BackgroundGlucagon-like peptide-1 (GLP-1) is an incretin hormone that has a wide range of effects on glucose metabolism and cardiovascular function (e.g., improving insulin sensitivity, reduction in appetite, modulation of heart rate, blood pressure and myocardial contractility). Metabolic syndrome (MetS) is associated with an increased risk of developing atherosclerotic cardiovascular diseases. Novel glycemic control drugs, the dipeptidyl-peptidase-4 (DPP-4) inhibitors, work by inhibiting the inactivation of incretin hormones, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). In spite of good effects of these drugs in diabetic patients, circulating levels of incretins and their role in MetS are largely unknown.MethodsTo examine relationships between incretin hormones and MetS risk factors, we measured circulating levels of incretins in obese high-risk patients for cardiovascular disease. Fasting serum GLP-1 and GIP levels were measured by ELISA. We performed a cross-sectional analysis of metabolic variables in the fasting state in two subject groups: with MetS (n = 60) and pre-MetS (n = 37).ResultsFasting levels of Serum GLP -1 in the peripheral circulation were significantly increased correlated with the accumulation of MetS risk factors components (r = 0. 470, P < 0.001). There was a significant interaction between circulating GLP-1 and GIP, serum high-density lipoprotein cholesterol, triglyceride, and serum uric acid concentrations but not waist circumference, fasting glucose, HbA1c, or presence of diabetes.ConclusionCirculating levels of GLP-1 in relation to the accumulation in MetS factors suggested that MetS patients with elevated levels of GLP-1 are high-risk patients for cardiovascular disease, independent with the presence of diabetes.

Serum IL-10 levels on admission enabled one to predict subsequent CS requiring MCSS and mortality of fulminant myocarditis patients.

Abstract. Erythropoietin (EPO) has been shown to enhance angiogenesis, but its precise mechanisms of enhancement during ischemia are not fully elucidated. We examined the effect of EPO on blood flow recovery from acute hind-limb ischemia induced by ligation of the femoral artery in male C57Bl/6 mice. The density of microvessels with platelet adhesion in ischemic tissues was assessed by intravital microscopy. Treatment with EPO (100 and 1000 IU/kg, i.p.) restored blood flow in a dose-dependent manner and increased plasma levels of soluble-P-selectin, vascular endothelial growth factor (VEGF), and stromal cell-derived factor (SDF-1). Flow cytometric analysis revealed increased P-selectin expression on platelets in EPO-treated mice compared to PBS-treated mice. Intravital microscopic studies showed that EPO increased density of microvessels with platelet adhesion selectively in the ischemic tissues. Neutralizing antibody against P-selectin reduced the density of microvessels with platelet adhesion enhanced with EPO and impaired blood flow recovery with reductions in VEGF and SDF-1 levels. These results suggest that EPO administration enhances recovery from hind-limb ischemia, and platelet adhesion to the microvessels is a key event to enhance the angiogenesis in the ischemic tissues.

Patients on hemodialysis (HD; n = 210) were examined for peripheral arterial disease (PAD) using ankle-brachial index (ABI) and toe-brachial index (TBI). The prevalence of PAD was 38.1%. Among patients with PAD, 87.5% were newly diagnosed with PAD, 42.5% were diagnosed with TBI <0.6 despite ABI ≥ 0.9, and 68.7% had no lower limb symptoms. In patients with PAD, the prevalence rate of cerebrovascular disease was 36.3%, coronary artery disease was 42.5%, spinal stenosis was 33.2%, and vertebral fracture 15.0% and was significantly higher than those of the non-PAD patients. Low high-density lipoprotein cholesterol was the most important biomarker among patients with PAD. PAD has been underdiagnosed and untreated in patients on HD because most patients do not have symptoms that could be due to diabetic neuropathy or have insufficient daily activity to experience exertional leg symptoms. Screening for PAD using the ABI and TBI increased diagnostic efficiency in patients on HD and may lead to effective early treatments, including pharmacotherapy, revascularization therapy, and exercise rehabilitation to avoid the worst possible scenario such as lower limb amputation, cardiovascular event, and death.

atients undergoing a cardiopulmonary crisis, who would previously not have survived under conventional emergency treatment, are now saved by mechanical cardiopulmonary support systems [intra-aortic balloon pump (IABP), percutaneous cardiopulmonary support (PCPS) and ventricular assist device (VAS)]. Fulminant myocarditis is one such disease in which patients can recover and return to normal life after being rescued from fatal cardiopulmonary crisis by mechanical cardiopulmonary support. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] However, this breakthrough in treatment has led to new problems, such as how to manage the mechanical cardiopulmonary support to improve survival, how to monitor the clinical course, and how to enhance the long-term prognosis of fulminant myocarditis.A national survey was planned to clarify these problems by investigating the current situation of patients with fulminant myocarditis requiring PCPS and thereby formulate therapeutic guidelines for the use of PCPS for this disease. To this end, the investigators (the scientific committee of the Japanese Circulation Society) gathered information on patients with fulminant myocarditis who were treated with Circulation Journal Vol.66, February 2002 PCPS in Japan for the 3-year period from April 1997 to March 2000. Methods PatientsIn hospitals affiliated with the investigators or in their referral hospitals, a retrospective cohort study was conducted on fulminant myocarditis patients treated with PCPS. The time of patient enrollment ranged from May 1989 to March 2000. The patients were diagnosed as active myocarditis histologically either from endomyocardial biopsy or from autopsy, and PCPS was regarded as essential for managing the clinical crisis. The primary issues investigated in a questionnaire (Table 1) prepared for cardiologists were (1) clinical features, disease course and patient prognosis in relation to PCPS treatment, (2) indications, management and cessation of PCPS, and avoidance of complications associated with PCPS, and (3) long-term prognosis. The investigators went to the admitting hospital of the patient and directly interviewed the doctors involved. The analyses mainly focused on (1) the clinical features of survivors and non-survivors, (2) the differences in the indications for PCPS and its outcome, (3) the characteristics of potential survivors who could be weaned off PCPS at some stage, and (4) which patients could be weaned off PCPS.Data were expressed as mean ± SD. Mann-Whitney's U test was used to compare differences between continuous Although fulminant myocarditis is known as a fatal disease, patients have been able to recover and return to normal life with the help of mechanical cardiopulmonary support. However, therapeutic guidelines for using percutaneous cardiopulmonary support (PCPS) for fulminant myocarditis have not been established, and the clinical course and long-term prognosis of such patients are still controversial issues. The present national survey considered the current situation of patient...

