Epicardial and pericardial adipose tissue: physiological importance and role of imaging techniques.

Epicardial adipose tissue (EAT) is becoming a cardiovascular risk factor. Multiple imaging techniques are used to measure it, each one with its prons and cons. We will review the literature realizing that there is still a lot of work that needs to be done.

Investigating the signal transduction pathways underlying remote ischemic conditioning in the porcine heart.

BACKGROUND: The mechanism underlying remote ischemic conditioning (RIC) remains unclear. We investigated whether RIC protects the heart through the activation of the adenosine receptor and the PI3K-Akt pathway at the onset of myocardial reperfusion. METHODS AND RESULTS: Domestic pigs (27-35 kg) were subjected to in situ left anterior descending coronary artery ischemia (60 min) followed by reperfusion (180 min) and randomised to the following: (1) Control- No additional intervention; (2) Remote ischemic preconditioning (RIPC)- Four-5 min cycles of lower limb ischemia/reperfusion were administered prior to myocardial ischemia; (3) RIPC + Wort or 8-SPT: Wortmannin (Wort 20 µg/kg, a PI3K inhibitor) or 8-sulfophenyltheophylline (8-SPT 10 mg/kg, an adenosine receptor inhibitor) were administered intravenously 30 s before myocardial reperfusion to RIPC-treated animals; (4) Remote ischemic perconditioning (RIPerC)--Four-5 min cycles of lower limb ischemia/reperfusion were applied 1 min before myocardial reperfusion; (5) RIPerC + Wort or 8-SPT: Wort or 8-SPT were given 30 s before myocardial reperfusion to RIPerC-treated animals. Both RIPC and RIPerC reduced myocardial infarct size (13.3 ± 2.2% with RIPC, 18.2 ± 2.0% with RIPerC versus 48.8 ± 4.2% in control:P < 0.05:N ≥ 5/group). Wortmannin abolished the infarct-limiting effects of RIPC (33.2 ± 6% with RIPC + Wort versus 13.3 ± 2.2% with RIPC:P < 0.05:N ≥ 5/group) but not RIPerC (18.0 ± 3.4% with RIPerC + Wort versus 18.2 ± 2.0% with RIPerC:P > 0.05:N ≥ 5/group). 8-SPT did not influence the infarct-limiting effects of either RIPC or RIPerC. Western blot analysis confirmed Wortmannin-sensitive PI3K and Akt activation at myocardial reperfusion in RIPC-treated hearts. CONCLUSIONS: In the porcine heart, both RIPC and RIPerC both reduce myocardial infarct size and with RIPC but not RIPerC this cardioprotective effect is associated with the activation of the PI3K-Akt pathway at reperfusion.

Effects of adiponectin in TNF-α, IL-6, and IL-10 cytokine production from coronary artery disease macrophages.

Adiponectin, an adipose tissue secreted protein, exhibits anti-inflammatory and antiatherogenic properties. We examined the effects of the globular and full-length adiponectin on cytokine production in macrophages derived from Coronary Artery Disease (CAD) patients and control individuals. Adiponectin's effects in human macrophages upon lipopolysaccharide (LPS) treatment were also examined. Full length adiponectin acted differently on TNF-α and IL-6 production by upregulating TNF-α and IL-6 protein production, but not their mRNA expression. Additionally, full length adiponectin was unable to abrogate LPS proinflammatory effect in TNF-α and IL-6 mRNA expression in CAD and NON-CAD macrophages. In contrast, globular adiponectin appeared to have proinflammatory properties by potently upregulating TNF-α and IL-6 mRNA and protein secretion in human macrophages while subsequently rendered cells resistant to further proinflammatory stimuli. Moreover, both forms of adiponectin powerfully suppressed scavenger MSR-AI mRNA expression and augmented IL-10 protein release, both occurring independently of the presence of LPS or CAD. These data indicate that adiponectin could potentially protect human macrophages via the elevated IL-10 secretion and the suppression of MSR-AI expression. It can also be protective in CAD patients since the reduced adiponectin-induced IL-6 release in CAD macrophages compared to controls, could be beneficial in the development of inflammation related atherosclerosis.

