Emergency Transcatheter Aortic Valve Implantation in a Surgical Aortic Bioprosthetic Valve for Acute Decompensated Heart Failure Caused by Sudden Progression of Structural Valve Deterioration.

Bioprosthetic aortic valves have limited durability. We herein report sudden progression of structural valve deterioration (SVD) and a successful case of emergency transcatheter aortic valve (TAV) implantation for acute decompensated heart failure (ADHF) caused by SVD. A 79-year-old man who had undergone a Bentall operation 11 years prior was diagnosed with ADHF due to suddenly progressive SVD. Emergency TAV implantation in the surgical bioprosthetic valve was selected based on the surgical risk. Ours and previous case reports suggest that SVD can progress suddenly, even after months of stability, and that emergency TAV implantation is effective.

Acute Myocardial Infarction Due to Coronary Artery Embolism during Chemotherapy with mFOLFOX-6 Plus Bevacizumab for Metastatic Colon Cancer.

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, may be associated with arterial embolisms. We herein report a case of acute myocardial infarction caused by coronary embolism during combination chemotherapy with mFOLFOX-6 and bevacizumab in a patient with metastatic colon cancer. Thromboembolism occurred only in the distal right posterolateral branch without stenotic lesions or plaque rupture in the proximal branch of the right coronary artery. Sole thromboaspiration was successfully performed; the final angiogram demonstrated no stenosis in the right coronary artery. Bevacizumab may be associated with acute coronary syndrome in patients with coronary risk factors, despite no significant coronary narrowing.

Subclinical and latent cardiac dysfunction in obstructive sleep apnea and effectiveness of continuous positive airway pressure.

PURPOSE: Obstructive sleep apnea (OSA) is associated with various cardiovascular disorders. This study aimed to investigate the effects of OSA on left ventricular (LV) function in patients with OSA who were at risk for heart failure but who had not yet developed structural heart changes. The study also sought to determine the effects of continuous positive airway pressure (CPAP) in these patients. METHODS: In a retrospective study, consecutive patients with polysomnographic OSA (apnea-hypopnea index [AHI] >5) were categorized into mild (AHI < 15), moderate (15 ≤ AHI < 30), and severe OSA (AHI ≥ 30) groups. The subjects were patients with OSA and at risk for heart failure who had not yet developed structural heart changes. All study participants underwent echocardiography and two-dimensional speckle tracking analysis, and their global longitudinal strain (GLS) was calculated. RESULTS: Of 275 patients, there were 31 with mild, 92 with moderate, and 152 with severe OSA. Of patients with moderate to severe OSA (AHI ≥ 20), 206 started CPAP and 92 patients underwent follow-up echocardiogram and speckle tracking echo analysis (median period of CPAP use: 283 days [258 to 391]). GLS was significantly reduced in patients with moderate and severe OSA compared with mild OSA (-17.8±3.1 vs. -18.0±2.6 vs. -19.3±2.8%, p=0.038). The proportion of patients with GLS ≥ -18% was significantly higher among the patients with moderate to severe OSA than among those with mild OSA. GLS improved after CPAP therapy in patients with moderate to severe OSA (GLS: -18.1±2.7% to -19.0±2.8%, p=0.004). Significant improvement in GLS was confirmed, particularly among patients with good CPAP adherence. CONCLUSION: Moderate to severe OSA is associated with LV dysfunction and can be significantly improved by CPAP therapy.

Difficulty Diagnosing Retrograde Type A Aortic Dissection with Intramural Hematoma and Risk of Re-dissection and Rupture: A Report of Two Cases.

Acute type A aortic dissection is a potentially fatal disease, and emergency surgery should be considered when it is diagnosed. We herein report two cases of retrograde type A aortic dissection with intramural hematoma, followed by re-dissection, rupture, and cardiac tamponade. The diagnoses in these cases had to be made carefully, as the false lumen of the ascending aorta was sometimes unclear on contrast-enhanced computed tomography.

