Role of circulating endothelial progenitor cells in the reparative mechanisms of stable ischemic myocardium.

BACKGROUND: Mobilization of endothelial progenitor cells (EPCs) into circulation from bone marrow in patients with acute myocardial infarction has strong scientific evidence; less is known about EPC mobilization in patients with stable coronary artery disease (CAD). The aim of this study was to investigate the association of stable ischemic heart disease with EPC levels in tissue and blood. METHODS: Fifty-five consecutive patients admitted to a single treatment center for valve or coronary artery bypass grafting (CABG) surgeries were included in the study. Blood samples were collected in the morning before surgery and analyzed by flow-cytometry to determine peripheral EPC levels (EPC/ml). Tissue EPC (CD34+VEGFR2+) levels were assessed on a right atrial appendage segment. RESULTS: Mean age was 76±5years, 48% were men, and 53% had CAD The number of CD34+ VEGFR2+ cells in the tissue of patients with CAD was significantly higher (p<0.005) and circulating EPC showed a tendency to be reduced by approximately 20% in peripheral blood of patients with CAD when compared to those without CAD. CONCLUSION: Patients with stable CAD had higher EPC density values (EPC/mm2) and were more likely to have lower EPC blood levels when compare with normal controls.

The effects of acute passive smoke exposure on endothelium-dependent brachial artery dilation in healthy individuals.

Passive smoking has both short-term and long-term vascular effects. It is not clear whether impairment of endothelial function reflects the acute effects of passive smoke exposure or the chronic effects. The purpose of this study was to assess the hypothesis that short-term exposure to passive smoke impairs endothelium-dependent vasodilation in healthy nonsmokers. Eighteen healthy young never smokers (12 men, 6 women) 21 to 55 years old (mean +/- SD: 34 +/-9 years) underwent ultrasonography measuring baseline brachial-artery diameter and brachial-artery diameter during hyperemia and after sublingual administration of nitroglycerin, twice: in a smoke-free environment, and then in the same environment polluted by 30 to 35 ppm carbon monoxide. Each subject served as his/her control. Carboxyhemoglobin was measured in blood samples of subjects tested. Mean value of carboxyhemoglobin was 0.6 +/-0.5% in a smoke-free environment and 1.4 +/- 0.5% in a smoking environment (p <0.02). Mean values of flow-mediated dilation (FMD) were 12.6% +/- 7.8% in a smoke-free environment versus 6.8 +/- 7.8% in a smoking environment (p <0.01). On the contrary, nitroglycerin-induced vasodilation did not show any statistical difference (21 +/- 9.8% versus 23 +/-1.4%). Finally, the increase of carboxyhemoglobin was related statistically to the impairment of flow-mediated dilation (r = 0.51; p <0.002). Passive smoking impaired flow-mediated vasodilation in healthy never smokers in a smoking environment. The impairment was strongly related to carboxyhemoglobin level.

An in vitro study on the free radical scavenging capacity of ergothioneine: comparison with reduced glutathione, uric acid and trolox.

