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Biomedical subjects

Jordi Soler-Soler

Publications and source records attributed to Jordi Soler-Soler.

At least 37 records · Page 2Linked to original sources
PubMed2005

Thrombin increases cardiomyocyte acute cell death after ischemia and reperfusion.

Thrombin exerts multiple actions on cardiomyocytes leading to increased intracellular Na+ and Ca2+ concentrations, and to activation of a Ca2+-independent PLA2, and has been proposed to favor the genesis of arrhythmias and ischemic injury in acute coronary syndromes. However, the influence of thrombin on cardiomyocyte cell death during ischemia-reperfusion has not been studied. A beneficial influence of low thrombin concentrations has been described in other cell types. HL-1 cardiomyocytes were subjected to simulated ischemia (SI) and reperfusion (SR) and cell death was assessed by means of LDH release to the incubation media. Thrombin dose-dependently increased cell death in normoxic cells, in cells subjected to SI, and in cells subjected to SR (by 20+/-8%, 95+/-32% and 35+/-9%, respectively, at 100 U/ml). The effects of thrombin were associated to increased cytosolic Ca2+ overload, mimicked by 100 microM PAR-1 agonist peptide SFLLRNPNDKYEPF, and reversed by the direct thrombin inhibitor lepirudin (IC50=1.3+/-0.2 microg/ml). The presence of thrombin during simulated ischemia-reperfusion increases cardiomyocyte cell death by a mechanism that involves activation of PAR-1 receptors and can be prevented by the direct thrombin inhibitor lepirudin.

Animals↗
PubMed2004

Acute cardiogenic pulmonary edema--relevance of multivessel disease, conduction abnormalities and silent ischemia.

The frequency distribution and severity of the cardiac disease underlying acute cardiogenic pulmonary edema (APE) to define appropriate subsequent diagnostic and management strategies were investigated in 216 consecutive patients. To this effect, the clinical, electrocardiographic, ecocardiographic and angiographic characteristics were analyzed. Coronary artery disease was identified in 185 patients (86%)-146 with acute myocardial infarction-as the underlying cause, isolated valvular disease in 10 (5%) and other causes in 21 (11%). Most patients were elderly (> or =70 years, 72%), hypertensive (71%) and diabetic (44%). Among coronary disease (CAD) patients, however, 105 (57%) showed conduction disturbances in the ECG (QRS>0.10 s) and 84 (45%) had no anginal pain during pulmonary edema. A 2D echocardiogram showed a 30% incidence of moderate-severe mitral regurgitation in coronary disease and non-coronary disease patients, and a 67% incidence of reduced ejection fraction (<50%), particularly in coronary disease patients (73%). A coronary angiography performed in 99 patients with coronary disease showed multivessel disease in 89 (91%) with a 32% incidence of significant left main disease. Therefore, these findings demonstrate that coronary disease is the most common cause of acute pulmonary edema and it is associated with a distinctly high prevalence of multivessel and left main disease. This diagnosis, however, may often be overlooked if no serial enzymatic sampling is performed given the increased frequency of conduction abnormalities and lack of anginal pain.

Acute Disease↗
PubMed2004

Effect of sarcolemmal rupture on myocardial electrical impedance during oxygen deprivation.

Plasma membrane disruption is a characteristic feature of cell death induced by hypoxia or ischemia. Here, we investigated whether analysis of tissue electrical impedance allows detection of ongoing cell membrane rupture and necrotic cell death in hypoxic or ischemic myocardium. Twenty-eight isolated rat hearts were submitted to 5 h of ischemia (n = 8) or hypoxia (n = 20). Myocardial electrical impedance and lactate dehydrogenase (LDH) release were monitored. The time course of hypoxia-induced cell death was modified by altering pH (pH 7.4 or 6.4, 5 h) or by adding 3 or 10 mM glycine. Ischemia and hypoxia induced an increase in electrical impedance, followed by a plateau, and later a reduction. During hypoxia, LDH release started after a prolonged lapse of time (80.00 +/- 8.37 min at pH 7.4 and 122.50 +/- 11.82 min at pH 6.4). The onset of LDH release was followed by the onset of the late reduction in electrical impedance, and both were delayed by acidic pH (P < 0.05) and by glycine (P < 0.05). The times of onset of LDH release and of late electrical changes were significantly correlated (r = 0.752, P < 0.001). In separate experiments, induction of sarcolemmal rupture with Triton X-100 (n = 6) mimicked the late effects of ischemia or hypoxia on tissue impedance. The protective effects of glycine and acidosis on membrane disruption were confirmed (propidium iodide) in energy-deprived HL-1 cardiomyocytes. These results describe for the first time a late fall in electrical impedance in myocardium submitted to prolonged oxygen deprivation and demonstrate that this fall allows detection of ongoing cell necrosis.

