Loss of cardioprotection induced by ischemic preconditioning after an initial ischemic period in isolated rat hearts

BACKGROUND:

The beneficial effect of ischemic preconditioning (PC) has been extensively studied in normal hearts but its effects on diseased hearts remain largely unknown. The effect of PC in the already ischemic myocardium has not been previously studied, although ischemia in varying intervals, which is difficult to assess, is often encountered in clinical practice.

OBJECTIVE:

To investigate whether the cardioprotective effect of PC is preserved when it is applied after a period of ischemia of varying duration.

METHODS:

Male Wistar rats were used for this study. Isolated normal rat hearts were perfused in Langendorff mode. Before 20 min of zero flow global ischemia followed by 45 min of reperfusion, hearts were subjected to an initial 20-min period of ischemia followed by 10 min of reperfusion (group A1); an initial 20-min period of ischemia followed by 10 min of reperfusion and two-cycle PC (3 min of ischemia, 5 min of reperfusion followed by 5 min of ischemia and 5 min of reperfusion) (group A2); and two-cycle PC followed by the initial 20-min period of ischemia and 10 min of reperfusion (group A3).Groups B and C were subjected to an initial ischemia of 15 min and 10 min, respectively, and subgroups 1, 2 and 3 were treated as above. Left ventricular end-diastolic pressure was measured at 45 min of reperfusion (LVEDP45 in mmHg). Postischemic recovery of left ventricular developed pressure was expressed as a percentage of the initial value (LVDP%).

RESULTS:

LVDP% and LVEDP45 were similar between groups A1 and A2, while when ischemic preconditioning preceded the two periods of ischemia (group A3), it resulted in significantly higher LVDP% and significantly lower LVEDP45 compared with groups A1 and A2. Left ventricular functional recovery was not increased in group B2 compared with group B1. LVDP% and LVEDP45 were similar among groups C1, C2 and C3.

CONCLUSION:

Ischemic preconditioning does not improve functional recovery in isolated rat hearts that have been initially subjected to 20 min or 15 min of zero-flow global ischemia, while an initial 10-min ischemic period seems to precondition the heart.     

Adenoid cystic carcinoma of the head and neck. Clinicopathological analysis of 23 patients and review of the literature

Adenoid cystic carcinoma (ACC) is a rare epithelial tumor with a distinct natural history characterized by an indolent but persistent growth, late onset of distant metastases and eventual death of patients. Between 1991 and 2003, 23 patients with ACC were treated in our Department. Surgery with a curative intent followed by radiotherapy (RT) was applied in 22 patients. Complete resection was achieved in 72.73% of patients. Local recurrence occurred in 26% of patients. Positive margins emerged as the only statistically significant parameter (p < 0.0001) influencing the development of local recurrence. Distant metastasis (DM) occurred in 47.8% of patients. In 54.5% of the patients developing DM, this occurred between 5 and 10 years after the initial treatment. DM was influenced by perineural invasion (p = 0.04) and was disassociated from local control of the tumor. The mean overall survival of our patients was 70.58 months and the mean disease free survival 61.85 months. Perineural invasion (p = 0.048) and DM (p = 0.001) had a statistically significant impact on final patients' outcome. The most important factor influencing survival was DM. Its late onset, irrespectively of local control, supports the hypothesis that ACC has a potential to develop DM in the very early phases of tumor growth.     

The value of computed tomography-derived coronary artery calcification score in coronary artery disease detection in asymptomatic hemodialysis patients

BACKGROUND: We evaluated the value of coronary artery calcification (CAC) score in coronary artery disease (CAD) detection in asymptomatic hemodialysis (HD) patients by evaluating the association among CAC score, exercise electrocardiography (EECG), and Thallium-201 dipyridamole scintigraphy. Correlation between aortic pulse wave velocity (PWV) and CAC score was also evaluated. METHODS: CAC score was assessed with conventional computed tomography in 40 patients. Thirty patients completed EECG and 25; those with a positive CAC score and/or a positive EECG performed Thallium dipyridamole scintigraphy. Carotid-femoral PWV was assessed in all patients. RESULTS: There was no association among CAC score and EECG or Thallium dipyridamole scintigraphy. In contrast, CAC score was correlated with aortic PWV. CONCLUSION: The previous results question the role of CAC score in the detection of CAD in asymptomatic HD patients. The correlation between CAC score and aortic PWV raises the possibility that CAC score represents more an indicator of coronary artery medial wall calcification than a marker of CAD.     

FoSTeS, MMBIR and NAHR at the human proximal Xp region and the mechanisms of human Xq isochromosome formation

The recently described DNA replication-based mechanisms of fork stalling and template switching (FoSTeS) and microhomology-mediated break-induced replication (MMBIR) were previously shown to catalyze complex exonic, genic and genomic rearrangements. By analyzing a large number of isochromosomes of the long arm of chromosome X (i(Xq)), using whole-genome tiling path array comparative genomic hybridization (aCGH), ultra-high resolution targeted aCGH and sequencing, we provide evidence that the FoSTeS and MMBIR mechanisms can generate large-scale gross chromosomal rearrangements leading to the deletion and duplication of entire chromosome arms, thus suggesting an important role for DNA replication-based mechanisms in both the development of genomic disorders and cancer. Furthermore, we elucidate the mechanisms of dicentric i(Xq) (idic(Xq)) formation and show that most idic(Xq) chromosomes result from non-allelic homologous recombination between palindromic low copy repeats and highly homologous palindromic LINE elements. We also show that non-recurrent-breakpoint idic(Xq) chromosomes have microhomology-associated breakpoint junctions and are likely catalyzed by microhomology-mediated replication-dependent recombination mechanisms such as FoSTeS and MMBIR. Finally, we stress the role of the proximal Xp region as a chromosomal rearrangement hotspot.     

