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Biomedical subjects

C Ceconi

Publications and source records attributed to C Ceconi.

At least 19 recordsLinked to original sources
PubMed2006

Tissue Doppler deformation imaging identifies myocardial stunning occurring during the Tako-Tsubo syndrome. Case report in a Caucasian patient.

Only a few reports are available on the Tako-Tsubo syndrome in Caucasian patients. The aetiology remains unknown but several pathophysiological mechanisms have been proposed so far. We believe that this condition is not so rare in Caucasian patients because many diagnoses may be missed or misinterpreted. Tissue Doppler evaluation identifies myocardial reversible dysfunction, putatively stunning, at the onset of cardiomyopathy. This can help in diagnosis, prognosis and in choosing the best time for coronary angiography.

Coronary Angiography↗
PubMed2006

Heart rate reduction by pharmacological If current inhibition.

Heart rate reduction is becoming a new strategy to treat coronary patients. The development of heart-rate-lowering drugs, with a more specific activity than Beta-blockers, coincides with the detection of the sinoatrial pacemaker I(f) current. The first selective I(f) inhibitor that has been approved for clinical use is ivabradine. Ivabradine has been shown to reduce heart rate, preserve myocardial contractility, increase diastolic filling and maintain both small and large coronary artery vasodilation, whatever the level of exercise, thus ensuring adequate endocardial blood perfusion during exercise. Furthermore ivabradine decreases myocardial oxygen consumption and improves myocardial energetics, protecting the myocardium during acute ischemic conditions and showing favorable antiremodelling properties in patients with chronic ischemic disease.

Benzazepines↗
PubMed2005

Specific properties and effect of perindopril in controlling the renin-angiotensin system.

Perindopril is a long-acting, once-daily lipophilic angiotensin-converting enzyme inhibitor with high tissue angiotensin-converting enzyme affinity, lowering angiotensin II and potentiating bradykinin. Its efficacy, safety, and tolerability are well established in the treatment of hypertension and heart failure. Moreover, large morbidity-mortality trials, such as the EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) and Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS), have shown that antihypertensive treatment with perindopril reduces and prevents cardiovascular disease in a large range of patients with vascular diseases, whether or not they are hypertensive. Thus, the outcomes of these and other trials support the concept of cardiovascular protective properties of angiotensin-converting enzyme inhibition with perindopril in addition to the obvious blood-pressure-lowering effect. Considering its properties and the clinical evidence on efficacy and tolerability that has been gathered, perindopril fulfils the criteria of the latest guidelines for hypertension and cardiovascular disease management and should therefore be considered as a first-line antihypertensive agent, forming a consistent part of the comprehensive strategy against hypertension and related cardiovascular complications.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Therapeutic effects of L-carnitine and propionyl-L-carnitine on cardiovascular diseases: a review.

Several experimental studies have shown that levocarnitine reduces myocardial injury after ischemia and reperfusion by counteracting the toxic effect of high levels of free fatty acids, which occur in ischemia, and by improving carbohydrate metabolism. In addition to increasing the rate of fatty acid transport into mitochondria, levocarnitine reduces the intramitochondrial ratio of acetyl-CoA to free CoA, thus stimulating the activity of pyruvate dehydrogenase and increasing the oxidation of pyruvate. Supplementation of the myocardium with levocarnitine results in an increased tissue carnitine content, a prevention of the loss of high-energy phosphate stores, ischemic injury, and improved heart recovery on reperfusion. Clinically, levocarnitine has been shown to have anti-ischemic properties. In small short-term studies, levocarnitine acts as an antianginal agent that reduces ST segment depression and left ventricular end-diastolic pressure. These short-term studies also show that levocarnitine releases the lactate of coronary artery disease patients subjected to either exercise testing or atrial pacing. These cardioprotective effects have been confirmed during aortocoronary bypass grafting and acute myocardial infarction. In a randomized multicenter trial performed on 472 patients, levocarnitine treatment (9 g/day by intravenous infusion for 5 initial days and 6 g/day orally for the next 12 months), when initiated early after acute myocardial infarction, attenuated left ventricular dilatation and prevented ventricular remodeling. In treated patients, there was a trend towards a reduction in the combined incidence of death and CHF after discharge. Levocarnitine could improve ischemia and reperfusion by (1) preventing the accumulation of long-chain acyl-CoA, which facilitates the production of free radicals by damaged mitochondria; (2) improving repair mechanisms for oxidative-induced damage to membrane phospholipids; (3) inhibiting malignancy arrhythmias because of accumulation within the myocardium of long-chain acyl-CoA; and (4) reducing the ischemia-induced apoptosis and the consequent remodeling of the left ventricle. Propionyl-L-carnitine is a carnitine derivative that has a high affinity for muscular carnitine transferase, and it increases cellular carnitine content, thereby allowing free fatty acid transport into the mitochondria. Moreover, propionyl-L-carnitine stimulates a better efficiency of the Krebs cycle during hypoxia by providing it with a very easily usable substrate, propionate, which is rapidly transformed into succinate without energy consumption (anaplerotic pathway). Alone, propionate cannot be administered to patients in view of its toxicity. The results of phase-2 studies in chronic heart failure patients showed that long-term oral treatment with propionyl-L-carnitine improves maximum exercise duration and maximum oxygen consumption over placebo and indicated a specific propionyl-L-carnitine effect on peripheral muscle metabolism. A multicenter trial on 537 patients showed that propionyl-L-carnitine improves exercise capacity in patients with heart failure, but preserved cardiac function.