Acids↗
PubMed2004

Ischemic preconditioning attenuates calpain-mediated degradation of structural proteins through a protein kinase A-dependent mechanism.

OBJECTIVES: It has been shown that sarcolemmal rupture can occur during reenergization in cardiomyocytes in which previous ischemia has induced sarcolemmal fragility by calpain-dependent hydrolysis of structural proteins. We tested the hypothesis that attenuated calpain activation contributes to the protection against reperfusion-induced cell death afforded by ischemic preconditioning (IPC), and investigated the involvement of protein kinase A (PKA) in this effect. METHODS: Calpain activity and degradation of different structural proteins were studied along with the extent of necrosis in isolated rat hearts submitted to 60 min of ischemia and 30 min of reperfusion with or without previous IPC (two cycles of 5 min ischemia-5 min reperfusion), and the ability of different treatments to mimic or blunt the effects of IPC were analyzed. RESULTS: IPC accelerated ATP depletion and rigor onset during ischemia but reduced LDH release during reperfusion by 69% (P<0.001). At the end off reperfusion, calpain activity was reduced by 66% (P<0.001) in IPC, and calpain-dependent degradation of sarcolemmal proteins was attenuated. Addition of the calpain inhibitor MDL-28170 mimicked the effects of IPC on protein degradation and reduced LDH release by 48% (P<0.001). The effects of IPC on calpain, alpha-fodrin, and LDH release were blunted by the application of the PKA inhibitor H89 or alprenolol during IPC, while transient stimulation of PKA with CPT-cAMP or isoproterenol before ischemia attenuated calpain activation, alpha-fodrin degradation, and markedly reduced LDH release (P<0.001). In hearts exposed to Na(+)-free perfusion, IPC attenuated calpain activation by 67% (P<0.001) and reduced by 56% (P<0.001) LDH release associated to massive edema occurring during Na(+) readmission without modifying its magnitude. CONCLUSION: These results are consistent with PKA-dependent attenuation of calpain-mediated degradation of structural proteins being an end-effector mechanism of the protection afforded by IPC.

Adrenergic beta-Antagonists↗
PubMed2004

Enhanced effect of gap junction uncouplers on macroscopic electrical properties of reperfused myocardium.

Transient inhibition of gap junction (GJ)-mediated communication with heptanol during myocardial reperfusion limits infarct size. However, inhibition of cell coupling in normal myocardium may be arrhythmogenic. The purpose of this study was to test the hypothesis that the consequences of GJ inhibition may be magnified in reperfused myocardium compared with normal tissue, thus allowing the inhibition of GJs in reperfused tissue while only minimally modifying overall macroscopic cell coupling in normal myocardium. Concentration-response curves were defined for the effects of heptanol, 18alpha-glycyrrhetinic acid, halothane, and palmitoleic acid on conduction velocity, tissue electrical impedance, developed tension and lactate dehydrogenase (LDH) release in normoxically perfused rat hearts (n= 17). Concentrations lacking significant effects on tissue impedance were added during the initial 15 min of reperfusion in hearts submitted to 60 min (n= 43) or 30 min (n= 35) of ischaemia. These concentrations markedly increased myocardial electrical impedance (resistivity and phase angle) in myocardium reperfused after either 30 or 60 min of ischaemia, and reduced reperfusion-induced LDH release after 1 h of ischaemia by 83.6, 57.9, 51.7 and 52.5% for heptanol, 18alpha-glycyrrhetinic acid, halothane and palmitoleic acid, respectively. LDH release was minimal in hearts submitted to 30 min of ischaemia, independently of group allocation. In conclusion, the present results strongly support the hypothesis that intercellular communication in postischaemic myocardium may be effectively reduced by concentrations of GJ inhibitors affecting only minimally overall electrical impedance in normal myocardium. Reduction of cell coupling during initial reperfusion was consistently associated with attenuated lethal reperfusion injury.

