Hypertension-induced changes in the rat myocardium during the development of cardiac hypertrophy – a comparison between the left and the right ventricle

The hypertrophy of the cardiac muscle is one of the most significant maladaptive mechanisms activated in response to increased workload. It is associated with histological and ultrastructural alterations, changes in the quantitative parameters and the expression of different enzymes. While the structural and functional consequences of systemic hypertension on the left ventricle have been well evaluated, the right ventricle has received less attention. The aim of the present study was to analyse and compare the changes in the left and right ventricle during the development of cardiac hypertrophy initiated by systemic hypertension in different age groups of spontaneously hypertensive rats. Therefore, we studied the histology and ultrastructure of the cells of the myocardium, evaluated the immunohistochemical expression of the enzyme neuronal nitric oxide synthase and conducted a quantitative analysis of several morphometric parameters. We used three groups of spontaneously hypertensive rats. For the quantitative analysis we also used three age groups of age- and weight-matched control animals (normotensive Wistar rats). In both ventricles, we described cardiomyocytic hypertrophy, focal myocytolysis and increased collagen deposition in the interstitial space. Our observations on the ultrastructural level were associated with changes in the cardiomyocytic nuclei, the arrangement, maturity and organisation of the myofibrils, the localisation and ultrastructure of the mitochondria, the development and maturity of the intercalated discs, as well as changes in the components of the interstitium. The immunohistochemical expression of neuronal nitric oxide synthase in the left ventricle was stronger than that in the right ventricle across all age groups. The comparative quantitative analysis revealed that changes in the studied morphometric parameters in the two ventricles occurred disproportionately. In conclusion, the present study characterised the development of cardiac hypertrophy in response to systemic hypertension in both ventricles and demonstrated the involvement of the right ventricle.     

缺血后适应的研究与进展

目的:缺血后适应即冠状动脉再灌注开始时对冠脉进行短暂、重复的开通及再闭过程,随后恢复冠状动脉血流,对缺血再灌注心脏有显著保护作用。总结并分析缺血后适应对缺血再灌注心脏的保护作用及其机制。资料来源:应用计算机检索Medline1986-01/2006-05关于缺血后适应的文章。检索词“myocardial protection,Ischemic postconditioning,Ischemia-reperfusion injury”并限定文章的语种类为English。资料选择:对资料进行初审,纳入标准:关于缺血后适应机制及心脏保护作用的研究。排除标准:重复性研究。资料提炼:共收集到符合上述要求的文献51篇,排除21篇重复性研究。30篇符合纳入标准:其中26篇关于缺血后适应的研究,4篇关于缺血后适应的综述。资料综合:缺血后适应对心脏的保护作用包括缩小心肌梗死面积、对抗心律失常等。缺血后适应对心脏的保护作用的机制涉及腺苷、一氧化氮、线粒体ATP敏感K通道、再灌注损伤存活激酶通路、线粒体可渗透转运孔隙等许多方面和信号传导途径。结论:缺血后适应现象已经被许多独立的实验室应用大、小动物在体和体外模型及细胞培养模型所观察。与缺血预适应相比,缺血后适应可能会有更广阔的临床应用前景,其机制需进一步研究。     

Biochemical expression of heterozygous hereditary hemochromatosis

Background: Hereditary hemochromatosis (HH) is a common autosomal recessive disease caused by an iron overload. Two mutations (C282Y and H63D) on the responsible HFE gene have been described. HH heterozygotes may have a slight iron overload that does not cause clinical disease. Compound heterozygosity may be associated with higher iron stores than C282Y heterozygosity. We studied biochemical iron parameters in HH C282Y and compound heterozygotes without a clinically significant iron overload. Methods: Data on hemoglobin, hematocrit, mean corpuscular volume, serum ferritin, serum iron, transferrin, and transferrin saturation were obtained from 40 C282 wild type controls (irrespective of H63D genotype), 61 C282Y heterozygotes, and 18 compound (C282Y/H63D) heterozygotes without clinical iron overload disease. Results: Serum ferritin levels were significantly higher in female HH heterozygotes, particularly in compound heterozygotes, than in normal women. In male heterozygotes, no difference in serum ferritin was found. We found higher mean serum iron and transferrin saturation levels in male and female HH heterozygotes than in normal controls, the highest in the group of compound heterozygotes. Conclusions: Mean serum ferritin (only in women), serum iron, and transferrin saturation are highest in compound heterozygotes and lowest in controls. C282Y heterozygotes seem to be an intermediate group between compound heterozygotes and the normal population.     