BACKGROUND: Treatment of oxidative stress-related pathologies is a possible therapeutical strategy for the future. Natural product with antioxidant properties could trigger this goal. The aim of this in vitro study was to assess the antioxidant activity of the natural product ergothioneine (EGT), a compound of plant origin, which is assimilated and conserved by mammals in erythrocytes, kidney, seminal fluid and liver. METHODS: We measured the antioxidant activity of EGT as its ability to antagonize the oxidation of alpha-keto-gamma-methiolbutyric acid (KMBA) by hydroxyl radical, peroxyl radicals and peroxynitrite. The results are expressed as total oxyradical scavenging capacity (TOSC) units. Glutathione (GSH), uric acid and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox), the water-soluble analog of vitamin E, were used as the reference antioxidants. RESULTS: EGT was the most active scavenger of free radicals as compared to classic antioxidants as GSH, uric acid and trolox. In particular, the highest antioxidant capacity exhibited by EGT vs. peroxyl radicals (5.53 +/- 1.27 units) resulted 25% higher than the value obtained with the reference antioxidant trolox (4.4 +/- 0.6 units, P < 0.01). The scavenging capacity of EGT towards hydroxyl radicals (0.34 +/- 0.09 units) was 60% higher, as compared to uric acid (0.21 +/- 0.04 units, P < 0.001), which represent the reference antioxidant vs. hydroxyl radicals. Finally, EGT showed the highest antioxidant activity also towards peroxynitrite (5.2 +/- 1.0 units), with a scavenging capacity 10% higher than that of uric acid (4.7 +/- 0.9 units, P < 0.05). CONCLUSIONS: This study showed that EGT has potent intrinsic anti-hydroxyl, anti-peroxyl and anti-peroxynitrite radicals antioxidant activity, as compared to classic molecules with antioxidant capacity as GSH, trolox and uric acid. This appears of interest, given the increasing use of non-vitamins cocktails for therapeutical approaches to many oxidative-induced pathologies.

Is transcutaneous oxygen and carbon dioxide monitoring indispensable in short- and long-term therapeutic management of non-reconstructable lower critical limb ischemia?

AIM: The aim of this study was to evaluate the capacity of transcutaneous partial pressure of O(2) (TCpO(2)) and CO(2) (TCpCO(2)) to predict clinical response to pharmacological treatment in short- and long-term follow-up of unreconstructable critical limb ischemia (CLI) treated with prostanoids; to suggest a diagnostic and therapeutic algorithm able to define the possibility of prostanoid therapy in unreconstructable CLI at high risk of limb loss. METHODS: Twenty-six consecutive patients with CLI (21 with distal trophic lesions, 31 symptomatic limbs) considered unreconstructable after peripheral angiography and with a history of type 2 diabetes mellitus underwent daily parenteral Iloprost treatment for 2-3 weeks. RESULTS: Transcutaneous gas-analytic monitoring (TGM) in non-reconstructable CLI treated with Iloprost divided patients into 2 groups: early responders (ER) with increased TcpO(2) and normalization of TcpCO2, and non responders (NR) with unchanged TcpO(2) and TcpCO(2) parameters. In the NR who underwent a second cycle of Iloprost within a few months of the first, TGM further divided the patients into another subgroup of late responders (LR) with TcpO(2) and TcpCO(2) similar to the ER group and a subgroup of NR, who, after pharmacological treatment failure, should undergo eventual surgical re-timing and/or spinal cord stimulation in a final attempt to save the limb. CONCLUSIONS: In the short-term follow-up of CLI, a marked reduction in supine/dependent TcpO(2) and a marked increase in supine TcpCO(2) at the symptomatic forefoot proved to be significant predictors of major amputation risk. In the long-term follow-up period, TGM showed that, in ER and in LR, the favourable effect of pharmacological therapy observed in the first 6 months will disappear over the next 6 months, suggesting an algorithm of 2- to 3-week cycles of prostanoid therapy repeated every year. In NR treated with surgical and/or alternative therapies who did not undergo major amputations, prolonged instrumental TGM will provide a constant evaluation of metabolic parameters, thus providing the possibility to save the limb with additional pharmacological therapy.

Quantitative evaluation of the regional left ventricular function in normal subjects by means of cineangiocardiography.

A method for analysing left ventricular cineangiograms is described, which not only provides information on the overall ventricular performance, but also evaluates the regional contraction of the left ventricle and the related haemodynamic patterns. This simplified Chapman's method (slice method) makes it possible to calculate the end-diastolic, end-systolic volumes, the stroke volume and the ejection fraction of the zones into which the left ventricle is divided by a longitudinal and by three transverse axes, according to Herman's technique. The hemiventriculograms of 21 normal subjects in the AP projection were evaluated using this method and a 10 of them were also studied in RAO projection. A uniform left ventricular contraction pattern was found for three hemiventricles outlined by the anterolateral, lateral, and postero-medial walls (ejection fraction 71.7 +/- 5.1%, 71.6 +/- 5.9%, 70.4 +/- 5.1%, respectively), the regional and zonal ejection fraction (EFR, EFZ) being similar in both projections. The ejection fraction of the hemiventricle outlined by the septal wall was, however, lower (65.6 +/- 6.0%). The standard zonal function curves of the left ventricle in normal subjects was then calculated on the basis of the results obtained, in order to assess, by comparison, zonal function abnormalities in cardiac patients.

