Hirokazu Akashi

Juntendo University · Department of Cardiovascular Surgery

Myostatin (MSTN) is a transforming growth factor (TGF)-β superfamily member that acts as a negative regulator of muscle growth and may play a role in cardiac remodeling. We hypothesized that inhibition of activin type II receptors (ACTRII) to reduce MSTN signaling would reduce pathologic cardiac remodeling in experimental heart failure (HF). C57BL/...

Clinical and experimental studies have suggested that the duration of left ventricular assist device (LVAD) support may affect remodeling of the failing heart. We aimed to (1) characterize the changes in calcium/calmodulin-dependent protein kinase type II (CaMKII)δ, growth signaling, structural proteins, fibrosis, apoptosis and gene expression befo...

Abnormal lipid metabolism may contribute to myocardial injury and remodeling. To determine whether accumulation of very long-chain ceramides occurs in human failing myocardium, we analyzed myocardial tissue and serum from patients with severe heart failure (HF) undergoing placement of left ventricular assist devices and controls. Lipidomic analysis...

Background: Myostatin (MSTN) is a negative regulator of muscle growth involved in cardiac remodeling and glucose sensitivity. MSTN can inhibit 5' AMP-activated protein kinase (AMPK), impairing cardiomyocyte metabolism. We studied the role of MSTN on AMPK regulation in heart failure (HF) and concomitant insulin resistance.

Background Left ventricular assist devices are increasingly being used in patients with advanced heart failure as both destination therapy and bridge to transplant. We aimed to identify histomorphometric, structural and inflammatory changes after pulsatile- and continuous-flow left ventricular assist device placement. Methods Clinical and echocard...

Background: Del Nido (DN) cardioplegia, a calcium-free, hyperkalemic solution containing lidocaine and magnesium has been developed to help reduce intracellular calcium influx and the resulting myocyte damage in the immediate postischemic period following cardiac arrest. DN cardioplegia has been used for pediatric cardiac surgery but its use in co...

Background: Previous studies have linked increased ceramide and dihydroceramide (DHC) synthesis to cardiotoxicity. However, the effects of ceramide synthesis inhibition on doxorubicin (DOX)-induced cardiomyopathy are unclear. Hypothesis: Inhibition of de novo ceramide synthesis by myriocin maintains heart function and survival rate. Methods: C57BL/...

-Skeletal muscle dysfunction and exercise intolerance are clinical hallmarks of patients with heart failure (HF). These have been linked to a progressive catabolic state, skeletal muscle inflammation and impaired oxidative metabolism. Prior studies suggest beneficial effects of ω-3 polyunsaturated fatty acids (PUFAs) and glutamine on exercise perfo...

Abnormal intracellular calcium (Ca(2+)) handling can trigger endoplasmic reticulum (ER) stress, leading to activation of the unfolded protein response (UPR) in an attempt to prevent cell death. Mechanical unloading with a left ventricular assist device (LVAD) relieves pressure-volume overload and promotes reverse remodeling of the failing myocardiu...

Background: Myostatin (MSTN) is a negative regulator of muscle growth that may improve insulin sensitivity. We hypothesized that systemic MSTN inhibition would improve cardiomyocyte glucose metabolism in experimental heart failure (HF).

Background Exercise intolerance in heart failure has been linked to impaired skeletal muscle oxidative capacity. Oxidative metabolism and exercise capacity are regulated by PPARδ signaling. We hypothesized that PPARδ stimulation reverts skeletal muscle oxidative dysfunction. Methods Myocardial infarction (MI) was induced in C57BL/6 mice and the dev...

Continuous-wave (CW) lasers have been commonly used for endovenous laser ablation (EVLA). However, as some undesired side effects such as postoperative pain and bruising occasionally happens, longer laser wavelength and specially-fabricated laser fibers have been developed. On the other hand, the pulsed-wave (PW) laser, which has a heat production...

Background and AimsThe immediate postischemic period is marked by elevated intracellular calcium levels, which can lead to irreversible myocyte injury. Del Nido cardioplegia was developed for use in the pediatric population to address the inability of immature myocardium to tolerate high levels of intracellular calcium following cardiac surgery. Ou...

Heart transplantation alone has been recognized to be contraindicated when pulmonary hypertension (PH) and elevated pulmonary vascular resistance (PVR) are irreversible, irrespective of any medical intervention by the use of inotropic agents or pulmonary vasodilators, because such patients are at an increased risk of post-transplantation right vent...

Background: Advanced heart failure (HF) is associated with myocardial metabolic derangements and insulin resistance. Acylcarnitine (AC) accumulation has been suggested to be a marker of abnormal fatty acid metabolism and mitochondrial dysfunction. We hypothesized that ACs accumulate in the failing myocardium and blood of patients with HF compared t...

A percentage of patients with a left ventricular assist device (LVAD) require device exchange. Although this is an important clinical entity, there are only a handful of relevant studies on this topic in the literature. From 2004 to 2012, 30 device exchanges (HeartMate II to HeartMate II) were performed. Since June 2011, we have employed the subcos...

