Skeletal Muscle Perfusion Research Articles

Effect of vibration on muscle perfusion: a systematic review

Vibration has become of increasing interest to health professionals, primarily owing to reports that vibration can increase tissue blood flow. The aim of this review was to investigate the available scientific evidence on the effects of exogenous vibration on skeletal muscle perfusion. The databases searched from inception to December 2010 included Ovid MEDLINE, EMBASE, CINAHL via EbscoHost and CENTRAL. Experimental and observational studies, where exogenous vibration was an intervention, were included in this review. The main outcomes of interest were muscle blood volume, blood flow, blood flow velocity, arterial diameter and muscle temperature. One reviewer selected studies for inclusion, extracted data and assessed the quality of the eligible studies. Percentage change in muscle perfusion outcome was the measure of treatment effect, and regression analysis was used to investigate associations between vibratory load and muscle perfusion. Twenty-two studies with a total of 302 participants were included in this review. Muscle blood volume increased with vibration in five of nine studies and decreased in two studies; muscle blood flow velocity increased with vibration in five of six studies; muscle blood flow increased with vibration in two of three studies; vibration had a positive effect on arterial diameter in three of three studies; vibration had no effect on muscle temperature in two of two studies. The magnitude of increase in muscle perfusion was positively associated with vibratory load (P<0·001). We conclude that vibration increases muscle perfusion with the magnitude of increase positively related to the vibratory load applied.

Potentiating exercise training with resveratrol

Potentiating exercise training with resveratrol

Candesartan Acutely Recruits Skeletal and Cardiac Muscle Microvasculature in Healthy Humans

Angiotensin II type 1 receptor (AT(1)R) tone restricts muscle microvascular blood volume (MBV) and decreases muscle insulin delivery and glucose use. The objective of the study was to examine whether acute AT(1)R blockade alters microvascular perfusion in skeletal and cardiac muscle in humans. The study was conducted at the General Clinical Research Center at the University of Virginia. Eight overnight-fasted healthy young adults were studied thrice in random order. In study 1, each subject received candesartan (32 mg) orally at time 0. In study 2, each subject received placebo at time 0 and a 1 mU/min · kg euglycemic insulin clamp from time 240 to 360 min. In study 3, each subject received candesartan (32 mg) orally at time 0 and insulin infusion from 240 to 360 min. Forearm skeletal and cardiac muscle MBV, microvascular flow velocity, and microvascular blood flow (MBF) were determined at baseline and at 240 and 360 min. Candesartan treatment acutely recruited microvasculature in both skeletal and cardiac muscle by significantly increasing MBV (P < 0.03 and P = 0.02, respectively) and MBF (P < 0.03 for both) without altering microvascular flow velocity. Insulin infusion significantly increased cardiac MBV (P = 0.02) and MBF (P < 0.02). Superimposing insulin infusion 4 h after candesartan ingestion did not further recruit microvasculature. Insulin-mediated whole-body glucose disposal did not differ with or without candesartan pretreatment. Acute AT(1)R blockade with candesartan recruits skeletal as well as cardiac muscle microvasculature in healthy humans without altering insulin-mediated whole-body glucose disposal. This may contribute to the observed improvement in the cardiovascular outcomes in patients receiving prolonged treatment with AT(1)R blockers.

Moderate increases in dietary fat impair microvascular but not myocyte actions of insulin in skeletal muscle of Sprague Dawley rats