Cardiotonic Agents↗
PubMed2004

Oxidative stress during myocardial ischaemia and heart failure.

Oxidative stress is a condition in which oxidant metabolites exert their toxic effect because of an increased production or an altered cellular mechanism of protection. The heart needs oxygen avidly and, although it has powerful defence mechanisms, it is susceptible to oxidative stress, which occurs, for instance, during post-ischaemic reperfusion. Ischaemia causes alterations in the defence mechanisms against oxygen free radicals, mainly a reduction in the activity of mitochondrial superoxide dismutase and a depauperation of tissue content of reduced glutathione. At the same time, production of oxygen free radicals increases in the mitochondria and leukocytes and toxic oxygen metabolite production is exacerbated by re-admission of oxygen during reperfusion. Oxidative stress, in turn, causes oxidation of thiol groups and lipid peroxidation leading first to reversible damage, and eventually to necrosis. In man, there is evidence of oxidative stress (determined by release of oxidised glutathione in the coronary sinus) during surgical reperfusion of the whole heart, or after thrombolysis, and it is related to transient left ventricular dysfunction or stunning. Data on oxidative stress in the failing heart are scant. It is not clear whether the defence mechanisms of the myocyte are altered or whether the production of oxygen free radicals is increased, or both. Recent data have shown a close link between oxidative stress and apoptosis. Relevant to heart failure is the finding that tumour necrosis factor, which is found increased in failing patients, induces a rapid rise in intracellular reactive oxygen intermediates and apoptosis. This series of events is not confined to the myocytes, but occurs also at the level of endothelium, where tumour necrosis factor causes expression of inducible nitric oxide synthase, production of the reactive radical nitric oxide, oxidative stress and apoptosis. It is therefore, possible that the immunological response to heart failure results in endothelial and myocyte dysfunction through oxidative stress mediated apoptosis. Clarification of these mechanisms may lead to novel therapeutic strategies.

Animals↗
PubMed2003

Preliminary observations on the effects of acute infusion of growth hormone on coronary vasculature and on myocardial function and energetics of an isolated and blood-perfused heart.

Recent studies have shown that growth hormone (GH) deficiency may deteriorate post-ischemic myocardial reperfusion damage. Furthermore, GH has been reported to be a promising therapeutic option in the treatment of chronic myocardial dysfunction. However, the exact mechanisms of action of GH on the cardiovascular system, particularly in the acute setting, are still unclear. The aim of our study consisted of monitoring the acute effects of GH infusion on isolated blood-perfused rabbit heart according to dose-response pattern and during ischemic conditions to test its anti-ischemic property. Seven blood-donors perfused isolated hearts were used as experimental model. The mechanical and metabolic data of the isolated organs were continuously monitored. Under aerobic conditions, dose-response curves were initially tested after intracoronary infusion of GH at increasing dosages (1, 2, 3 mg/l). After a stabilization period, the effects of GH infusion (5 mg/kg) administered 30 minutes prior to acute global myocardial ischemia (30 minutes) were also investigated. At the doses tested, GH did not induce any changes either in the developed or in the diastolic pressures of the isolated organ. However, transient reduction of the coronary perfusion pressure was observed at the dosage of 3 mg/l. During the ischemia/reperfusion study, at the dosages used in this study, GH did not modify either the degree of stunning in the early reperfusion or the recovery of the developed pressure at the end of reperfusion. In addition, GH did not prevent either the increase of diastolic pressure during ischemia or the release of lactate and CPK during reperfusion. Tissue content of high-energy phosphates was also not changed by GH infusion. In our experimental model, acute GH infusion did not reduce the ischemic/reperfusion damage of the myocardium. However, GH transiently induced coronary vasodilation without modifying the myocardial contractility. Acute effects of GH appear, therefore, to predominantly relate to vascular dilation suggesting that the effects on myocardial contractility may require long-lasting intake being likely linked to enhancement of specific protein synthesis or gene expression of cardiac myocytes.