Background: Ezetimibe (Zetia ® ) is a potent inhibitor of cholesterol absorption that has been approved for the treatment of hypercholesterolemia. Statin, an inhibitor of cholesterol synthesis, is the first-choice drug to reduce low-density lipoprotein-cholesterol (LDL-C) for patients with hypercholesterolemia, due to its strong effect to lower the circulating LDL-C levels. Because a high dose of statins cause concern about rhabdomyolysis, it is sometimes difficult to achieve the guideline-recommended levels of LDL-C in high-risk patients with hypercholesterolemia treated with statin monotherapy. Ezetimibe has been reported to reduce LDL-C safely with both monotherapy and combination therapy with statins.

The appropriate indication for, management of and limitations to extracorporeal life support (ECLS) and the timing of a switch to a ventricular assist device (VAD) remain controversial issues in patients with acute myocardial infarction (AMI) complicated with cardiogenic shock or cardiopulmonary arrest. To evaluate and discuss these issues, we studied patients with AMI treated with ECLS and compared deceased and discharged patients. Thirty-eight patients with AMI who needed ECLS [35 men (92.1 %), aged 59.9 ± 13.5 years] were enrolled in this study. Of these 38 patients, 34 subsequently underwent percutaneous coronary intervention (PCI), and four subsequently received coronary artery bypass grafting (CABG). Fourteen patients (36.8 %) were discharged from the hospital. The outcome was not favorable for those patients with deteriorating low output syndrome (LOS) and the development of leg ischemia, hemolysis and multiple organ failure during ECLS. Levels of creatine kinase, creatine kinase-MB (CK-MB), lactate dehydrogenase, serum creatinine (Cr) and amylase after the patient had been put on ECLS and fluctuation of the cardiac index, blood pressure, arterial blood gas analysis and CK-MB and Cr levels during ECLS were indicators to switch from the ECLS to VAD. In the case of patients with no complication associated with ECLS, 4.6-5.6 days after initiation of ECLS was assumed to be the threshold to decide whether to switch from ECLS to VAD. Patients with AMI who suddenly developed refractory pulseless ventricular tachycardia or ventricular fibrillation without deteriorating LOS and who underwent successful PCI or CABG, and who prevented the complications associated with ECLS, showed a high probability of recovering with ECLS.

SummaryAlthough extracorporeal membrane oxygenation (ECMO) is widely used as temporary circulation support, there are no reports of direct parameters indicating cardiac recovery to determine the timing of weaning off.Twenty-five patients supported by ECMO due to hemodynamic deterioration were divided into 2 groups according to their outcome: weaned ECMO (W: n = 18) or not (NW: n = 7). In the W group, we examined the differences in parameters between the 2 time points, ECMO introduction, and the reduction in ECMO flow to 40% of the initial setting known as the conventional recovery point (C-point). Significant differences were observed in systolic pulmonary artery pressure, the cardiac index measured by the thermodilution method, C-reactive protein, lactate, base excess, and the end-tidal CO 2 concentration (ETCO 2 ). Next, by closely examining these 6 parameters measured every 12 hours, we found that only ETCO 2 had always changed steeply, like a 'flexion point' (E-point), in all W cases, but not in NW. The E-point was defined as an initial increase in ETCO 2 of ≥ 5 mmHg over the preceding 12 hours with a continued rise over the next 12 hours. E-points appeared as much as 95 ± 60 hours earlier than C-points and also preceded weaning off of ECMO.ETCO 2 can be a useful continuous parameter for predicting the adequate timing of weaning off of ECMO for circulatory failure at the bedside. (Int Heart J 2010; 51: 116-120) Key words: End-tidal carbon dioxide, Extracorporeal membrane oxygenation, Hemodynamic deterioration, Clinical predictor, Weaning E xtracorporeal membrane oxygenation (ECMO) is widely used not only for temporary cardiopulmonary support in cases of hemodynamic deterioration, but also in bridge therapy for left ventricular assist system (LVAS) as well as cardiac transplantation.1,2) Although setting up the equipment is easy, a quick overall methodology during management has not been fully established. There have been few guidelines concerning its utilization in relation to the treatment of fulminant myocarditis.3) The guidelines say, for example, that ECMO flow of 3-3.5 L/min initially should be reduced gradually with improved cardiac function to around 1.0 L/min, followed by weaning off. As for the predictive indicators, resultant ECMO flow fell to about 40% of the initial flow, implying cardiac recovery, and patients can subsequently be weaned off ECMO.3) Under conventional methodology using 'trial and error' as described above, however, there are no reports of direct parameters indicating cardiac recovery to determine the timing of weaning patients off ECMO. In this study, we focused on clinical variables measured continuously at the patient's bedside, especially the end-tidal carbon dioxide concentration (ETCO 2 ), to determine the appropriate time to wean patients off ECMO. MethodsPatient population and clinical classification: Thirty-seven consecutive patients with cardiovascular disorders treated with ECMO at our institution between 1996-2008 were investigated. We excluded patients in whom ECMO wa...