Incremental predictive value of carotid intima-media thickness to arterial stiffness for impaired coronary flow reserve in untreated hypertensives.

Coronary microcirculation is disturbed in patients with arterial hypertension. Carotid intima-media thickness (IMT) and arterial stiffness are markers of subclinical atherosclerosis with prognostic significance. We investigated whether the combination of increased carotid IMT and arterial stiffness has a greater predictive value for the presence of impaired coronary flow reserve (CFR) than each index alone in never-treated hypertensives. We studied 110 untreated patients (age: 54.5+/-12 years) with newly diagnosed arterial hypertension. We measured (1) carotid-to-femoral artery pulse wave velocity (PWV), (2) carotid IMT and (3) CFR by means of color-guided Doppler echocardiography after adenosine infusion. Among other confounders, arterial stiffness and IMT were independent determinants of CFR (coefficient B=-0.146 and B=-0.006, P<0.05). Arterial stiffness and IMT had an incremental value for the determination of CFR when added to a model including other confounders (chi(2) change=4.423, P for change=0.038 after addition of IMT; and chi(2) change=5.369, P for change=0.020 after addition of PWV). Receiver operating curve analysis showed that PWV>10.2 m s(-1) and IMT>1 mm were the optimal cutoff values to predict a CFR<2.5. Patients with IMT>1 mm, PWV>10.2 m s(-1) or their combination had an odds ratio of 3.5, 5.0 and 11.2, P<0.05, for a CFR<2.5, respectively. The combination of increased carotid IMT and arterial stiffness has a greater predictive value for impaired CFR than each index alone in never-treated hypertensives.

Hypertension and paroxysmal atrial fibrillation: a novel predictive role of high sensitivity C-reactive protein in cardioversion and long-term recurrence.

The role of inflammation in maintenance of paroxysmal atrial fibrillation (PAF) in patients with hypertension and no other heart disease has not been fully elucidated yet. We investigated the association of various inflammatory markers with cardioversion and recurrence of PAF in patients with hypertension. We studied 75 patients (44 male, mean age 67.9+/-9.9 years) with PAF (duration from onset of symptoms<24 h) secondary to hypertension. None had heart failure or any other ongoing inflammatory process. All patients received anticoagulation and intravenous amiodarone for cardioversion. High sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and tumour necrosis factor (TNF)-alpha were measured on admission and 48 h later. By 48 h from admission 61/75 patients (81.3%) regained sinus rhythm (cardioverted), whereas 14/75(18.7%) remained in AF (non-cardioverted). hsCRP, IL-6 and TNF-alpha serum levels on admission were similar between groups. hsCRP at 48 h was the most significant factor correlated with cardioversion outcome (OR: 0.06, 95% CI: 0.01-0.47, P=0.008). During a 1-year follow-up, AF recurred in 28/61(45.9%) patients. The strongest factor associated with AF recurrence was hsCRP at 48 h > or =2.27 mg l(-1) (hazard ratio: 6.2, 95% CI: 2.2-17.6, P=0.001). hsCRP at 48 h after admission correlates with cardioversion outcome and may predict long-term AF recurrence.

Lowering interleukin-1 activity with anakinra improves myocardial deformation in rheumatoid arthritis.