Animals↗
PubMed2002

[An older female patient with refractory anemia and hemochromatosis].

CASE HISTORY AND CLINICAL FINDINGS: A 69-year-old woman was admitted because of a normocytic anemia. One year before an acute B19 parvovirus infection had been diagnosed, but the anemia was attributed to intestinal bleeding caused by a dysplastic colonic polyp. However, anemia persisted despite polypectomy. There was an excessive elevation of serum ferritin. ADDITIONAL EXAMINATIONS: A bone marrow biopsy and aspirate led to the diagnosis of a myelodysplastic syndrome (pure sideroblastic anemia). Ultrasound demonstrated advanced fibrosis of the liver. Fibrosis in association with severe parenchymatous siderosis was also demonstrated by histology. Analysis of the hemochromatosis gene (B-HFE, nt 845, G/A) was negative. DIAGNOSIS, THERAPY AND CLINICAL COURSE: The patient had secondary hemochromatosis due to a myelodysplastic syndrome. An acute infection with parvovirus B19 had been noted at the time of the first admission, one year before MDS was diagnosed. At that time, hemochromatosis had already caused fibrosis of the liver. However, complete regression of organ siderosis was achieved by deferoxamine administration. The myelodysplastic syndrome itself did not show any progression even 7 years after the diagnosis was established. CONCLUSION: Our case demonstrates the uncommon association between sideroblastic anemia and secondary hemochromatosis. Acute parvovirus infection may induce severe anemia in myelodysplastic syndromes. In acute B19 parvovirus infections an underlying hematologic disease should be excluded.

Aged↗
PubMed2002

Chromogranin A in heart failure; a novel neurohumoral factor and a predictor for mortality.

BACKGROUND: In chronic heart failure, several hormonal systems are activated with diagnostic and prognostic implications. We tested the hypotheses that serum Chromogranin-A (CgA) -- a 49 kDa acid protein present in the secretor granules of neuroendocrine cells -- is increased in chronic heart failure and that CgA levels are a predictive factor for mortality. METHOD AND RESULTS: In 160 patients with chronic heart failure, we measured serum CgA and other neuroendocrine hormones. The results showed that CgA is increased in chronic heart failure and the increase is related to the clinical severity of the syndrome: CgA levels in New York Heart Failure (NYHA) class II (median 146.9 ng x ml(-1), inter-quartiles 108.3-265.5) were significantly higher (P<0.05) than in class I (median 109.7 ng x ml(-1), inter-quartiles 96.7-137.6), and significantly lower (P<0.05) than in class III (median 279.0 ng x ml(-1), inter-quartiles 203.6-516.1). Class IV patients showed the highest serum levels of CgA (median 545.0 ng. ml(-1), inter-quartiles 231.8-1068.3), being statistically significantly different from class III patients (P<0.001). The association between survival and some recognized variables of prognostic significance, including CgA was also studied. The results showed that ejection fraction, noradrenaline, atrial natriuretic peptide, NYHA class and CgA were significant univariate prognosticators; however, in the multivariate analysis by the Cox proportional-hazard model, CgA and NYHA class were the only independent predictive factors for mortality (P<0.005, RR=1.22, 95% CI=1.06-1.41 and P=0.04, RR=1.58, 95% CI=1.02-2.46, respectively). CONCLUSIONS: CgA is a pro-hormone, precursor of several active fragments likely to exert biological effects in chronic heart failure. CgA serum levels are increased in patients with chronic heart failure and are a predictive factor for mortality.

Adult↗
PubMed2002

Revascularization of hibernating myocardium: rate of metabolic and functional recovery and occurrence of oxidative stress.