Amyloid angiopathy of the human brain: immunohistochemical studies using markers for components of extracellular matrix, smooth muscle actin and endothelial cells

Cerebral amyloid angiopathies comprise a heterogeneous group of conditions characterised by amyloid deposition in leptomeningeal and cortical vessels. We have studied the deposition of extracellular matrix components in such vessels from controls and ten cases with marked amyloid angiopathy. Arterial vessels which were heavily loaded with amyloid often showed lack of immunostaining to collagen type I, III, V and VI in the amyloid-containing parts of the vessel wall but some immunoreactivity remained in the adventitia. The subintimal region of some arterioles presented a faint staining with collagen V and collagen VI antisera. Immunostaining to collagen IV and laminin revealed normal reactivity in the vascular basal lamina and frequently remaining activity in the media. Immunostaining for actin showed a complete or partial loss of reactivity in the amyloid-containing parts of the media but often there was a thin line of staining at the position of pericytes. The endothelial markers did not reveal any changes compared with controls. In other cerebral microangiopathies, for instance Binswanger’s leukoencephalopathy, CADASIL and cases presenting hyalinosis there is a deposition of fibrillary collagens in the wall of afflicted microvessels. Degeneration of smooth muscle cells and absence of marked fibrosis in some of the arterial vessels in cases of amyloid angiopathy may explain why such vessels are susceptible to ruptures and haemorrhages. Received: 5 November 1996 / Revised: 25 March 1997, 8 June 1998 / Accepted: 9 June 1998     

Thirty-month follow-up of coronary artery calcification in hemodialysis patients: different roles for inflammation and abnormal calcium-phosphorous metabolism?

BACKGROUND: Cardiovascular disease is the leading cause of death in hemodialysis (HD) patients. Coronary artery calcification (CAC) is considered a marker of atherosclerosis and coronary artery disease (CAD). The CAC progression and factors that influence it were evaluated during a 30-month period. METHODS: Forty HD patients without a history of CAD were enrolled into the study. CAC score was assessed with conventional CT repeated every six months. The circulating factors of phosphorous, calcium, calcium-phosphorous product, intact parathyroid hormone, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, lipoprotein-alpha, albumin, high sensitivity C-reactive protein, and fibrinogen were measured monthly. Hypertension and calcium intake during the study period were taken into account as well. RESULTS: At baseline, CAC score was correlated with age and duration of HD therapy. From all evaluated factors, CAC initiation was influenced only by older age and C-reactive protein. CAC, when it was started, was aggravated continuously and was influenced only by elevated serum phosphorous and calcium-phosphorous product. Hypertension, lipid profile, and calcium intake did not affect CAC initiation or progression. CONCLUSIONS: Once CAC progression starts, it is an uninterrupted process. The roles of inflammation and abnormal calcium-phosphorous metabolism in CAC differ. Inflammation is the major factor that contributes in CAC initiation. Elevated serum phosphorous and calcium-phosphorous product accelerates CAC progression.     

Left atrial volume and N-terminal pro-B type natriuretic peptide are associated with elevated pulmonary artery pressure in patients with systemic sclerosis

Early detection of pulmonary hypertension (PH) in patients with systemic sclerosis (SSc) is essential as it leads to substantial morbidity and mortality irrespective of its etiology. The aim of our study was to determine whether noninvasive biochemical and/or echocardiographic indices can predict the presence of PH in these patients. We prospectively studied 66 patients (mean age of 57.7?±?12.1 years, 63 women) with SSc without clinical manifestations of heart failure. All patients underwent standard and tissue Doppler echocardiography. Plasma N-terminal pro-B type natriuretic peptide (NT-proBNP) and asymmetric dimethylarginine (ADMA) levels were also measured. In 24 (36%) patients, the diagnosis of PH was established by echocardiography (systolic pulmonary artery pressure value ≥40 mmHg). Left atrial (LA) volume, NT-proBNP, ADMA, ratio of early transmitral filling velocity to early diastolic velocity of the mitral annulus (mitral E/E _m), and right ventricular myocardial performance index (MPI) were univariate predictors of PH. In multivariate analysis, NT-proBNP, LA volume, and right ventricular MPI were independent predictors of PH in SSc patients. LA volume and NT-proBNP may be useful noninvasive markers for the prediction of elevated pulmonary artery pressure in patients with SSc. These parameters should be considered when assessing this population for risk stratification and for identification of patients demanding further investigation and institution of specific therapy for the disease at the time when it is most likely to be effective.