OBJECTIVE: Inhibition of interleukin-1 activity improves nitro-oxidative stress, endothelial and coronary function. The authors investigated (a) the association of nitro-oxidative stress and endothelial function with myocardial deformation, (b) the effects of anakinra, an interleukin-1a receptor antagonist on myocardial deformation in patients with rheumatoid arthritis (RA). METHODS: The authors compared 46 RA patients to 23 normal controls. 23 patients received anakinra (150 mg subcutaneously once daily) and 23 patients a 5-mg increase of prednisolone dose for 30 days. At baseline and post-treatment this study assessed (a) the left ventricular (LV) longitudinal, circumferential and radial strain and strain rate, using speckle tracking echocardiography, (b) the coronary flow reserve (CFR), (c) the flow-mediated endothelial-dependent dilation of the brachial artery (FMD) and (d) nitrotyrosine (NT) and malondialdehyde blood levels. RESULTS: Patients had impaired baseline myocardial deformation indices compared to controls (p<0.05). CFR and NT levels were related to longitudinal strain, systolic and diastolic strain rate, circumferential strain and systolic strain rate (p<0.05). FMD was related to longitudinal and circumferential diastolic strain rate (p<0.01). Compared to baseline, anakinra-treated patients increased the longitudinal strain (-17.8% (3.7%) vs -22.1% (3.5%)), systolic (-1.02 (0.23) l/s vs -1.25 (0.23) l/s) and diastolic (0.96 (0.37) l/s vs 1.20 (0.39) l/s) longitudinal strain rate, circumferential strain and strain rate (p<0.05 for all comparisons). No significant changes were observed among prednisolone-treated patients CONCLUSIONS: Myocardial deformation is impaired in RA patients and is related to nitro-oxidative stress and endothelial dysfunction. Chronic inhibition of IL-1 improves LV deformation in parallel with endothelial function and nitro-oxidative stress.

Remote postconditioning is more potent than classic postconditioning in reducing the infarct size in anesthetized rabbits.

PURPOSE: Postconditioning confers protection to the heart after a potentially lethal episode of prolonged ischemia. There is evidence that it may also be protective when applied at a distal artery. In the present study, we sought to determine whether remote postconditioning within the heart (local) or outside the heart (distal) is effective in salvaging the ischemic heart in vivo and to compare its effect with that of the classic postconditioning. METHODS: Twenty seven open chest New Zealand white anesthetized male rabbits were divided into four groups and were exposed to 30 min regional myocardial ischemia (isc), after ligation of a prominent coronary artery, followed by 3 h reperfusion (rep) after releasing the snare. Control group (n = 7) was subjected to no additional interventions, postC group (n = 6) was subjected to four cycles of 1 min isc/1 min rep of the same coronary artery at the beginning of reperfusion, remote local postC group (n = 7) to four cycles of 1 min isc/1 min rep of another coronary artery 30 s before the end of index isc and remote distal postC group (n = 7) to four cycles of 1 min isc/1 min rep of another (carotid) artery again 30 s before the end of index isc. Infarct size (I) and area at risk (R) were delineated with the aid of TTC staining and green fluorescent microspheres respectively and their ratio was expressed in percent (%I/R). RESULTS: Remote local and remote distal postC reduced the % I/R ratio (17.7 +/- 1.7% and 18.4 +/- 1.6%, respectively vs 47.0 +/- 2.5% in the control group, P < 0.01). Classic PostC had an intermediate protective effect (33.1 +/- 1.7%, P < 0.05 vs all the other groups). CONCLUSION: Remote postconditioning consisted of 1 min isc/1 min rep protects the ischemic rabbit heart in vivo, independently of the site of the remote artery. This intervention seems to confer a stronger protection than the classic postconditioning.

Evaluation of left atrial longitudinal function in patients with hypertrophic cardiomyopathy: a tissue Doppler imaging and two-dimensional strain study.