Endothelin-1 release from atherosclerotic plaque after percutaneous transluminal coronary angioplasty in stable angina pectoris and single-vessel coronary artery disease.

To assess the effects of percutaneous transluminal coronary angioplasty on endothelin-1 (ET-1) release, we assessed ET-1 concentrations at different sites of the coronary circulation in patients submitted to elective procedures. ET-1 levels immediately downstream from the plaque and ET-1 aortocoronary gradient increased significantly after the procedure, which was related to mechanical wall stress in patients only receiving balloons, but not in those undergoing stent percutaneous transluminal coronary angioplasty. No changes were found in the coronary sinus; these results suggest ET-1 release from the plaque rather than an ischemia/reperfusion-related production from the distal myocardium.

Thrombolytic therapy in peripheral arterial disease.

The two main causes of peripheral arterial occlusion (PAO) are embolism and thrombosis. Surgical treatment of acute limb ischemia, because of related complications, has a 30-day mortality rate of 15% to 25%. Intra-arterial thrombolysis for lower extremity ischemia is a well-accepted and frequently used technique. It may offer definitive treatment without the need for major surgery in a significant series of patients with acute occlusion of a native leg artery or a by-pass graft. Thrombolysis can offer several potential advantages when compared with surgical therapy. Thrombolytic agents include streptokinase (SK), urokinase (UK), pro-UK and recombinant tissue plasminogen activators (rt-PA-Alteplase and r-PA-Reteplase). All these agents induce a systemic fibrinolytic state. Three prospective randomized trials, ROCHESTER, STILE, and TOPAS, which compared thrombolytic therapy with traditional surgical revascularization for lower limb ischemia, have recently been published. They suggest that thrombolysis, as an initial therapy, reduces the risk of subsequent surgery and improves limb salvage for patients with PAO. Using this approach, the underlying lesions can be identified and treated by transluminal balloon angioplasty or stenting, or by elective surgical revascularization. However, severe bleeding is still a non rare complication of intra-arterial thrombolysis and the risk of intracranial hemorrhage is 1-2%.

Dissociation between microalbuminuria and common carotid thickness in essential hypertensive men.

BACKGROUND: The reasons why microalbuminuria (albuminuria > or = 15 microg/min), an expression of a renal microcirculatory abnormality, predicts cardiovascular disease in essential hypertension are unsettled. To test the hypothesis that microalbuminuria represents a marker of subclinical atherosclerosis, we evaluated its association with common carotid artery (CCA) intima media thickness (IMT), a measure of preclinical atherosclerosis and an independent predictor of cardiac and cerebrovascular events, in uncomplicated essential hypertensive individuals. MATERIALS AND METHODS: Albuminuria, ultrasonographic CCA IMT (the mean of six bilateral far wall measurements within 1.5 cm proximally to the flow divider), brachial blood pressure (BP), smoking habits and lipids were evaluated in 136 stage 1-3 untreated essential hypertensive men free of cardiovascular disease. RESULTS: CCA IMT did not differ between normo- (n = 99) and microalbuminuric (n = 37) patients. The correlation between CCA IMT and albuminuria was not significant, and the prevalence of microalbuminuria across IMT quartiles was not different. Microalbuminuric patients showed higher systolic BP and that parameter was the only independent correlate in a multivariate logistic regression model including also age, CCA IMT, diastolic BP, lipids and smoking habits as independent variables and microalbuminuria as the dependent one. CONCLUSION: This cross-sectional study in hypertensive subjects free of cardiovascular disease has shown a dissociation between microalbuminuria and CCA IMT, a surrogate measure of subclinical atherosclerosis, and a parameter linearly related to cardiovascular events. The data do not support the theory of microalbuminuria as a surrogate measure of subclinical atherosclerosis, while confirming the importance of systolic BP levels as an independent correlate of increased albuminuria in essential hypertension. Journal of Human Hypertension (2000) 14, 831-835

Left ventricular aneurysm: clinical and hemodynamic data.

