A 75-year-old man with moderate aortic stenosis and regurgitation admitted due to heart failure underwent uneventful aortic valve replacement with a Carpentier-Edwards pericardial bioprosthesis valve. A quadricuspid aortic valve discovered incidentally during surgery consisted of 4 of different sizes and a supernumerary cusp between the right and noncoronary cusps. No coronary abnormality was involved. Resected cusps showed fibrotic thickening with calcification and no sign of previous inflammatory disease. Although quadricuspid aortic valve is a very rare anomaly, its potential for severe valve failure in adulthood should not be neglected.

Background: Oral administration of tolvaptan, a vasopressin V2 receptor antagonist, significantly reduces deterioration of renal function, which has recently been highlighted as an exacerbating factor for adverse events in patients with acute heart failure. In the present study we tested the hypothesis that concomitant administration of tolvaptan with a conventional diuretic is beneficial for perioperative body fluid management in patients who have undergone cardiac surgery. Methods and Results:In all, 280 patients who underwent cardiac surgery were prospectively randomized to concomitant treatment with tolvaptan and a conventional diuretic (tolvaptan group; 147 patients) or treatment with a conventional diuretic alone (control group; 133 patients). Groups were compared in terms of the time required to restore preoperative body weight and the incidence of worsening renal function (WRF), defined as an increase in the serum creatinine level ≥0.3 mg/dL. The time required to restore preoperative body weight was significantly shorter in the tolvaptan than control group (mean [±SD] 3.97±1.95 vs. 5.02±2.83 days, respectively; P<0.001). The incidence of WRF was significantly lower in the tolvaptan than control group (n=11 [7.5%] vs. n=25 [18.8%], respectively; P=0.011). Conclusions:Administration of tolvaptan with conventional diuretics in the early postoperative period after cardiac surgery could be beneficial in maintaining urine output without affecting renal function and may thus help avoid WRF.

Adipose stem cells (ASCs) are a source of regenerative cells available for autologous transplantation to hearts. We compared protective actions of ASC sheets on rat myocardial infarction (MI) in comparison with those of skeletal myoblast cell sheets. Their effects on infarcted hearts were evaluated by biological, histochemical as well as physiological analyses. ASC sheets secreted higher concentrations of angiogenic factors (HGF, VEGF, and bFGF; P < 0.05) under normoxic and hypoxic conditions than those of myoblast cell sheets, associated with reduction of cell apoptosis (P < 0.05). Like myoblast cell sheets, ASC sheets improved cardiac function (P < 0.05) and decreased the plasma level of ANP (P < 0.05) in MI hearts. ASC sheets restored cardiac remodeling characterized by fibrosis, cardiac hypertrophy and impaired angiogenesis (P < 0.05), which was associated with increases in angiogenic factors (P < 0.05). In isolated perfused rat hearts, ASC sheets improved both systolic and diastolic functions, which was comparable to cardiac functions of myoblast cell sheets, while both cell sheets failed to restore cardiac contractile response to either isoproterenol, pimobendan or dibutyryl cAMP. These results indicated that ASC sheets improved cardiac function and remodeling of MI hearts mediated by their paracrine action and this improvement was comparable to those by myoblast cell sheets.