OBJECTIVE: We sought to quantify left atrial longitudinal function by tissue Doppler (TDI) and two-dimensional (2D) strain in patients with hypertrophic cardiomyopathy (HCM). DESIGN: Case-control study. SETTING: Tertiary university hospital. PATIENTS: 43 consecutive patients with familial HCM, aged 49 (SD 18) years, along with 21 patients with non-HCM left ventricular hypertrophy (LVH, aged 52 (12) years) and 27 healthy volunteers (aged 42 (13) years). INTERVENTIONS: Subjects were studied by both TDI and 2D left atrial strain during all three atrial phases (reservoir, conduit, contractile), as well as by left ventricular systolic strain; total atrial deformation (TAD) was defined as the sum of maximum positive and maximum negative strain during a cardiac cycle. MAIN OUTCOME MEASURES: Left atrial longitudinal function. RESULTS: Both TDI and 2D atrial strain and TAD were significantly reduced in HCM, compared to the other two groups in all atrial phases (p<0.001 in most cases); left ventricular systolic strain was also significantly reduced in HCM (p<0.001). Adding 2D contractile atrial strain to a model of conventional echo measurements (including left atrial diameter and volume index, interventricular septal thickness and E/A ratio and E/e' ratios) increased its prognostic value in differentiating HCM from non-HCM LVH (p value of the change <0.001), while addition of TDI atrial strain or left ventricular strain did not. A cut-off for 2D contractile strain of -10.82% discriminated HCM from non-HCM LVH with a sensitivity of 82% and a specificity of 81%. Intra-observer and inter-observer variabilities for atrial strain in HCM were 16% and 17.5% for TDI and 8% and 9.5% for 2D, respectively. Processing time per case in HCM was 12.5 (2.6) minutes for TDI versus 3.8 (1.2) minutes for 2D strain (p<0.001). CONCLUSION: Left atrial longitudinal function is reduced in HCM compared to non-HCM LVH and healthy controls. In addition, 2D atrial strain has an additive value in differentiating HCM from non-HCM LVH and it is more reproducible and less time consuming than TDI strain.

Alternative pharmacological interventions that limit myocardial infarction.

Despite current optimal treatment, the morbidity and mortality of coronary heart disease remain significant worldwide and open the way for the development of novel cardioprotective therapies. In the last two decades, a remarkable scientific effort has focused on the limitation of infarct size. Important input from experimental studies has led the way in this direction. However, clinical and preclinical results using various cardioprotective strategies to attenuate reperfusion injury have generally not been applicable for every day clinical practice. Protection of the ischemic myocardium is known to occur as a result of ischemic preconditioning (PC), in which repetitive brief periods of ischemia protect the heart from a subsequent prolong ischemic insult. Although PC is a powerful form of protection, it is of limited clinical application for obvious ethical and practical reasons. Another endogenous form of cardioprotection, similar to PC but applicable at the time of reperfusion, termed postconditioning (PostC), has been recently described. Short series of repetitive cycles of brief reperfusion and re-occlusion of the coronary artery applied at the onset of reperfusion, reduce the infarct size and coronary artery endothelial dysfunction. At present, pharmacological PC and PostC are possible alternative methods that may substitute pharmaceutical treatments the short ischemic insults. Adenosine, nicorandil and other agents have been already used as pharmacological mimetics of ischemic PC in multicenter trials. We summarize the recent research efforts on novel therapeutic strategies and on the design of new compounds, based on the accumulated knowledge of the ligands, receptors and intracellular signaling pathways of PC and PostC.

Plasma levels of osteopontin before and 24 h after percutaneous coronary intervention.

OBJECTIVE: Previous studies demonstrated that osteopontin (OPN) was increased after vascular injury, such as atherosclerosis and restenosis following angioplasty. We sought to determine the effects of percutaneous coronary intervention (PCI) on plasma OPN levels compared with coronary arteriography (CA). METHODS: Plasma OPN levels were determined in 103 patients who underwent CA or PCI with stent implantation, at baseline and 24 h after the procedure. Patients were divided into three groups; group I: patients without significant coronary artery stenosis, group II: patients with coronary artery disease in whom only CA was performed, group III: patients with coronary artery disease who had PCI and stent implantation. RESULTS: Plasma OPN levels before the procedure were similar in all three groups. OPN levels 24 h after the procedure were significantly higher only in group III compared with baseline. Among three groups, the OPN levels observed in 24 h were significantly higher in group III compared with group I. Patients in group III had significantly higher OPN values after the procedure, depending on the number of stents implanted (p = 0.03). CONCLUSION: The increase in OPN levels after PCI suggests that vascular injury due to PCI is responsible for this phenomenon.