Preventing left ventricular hypertrophy by ACE inhibition in hypertensive patients with type 2 diabetes: a prespecified analysis of the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT)

OBJECTIVE—In patients with type 2 diabetes, left ventricular hypertrophy (LVH) predicts cardiovascular events, and the prevention of LVH is cardioprotective. We sought to compare the effect of ACE versus non-ACE inhibitor therapy on incident electrocardiographic (ECG) evidence of LVH (ECG-LVH).RESEARCH DESIGN AND METHODS—This prespecified study compared the incidence of ECG-LVH by Sokolow-Lyon and Cornell voltage criteria in 816 hypertensive type 2 diabetic patients of the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT), who had no ECG-LVH at baseline and were randomly assigned to at least 3 years of blinded ACE inhibition with trandolapril (2 mg/day) or to non-ACE inhibitor therapy. Treatment was titrated to systolic/diastolic blood pressure <130/80 mmHg. ECG readings were centralized and blinded to treatment.RESULTS—Baseline characteristics of the two groups were similar. Over a median (interquartile range) follow-up of 36 (24–48) months, 13 of the 423 patients (3.1%) receiving trandolapril compared with 31 of the 376 patients (8.2%) receiving non-ACE inhibitor therapy developed ECG-LVH (hazard ratio [HR] 0.34 [95% CI 0.18–0.65], P = 0.0012 unadjusted, and 0.35 [0.18–0.68], P = 0.0018 adjusted for predefined baseline covariates). The HR was significant even after adjustment for follow-up blood pressure and blood pressure reduction versus baseline. Compared with baseline, both Sokolow-Lyon and Cornell voltages significantly decreased with trandolapril but did not change with non-ACE inhibitor therapy.CONCLUSIONS—ACE inhibition has a specific protective effect against the development of ECG-LVH that is additional to its blood pressure–lowering effect. Because ECG-LVH is a strong cardiovascular risk factor in people with hypertension and diabetes, early ACE inhibition may be cardioprotective in this population.Left ventricular hypertrophy (LVH), a cardinal manifestation of preclinical cardiovascular disease, strongly predicts myocardial infarction, stroke, and cardiovascular death in patients with hypertension (1) or coronary artery disease (2), as well as in the general population (3). In the Framingham Study, electrocardiographic (ECG) evidence of LVH (ECG-LVH) was associated with a twofold increase in mortality over that resulting from hypertension alone (4).Studies have consistently shown that antihypertensive therapy may effectively limit the incidence of ECG-LVH, regardless of the treatments used to reduce blood pressure (5). However, the Heart Outcomes Prevention Education (HOPE) (6) and the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trials (7) showed that, in patients with ECG-LVH at inclusion, the ACE inhibitor ramipril and the angiotensin receptor blocker (ARB) losartan, respectively, regressed LVH more effectively than drugs that do not directly interfere with the renin-angiotensin-aldosterone system (RAAS). The finding in both trials that this benefit was significant even after adjustments for the small differences in blood pressure between the two treatment groups provided consistent evidence that RAAS inhibitor therapy has a specific cardioprotective effect that exceeds expectations based on changes in blood pressure alone. However, the HOPE trial (6) was not powered to assess the treatment effect on new-onset LVH in the subgroup with no ECG-LVH at baseline, and the LIFE trial (7) included only patients with LVH. Thus, whether RAAS inhibitor therapy may also prevent new-onset LVH in subjects with normal left ventricular mass to start with is unknown. To formally explore this issue, we compared the effect of ACE versus non-ACE inhibitor therapy on incident ECG-LVH in patients from the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) (8–11) who had no ECG-LVH at inclusion.     

Health-related quality of life of Southern Chinese with chronic hepatitis B infection

Background  

Few studies have evaluated the health-related quality of life (HRQOL) of Southern Chinese with chronic hepatitis B (CHB) infection.     

Antitumor activity of glycosylated molluscan hemocyanins via Guerin ascites tumor

As observed in most molluscan hemocyanins, high-mannose type glycans were identified in hemocyanins from Rapana venosa (RvH), Helix lucorum (HlH) and keyhole limpet (Megatura crenulata). In addition, a glycan with a branching structure containing xylose, fucose and terminal methyl hexose was identified in β-HlH. We have examined the immuno-adjuvant properties of hemocyanins, their derivatives and conjugates associated with the cell mediated immunity in experimental tumor-bearing animals with ascites tumor of Guerin. After immunization of the animals with the experimental vaccine preparations, the highest values of splenic lymphocytes were observed in groups immunized with the conjugates RvH-TAg, β-HlH-TAg and KLH-TAg (42.3%; 40.8% and 40.58%, respectively) than with the native hemocyanins (36.5%; 35.1% and 32.4%, respectively). The immunization of rats with the hemocyanins β-HlH, RvH and KLH and their conjugates, prolonged the median survival time of tumor-bearing animals compared with non-immunized animals (39, 33, 31 and 7 days, respectively). Both hemocyanins β-HlH and RvH activate the immune system of the experimental animals and therefore could be a good alternative for KLH. For this reason they could be included into the composition of non-specific anti-tumor vaccines to enhance their effectiveness.