The Diagnosis of Spontaneous Coronary Artery Dissection by Optical Coherence Tomography.

Spontaneous coronary artery dissection (SCAD) is rare, but it frequently presents as acute myocardial infarction. It is frequently fatal and most cases are diagnosed at autopsy. We herein present the case of a 65-year-old woman with ST-elevation and myocardial infarction due to SCAD. Optical coherence tomography (OCT) helped us to confirm the diagnosis. The information on the intravascular morphology provided by OCT imaging is much more detailed in comparison to that provided by coronary angiography (CAG) and intravascular ultrasound (IVUS).

Endoplasmic reticulum Ca2+ depletion induces endothelial cell apoptosis independently of caspase-12.

OBJECTIVE: Apoptosis of endothelial cells is considered an initial step in the development of atherosclerosis. Recent studies have indicated that depletion of the endoplasmic reticulum (ER) Ca(2+) content plays an important role in apoptosis. Caspase-12 is a key signal in ER stress-induced apoptosis. However, it is not known whether the depletion of ER Ca(2+) is linked to caspase-12 signalling in endothelial cells. Here we have investigated the interaction of Ca(2+) signalling and caspase-12 cleavage in apoptosis of endothelial cells. METHODS: Cytosolic Ca(2+) concentration ([Ca(2+)](i)) of primary porcine aortic endothelial cells was measured using fura-2/AM. Apoptosis was assessed by DNA fragmentation, and cleavage of caspase-12 using Western blotting techniques. RESULTS: Thapsigargin (5 microM), an inhibitor of the ER Ca(2+)-ATPase, depleted ER Ca (2+) content, increased [Ca(2+)](i), cleaved caspase-12, and induced apoptosis. Bradykinin (10 nM) also increased [Ca(2+)](i) but did not cleave caspase-12 or induce apoptosis. However, when intracellular Ca(2+) was chelated with BAPTA/AM (100 microM), bradykinin caused ER Ca(2+) depletion and apoptosis without accompanying caspase-12 cleavage. A non-selective caspase inhibitor, z-VAD.fmk (100 microM), inhibited apoptosis and cleavage of caspase-12 stimulated by thapsigargin, while a calpain inhibitor, MDL 28170 (120 microM), inhibited caspase-12 cleavage but not apoptosis. CONCLUSIONS: Thus, increases in intracellular Ca(2+) concentration are not sufficient for the induction of apoptosis in endothelial cells, and ER Ca(2+) depletion appears to induce apoptosis independently of caspase-12.

Akt and Ca2+ signaling in endothelial cells.

The protein kinase Akt participates in such important functions of endothelial cells as nitric oxide production and angiogenesis, activities that involve changes in cytosolic Ca2+ concentration. However, it is not known if activation of Akt is itself involved in the regulation of Ca2+ signals produced in these cells. The objective of this study was to examine if Akt is involved in the regulation of Ca2+ signaling in endothelial cells. Agonist-stimulated Ca2+ signals, assessed using fura-2, were compared in porcine aortic endothelial cells under control conditions or conditions in which Akt was blocked either by different inhibitors of phosphatidylinositol 3-kinase (PI3 kinase)/Akt or by transient expression of a dominant-negative form of Akt (dnAkt). We found that the release of intracellular Ca2+ stores stimulated by bradykinin or thapsigargin is not affected by the PI3 kinase inhibitors LY294002 and wortmannin, or by expression of dnAkt. LY294002 dose-dependently inhibits store-operated Ca2+ entry, an effect not seen with wortmannin. Expression of dnAkt has no effect on store-operated Ca2+ entry. We conclude that Akt is not involved in the regulation of agonist-stimulated Ca2+ signals in endothelial cells. The compound LY294002 inhibits store-operated Ca2+ entry in these cells by a mechanism independent of PI3 kinase/Akt inhibition.

