography enabled components of the mitral valve to be examined systematically, and provided important information on the pathophysiological mechanism of mitral regurgitation before surgical repair. The method also allowed the surgical outcome to be assessed, offering the possibility of optimal repair.

Effect of enoximone alone and in combination with metoprolol on myocardial function and energetics in severe congestive heart failure: improvement in hemodynamic and metabolic profile.

The hemodynamic and myocardial metabolic effects of enoximone (phosphodiesterase III inhibitor), alone or in combination with metoprolol (beta-adrenergic blocker), were studied in patients with congestive heart failure. Ten patients (New York Heart Association Class III-IV) underwent right heart and coronary sinus catheterization, and parameters were assessed at basal condition, at peak enoximone response (mean intravenous loading dose = 2.2 mg/kg), and after the combination with metoprolol (mean intravenous dose = 8.5 mg). Heart rate tended to increase during enoximone administration (from 102 +/- 16 to 107 +/- 16 min-1, ns) and was reduced during enoximone plus metoprolol (to 88 +/- 15 min-1, p < 0.05 vs. basal). Cardiac index was increased during enoximone (from 2.2 +/- 0.2 to 3.8 +/- 0.5 1/min/m2, p < 0.05) and decreased during enoximone plus metoprolol (to 2.8 +/- 0.5 1/min/m2, p < 0.05 vs. enoximone). Mean pulmonary wedge pressure fell during enoximone and remained reduced during enoximone plus metoprolol (from 27 +/- 9 to 9 +/- 3 and to 13 +/- 4 mmHg, respectively, both p < 0.05). Myocardial oxygen consumption did not change during enoximone (from 27 +/- 8 to 25 +/- 13 ml/min, ns) and was reduced during enoximone plus metoprolol (to 19 +/- 8 ml/min, p < 0.05 vs. basal). Myocardial lactate extraction tended to be lower during enoximone and during enoximone plus metoprolol conditions (from 38 +/- 17% to 26 +/- 20% and to 29 +/- 24%, respectively), but no statistical significance was found. Myocardial efficiency was increased during enoximone and during enoximone plus metoprolol (from 9 +/- 3% to 15 +/- 6% and to 14 +/- 6%, respectively, both p < 0.05). Thus in patients with congestive heart failure enoximone improves hemodynamics and, in most cases, it does not influence energetics. The addition of metoprolol to enoximone reduces heart rate, cardiac index, and myocardial oxygen consumption without any other major changes, producing a more physiologic hemodynamic and metabolic profile.