BACKGROUND: Left ventricular (LV) dysfunction due to coronary artery disease (CAD) may improve after revascularization in patients with hibernating myocardium (HM). METHODS AND RESULTS: We compared the rate of metabolic (arterial-great cardiac vein differences of lactate, glucose and pyruvate) and functional (intra-operative transesophageal and epicardial echocardiography) recovery and occurrence of oxidative stress (myocardial release of oxidized glutathione (GSSG)) early after surgical revascularization, in patients with CAD, LV dysfunction and HM (n=16) vs those with preserved LV function (n=15). By comparing the two groups, we observed that, after de-clamping, in patients with HM (a) the kinetic of lactate production was converted to extraction (P<0.01 at 1, 5, 10 and 20 min after revascularization), (b) myocardial extraction of pyruvate increased (P<0.01 during the first 5 min after revascularization), (c) GSSG release was less and of shorter duration (P<0.01 at all times), (d) segmental wall motion score improved from 2.4+/-0.3 to 1.7+/-0.5 (P<0.01) as did the thickening of the akinetic territories corresponding to the antero-distal septum and to the distal anterior wall regions (to 36+/-23%, and to 36+/-13%, respectively). There was a correlation between the rate of recovery of metabolic and functional indices. CONCLUSIONS: The contractile and metabolic recovery of HM is more rapid than that of non-HM, and it is not accompanied by oxidative stress.

Blood Glucose↗
PubMed2002

Transperitoneal approach for pericardial drainage.

A variety of surgical approaches for pericardial drainage have been proposed. The choice of the best approach can be, therefore, oriented depending on the cause of the pericardial effusion. Recently a different approach, for neoplastic or post-traumatic pericardial effusion, has been proposed, in order to create a peritoneal-pericardial window avoiding the insertion of a tube. We report a case of late postoperative cardiac tamponade in a patient with a previous coronary surgery in which, due to extensive adhesion of the anterior wall a modified transperitoneal approach to the pericardium, was used.

Cardiac Tamponade↗
PubMed2001

Beta-adrenergic receptors and intracellular signalling pathway in stunned and non-ischemic regions of pig myocardium.

The beta-adrenergic pathway may have a role in the pathophysiology of ischemic syndromes characterised by reversible left ventricular dysfunction, such as myocardial stunning and other clinical conditions of unstable angina or coronary spasms, or chronic reversible left ventricular dysfunction, which might be a consequence of repeated events of short-term ischemia ("repetitive stunning"). A partial-to-total occlusion of the left anterior descending coronary artery in pigs was used to induce short periods of ischemia (total ischemic time 12 +/- 2 min). Hypokinesis and dyskinesis of the myocardium were considered signs of myocardial dysfunction. We found a maintained function of the beta-adrenergic signalling system. Density and affinity of beta-adrenergic receptors were not different in stunned and non-ischemic regions, nor were cyclic AMP and cyclic GMP intracellular contents and ratio, nor well as the ratio of stimulatory/inhibitory G protein a subunits. Our findings are in agreement with a maintained beta-adrenergic signalling system in the pathophysiology of chronic reversible left ventricular dysfunction.

Animals↗
PubMed2001

Long-term results of coronary artery bypass grafting procedure in the presence of left ventricular dysfunction and hibernating myocardium.

OBJECTIVE: Long-term left ventricular (LV) performance and patient outcome after coronary artery bypass grafting (CABG) procedure in the presence of depressed LV function and hibernating myocardium (HM) have been poorly determined. Therefore, we prospectively evaluated patients undergoing CABG with severe LV dysfunction and HM to elucidate postoperative prognosis. METHODS: We enrolled 120 consecutive patients undergoing CABG with severe LV dysfunction and HM as assessed by dobutamine echocardiography and by rest-redistribution radionuclide (Thallium-201) study. Mean patient age was 60+/-9 years (range 31-77 years). Mean preoperative LVEF was 28%+/-9 (range 10-40%). All patients underwent echocardiographic study to assess LV recovery of function intraoperatively, prior to hospital discharge, at 3 months, at 1 year, and yearly during the follow-up. Univariate and multivariate analysis were performed to to evaluate predictors of postoperative survival. RESULTS: There were 2 hospital (1.6%) and 15 late (12.5%) deaths, mainly for heart failure, leading to an actuarial survival of 80+/-6% and 60+/-9% at 5 and 8 years, respectively. LVEF significantly improved perioperatively (from 28+/-9% to 40+/-2%, P<0.01). Increase in LVEF, however, was gradually offset over the time (EF of 33+/-9%, 32+/-8%, and 30+/-9% at 3 months, and 12 months, and 8 years after surgery, respectively). Furthermore, patients who experienced limited LV functional recovery perioperatively had a more remarkable decline of LVEF thereafter, and suffered from recurrence of heart failure symptoms (freedom from heart failure 82+/-5% and 60+/-8% at 4 and 8 years respectively). Advanced preoperative NYHA Class, and age were independent risks factors for reduced postoperative survival. Preoperative angina and use of arterial conduits apparently did not influence patient morbidity and mortality at long term. CONCLUSION: CABG procedure in the presence of HM enhances LV recovery of function and has a favourable prognosis. Functional benefit of the left ventricle, however, appears to be time-limited, despite remarkable improvement in patient functional capacity. Advanced preoperative heart failure, minimal perioperative improvement of LVEF, and age account for a poor long-term prognosis.