Hemolysis is a well-known complication of left ventricular assist device (LVAD) implantation that contributes to hemodynamic derangement and end-organ damage. Micro-RNAs (miRs) are non-coding RNA species that control gene expression by targeting specific messenger RNAs for degradation. MiR-451 is specifically expressed in erythrocyte precursors and...

Background Left ventricular assist devices (LVADs) are increasingly used for patients with advanced heart failure. Continuous flow LVADs (cfLVADs) have replaced older pulsatile LVADs (pLVADs); however, effects of attenuated pulse pressure waveforms are largely unknown. We compared vascular histomorphometric and molecular changes in patients on cfLV...

Background Exercise intolerance in heart failure (HF) has been linked to impaired skeletal muscle oxidative capacity. PPARδ signaling regulates oxidative metabolism and exercise capacity. We hypothesized that decreased skeletal muscle oxidative capacity in HF can be reverted by PPARδ agonists. Methods Left ventricular (LV) dysfunction was induced i...

Aldose reductase (AR), an enzyme mediating the first step in the polyol pathway of glucose metabolism, is associated with complications of diabetes mellitus and increased cardiac ischemic injury. We investigated whether deleterious effects of AR are due to its actions specifically in cardiomyocytes. We created mice with cardiac specific expression...

Cardiac mRNA expression and echocardiographic measurement in 3-month old MHC-hAR mice. (A) Cardiac mRNA expression. (B–D) Heart to body ratio and echocardiography results. Data are shown as mean ± SD (n = 6–8). (PDF)

MHC-hAR expression increased cardiac glucose uptake in MHC-hAR/PPARα−/− mice. (A) Plasma clearance for 2-deoxy-d-[3H]-glucose and (B) cardiac glucose uptake in the MHC-hAR/PPARα−/− mice and wild type controls. Data are shown as mean ± SD. *P<0.05 compared with MHC -hAR mice. (PDF)

Echocardiography results from 3- to 13-month old mice. Data are shown as mean ± SD (n = 6–13). **P<0.01 compared with MHC -hAR mice. (PDF)

Plasma TG, TC, FFA and Glucose in 3- and 15-month old MHC-hAR mice. (PDF)

Plasma TG, TC, FFA and Glucose in 7-month old MHC-hAR and MHC-hAR/PPARα−/− mice. (PDF)

Strategy for creating MHC-hAR/PPARα−/− mice. (PDF)

Background: Controversy exists whether heart transplantation (HTx) is an appropriate treatment option for patients with cardiac sarcoidosis due to its potential recurrence and multi-organ involvement. Recent data from the United Network for Organ Sharing dataset suggest that the clinical outcome of cardiac sarcoidosis patients is equivalent or eve...

Background: Chronic heart failure is associated with higher risk for developing diabetes mellitus. Secretory products from adipocytes may contribute to the deterioration in glycemic control and increased insulin resistance (IR). Retinol binding protein 4 (RBP4) is an adipose tissue-derived protein with pro-diabetogenic effects. The aim of the pres...

Cardiac extracellular matrix (ECM) is a dynamic and metabolically active collagenous network that responds to mechanical strain. The association between ECM turnover and right ventricular failure (RVF) development after left ventricular assist device (LVAD) implantation in patients with advanced heart failure (HF) was investigated. Circulating leve...

Continuous-flow left ventricular assist devices (LVAD) are increasingly used for patients with end-stage heart failure (HF). We analyzed the effects of ventricular decompression by continuous-flow versus pulsatile-flow LVADs on myocardial structure and function in this population. Sixty-one patients who underwent LVAD implantation as bridge-to-tran...

Infections, especially those involving drivelines, are among the most serious complications that follow ventricular assist device implantation. Staphylococci are the most common causes of these infections. Once driveline infections are established, they can remain localized or progress as an ascending infection to cause metastatic seeding of other...

Purpose Heart failure (HF) is a complex syndrome involving multiple organ systems. With the advancement of the disease there is progressive decline in organ system functions. Degree of end organ damage (EOD) caused by HF is believed to be associated with poor outcomes after mechanical circulatory support device (MCSD) implantation but more quantita...

Purpose Neurological complications (NC) are a major adverse event following left ventricular assist device (LVAD) surgery. Pre- and post-operative factors associated with NC were investigated. Methods and Materials We reviewed 287 consecutive patients who underwent LVAD surgery [167 Heart Mate (HM) I and 121 HM II] at Columbia University Medical C...

Objective: Differences in B-type natriuretic peptide (BNP) values before and after left ventricular assist device (LVAD) surgery were evaluated as a predictor of survival after the surgery. Background: The impact of reduction of pre-operative BNP values, following LVAD surgery, on post-operative survival in heart failure (HF) patients is not known....

Staphylococcus epidermidis remains the predominant pathogen in prosthetic-device infections. Ventricular assist devices, a recently developed form of therapy for end-stage congestive heart failure, have had considerable success. However, infections, most often caused by Staphylococcus epidermidis, have limited their long-term use. The transcutaneou...