Clinical and hemodynamic data of 30 patients with left ventricular aneurysm (27 men, 3 women, mean age 54.9 years) were compared with those of 30 patients with previous myocardial infarction and segmental hypo- or akinesis (28 men, 2 women, mean age 51 years). In each group, 10 patients were affected by one-, two-, or three-vessel disease. A semiquantitative evaluation of collateral coronary circulation showed no significant differences between the two groups. Mean end-diastolic volume was higher in patients with left ventricular aneurysm (p less than .025, less than .05, and less than .001 in 1-, 2-, and 3-vessel disease, respectively) and ejection fraction was lower only in patients with one-, (p less than .001) and two- (p less than .05) vessel disease in comparison with patients without left ventricular aneurysm. No significant difference was evidenced in basal or isometric exercise end-diastolic pressure. The incidence of thrombosis detected by ventriculography was higher in patients with left ventricular aneurysm (33.3 vs. 6.6%). The mean duration of follow-up was 20.7 months in patients with left ventricular aneurysm and 20.6 in the control group. No significant difference was found either in mortality or in reinfarction rate as far as incidence and severity of angina. The incidence of congestive heart failure was more evident, but not significant in patients with left ventricular aneurysm. One embolic episode was present in one patient with aneurysm and intraventricular thrombosis. Left ventricular performance is influenced by an aneurysm when a limited coronary compromise is present (one- and two-vessel disease) while it is not affected in the case of a coexisting three-vessel disease.

Asynergy and left ventricular performance in dilative cardiomyopathy.

The purpose of this work was to evaluate the presence and importance of asynergy in dilative cardiomyopathy. A semiautomatized analysis of left ventriculograms was performed in 18 cases, the morphology of longitudinal and transverse axes time-length curves was evaluated, and mathematical indices of asynchrony and hypokinesis were defined. Ten normal subjects and 9 patients affected by aortic regurgitation were used as controls. In dilative cardiomyopathy, anomalous (polyphasic) time-length curves were present in 55% of the cases, while they were absent in aortic regurgitation and in all normal subjects but one. In addition, the asynchrony index was slightly increased and the hypokinesis index significantly increased (28.8 +/- 7.2% vs. 17.8 +/- 7.1%, p less than 0.001). A negative correlation existed between the asynchrony index and the ejection fraction (r = -0.483, p less than 0.05) and both the ejection fraction and the maximum normalized velocity of contraction were reduced in the patients with the anomalous curves (29.7 +/- 6.9% vs. 46.0 +/- 11.5%, p less than 0.01; 1.66 +/- 0.52 s-1 vs. 2.86 +/- 1.33 s-1, p less than 0.02). It was concluded that asynergy, and especially asynchrony, is frequent in dilative cardiomyopathy and it is strongly associated with a major impairment of overall left ventricular function.

Evaluation of pulmonary vascular pressures in cardiac patients: the role of the chest roentgenogram.

In 77 patients (34 with left heart valvulopathy, 17 with dilated cardiomyopathy, and 26 with chronic coronary artery disease) pulmonary vascular pressures were estimated from the chest film by means of a new scoring system. Standard chest x-ray films taken immediately before diagnostic right and left cardiac catheterization were analyzed independently by three readers without knowledge of the hemodynamic findings. The radiographic signs were subdivided into three groups as follows, and to each one a score derived from a retrospective statistical analysis was attributed: (A) signs of interstitial edema, (B) patterns of pulmonary blood flow distribution, and (C) alterations in the pulmonary arteries. The sum of the scores of groups A and B x-ray findings correlated well with pulmonary wedge pressure, and the sum of the scores of groups A, B, and C correlated more strongly with the mean pulmonary artery pressure. These results confirm that it is possible, in patients with chronic heart disease, to assess accurately the pulmonary artery and wedge pressures by means of the noninvasive and easily performed chest roentgenogram.