Adult↗
PubMed2001

Role of bradykinin and eNOS in the anti-ischaemic effect of trandolapril.

1. Angiotensin converting enzyme (ACE) inhibitors are under study in ischaemic heart diseases, their mechanism of action being still unknown. 2. The anti-ischaemic effect of trandolapril and the possible involvement of a bradykinin-modulation on endothelial constitutive nitric oxide synthase (eNOS) in exerting this effect, were investigated. 3. Three doses of trandolapril, chronically administered in vivo, were studied in isolated perfused rat hearts subjected to global ischaemia followed by reperfusion. 4. Trandolapril has an anti-ischaemic effect. The dose of 0.3 mg kg(-1) exerted the best effect reducing diastolic pressure increase during ischaemia (from 33.0+/-4.5 to 14.0+/-5.2 mmHg; P<0.05 vs control) and reperfusion (from 86.1+/-9.4 to 22.2+/-4.1 mmHg; P<0.01 vs control), improving functional recovery, counteracting creatine phosphokinase release and ameliorating energy metabolism after reperfusion. 5. Trandolapril down-regulated the baseline developed pressure. 6. Trandolapril increased myocardial bradykinin content (from 31.8+/-6.1 to 54.8+/-7.5 fmol/gww; P<0.05, at baseline) and eNOS expression and activity in aortic endothelium (both P<0.01 vs control) and in cardiac myocytes (from 11.3+/-1.5 to 17.0+/-2.0 mUOD microg protein(-1) and from 0.62+/-0.05 to 0.80+/-0.06 pmol mg prot(-1) min(-1); both P<0.05 vs control). 7. HOE 140 (a bradykinin B(2) receptor antagonist) and NOS inhibitors counteracted the above-reported effects. 8. There was a negative correlation between myocyte's eNOS up-regulation and myocardial contraction down-regulation. 9. Our findings suggest that the down-regulation exerted by trandolapril on baseline cardiac contractility, through a bradykinin-mediated increase in NO production, plays a crucial role in the anti-ischaemic effect of trandolapril by reducing energy breakdown during ischaemia.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Reduction of oxidative stress by carvedilol: role in maintenance of ischaemic myocardium viability.

OBJECTIVES: To differentiate the impact of the beta-blocking and the anti-oxidant activity of carvedilol in maintaining myocardium viability. METHODS: Isolated rabbit hearts, subjected to aerobic perfusion, or low-flow ischaemia followed by reperfusion, were treated with two doses of carvedilol, one dose (2.0 microM) with marked negative inotropic effect due to beta-blockage and the other (0.1 microM) with no beta-blockage nor negative inotropism. Carvedilol was compared with two doses of propranolol, 1.0 - without - and 5.0 microM - with negative inotropic effect. Anti-oxidant activity was measured as the capacity to counteract the occurrence of oxidative stress and myocardium viability as recovery of left ventricular function on reperfusion, membrane damage and energetic status. RESULTS: Carvedilol counteracted the ischemia and reperfusion induced oxidative stress: myocardial content of reduced glutathione, protein and non-protein sulfhydryl groups after ischaemia and particularly after reperfusion, was higher in hearts treated with carvedilol, while the myocardial content of oxidised glutathione was significantly reduced (0.30+/-0.03 and 0.21+/-0.02 vs. 0.39+/-0.03 nmol/mg prot, both P<0.01, in 0.1 and 2.0 microM). At the same time, carvedilol improved myocardium viability independently from its beta-blocking effect. On the contrary, propranolol maintained viability only at the higher dose, although to a lesser extent than carvedilol. This suggests that the effects of propranolol are dependent on energy saving due to negative inotropism. The extra-protection observed with carvedilol at both doses is likely due to its anti-oxidant effect. CONCLUSIONS: Our data show that the anti-oxidant activity of carvedilol is relevant for the maintenance of myocardium viability.

