Walk training with blood flow occlusion (OCC-walk) leads to muscle hypertrophy; however, cardiorespiratory endurance in response to OCC-walk is unknown. Ischemia enhances the adaptation to endurance training such as increased maximal oxygen uptake (VO₂(max)) and muscle glycogen content. Thus, we investigated the effects of an OCC-walk on cardiorespiratory endurance, anaerobic power, and muscle strength in elite athletes. College basketball players participated in walk training with (n = 7) and without (n = 5) blood flow occlusion. Five sets of a 3-min walk (4-6 km/h at 5% grade) and a 1-min rest between the walks were performed twice a day, 6 days a week for 2 weeks. Two-way ANOVA with repeated measures (groups x time) was utilized (P < 0.05). Interactions were found in VO₂(max) (P = 0.011) and maximal minute ventilation (VE(max); P = 0.019). VO₂(max) (11.6%) and VE(max) (10.6%) were increased following the OCC-walk. For the cardiovascular adaptations of the OCC-walk, hemodynamic parameters such as stroke volume (SV) and heart rate (HR) at rest and during OCC-walk were compared between the first and the last OCC-walk sessions. Although no change in hemodynamics was found at rest, during the last OCC-walk session SV was increased in all five sets (21.4%) and HR was decreased in the third (12.3%) and fifth (15.0%) sets. With anaerobic power an interaction was found in anaerobic capacity (P = 0.038) but not in peak power. Anaerobic capacity (2.5%) was increased following the OCC-walk. No interaction was found in muscle strength. In conclusion, the 2-week OCC-walk significantly increases VO₂(max) and VE(max) in athletes. The OCC-walk training might be used in the rehabilitation for athletes who intend to maintain or improve endurance.

The heart is an unusual site of metastasis from any malignancy. We report a case of cardiac metastasis from colorectal cancer. A 70-year-old woman was referred with a presumptive diagnosis of sigmoid colon cancer with cardiac myxoma. Two-dimensional echocardiography showed a 4 cm × 4.5 cm mobile mass on the lateral right atrial wall, and computed tomography revealed a low attenuated lobulating mass in the right atrium. The patient underwent anterior resection for sigmoid colon cancer (T4N2). Thereafter, she experienced progressive shortness of breath. Therefore, a cardiac operation was performed 2 wk after the colorectal operation. Histological examination revealed adenocarcinoma, which was identical to the primary lesion. Although twodimensional echocardiography has become the diagnostic test of choice for detecting cardiac tumors, in patients with colorectal cancer showing a cardiac mass, further diagnostic evaluation such as a magnetic resonance imaging might be necessary.

While acute treatment with beetroot juice (BRJ) containing nitrate (NO3 (-)) can lower systolic blood pressure (SBP), afterload, and myocardial O2 demand during submaximal exercise, effects of chronic supplementation with BRJ (containing a relatively low dose of NO3 (-), 400 mg) on cardiac output (CO), SBP, total peripheral resistance (TPR), and the work of the heart in response to dynamic exercise are not known. Thus, in 14 healthy males (22 ± 1 yr), we compared effects of 15 days of both BRJ and nitrate-depleted beetroot juice (NDBRJ) supplementation on plasma concentrations of NOx (NO3 (-)/NO2 (-)), SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP), CO, TPR, and rate pressure product (RPP) at rest and during progressive cycling exercise. Endothelial function was also assessed via flow-mediated dilation (FMD). BRJ supplementation increased plasma NOx from 83.8 ± 13.8 to 167.6 ± 13.2 μM. Compared with NDBRJ, BRJ reduced SBP, DBP, MAP, and TPR at rest and during exercise (P < 0.05). In addition, RPP was decreased during exercise, while CO was increased, but only at rest and the 30% workload (P < 0.05). BRJ enhanced FMD-induced increases in brachial artery diameter (pre: 12.3 ± 1.6%; post: 17.8 ± 1.9%). We conclude that 1) chronic supplementation with BRJ lowers blood pressure and vascular resistance at rest and during exercise and attenuates RPP during exercise and 2) these effects may be due, in part, to enhanced endothelium-induced vasodilation in contracting skeletal muscle. Findings suggest that BRJ can act as a dietary nutraceutical capable of enhancing O2 delivery and reducing work of the heart, such that exercise can be performed at a given workload for a longer period of time before the onset of fatigue.