Action Potentials↗
PubMed2004

Glycine protects cardiomyocytes against lethal reoxygenation injury by inhibiting mitochondrial permeability transition.

Post-ischaemic reperfusion may precipitate cardiomyocyte death upon correction of intracellular acidosis due in part to mitochondrial permeability transition. We investigated whether glycine, an amino acid with poorly understood cytoprotective properties, may interfere with this mechanism. In cardiomyocyte cultures, addition of glycine during re-energization following 1 h of simulated ischaemia (NaCN/2-deoxyglucose, pH 6.4) completely prevented necrotic cell death associated with pH normalization. Glycine also protected against cell death associated with pH normalization in reoxygenated rat hearts. Glycine prevented cyclosporin-sensitive swelling and calcein release associated with re-energization in rat heart mitochondria submitted to simulated ischaemia or to Ca(2+) stress under normoxia. NMR spectroscopy revealed a marked glycine depletion in re-energized cardiomyocytes that was reversed by exposure to 3 mm glycine. These results suggest that intracellular glycine exerts a previously unrecognized inhibition on mitochondrial permeability transition in cardiac myocytes, and that intracellular glycine depletion during myocardial hypoxia/reoxygenation makes the cell more vulnerable to necrotic death.

Animals↗
PubMed2004

Effusive-constrictive pericarditis.

BACKGROUND: Effusive-constrictive pericarditis is an uncommon pericardial syndrome characterized by concomitant tamponade, caused by tense pericardial effusion, and constriction, caused by the visceral pericardium. We conducted a prospective study of its clinical evolution and management. METHODS: From 1986 through 2001, all patients with effusive-constrictive pericarditis were prospectively evaluated. Combined pericardiocentesis and cardiac catheterization were performed in all patients, and pericardiectomy was performed in those with persistent constriction. Follow-up ranged from 1 month to 15 years (median, 7 years). RESULTS: A total of 1184 patients with pericarditis were evaluated, 218 of whom had tamponade. Of these 218, 190 underwent combined pericardiocentesis and catheterization. Fifteen of these patients had effusive-constrictive pericarditis and were included in the study. All patients presented with clinical tamponade; however, concomitant constriction was recognized in only seven patients. At catheterization, all patients had elevated intrapericardial pressure (median, 12 mm Hg; interquartile range, 7 to 18) and elevated right atrial and end-diastolic right and left ventricular pressures. After pericardiocentesis, the intrapericardial pressure decreased (median value, -5 mm Hg; interquartile range, -5 to 0), whereas right atrial and end-diastolic right and left ventricular pressures, although slightly reduced, remained elevated, with a dip-plateau morphology. The causes were diverse, and death was mainly related to the underlying disease. Pericardiectomy was required in seven patients, all of whom had involvement of the visceral pericardium. Three patients had spontaneous resolution. CONCLUSIONS: Effusive-constrictive pericarditis is an uncommon pericardial syndrome that may be missed in some patients who present with tamponade. Although evolution to persistent constriction is frequent, idiopathic cases may resolve spontaneously. In our opinion, extensive epicardiectomy is the procedure of choice in patients requiring surgery.

Adolescent↗
PubMed2004

Prognostic value of clinical and morphologic findings in short-term evolution of aortic intramural haematoma. Therapeutic implications.