Relationship between plasma osteopontin and oxidative stress in patients with coronary artery disease.

BACKGROUND: It is known that oxidative stress plays an important role in the pathogenesis of atherosclerosis and that an association exists between osteopontin (OPN) and atherosclerosis. OBJECTIVES: It was proposed that malondialdehyde (MDA), a biomarker of lipid peroxidation and oxidative stress, would be related to plasma OPN levels in patients with coronary artery disease (CAD). METHODS/RESULTS: Plasma OPN and MDA levels were measured in 71 patients (60 males and 11 females; mean age 61.7 +/- 10 years). Fifty-eight patients had significant CAD (group I) and 13 patients were free of CAD as defined angiographically (group II). Plasma OPN was measured by enzyme-linked immunosorbent assay (ELISA), while MDA was determined spectrophotometrically. Multivariate regression analysis revealed that ln-transformed OPN levels were independently associated with MDA after adjustment for age, hypertension and diabetes mellitus (R(2) = 0.278, p = 0.0004 and beta regression coefficient = 0.252 [standard error = 0.0958], p = 0.011). OPN and MDA levels were higher in patients with diabetes (73.6 +/- 36.2 ng/ml versus 56.1 +/- 30.9 ng/ml, p = 0.02 and 2.5 +/- 0.5 microM versus 2.0 +/- 0.5 microM, p = 0.002, respectively). CONCLUSIONS: The association between OPN and MDA levels in patients with CAD suggests an interaction between OPN and oxidative stress. This interaction may play a role in the pathogenesis of atherosclerosis.

Molecular diagnosis of the viral component in cardiomyopathies: pathophysiological, clinical and therapeutic implications.

BACKGROUND: Myocarditis is defined as the inflammation of myocardium associated with cardiac dysfunction. Despite this clear-cut definition, diagnosis and etiologic treatment continue to create considerable debate. Viral infections are frequent causes of myocarditis and there is evidence that persistent viral infection is associated with poor prognosis in different subtypes of cardiomyopathy. OBJECTIVE: To review methods for diagnosis of viral myocarditis and present the use of polymerase chain reaction (PCR)-based protocols for evaluating viral infection in myocarditis/cardiomyopathies. METHODS: A review of published literature. RESULTS/CONCLUSION: There is increasing evidence that PCR-based protocols can provide reliable molecular evidence for the presence of viral infection in myocardium. Thus application of molecular techniques will allow collection and analysis of more information on the epidemiology of viral cardiomyopathies, patient risk stratification and appropriate medical treatment.

Usefulness of inflammatory and haemostatic markers to predict short-term risk for death in middle-aged ischaemic stroke patients.

OBJECTIVES: There is increasing evidence that inflammation and hypercoagulability play an important role in the pathophysiology of acute ischaemic stroke. We examined the in-hospital prognostic value on mortality of C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha), fibrinogen and D-dimer in middle-aged ischaemic stroke patients. MATERIALS AND METHODS: We recruited 231 consecutive patients <66 years with acute ischaemic stroke. CRP, TNF-alpha, fibrinogen and D-dimer levels were determined within 12 h from admission. RESULTS: Fifteen (6.5%) patients died during hospitalization. CRP, fibrinogen and D-dimer levels were significantly higher in patients who died compared with those who survived but only CRP and fibrinogen were independently associated with death, after adjusting for various confounding factors. For 1 mg/l increase in CRP there was a 20% higher risk of dying while for 10 mg/dl increase in fibrinogen the additive risk was 18%. CRP levels >18 mg/l and fibrinogen levels >490 mg/dl were the optimal points that discriminated those who died from the rest. CONCLUSIONS: CRP and fibrinogen levels can predict independently the risk of early death in middle-aged ischaemic stroke patients emphasizing the role of inflammation and coagulation in the evolution of ischaemic stroke.