Enhanced microvascular perfusion in skeletal muscle is important for insulin‐mediated glucose disposal. We have previously demonstrated that high fat‐fed rats (36% fat wt/wt, 4 weeks) have impaired insulin‐stimulated microvascular perfusion and reduced insulin‐stimulated muscle glucose uptake (IMGU). We hypothesised that moderate increases in dietary fat might impair microvascular responses without altering myocyte insulin sensitivity. Rats were fed 5% (5%FD) or 9% (9%FD) fat (wt/wt) diets. After 4 weeks anesthetized rats were subjected to either a hyperinsulinemic euglycemic clamp, and microvascular perfusion measured from hindleg disappearance of 1‐methylxanthine, or pump‐perfusion of the isolated rat hindlimb, which allows myocyte insulin responses to be measured in the absence of altered perfusion. Body weight, epididymal fat pad weight, and fasting plasma glucose were not altered by the diets. Fasting plasma insulin concentrations were moderately elevated, and plasma free fatty acid concentrations were significantly increased in 9%FD. Glucose infusion rate, IMGU and microvascular perfusion during the clamp were significantly impaired in 9%FD. In contrast, IMGU in the isolated, perfused hindlimb was unaltered by diet. These data show that increased dietary fat impairs microvascular insulin responses before those of skeletal myocytes, but still leads to muscle insulin resistance in vivo.

Fibromyalgia as a Disorder Related to Distress and its Therapeutic Implications

Fibromyalgia as a Disorder Related to Distress and its Therapeutic Implications

Ray-based approach to skeletal muscle perfusion measurement on interventional x-ray systems

Periprocedural assessment of tissue perfusion by imaging methods could improve outcome control during treatment of peripheral vascular disease. Currently, endovascular revascularization treatments are assessed by planar angiography which only allows for qualitative inspection of blood flow in vessels. In this paper, we present a method for periprocedural perfusion estimation based on temporal attenuation curves in skeletal muscles using angiographic C-arm systems. The proposed method tackles the loss of spatial depth information which occurs in conventional angiography by combining the acquired angiograms with two additional C-arm rotational soft tissue scans. The area subject to contrast propagation is segmented from the two images that are tomographically reconstructed from the rotational scans and is then used to estimate the spatially averaged temporal contrast attenuation along the x-ray directions from the angiograms. A segmentation method which is tailored to the estimation procedure is applied to limit inaccuracies in the estimation. The accuracy of the method in estimating tissue blood flow in muscular tissue is evaluated in a simulation study using experimental data from CT perfusion acquisitions. Results show that perfusion estimation accuracy is limited owing to spatial inhomogeneity of contrast in muscular tissue and to the presence of vessels along the x-ray directions. Nonetheless, the spatially averaged perfusion quantification allows for improved visual differentiation of normal and hypoperfused tissue in comparison with conventional digital subtraction angiography. Periprocedural assessment of muscle perfusion through digital subtraction angiography is challenging due to lack of longitudinal information in the planar projections. By including additional 3D information on the anatomy retrieved from rotational soft tissue scans, the visualization and differentiation of normal and hypoperfused areas can be improved.

Influence of passive stretching on inhibition of disuse atrophy and hemodynamics of rat soleus muscle.

The purpose of this study was to determine the influence of passive stretching on inhibition of disuse atrophy and hemodynamics among longitudinal regions of the rat soleus muscle. Disuse muscle atrophy was induced by hindlimb suspension for two weeks. Muscle blood flow was evaluated using thallium-201 ((201)Tl) which is a radiotracer that has been reported to be useful to assess blood perfusion in skeletal muscle. Thirty-nine male Wistar rats were divided randomly into 5 groups: control (C: n = 10), a group with hindlimb suspension (HS: n = 7), a group with hindlimb suspension and stretching (ST: n = 7), a group receiving only a single session of stretching after the hindlimb suspension period that was killed just after stretching (HSB: n = 7), and a group receiving only a single session of stretching hindlimb suspension and stretching period that was killed just after stretching (STB: n = 8). From the results of the cross-sectional area (CSA) and the capillary-to-fiber ratio (C/F), muscle atrophy and inhibition of atrophy were shown more in proximal than in distal regions of experimental groups. These results suggest that the alterations of the C/F and CSA were different among muscle regions in experimental groups. These differences may depend on the level of stretching. Moreover, alteration of blood flow resulting from alteration of the mechanical environment had little influence on muscle atrophy or inhibition of atrophy.