AIMS: Intramural haematoma (IMH) forms part of the acute aortic syndrome presenting physiopathologic and evolutive patterns different from those of aortic dissection. The aim of this study was to determine the mortality and predictive factors of IMH in the first 3 months of evolution. METHODS AND RESULTS: Sixty-eight consecutive patients diagnosed of IMH (12 type A, 56 type B) were prospectively studied. Ten patients (eight type A, two type B) were surgically treated for clinical or haemodynamic evolution. Mortality rate was 19% (six type A and seven type B): five surgically treated (three type A, two type B) and eight medically treated (three type A, five type B). No relationship was observed between clinical variables and evolution. Maximum aortic diameter was greater in the group of patients who died (65.5+/-14.4 mm vs 46.0+/-7.6 mm; P<0.0001). Mortality rate in patients with aortic diameter >50 mm was 50% (P<0.0001). Significant periaortic bleeding was mortality-related (47%; P<0.005). Multivariate analysis showed only a significant relationship between mortality and maximum aortic diameter >50 mm (OR=11.33; P<0.005) and ascending aorta involvement (OR=11.18; P<0.05). CONCLUSION: Intramural haematoma mortality in the first 3 months of evolution is high (19%). Maximum aortic diameter >50 mm and ascending aorta involvement are predictive of early mortality.

Aged↗
PubMed2004

The prevalence of abnormal glucose regulation in patients with coronary artery disease across Europe. The Euro Heart Survey on diabetes and the heart.

AIM: The objective behind the Euro Heart Survey on diabetes and the heart was to study the prevalence of abnormal glucose regulation in adult patients with coronary artery disease (CAD). METHODS AND RESULTS: The survey engaged 110 centres in 25 countries recruiting 4196 patients referred to a cardiologist due to CAD out of whom 2107 were admitted on an acute basis and 2854 had an elective consultation. Patient data were collected via a web-based case record form. An oral glucose tolerance test (OGTT) was used for the characterisation of the glucose metabolism. Thirty-one per cent of the patients had diabetes. An OGTT was performed on the 1920 patients without known diabetes, of whom 923 had acute and 997 had a stable manifestation of CAD, respectively. In patients with acute CAD, 36% had impaired glucose regulation and 22% newly detected diabetes. In the stable group these proportions were 37% and 14%. CONCLUSION: This survey demonstrates that normal glucose regulation is less common than abnormal glucose regulation in patients with CAD. OGTT easily discloses the glucometabolic state and should be a routine procedure. The knowledge of glucometabolic state among these patients should influence their future management because it has great potential to improve the outcome.

Adult↗
PubMed2004

Tolerability of carvedilol and ACE-Inhibition in mild heart failure. Results of CARMEN (Carvedilol ACE-Inhibitor Remodelling Mild CHF EvaluatioN).

BACKGROUND: Management guidelines for heart failure recommend ACE-I and beta-blockers. The perception of difficult up-titration might have added to the slow uptake of beta-blockers despite their mortality and morbidity benefits. AIMS: CARMEN offered a possibility to study safety and tolerability of enalapril against carvedilol and their combination. METHODS: Five hundred and seventy-two patients were blindly up-titrated on carvedilol (target 25 mg bid) and/or enalapril (target 10 mg bid), and continued for 18 months. In the combination arm, carvedilol was up-titrated before enalapril. RESULTS: There was no group related difference in adverse events during up-titration. Withdrawal rates were 31, 30 and 30%, and serious adverse events 28, 29 and 34% in the combination, carvedilol and enalapril arms. Mortality was similar in all groups (all-cause N=14, 14 and 14; cardiovascular N=9, 13 and 14). All-cause and cardiovascular hospitalizations occurred in 26, 27 and 32%, and in 12, 16 and 22% in the combination, carvedilol and enalapril arms, respectively. CONCLUSION: The safety profile was similar in all treatment arms. In contrast to common perception, there was no difference in tolerability between the ACE-I and carvedilol. This result is even more remarkable as the high prestudy use of ACE-I (65%) might have introduced a bias by selecting ACE-I tolerant patients, who were only switched from their former ACE-I to enalapril.

Adolescent↗
PubMed2004

The benefits of early combination treatment of carvedilol and an ACE-inhibitor in mild heart failure and left ventricular systolic dysfunction. The carvedilol and ACE-inhibitor remodelling mild heart failure evaluation trial (CARMEN).