This study determined whether an elevated muscle metaboreflex contributes to the excessive blood pressure response to exercise in postmenopausal women. Thirty healthy female volunteers were studied (15 postmenopausal and 15 premenopausal). Stroke volume, heart rate, cardiac output (CO), systolic blood pressure, diastolic blood pressure, and total vascular conductance (TVC) were continuously assessed throughout the experiment. To activate the muscle metaboreflex, occlusion of the vasculature was induced via inflation of a blood pressure cuff (2 min) on the upper arm following static handgrip exercise. Muscle metaboreflex activation increased mean arterial pressure (MAP) in both groups. However, this pressor response was greater in the postmenopausal women (ΔMAP: 21.4 ± 3 vs. 14.5 ± 2 mmHg) (P < 0.05) even though the corresponding increase in CO was less (ΔCO: 0.0 ± 0.2 vs. 0.3 ± 0.2 l/min) (P < 0.05). TVC decreased in both the groups but was more pronounced in the postmenopausal group (ΔTVC: -10.7 ± 2.6 vs. -17.1 ± 3.6 ml/min/mmHg) (P < 0.05). In conclusion, the exaggerated blood pressure response to exercise in postmenopausal women is mediated, in part, by an overactive metaboreflex that is associated with enhanced peripheral vasoconstriction.

This study investigated the hemodynamic mechanisms underlying the exaggerated blood pressure response to muscle contraction in prehypertensive humans and the potential role of skeletal muscle metabo- and mechanoreceptors in this response. To accomplish this, changes in peak mean arterial blood pressure (ΔMAP), cardiac output, and total peripheral resistance (ΔTPR) were compared between prehypertensive (n = 23) and normotensive (n = 19) male subjects during 2 min of static contraction (at 50% of maximal tension), 2 min of postexercise muscle ischemia (metaboreflex), and 1 min of passive dorsiflexion of the foot (tendon stretch, mechanoreceptor reflex). These variables were assessed before and during the interventions. Percentage increases from baseline in MAP and TPR in response to the exercise pressor reflex were augmented in the prehypertensives, compared with the normotensives (44% ± 5% vs. 33% ± 4% and 34% ± 15% vs. 2% ± 8%, respectively) (p < 0.05). Metaboreflex-induced increases in MAP and TPR were also augmented in the prehypertensives (28% ± 5% vs. 14% ± 4% and 36% ± 12% vs. 14% ± 9%, respectively) (p < 0.05). In response to the mechanoreflex, no differences in the percentage increase in MAP or TPR were seen between groups. The results indicate that the reflex pressor response to static contraction is augmented in prehypertension and suggest that this phenomenon is due, at least in part, to enhanced activation of metaboreceptors.

Complements, such as C1q and C3, and macrophages in the splenic marginal zone (MZMs) play pivotal roles in the efficient uptake and processing of circulating apoptotic cells. SIGN-R1, a C-type lectin that is highly expressed in a subpopulation of MZMs, regulates the complement fixation pathway by interacting with C1q, to fight blood-borne Streptococcus pneumoniae. Therefore, we examined whether the SIGN-R1-mediated classical complement pathway plays a role in apoptotic cell clearance and immune tolerance. SIGN-R1 first-bound apoptotic cells and this binding was significantly enhanced in the presence of C1q. SIGN-R1-C1q complex then immediately mediated C3 deposition on circulating apoptotic cells in the MZ, leading to the efficient clearance of them. SIGN-R1-mediated C3 deposition was completely abolished in the spleen of SIGN-R1 knockout (KO) mice. Given that SIGN-R1 is not expressed in the liver, we were struck by the finding that C3-deposited apoptotic cells were still found in the liver of wild-type mice, and dramatically reduced in the SIGN-R1 KO liver. In particular, SIGN-R1 deficiency caused delayed clearance of apoptotic cells and aberrant secretion of cytokines, such as TNF-a, IL-6, and TGF-b in the spleen as well as in the liver. In addition, anti-double-and single-stranded DNA antibody level was significantly increased in SIGN-R1-depleted mice compared with control mice. These findings suggest a novel mechanism of apoptotic cell clearance which is initiated by SIGN-R1 in the MZ and identify an integrated role of SIGN-R1 in the systemic clearance of apoptotic cells, linking the recognition of apoptotic cells, the opsonization of complements, and the induction of immune tolerance.