Echocardiographic and surgical findings of a ball-like thrombus floating freely in the left atrium.

The M-Mode, two-dimensional echocardiographic and surgical findings of a ball-like thrombus floating freely in the left atrium are described in a patient with mitral stenosis. These echocardiographic features are so impressive that further diagnostic procedures are not required for operation.

Platelet aggregation behaviour in patients treated with ticlopidine.

Thirty patients (18 women, 12 men) with permanent or paroxysmal atrial fibrillation were treated with a new antiplatelet drug, ticlopidine, in order to study platelet aggregation behaviour, to see whether the drug prevents thromboembolisms and to observe side-effects over a period of 6 months. A further comparative study of the effects of ticlopidine and dipyridamole + aspirin on platelet aggregation was carried out in 20 patients. All appropriate haematological parameters were tested every 3 months, while platelet aggregation curves with ADP were examined also after 15 days. At the end of the period an echocardiogram was performed to check for any sign of thrombosis. The reduction in the aggregation curves was statistically significant for all the ADP stimuli, except at low doses. In the comparison with dipyridamole + aspirin, ticlopidine gave better results; with the former there was no significant reduction in platelet aggregation. A more significant reduction was seen in patients who had showed hyperaggregation at the outset. Bleeding time was increased and platelet adhesivity was reduced. During the 6-month period a slight reduction in white blood cells and a slight increase in creatinine were observed, both remaining within the normal range. Some 33.3% of the patients experienced side-effects. No embolic event or thrombosis in the left atrium was seen. Ticlopidine seems to be an effective antiplatelet drug, especially for patients with hyperaggregation.

Usefulness of carotid intima-media thickness measurement and peripheral B-mode ultrasound scan in the clinical screening of patients with coronary artery disease.

Previous observational studies have shown a relationship between carotid intima-media thickness (IMT) and coronary artery disease (CAD). In this study the authors evaluated the accuracy of the common carotid IMT measurement in predicting the presence and severity of CAD and the additional information offered by the detection of carotid, iliac, and lower limb plaques. One hundred and fifty consecutive patients were subjected to coronary angiography and carotid, iliac, and lower limb ultrasound scan. The mean value of six IMT measurements of the far wall of the common carotid artery was calculated in each patient. The mean IMT was significantly correlated to the number of stenosed coronary vessels (r = 0.43, p<0.001), although the positive and negative predictive value of mean IMT in identifying patients with CAD was low (81% and 46%, respectively). The combined information offered by IMT measurements and peripheral (carotid, iliac, and lower limb) plaque detection was then used to obtain the best multivariate regression model able to predict CAD status. The multivariate model showed a highly significant multiple correlation coefficient (r = 0.60, p<0.0001) and a sharp improvement in the negative predictive value (92%) with respect to the univariable model. B-mode ultrasound scan including common carotid IMT measurement and peripheral plaque detection may be of clinical value in the screening of patients with CAD.

Surgical angioplasty for isolated coronary ostial stenosis.

