We investigated efficacy and safety of implantation of autologous bone marrow mononuclear cells plus platelets, including endothelial progenitor cells (EPCs), for recovering refractory chronic peripheral arterial disease (PAD) using visual and quantitative analyses by Tc-tetrofosmin (TF) perfusion scintigraphy, and also investigated various quantitative assessments objectively. We performed 12 consecutive cases and 19 limbs and hands with severe chronic PAD that were almost Fontaine class IV (11/12 cases, about 92%) in this trial. This treatment was very effective in relieving severe pain of PAD, especially for Buerger's disease. We used a visual analog scale (VAS) for measurement of pain level. The maximum pain level before implantation was 66.5 ± 5.0 mm, and it decreased to 12.1 ± 2.2 mm after implantation ( p < 0.001). Rest pain in legs and fingers was resolved in 11 cases (11/12 cases, 92%). All patients could measure pain-free walking time on a treadmill, which improved remarkably (140 ± 53 s before implantation vs. 451 ± 74 s after implantation, p = 0.034). Resting ankle brachial pressure index (ABI) in legs implanted with bone marrow mononuclear cells was also improved (0.65 ± 0.08 before implantation vs. 0.73 ± 0.07 after implantation, p = 0.055). According to 99m Tc-TF perfusion scintigraphy, the proximal area (region from knee to ankle) was 1.32 ± 0.10 before implantation versus 1.56 ± 0.11 after implantation ( p = 0.007). Tc-TF perfusion scintigraphy in the distal area (region from ankle to end of toes, or from wrist to end of fingers) was 0.79 ± 0.06 before implantation versus 0.83 ± 0.06 after implantation ( p = 0.29). Ischemic legs and hands that were injected showed increased perfusion blood flow. Tc-TF perfusion scintigraphy was effective to estimate visual and quantitative analysis of collateral vessels in neovascularization. We were successful with this new treatment for the most severe, chronic PAD that was not curable by any of the current treatments. Thus, this therapeutic angiogenesis could be a new strategy for saving severe ischemic limbs and hands.

These findings suggest that an increased circulating MCSF concentration reflects atherosclerotic progression in patients with CAD and predicts future cardiac events.

Continuous positive airway pressure (CPAP) treatment improves endothelial function and sympathetic activity in patients with obstructive sleep apnea (OSA). However, the long-term effects of CPAP on pulse wave velocity (PWV), which reflects arterial stiffness that is associated with cardiovascular events, have not been evaluated in OSA patients with or without hypertension (HT). In this study, 212 male OSA patients who had been receiving CPAP treatment for 2 years and were divided into two groups, those with HT (n¼114) and those without (n¼98), were studied. In both HT and normotensive (NT) patients, PWV decreased significantly over the first 6 months of treatment (P¼0.005 and 0.010, respectively), before increasing gradually from 6 to 24 months. Body mass index (BMI), body weight, heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels decreased significantly in the HT group over the 2 years of CPAP treatment (Po0.001 for all). In contrast, only HR decreased significantly in the NT group over the 2 years of treatment (Po0.001). Multivariate regression analysis revealed that age (P¼0.008), decreases in DBP (Po0.001) and HR (Po0.001) and higher initial levels of serum high-density lipoprotein-cholesterol (P¼0.040) were independent factors related to changes in PWV over the 2 years of CPAP treatment in all patients. In conclusion, we found a significant decrease in PWV in both NT and HT patients after 6 months of CPAP treatment. In HT patients, long-term CPAP treatment significantly decreases blood pressure, which may contribute to explain the PWV improvement.

Alpha1-adrenoceptor (alpha1-AR) stimulation increases sarcolemmal Na+-H+ exchanger (NHE) activity. The present study was designed to determine the role(s) of alpha1-AR subtype(s) in mediating this response. As an index of NHE activity, acid efflux rates (JHs) were determined in single rat ventricular myocytes loaded with the pH-sensitive fluoroprobe carboxy-seminaphthorhodafluor-1 after 2 consecutive intracellular acid pulses in bicarbonate-free medium. JH at pHi 6.90 did not change significantly during the second pulse relative to the first in control cells but increased in a dose-dependent manner when the second pulse occurred in the presence of phenylephrine (nonselective alpha1-AR agonist) or A61603 (alpha1A-AR-selective agonist), with EC50 values of 1.24 micromol/L and 3.6 nmol/L, respectively (both agonists given together with 1 micromol/L atenolol). Stimulation of NHE activity by 10 micromol/L phenylephrine was inhibited in a dose-dependent manner by the competitive antagonists prazosin, WB4101, and 5-methylurapidil, with IC50 values of 12, 32, and 149 nmol/L, respectively. Analyses of the relative EC50 and IC50 values obtained (and Ki values estimated from the antagonist IC50s) in relation to the relative potencies of these agents at native rat alpha1-AR subtypes and their relative affinities for recombinant rat alpha1-ARs suggest that alpha1-adrenergic stimulation of sarcolemmal NHE activity is likely to be mediated selectively by the alpha1A-AR.

Cardiac ruptures after myocardial infarction are classified as ventricular free wall ruptures (FWR), ventricular septal ruptures (VSR), and papillary muscle ruptures (PMR). A combination of any two types of rupture is called "ventricular double rupture;" (VDR) and shows a specific clinical course. 3,284 patients with acute myocardial infarction (AMI) were admitted to the CCU of our hospital between April, 1973 and December, 2001, and 10 patients (8 males and 2 female, aged 54 through 82 years) with VDR were clinicopathologically evaluated. All were diagnosed as VDR consisting of FWR and VSR. VDR was observed in 0.30% of all patients with AMI, in 3.0% of those with FWR, and in 16.1% of those with VSR. The infarct site was anteroseptal in 3 patients, anterolateral in 3, inferior in 3, and posterolateral in 1. Two patients with inferior infarction complicated RV infarction and a patient with posterolateral infarction had healed inferior infarction. The risk factors related to VDR were age, a history of hypertension, increased sympathetic tone to improve hemodynamic aggravation after perforation, cardiotonic agents, thrombolytic agents, delayed reperfusion, right ventricular volume overload by shunt and re-infarction. However, these factors might have played only a subsidiary role. The most important factor in VDR was the pathological findings. The site of septal perforation was the apex close to the septum-free wall junction in 9 patients and the site of rupture was also apical in 8 patients. Four patients already had VSR on admission to our CCU. FWR developed soon after VSR was demonstrated in 4 patients. FWR and VSR occurred simultaneously in one patient. These results suggest that VSR in the apical region is a precursor of VDR and requires the earliest surgical treatment. Surgical treatment was carried out in the operating room in 5 patients and 3 (60.0%) of them survived for 4 months or more. Two patients with rupture incidentally detected during operation for VSR were discharged and are still alive, though another one with free wall blow out rupture died 129 days after operation. Bedside thracotomy was performed in 3 patients and all of them died.