AIMS: Heart failure (HF) treatment guidelines of the ESC recommend ACE-inhibitors (ACE-I) as first-line treatment and beta-blockers added if patients remain symptomatic. CARMEN explored the need for combined treatment for remodelling and order of introduction by comparing the ACE-I enalapril against carvedilol and their combination. METHODS: In a parallel-group, 3-arm study of 18 months duration, 572 mild heart failure patients were randomly assigned to carvedilol (N = 191), enalapril (N = 190) or their combination (N = 191). In the latter, carvedilol was up-titrated before enalapril. Left ventricular (LV) remodelling was assessed by transthoracic echocardiography (biplane, modified Simpson) at baseline and after 6, 12 and 18 months of maintenance therapy. Primary comparisons considered the change in LV end-systolic volume index (LVESVI) from baseline to month 18 between the combination and enalapril, and between carvedilol and enalapril. RESULTS: In the first primary comparison, LVESVI was reduced by 5.4 ml/m2 (p = 0.0015) in favour of combination therapy compared to enalapril. The second primary comparison tended to favour carvedilol to enalapril (NS). In the within treatment arm analyses, carvedilol significantly reduced LVESVI by 2.8 ml/m2 (p = 0.018) compared to baseline, whereas enalapril did not. LVESVI decreased by 6.3 ml/m2 (p = 0.0001) with combination therapy. All three arms showed similar safety profiles and withdrawal rates. CONCLUSION: CARMEN is the first study to demonstrate that early combination of ACE-I and carvedilol reverses LV remodelling in patients with mild to moderate HF and LV systolic dysfunction. The results of the CARMEN study support a therapeutic strategy in which the institution of beta-blockade should not be delayed.

Adrenergic beta-Antagonists↗
PubMed2004

Regional wall motion and wall thickening visual scores from gated SPECT in anterior and infero-lateral myocardial infarctions.

BACKGROUND: The relationship between the visual scores for wall motion (WM) and wall thickening (WT) of different left ventricular regions in patients with anterior and infero-lateral myocardial infarctions was evaluated using gated SPECT. METHODS: Ninety consecutive patients (79 men and 11 women; mean age 56 +/- 9 years) with previous myocardial infarction (33 anterior and 57 infero-lateral) were included. Left ventricular volumes and ejection fractions (EFs) were calculated from quantitative rest gated SPECT 99mTc tetrofosmin images by using the QGS automatic algorithm. Global and regional (anterior, septal, inferior and lateral) wall motion and wall thickening scores were calculated by consensus of three experienced observers. RESULTS: The correlation between EFs and wall motion and wall thickening scores was better for WM scores in anterior (r=0.904, P<0.0001) than infero-lateral infarctions (r=0.674, P<0.0001). Correlation between wall motion and wall thickening scores was also better for anterior (r=0.898, P<0.0001) than for infero-lateral infarctions (r=0.750, P<0.0001). Except in septal regions, WT scores of the different regions were higher than WM scores (P<0.05) but the statistical significance was higher (P<0.001) in inferior and lateral regions of infero-lateral infarctions. CONCLUSION: Visual global wall motion and wall thickening scores obtained by gated SPECT showed good correlation between them and with the EF, but differences were observed between regional wall motion and wall thickening, especially in inferior and lateral regions of patients with infero-lateral infarctions.

Aged↗
PubMed2004

[Early myocardial perfusion gated-SPECT in patients with chest pain and non-diagnostic ECG in the emergency department].