Clinical and prognostic implications of self-rating depression scales and plasma B-type natriuretic peptide in hospitalised patients with chronic heart failure.

BACKGROUND: Depression is common among patients with chronic heart failure (CHF) and has been independently associated with a poorer prognosis. PURPOSE: This study evaluated the clinical and prognostic value of depression scales (Beck Depression Inventory (BDI), Zung Self-rating Depression Scale (Zung SDS)) along with plasma B-type natriuretic peptide (BNP) in CHF. METHODS: 155 hospitalised CHF patients (ejection fraction 26.9% (SD 6.4%)) were studied by depression (BDI, Zung SDS) and functional questionnaires (Kansas City Cardiomyopathy Questionnaire (KCCQ), Duke Activity Status Index (DASI)), BNP and 6-minute walk test (6MWT). Patients were followed for 6 months for cardiovascular events, including death from any cause or rehospitalisation for CHF decompensation. RESULTS: Seventy-six (49%) patients with depressive symptoms, as estimated by both scales, had significantly lower DASI and KCCQ scores (13.2 (SD 9.9) vs 23.6 (SD 13.0) and 26.6 (SD 15.0) vs 45.0 (SD 17.0), respectively; p<0.001), higher BNP (921 (SD 889) vs 439 (SD 267) pg/ml, p = 0.001) and reduced 6MWT (270 (SD 130) vs 337 (SD 133); p<0.001). According to logistic regression analysis, Zung SDS and BNP were independently associated with adverse clinical outcomes; values of Zung SDS >or=40 and of BNP >or=290 pg/ml predicted future events with a sensitivity of 82% and 94% and a specificity of 45% and 46%, respectively. The combination of Zung SDS plus BNP had an additive prognostic value, predicting events with a sensitivity of 77% and a specificity of 70% (event-free survival: Zung <40 and BNP <290 pg/ml; 170 (SD 9) days; Zung >or=40 and BNP <290 pg/ml, 159 (SD 14) days; Zung <40 and BNP >or=290 pg/ml, 118 (SD 15) days; Zung >or=40 and BNP >or=290 pg/ml, 73 (SD 8) days, p<0.001). CONCLUSIONS: CHF patients with depressive symptoms have impaired physical activity, associated with excessive neurohormonal activation. Among the studied scales, Zung SDS seemed to independently predict clinical outcome, especially in patients with increased plasma BNP concentration. Hence, the combination of those two modalities provides a practical means for risk stratification in CHF.

Effects of serial levosimendan infusions on left ventricular performance and plasma biomarkers of myocardial injury and neurohormonal and immune activation in patients with advanced heart failure.

BACKGROUND: Levosimendan is a novel inodilator that improves central haemodynamics and symptoms of patients with decompensated chronic heart failure. The role, however, of repeated levosimendan infusions in the management of these patients has not yet been properly assessed. PURPOSE: This randomised placebo-controlled trial investigated the effects of serial levosimendan infusions on cardiac geometry and function, and on biomarkers of myocardial injury and neurohormonal and immune activation (troponin T, N-terminal B-type natriuretic pro-peptide (NT-proBNP), C reactive protein (CRP) and interleukin (IL) 6) in patients with advanced heart failure. METHODS: 25 patients with decompensated chronic heart failure were randomised (2:1) to receive five serial 24-h infusions (every 3 weeks) of either levosimendan (n = 17) or placebo (n = 8), and were evaluated echocardiographically and biochemically before and after each drug infusion and 30 days after the final infusion. RESULTS: Following treatment, cardiac end-systolic and end-diastolic dimension and volume indices were significantly reduced only in the levosimendan-treated patients (p<0.01). A significant decrease in NT-proBNP (p<0.01), high-sensitivity CRP (p<0.01) and plasma IL6 (p = 0.05) was also observed in the levosimendan group, whereas these markers remained unchanged in the placebo group; similar changes were observed after each drug infusion. Although the number of patients with a positive troponin T (>or=0.01 ng/ml) was not different between the two groups at baseline, it was significantly higher in the placebo-treated group during the final evaluation (p<0.05). CONCLUSION: Serial levosimendan treatments improved left ventricular performance and modulated neurohormonal and immune activation beneficially in patients with advanced heart failure, without increasing myocardial injury.

