Changes in cellular Ca2+ and Na+ regulation during the progression towards heart failure in the guinea pig.

KEY POINTS: During compensated hypertrophy in vivo fractional shortening (FS) remains constant until heart failure (HF) develops, when FS decreases from 70% to 39%. Compensated hypertrophy is accompanied by an increase in INa,late and a decrease in Na+ ,K+ -ATPase current. These changes persist as HF develops. SR Ca2+ content increases during compensated hypertrophy then decreases in HF. In healthy cells, increases in SR Ca2+ content and Ca2+ transients can be achieved by the same amount of inhibition of the Na+ ,K+ -ATPase as measured in the diseased cells. SERCA function remains constant during compensated hypertrophy then decreases in HF, when there is also an increase in spark frequency and spark-mediated Ca2+ leak. We suggest an increase in INa,late and a decrease in Na+ ,K+ -ATPase current and function alters the balance of Ca2+ flux mediated by the Na+ /Ca2+ exchange that limits early contractile impairment. ABSTRACT: We followed changes in cardiac myocyte Ca2+ and Na+ regulation from the formation of compensated hypertrophy (CH) until signs of heart failure (HF) are apparent using a trans-aortic pressure overload (TAC) model. In this model, in vivo fractional shortening (FS) remained constant despite HW:BW ratio increasing by 39% (CH) until HF developed 150 days post-TAC when FS decreased from 70% to 39%. Using live and fixed fluorescence imaging and electrophysiological techniques, we found an increase in INa,late from -0.34 to -0.59 A F-1 and a decrease in Na+ ,K+ -ATPase current from 1.09 A F-1 to 0.54 A F-1 during CH. These changes persisted as HF developed (INa,late increased to -0.82 A F-1 and Na+ ,K+ -ATPase current decreased to 0.51 A F-1 ). Sarcoplasmic reticulum (SR) Ca2+ content increased during CH then decreased in HF (from 32 to 15 µm l-1 ) potentially supporting the maintenance of FS in the whole heart and Ca2+ transients in single myocytes during the former stage. We showed using glycoside blockade in healthy myocytes that increases in SR Ca2+ content and Ca2+ transients can be driven by the same amount of inhibition of the Na+ ,K+ -ATPase as measured in the diseased cells. SERCA function remains constant in CH but decreases (τ for SERCA-mediated Ca2+ removal changed from 6.3 to 3.0 s-1 ) in HF. In HF there was an increase in spark frequency and spark-mediated Ca2+ leak. We suggest an increase in INa,late and a decrease in Na+ ,K+ -ATPase current and function alters the balance of Ca2+ flux mediated by the Na+ /Ca2+ exchange that limits early contractile impairment.

Metallothionein 2A genetic polymorphism and its correlation to coronary heart disease.

OBJECTIVE: To investigate the gene polymorphism of metallothionein 2A (MT2A)-838G/C and its correlation to coronary heart disease in the Han population of Jiangsu, China. PATIENTS AND METHODS: The MT2A-838G/C was examined in 287 patients with coronary heart disease (CHD group) and 226 healthy controls (control group) by using mono-labeled fluorescent probes. Meanwhile, relevant variables of all subjects were measured, including blood lipid and glucose profiles and body mass index (BMI). The extent of the coronary artery disease was evaluated based on Gensini's coronary artery scoring method. RESULTS: Three distinct genotypes were identified. The highest frequency was observed for genotype GG, followed by genotype GC and CC. There were statistically significant differences in the genotype and allele frequency distribution of the MT2A gene-838G/C polymorphism between the CHD and the control group (p < 0.05). The allele frequency of MT2A-838C in the CHD patients were higher than that in the healthy controls (31.4% vs 24.6%, p = 0.016). The CHD risk in C allele carriers (including genotype GC+CC) was 1.562 folds as high as in GG allele carriers (OR = 1.562, 95% confidence intervals (CI): 1.099-2.218, p = 0.013). According to the results of logistic regression analysis, the C allele was an independent risk factor for CHD (p < 0.05). Gensini's coronary artery disease score were higher in C allele carriers than in non-C allele carriers (p < 0.05). CONCLUSIONS: The gene polymorphism of MT2A-838G/C is correlated to CHD. The C allele might be a CHD-susceptible gene and might also have an effect on the extent of coronary artery disease.

Cardiac hemangioma located at the apex of the left ventricle: a rare case report.

We report the case of a 67-year-old man who was found to have asymptomatic murmurs during his health check-up. Echocardiography revealed a mobile spherical mass in the left ventricle (LV), whereas magnetic resonance imaging (MRI) study revealed a well-circumscribed heterogeneous mass in the LV with its base attached to the LV apex. To the best of our knowledge, such a case of hemangioma, particularly its rare location at the apex of the LV, and its asymptomatic conduction disturbance has not yet been reported in the medical literature. Because of successful surgical intervention, the patient is in good health without any further tumor recurrence at 24 months after the diagnosis.

Spontaneous massive haemothorax caused by rupture of an intercostal vein.

Spontaneous massive haemothorax is rare. We describe a healthy 44 year old woman who experience sudden onset chest pain while sleeping. Chest radiograph revealed massive right pleural effusion. Progressive dyspnoea, cold sweating, and tachycardia developed later. A tube thoracostomy was performed immediately and massive haemothorax was noted. An emergency thoracotomy was performed because of unstable vital signs. Disruption of the right third intercostal vein with continuous bleeding was observed, and suture ligation of the vein was performed. The total blood loss was about 4000 ml. The patient recovered uneventfully, and her condition at follow up visits to the outpatient department was satisfactory.