]m reduction. Cytosolic Na ϩ concentrations that yielded one-half maximal activity levels for mitoNCX were 3.6 mM at normal ⌬⌿ m and 7.6 mM at ⌬⌿m dissipation. We conclude that 1) the mitochondrial Ca 2ϩ uniporter accumulates Ca 2ϩ in a manner that is dependent on ⌬⌿m at the physiological range of [Ca 2ϩ ]c; 2) ⌬⌿m dissipation opens the mPTP and results in Ca 2ϩ influx to mitochondria; and 3) although mitoNCX activity is impaired, mitoNCX extrudes Ca 2ϩ from the matrix even after ⌬⌿m dissipation. permeability transition pore; Na ϩ /Ca 2ϩ exchange; depolarization; ischemia-reperfusion injury ACCUMULATING EVIDENCE REVEALS that mitochondria play primary roles in fatal cell damage during ischemia-reperfusion (33). Key events that occur during ischemia include cytosolic Ca 2ϩ elevation, ATP depletion, high P i concentration, depolarized membrane potential, and acidotic pH. On reperfusion and recovery of normal pH, a burst of reactive oxygen species occurs, mitochondrial Ca 2ϩ overload ensues, and these lead to opening of the mitochondrial permeability transition pore (mPTP; Refs. 8,12,34). Opening of the mPTP allows water and solutes Յ1,500 Da in size to enter the matrix and cause mitochondrial swelling, rupture of the outer mitochondrial membrane, and release of cytochrome c or apoptosis-inducing factor, which initiates apoptotic programmed cell death (12,24,34). Because previous studies (8,12,13) (10,11). Furthermore, recent studies (4,8,10,11,18) also suggest a possible contribution by the mPTP to Ca 2ϩ homeostasis in both the cytosol and mitochondria. Despite the considerable attention given to the pathophysiological significance of mitochondrial Ca 2ϩ , the regulation and/or modulation of mitochondrial Ca 2ϩ during pathophysiological conditions such as ischemia-reperfusion injury are unclear. In previous studies, information about mitochondrial Ca 2ϩ was obtained using isolated mitochondria, whereby the structural and functional properties of organelles were seriously affected, and other cellular architectures were separated from the mitochondria. In this study, we measured [Ca 2ϩ ] m in saponin-permeabilized rat ventricular myocytes and investigated how ⌬⌿ m depolarization affects [Ca 2ϩ ] m and mitochondrial Ca 2ϩ transport systems such as the Ca 2ϩ uniporter, the mPTP, and mitoNCX.

BackgroundOur study aimed to investigate both the clinical implications of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) and the relation of LGE to clinical findings in patients with Takotsubo cardiomyopathy (TTC).MethodsWe evaluated 20 consecutive patients (2 men, 18 women; median age, 77 years; interquartile range [IQR] 67-82 years) who were admitted to our hospital with the diagnosis of TTC. CMR was performed within 1 week after admission, and follow-up studies were conducted 1.5 and 6 months later.ResultsIn 8 patients, CMR imaging during the sub-acute phase revealed LGE in the area matched with wall motion impairment. Cardiogenic shock was more frequently observed in patients with LGE than in those without LGE (38% vs 0%, p = 0.049). The patients with LGE needed a longer duration for ECG normalization and recovery of wall motion than did those without LGE (median 205 days, IQR [152-363] vs 68 days, [43-145], p = 0.005; 15 days, [10-185] vs 7 days, [4-13], p = 0.030, respectively). In 5 of these 8 patients, LGE disappeared within 45-180 days (170, IQR [56-180]) of onset. The patients with LGE remaining in the chronic phase had higher peak creatine kinase levels than did those without LGE (median 307 IU/L, IQR [264-460] vs 202 IU/L, [120-218], p = 0.017).ConclusionLGE by CMR in the sub-acute phase may be associated with the severity and prolonged recovery to normal of clinical findings in TTC.

Aldosterone has non-genomic effects that express within minutes and modulate intracellular ion milieu and cellular function. However, it is still undefined whether aldosterone actually alters intracellular ion concentrations or cellular contractility. To clarify the non-genomic effects of aldosterone, we measured [Na+]i, Ca2+ transient (CaT), and cell volume in dye-loaded rat ventricular myocytes, and we also evaluated myocardial contractility. We found the following: (i) aldosterone increased [Na+]i at the concentrations of 100 nmol/L to 10 micromol/L; (ii) aldosterone (up to 10 micromol/L) did not alter CaT and cell shortening in isolated myocytes, developed tension in papillary muscles, or left ventricular developed pressure in Langendorff-perfused hearts; (iii) aldosterone (100 nmol/L) increased the cell volume from 47.5 +/- 3.6 pL to 49.8 +/- 3.7 pL (n=8, p<0.05); (iv) both the increases in [Na+]i and cell volume were blocked by a Na+-K+-2Cl- co-transporter (NKCCl) inhibitor, bumetanide, or by a Na+/H+ exchange (NHE) inhibitor, 5-(N-ethyl-N-isopropyl) amiloride; and (v) spironolactone by itself increased in [Na+]i and cell volume. In conclusion, aldosterone rapidly increased [Na+]i and cell volume via NKCC1 and NHE, whereas there were no changes in CaT or myocardial contractility. Hence the non-genomic effects of aldosterone may be related to cell swelling rather than the increase in contractility.

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The aim of this study was to assess the efficacy of a biolimus A9-eluting stent in patients with a right coronary artery (RCA) ostial lesion. Ostial lesions of the RCA have been a limitation of percutaneous coronary intervention even in the drug-eluting stent (DES) era. However, clinical outcomes after the deployment of a second generation DES to an RCA ostial lesion with intravascular ultrasound (IVUS) guidance have not been fully elucidated. From September 2011 to March 2013, 74 patients were enrolled in 17 centers from Japan. RCA ostial lesion was defined as de novo significant stenotic lesion located within 15 mm from ostium. IVUS was used for all cases to confirm the location of ostium and evaluate stent coverage of ostium. Patients with hemodialysis were excluded. The primary endpoint is a major adverse cardiac event (MACE) at 1 year. Forty two percent of patients had multi-vessel disease. Angiographically severe calcification was observed in 26% of the lesions. The mean stent diameter was 3.3 ± 0.3 mm (3.5 mm, 72%, 3.0 mm, 25%, and 2.75 and 2.5 mm, 3%), stent length was 17.5 ± 5.8 mm, and dilatation pressure of stenting was 15.6 ± 4.1 atm. RCA ostium was covered by stent in all lesions in IVUS findings. Post dilatation was performed for 64% of lesions (balloon size 3.7 ± 0.6 mm). MACE rate at 1 year was 5.4% (target lesion revascularization 5.4%, myocardial infarction 1.2%, and no cardiac death). The biolimus A9-eluting stent for RCA ostial lesions with IVUS guidance showed favorable results at 1-year follow-up.