Aspirin reduces anticardiolipin antibodies in patients with coronary artery disease.

BACKGROUND: Anticardiolipin antibodies (aCL) have been found to be elevated in patients with coronary artery disease (CAD) and have been associated with an adverse outcome owing to their prothrombotic activity. The aim of this study was to investigate the effect of aspirin treatment on aCL levels in patients with chronic CAD. MATERIALS AND METHODS: Forty patients with chronic CAD scheduled for elective coronary artery bypass graft surgery (CABG) and 40 healthy controls participated in the study. Patients were treated with 300 mg of aspirin once daily (o.d.) for the first 12 days and placebo for the following 12 days before CABG in a double-blind, cross-over trial. Immunoglobulin (Ig) G-, IgM-, IgA-aCL and C-reactive protein (CRP) levels were measured in the controls and at the end of each treatment period in the patients with CAD. RESULTS: The IgA- and IgG-aCL levels were greater in patients with CAD than in the controls. Compared with the placebo, IgA, IgG subtypes and CRP levels were reduced after aspirin treatment (P = 0.001, P = 0.02, P = 0.04, respectively). The percentage reduction of IgA- and IgG-aCL was related to the percentage reduction of CRP after aspirin (P < 0.05). CONCLUSION: Aspirin treatment with 300 mg o.d. reduced the serum levels of IgA and IgG subtypes in patients with chronic CAD in parallel to a reduction in CRP. These findings offer an additional pathophysiological mechanism of the beneficial effects of aspirin in patients with chronic CAD.

Ischemic but not mechanical preconditioning attenuates ischemia/reperfusion induced myocardial apoptosis in anaesthetized rabbits: the role of Bcl-2 family proteins and ERK1/2.

OBJECTIVE: Recent studies suggest that ischemic preconditioning (IPC) inhibits myocardial apoptosis after ischemia and reperfusion. This study aimed first, to examine whether short mechanical stretch with acute pressure overload (MPC), which has been shown to reduce infarct size after ischemia/reperfusion, mimics IPC in attenuating myocardial apoptosis and second, to evaluate whether induced cardioprotection involves modulation of the expression of the Bcl-2 family proteins and phosphorylation of prosurvival kinases. METHODS AND RESULTS: A model of anaesthetized rabbit was used and the preconditioning protocol included one cycle of short ischemia/reperfusion, or short mechanical stretch with acute pressure overload. Preconditioning stimuli were equally effective in reducing the infarct size, determined after 4 h reperfusion. However, IPC but not MPC attenuated myocardial apoptosis. IPC restored the decreased expression of Bcl-2 and Bcl-xL observed in hearts subjected to ischemia and reperfusion only. Bax levels were not different among the groups. ERK1/2 were activated during reperfusion in both IPC and MPC groups. CONCLUSIONS: The data provide further evidence that apoptosis and necrosis contribute independently to infarct size after ischemia and reperfusion. Inhibition of the myocardial apoptotic processes by IPC may involve modulation of the expression of anti-apoptotic proteins, Bcl-2 and Bcl-xL. ERK1/2 may be involved in the inhibition of both apoptosis and necrosis.