Patch angioplasty has been reported as a suitable surgical option for patients with isolated coronary ostial stenosis, but controversy still exists concerning its effectiveness. We report the cases of 4 additional patients in whom this procedure was performed, including that of a patient with bilateral ostial stenosis; and we review the literature pertaining to bilateral ostial stenosis. Four patients, 3 with isolated stenosis of the left main coronary ostium and 1 with bilateral ostial stenosis, had direct surgical ostioplasty from January through November 1994. We considered the cause of ostial stenosis to be aortitis (of suspected syphilitic origin) in 1 patient, atherosclerotic plaque in 2 patients, and a fibrous membrane in the 4th. Ostioplasty was performed with a patch of autologous pericardium in 3 patients (fresh pericardium in 2 and glutaraldehyde-fixed in 1) and a patch of saphenous vein in 1. There were no operative deaths. One patient underwent successful reoperation for left main coronary artery restenosis after 3 months. All other patients are asymptomatic at 16, 18, and 24 months postoperatively. In the patient who underwent bilateral ostioplasty, coronary angiography showed patent ostia at 1 year. Surgical ostioplasty should be considered in the treatment of patients who have isolated ostial stenosis but no distal coronary disease. Careful patient selection seems to be a prerequisite for surgical success.

Post-traumatic tricuspid valve insufficiency. 2 cases of delayed clinical manifestation.

We present 2 cases of tricuspid insufficiency following blunt chest trauma: 1 was diagnosed 5 months after the trauma and the other, 20 years after the trauma. In both patients, the tricuspid valve was replaced with a porcine bioprosthesis, because valve repair was not considered feasible. These cases emphasize the variability of clinical presentation of post-traumatic tricuspid valve insufficiency and indicate the need for close follow-up of patients after major thoracic trauma.

Late patency of recycled internal mammary artery: verification by Doppler echocardiography and coronary angiography.

We report the case of a 57-year-old man who had presented with exertional angina early in 1997 and had subsequently undergone myocardial revascularization with the use of both internal mammary arteries. Two months after surgery, the patient was readmitted to the hospital with unstable angina. Coronary angiography revealed a 90% occlusion of the left internal mammary artery anastomosis, which was attached to the left anterior descending coronary artery. At reoperation, the left internal mammary artery was detached from the left anterior descending coronary artery, probed and injected with papaverine, checked for patency, and regrafted to the same coronary artery. Recycling of the left internal mammary artery was facilitated by the harvesting and routing technique that had been used during the previous operation. At the patient's 1-year follow-up visit, both Doppler echocardiography and coronary angiography showed patency of the recycled graft. We conclude that recycling of the left internal mammary artery is a safe and effective option in selected patients who require reoperation after myocardial revascularization.

Frequency and clinical correlates of bipolar features in acute coronary syndrome patients.

BACKGROUND: Depression and acute coronary syndrome (ACS) are both extremely prevalent diseases. Studies aimed at evaluating whether depression is an independent risk factor for cardiac events provided no definitive results. In most of these studies, depression has been broadly defined with no differentiation between unipolar (MDD) versus bipolar forms (BD). The aim of this study was to evaluate the frequency of DSM-IV BD (bipolar I and bipolar II subtypes, cyclothymia), as well as temperamental or isolated bipolar features in a sample of 171 patients hospitalized for ACS. We also explored whether these psychopathological conditions were associated with some clinical characteristics of ACS. METHODS: Patients with ACS admitted to three neighboring Cardiac Intensive Care Units (CICUs) in a 12-month continuative period of time were eligible for inclusion if they met the criteria for either acute myocardial infarct with or without ST-segment elevation or unstable angina, verified by standard ACS criteria. All patients underwent standardized cardiological and psychopathological evaluations. RESULTS: Of the 171 ACS patients enrolled, 37 patients (21.7%) were found to have a DSM-IV mood disorder. Of these, 20 (11.7%) had bipolar type I or type II or cyclothymia, while 17 (10%) were the cases of MDD. Rapid mood switches ranged from 11% of ACS patients with no mood disorders, to 47% of those with MDD to 55% of those with BD. Linear regression analysis showed that a diagnosis of BD (p=.023), but not that of MDD (p=.721), was associated with a significant younger age at the index episode of ACS. A history of previous coronary events was more frequent in ACS patients with BD than in those with MDD. CONCLUSIONS: Our data indicate that bipolar features and diagnosis are frequent in ACS patients. Bipolar disorder has a negative impact on cardiac symptomatology. Further research in this area is warranted.