OBJECTIVE: To analyze the value of early resting myocardial perfusion gated-SPECT in patients with chest pain and non-diagnostic ECG in the emergency department. PATIENTS AND METHOD: 222 patients (49% women, mean age 61 [13] years) with atypical chest pain and with non-diagnostic ECG were randomized into two groups. Group A comprised 111 patients in whom early resting myocardial perfusion gated-SPECT (<6 hours since the end of chest pain) was performed and CK-MB mass and troponin I were determined at 0, 4 and 8 hours. Group B comprised 111 patients with conventional management in the emergency department without gated-SPECT. RESULTS: Myocardial perfusion gated-SPECT was positive in all 8 patients with increased levels of CK-MB mass and troponin I. This corresponded to a sensitivity and a negative predictive value of 100% for the diagnosis of AMI. Specificity was 84% and positive predictive value was 33% when doubtful results were considered as negative. The number of patients admitted (18.4% vs 32.7%, P<.027) and length of stay (13 [6] hours vs 15.9 [8.6] hours, P<.009) in the emergency department were lower in group A. CONCLUSIONS: In patients with atypical chest pain and non-diagnostic ECG in the emergency department, early resting gated-SPECT was highly sensitive and showed good negative predictive value for the diagnosis of AMI, but positive predictive value was low. This technique may reduce the number of hospitalized patients and length of stay in the emergency department.

Chest Pain↗
PubMed2004

[Localization and quantification of myocardium at risk by myocardial perfusion SPECT during coronary artery occlusion].

INTRODUCTION AND OBJECTIVES: The aim of this study was to analyze the distribution and extent of the myocardium at risk using polar maps obtained with myocardial perfusion SPECT. Myocardial perfusion of territories irrigated by the left anterior descending (LAD), right coronary (RCA) and left circumflex artery (CX) was studied with the help of a technetium-radiolabeled tracer during occlusion of the vessels in the course of percutaneous coronary angioplasty. PATIENTS AND METHOD: We studied 50 patients (24 LAD, 15 RCA and 11 CX). The 99mTc compound was injected immediately after inflation of the balloon, and the artery was occluded for approximately 90 seconds. Tomographic images were acquired, and polar maps showing the extent of the ischemic region (uptake < 50% of maximum) were generated. RESULTS: Mean percentage extent of the ischemic territory was 49.8 +/- 10.3% (minimum 35%, maximum 67%), for the proximal LAD, 39.8 (8.3%) (minimum 20%, maximum 51%) for the mid LAD, 20.3 (7.6%) (minimum 8.3%, maximum 35%) for the RCA, and 21.3 (10.8%) (minimum 10.2%, maximum 30%) for the CX. CONCLUSIONS: The contours and extent of the jeopardized myocardial territory found during coronary occlusion allowed us to generate polar maps that illustrated actual coronary risk. The distribution and extent of the areas at risk differed from those in polar maps generated by most current applications used with myocardial perfusion SPECT.

Adult↗
PubMed2003

Prognostic value of lead aVR in patients with a first non-ST-segment elevation acute myocardial infarction.

BACKGROUND: ST-segment elevation in lead aVR has been associated with severe coronary artery lesions in patients with acute coronary syndromes, but the prognostic significance of this finding is unknown. METHODS AND RESULTS: We analyzed the initial ECG in 775 consecutive patients admitted to our center with a first acute myocardial infarction without ST-segment elevation in leads other than aVR or V1. The rates of in-hospital death in patients without (n=525) and with 0.05 to 0.1 mV (n=116) or > or =0.1 mV (n=134) of ST-segment elevation in lead aVR were 1.3%, 8.6%, and 19.4%, respectively (P<0.001). After adjustment for the baseline clinical predictors and for ST-segment depression on admission, the odds ratios for death in the last 2 groups were, respectively, 4.2 (95% CI, 1.5 to 12.2) and 6.6 (95% CI, 2.5 to 17.6). The rates of recurrent ischemic events and heart failure during hospital stay also increased in a stepwise fashion among the groups, whereas creatine kinase-MB levels were similar. Among the 437 patients that were catheterized within 6 months, the prevalence of left main or 3-vessel coronary artery disease in the 3 groups was 22.0%, 42.6%, and 66.3%, respectively (P<0.001). CONCLUSIONS: Lead aVR contains important short-term prognostic information in patients with a first non-ST-segment elevation acute myocardial infarction. Because the poorer outcome predicted by ST-segment elevation in lead aVR seems to be related to a more severe coronary artery disease, an early invasive approach might be especially beneficial in patients presenting with this finding.

Aged↗