Nitric oxide: inhibitory effects on endothelial cell calcium signaling, prostaglandin I2 production and nitric oxide synthase expression.

OBJECTIVE: Nitric oxide (NO) produced in large amounts by inducible nitric oxide synthase exerts many harmful effects such as stimulation of inflammation and induction of apoptosis. The effects of excessive NO production on functions of endothelial cells, the major physiological source of NO, are not completely known. The aim of this study was to investigate the role of NO on the regulation of endothelial cell Ca2+ signaling and endothelial cell function. METHODS: Primary porcine aortic endothelial cells (PAECs) were used for all these studies. Intracellular Ca2+ concentrations ([Ca2+]i) were measured using fura-2/AM. Production of prostaglandin I2 (PGI2) and cyclic GMP were assessed using enzyme immunoassays, and endothelial NO synthase protein expression was evaluated by Western blotting. RESULTS: Bradykinin (BK, 10 nM) and thapsigargin (TG, 1 microM) provoked large increases in [Ca2+]i. The NO donor NOC12 reduced these responses, respectively, by 21% and 31% at 100 microM, 60% and 55% at 300 microM, and 74% and 78% at 500 microM. These effects were also observed with other NO donors including spermine NONOate and NOC18, and were completely prevented by carboxy-PTIO (200 microM), an NO scavenger. 8-Bromo-cGMP, however, had no effects on BK- and TG-stimulated Ca2+ responses. A 30-fold increase in PGI2 production was observed in cells stimulated with BK. NOC12 again reduced this response by 12%, 54%, 83% and 95% at 10, 100, 300 and 500 microM, respectively. Endothelial NO synthase protein level was reduced by 2%, 15%, 36 and 47% after 2, 6, 12 and 24 h, respectively, of incubation with NOC18, a NO donor with long half-life. CONCLUSIONS: NO, when produced in large amounts, can inhibit agonist-induced Ca2+ responses independently of cyclic GMP, reduce the production of endothelium-derived relaxing factors (EDRFs) and interfere with endothelial NO synthase protein expression.

Effects of cytochrome P450 inhibitors on agonist-induced Ca2+ responses and production of NO and PGI2 in vascular endothelial cells.

Production of endothelium-dependent vascular relaxing factors, such as nitric oxide (NO) and prostaglandin I2 (PGI2), and endothelium-derived hyperpolarizing factor (EDHF), is regulated in part by changes in intracellular Ca2+ concentration ([Ca2+]i) in vascular endothelial cells (ECs). Cytochrome P450 (CYP), shown to mediate endothelium-dependent hyperpolarization via epoxyeicosatrienoic acids, is one of the candidates for EDHF. In this study we tested the hypotheses that CYP might be involved in EC Ca2+ signaling and that CYP activity might be linked with production of vasodilating factors other than EDHF. To this end, structurally different CYP inhibitors including SKF 525A, econazole and miconazole were tested on primary cultured porcine aortic endothelial cells. Intracellular Ca2+ concentration was measured using the fluorescent Ca2+ indicator fura-2/AM. Bradykinin (BK, 10 nM) and thapsigargin (TG 1 microM) provoked large biphasic increases in [Ca2+], which consist of Ca2+ release from intracellular stores and transplasmalemmal Ca2+ entry. SKF 525A dose-dependently (30-100 microM) inhibited BK- and TG-stimulated Ca2+ entry, but not intracellular Ca2+ store release. Econazole (10 microM) and miconazole (10 microM) had the same effect as SKF 525A on the Ca2+ entry. SKF 525A also dose-dependently inhibited BK-stimulated production of NO and PGI2, assessed by measuring cGMP and 6-keto-PGF(1alpha) concentration. These data suggest that, in addition to its regulation of EDHF production, CYP also contributes to the regulation of other endothelium-dependent vasorelaxing factors by modifying EC Ca2+ signaling.