Adenosine Diphosphate↗
PubMed2000

New insights on myocardial pyridine nucleotides and thiol redox state in ischemia and reperfusion damage.

OBJECTIVE: to investigate the changes of pyridine nucleotides and thiol redox state in cardiac tissue following ischemia and reperfusion. NADH/NAD and NADPH/NADP redox couples were specifically studied and the influence of NADPH availability on cellular thiol redox was also investigated. METHODS: isolated rabbit hearts were Langendorff perfused and subjected to a protocol of ischemia and reperfusion. An improved technique for extraction and selective quantitation of pyridine nucleotides was applied. RESULTS: ischemia and reperfusion induced an increase in diastolic pressure, limited recovery in developed pressure and loss of creatine phosphokinase. Creatine phosphate and ATP were decreased by ischemia and only partially recovered during reperfusion. NADH was increased (from 0. 36+/-0.04 to 1.96+/-0.15 micromol/g dry wt. in ischemia, P<0.001), whereas NADPH decreased during ischemia (from 0.78+/-0.04 to 0. 50+/-0.06 micromol/g dry wt., P<0.01) and reperfusion (0.45+/-0.03 micromol/g dry wt.). Furthermore, we observed: (a) release of reduced (GSH) and oxidised glutathione (GSSG) during reperfusion; (b) decreased content of reduced sulfhydryl groups during ischemia and reperfusion (GSH: from 10.02+/-0.76 to 7.11+/-0.81 nmol/mg protein, P<0.05, and to 5.48+/-0.57 nmol/mg protein; protein-SH: from 280.42+/-12.16 to 135.11+/-17.00 nmol/mg protein, P<0.001, and to 190.21+/-11.98 nmol/mg protein); (c) increased content in GSSG during reperfusion (from 0.17+/-0.02 to 0.36+/-0.02 nmol/mg protein, P<0.001); (d) increased content in mixed disulphides during ischemia (from 6.14+/-0.13 to 8.31+/-0.44 nmol/mg protein, P<0.01) and reperfusion (to 9.87+/-0.82 nmol/mg protein, P<0.01). CONCLUSIONS: under severe low-flow ischemia, myocardial NADPH levels can decrease despite the accumulation of NADH. The reduced myocardial capacity to maintain NADPH/NADP redox potential can result in thiol redox state changes. These abnormalities may have important consequences on cellular function and viability.

Adenosine Triphosphate↗
PubMed2000

Enhanced expression and activity of xanthine oxidoreductase in the failing heart.

The molecular basis for heart failure is unknown, but oxidative stress is associated with the pathogenesis of the disease. We tested the hypothesis that the activity of xanthine oxidoreductase (XOR), a free-radical generating enzyme, increases in hypertrophied and failing heart. We studied XOR in two rat models: (1) The monocrotaline-induced right ventricular hypertrophy and failure model; (2) coronary artery ligation induced heart failure, with left ventricular failure and compensatory right ventricular hypertrophy at different stages at 3 and 8 weeks post-infarction, respectively. XOR activity was measured at 30 degrees C and the reaction products were analysed by HPLC. In both models XOR activity in hypertrophic and control ventricles was similar. In the monocrotaline model, the hearts showed enhanced XOR activity in the failing right ventricle (65+/-5 mU/g w/w), as compared to that in the unaffected left ventricle (47+/-3 mU/g P<0.05, n=6-7). In the coronary ligation model, XOR activities did not differ at 3 and 8 weeks. In the infarcted left ventricle, XOR activity increased from 29.4+/-1.4 mU/g (n=6) in sham-operated rats, to 48+/-3 and 80+/-6 mU/g (n=8 P<0.05 v sham) in the viable and infarcted parts of failing rat hearts, respectively. With affinity-purified polyclonal antibody, XOR was localized in CD68+ inflammatory cells of which the number increased more in the failing than in sham-operated hearts. Our results show that the expression of functional XOR is elevated in failing but not in hypertrophic ventricles, suggesting its potential role in the transition from cardiac hypertrophy into failure.

Animals↗