Cell transplantation prevents cardiac dysfunction after myocardial infarction. However, because most implanted cells are lost to ischemia and apoptosis, the benefits of cell transplantation on heart function could be improved by increasing cell survival. To examine this possibility, male Lewis rat aortic smooth muscle cells (SMCs; 4 ϫ 10 6 ) were pretreated with antiapoptotic Bcl-2 gene transfection or heat shock and then implanted into the infarcted myocardium of anesthetized, syngenic female rats (n ϭ 23 per group). On the first day after transplantation, apoptotic SMCs were quantified by using transferase-mediated dUTP nick-end labeling staining. On days 7 and 28, grafted cell survival was quantified by using real-time PCR, and heart function was assessed with the use of echocardiographyandtheLangendorffapparatus.SMCsgivenantiapoptotic pretreatments exhibited improvements in each measure relative to controls. Apoptosis was reduced in Bcl-2-treated cells relative to all other groups (P Ͻ 0.05), whereas survival (P Ͻ 0.01) was increased. Heat shock also significantly decreased apoptosis and increased survival relative to control groups (P Ͻ 0.05 for group effect), although these effects were less pronounced than in the Bcl-2-treated group. Further, scar areas were reduced in both Bcl-2-and heat shock-treated groups relative to controls (P Ͻ 0.05), and fractional area change and cardiac function were greater (P Ͻ 0.05 for both measures). These results indicate that antiapoptosis pretreatments reduced grafted SMC loss after transplantation and enhanced grafted cell survival and ventricular function, which was directly related (r ϭ 0.72; P ϭ 0.002) to the number of surviving engrafted cells. cell therapy; Bcl-2; heat shock; ventricular modulation; angiogenesis SKELETAL MYOBLAST TRANSPLANTATION prevents scar thinning and ventricular dilatation after a myocardial infarction and has been associated with improved regional and global function in both animal experimentation (5,17,26) and the initial clinical trials of this intervention (6, 15). The mechanism responsible for this beneficial effect has not been elucidated but may include angiogenesis, altering the elasticity of the ventricular wall, and/or modifying matrix remodeling. These mechanisms were suggested because none of the myriad of implanted cells have been demonstrated to differentiate into functioning cardiomyocytes, nor have they been demonstrated to beat synchronously with the remaining recipient cardiomyocytes. Therefore, the goal of cell transplantation is to establish a graft of viable cells within the infarct region to modify ventricular remodeling and prevent congestive heart failure. If the grafted cells could contribute to the contractility of the infarct scar, the beneficial effect would be enhanced. In the present study, our first aim was to evaluate the efficacy of smooth muscle cell (SMC) transplantation to augment cardiac function, because these cells routinely induce angiogenesis and matrix remodeling and might be ideally suited to efficient...

Prostaglandin E (PGE) in the hypothalamus is a principal mediator of the febrile response. However, the role of organic anion transporting polypeptide 2A1 (OATP2A1/), a prostaglandin transporter, in facilitating this response is unknown. Here, we investigated the effect of deficiency on the body core temperature (Tc) and on the PGE concentration in hypothalamus interstitial fluid () and CSF () of lipopolysaccharide (LPS; 100 μg/kg, i.p.)-treated mice of both sexes. mice did not develop a febrile response. was increased in and mice, and of mice was well maintained at 5 h after LPS injection (1160 pg/ml) compared with mice (316 pg/ml). A microdialysis study revealed that peaked at 2 h after LPS injection in mice (841 pg/ml), whereas the increase in was negligible in mice. The PGE plasma concentration in mice (201 pg/ml) was significantly higher than that in mice (54 pg/ml) at 1 h after LPS injection, whereas the two groups showed similar PGE concentrations in the hypothalamus. Strong Oatp2a1 immunoreactivity was observed in F4/80-positive microglia and perivascular cells and in brain capillary endothelial cells. The changes in Tc and seen in LPS-injected mice were partially attenuated in monocyte-/macrophage-specific (/) mice. Thus, OATP2A1 facilitates the LPS-induced febrile response by maintaining a high level of , possibly by regulating PGE secretion from F4/80-positive glial cells and/or facilitating PGE transport across the blood-brain barrier. These findings suggest that OATP2A1 is a useful therapeutic target for neuroinflammation. Fever is a physiological response caused by pyrogen-induced release of prostaglandin E (PGE) in the hypothalamus, which plays a central role in regulating the set-point of body temperature. However, it is unclear whether the prostaglandin transporter OATP2A1/ is involved in this response. We show here that LPS-induced fever is associated with increased PGE concentration in hypothalamus interstitial fluid (), but not in CSF (), by means of a microdialysis study in global -knock-out mice and monocyte-/macrophage-specific-knock-out mice. The results suggest that OATP2A1 serves as a regulator of in F4/80-positive glial cells. OATP2A1 was detected immunohistochemically in brain capillary endothelial cells and, therefore, may also play a role in PGE transport across the blood-brain barrier.

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