Background and purpose: Hypoxia-inducible factor (HIF) is a transcription factor induced by hypoxia and degraded by ubiquitin-dependent proteasomes in normoxic conditions. Under hypoxic conditions, hydroxylation of HIF-1a subunit by prolyl hydroxylase (PHD) is suppressed, thus leading to increased levels of HIF. Although PHD2 plays a key role in regulating the levels of HIF, chemical activators of PHD2 are relatively unknown. The aim of this study was to identify small molecule activators of PHD2 that could be used, eventually, to suppress the level of HIF-1a. Experimental approach: By using the overproduced PHD2 as a target, a molecular library consisting of more than 600 small molecules with a benzopyran structure was screened with an HPLC assay method. Key results: We found a potent activator of PHD2, KRH102053 (2-amino-4-methylsulphanyl-butylic acid-4-methoxy-6-(4-methoxy-benzylamino)-2,2-dimethyl-chroman-3-yl ester). The effects of KRH102053 on controlling HIF were studied in human HOS osteosarcoma, rat PC12 phaeochromocytoma and human HepG2 hepatoma cells. Under our experimental conditions, KRH102053 decreased the protein level of HIF-1a and the mRNA levels of HIF-regulated downstream target genes, such as vascular endothelial growth factor, aldolase A, enolase 1 and monocarboxylate transporter 4. Consistent with these results, KRH102053 also inhibited the rates of HIF-related migration and invasion of HOS cells as well as the degree of tube formation in human umbilical vein endothelium cells. Conclusions and implications:These results suggest that KRH102053 and its structural analogues have the potential for use as therapeutic agents against various diseases associated with HIF.

Introduction AMS 700CX/CXM inflatable penile prosthesis is increasingly applied for the treatment of erectile dysfunction (ED). However, there are a few long-term survival data of the inflatable penile prosthesis (IPP) over 10 years. Aim To determine the long-term mechanical reliability of AMS 700CX/CXM inflatable penile prosthesis in patients with ED. Methods A total of 438 consecutive patients with ED received implantation of an AMS 700CX/CXM penile prosthesis at our institution from January 1991 to April 2009. In 397 patients (90.7%), the medical records were available and current status of penile prosthesis could be obtained by a direct telephone interview. The overall and mechanical survival rates of penile prosthesis were evaluated using Kaplan–Meier method. Main Outcome Measures Assessing the mechanical and overall survival rates of the AMS 700CX/CXM penile prosthesis using Kaplan–Meier analysis, and looking for clinical factors related to survival of the CX/CXM using log-rank test. Results Mean age of 397 patients was 63.1 years (range, 24-93) and follow-up duration was 113 months (range 1-219). Eighty-two patients (20.6%) experienced mechanical failure at a median follow-up of 82 months. Mechanical survival rate of the penile prosthesis was 97.6%, 93.2% and 78.2% at 3, 5, and 10 years after implantation, respectively. 12 patients (3.0%) experienced nonmechanical failure including infections, tissue erosion resulting in cylinder protrusion at the meatus and chronic discomfort. Overall survival rate of the penile prosthesis was 95.0%, 91.0% and 75.5% at 3, 5, and 10 years after implantation, respectively. Patients with neurogenic cause for ED showed lower median overall survival of penile prosthesis compared with patients with non-neurogenic cause. Patient age, obesity, and diabetes mellitus had no association with overall survival of penile prosthesis after implantation. Conclusions The AMS 700CX/CXM could be accepted and applied in more patients as a reliable treatment alternative of ED.