Bone marrow–derived CMPs and GMPs represent highly functional proangiogenic cells: implications for ischemic cardiovascular disease

AbstractClinical studies using bone marrow–derived proangiogenic cells (PACs) have demonstrated modest improvements of function and/or perfusion of ischemic myocardium or skeletal muscle. Because the identities of these PACs and their functional ability to promote neovascularization remain poorly understood, it is possible that a subset of robust PACs exists but is obscured by the heterogeneous nature of this cell population. Herein, we found that common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs) preferentially differentiate into PACs compared with megakaryocyte-erythrocyte progenitors, hematopoietic stem cells, and common lymphoid progenitors. In vivo hindlimb ischemia studies and Matrigel plug assays verified the enhanced neovascularization properties uniquely associated with PACs derived from CMPs and GMPs. Taken together, these observations identify CMPs and GMPs as key bone marrow progenitors for optimal PAC function in vitro and in vivo and provide a foundation for novel therapeutic approaches to modulate angiogenesis.

Influence of erythrocyte oxygenation and intravascular ATP on resting and exercising skeletal muscle blood flow in humans with mitochondrial myopathy

Oxygen (O2) extraction is impaired in exercising skeletal muscle of humans with mutations of mitochondrial DNA (mtDNA), but the muscle hemodynamic response to exercise has never been directly investigated. This study sought to examine the extent to which human skeletal muscle perfusion can increase without reductions in blood oxygenation and to determine whether erythrocyte O2 off-loading and related ATP vascular mechanisms are impaired in humans with mutations of mtDNA. Leg vascular hemodynamic, oxygenation and ATP were investigated in ten patients with mtDNA mutations and ten matched healthy control subjects: 1) at rest during normoxia, hypoxia, hyperoxia and intra-femoral artery ATP infusion, and 2) during passive and dynamic one-legged knee-extensor exercises. At rest, blood flow (LBF), femoral arterial and venous blood oxygenation and plasma ATP were similar in the two groups. During dynamic exercise, LBF and vascular conductance increased 9–10 fold in the patients despite erythrocyte oxygenation and leg O2 extraction remained unchanged (p<0.01). In the patients, workload-adjusted LBF was 28% to 62% higher during submaximal- and maximal exercises and was associated with augmented plasma ATP. The appropriate hemodynamic adjustments during severe hypoxia and ATP infusion suggest that erythrocyte O2 off-loading and related ATP vascular mechanisms are intact in patients with mtDNA mutations. Furthermore, greater increase in plasma ATP and LBF at a given metabolic demand in the patients, in concert with unchanged oxyhemoglobin, suggest that erythrocyte O2 off-loading is not obligatory for the exercise-induced increase in blood flow and intravascular ATP concentration.

A selective phosphodiesterase 3 inhibitor rescues low Po2-induced ATP release from erythrocytes of humans with type 2 diabetes: implication for vascular control

Erythrocytes, via release of ATP in areas of low oxygen (O(2)) tension, are components of a regulatory system for the distribution of perfusion in skeletal muscle ensuring optimal O(2) delivery to meet tissue needs. In type 2 diabetes (DM2), there are defects in O(2) supply to muscle as well as a failure of erythrocytes to release ATP. The goal of this study was to ascertain if a phosphodiesterase 3 (PDE3) inhibitor, cilostazol, would rescue low O(2)-induced ATP release from DM2 erythrocytes and, thereby, enable these cells to dilate isolated erythrocyte-perfused skeletal muscle arterioles exposed to decreased extraluminal O(2). Erythrocytes were obtained from healthy humans (HH; n = 12) and humans with DM2 (n = 17). We determined that 1) PDE3B is similarly expressed in both groups, 2) mastoparan 7 (G(i) activation) stimulates increases in cAMP in HH but not in DM2 erythrocytes, and 3) pretreatment of DM2 erythrocytes with cilostazol resulted in mastoparan 7-induced increases in cAMP not different from those in HH cells. Most importantly, cilostazol restored the ability of DM2 erythrocytes to release ATP in response to low O(2). In contrast with perfusion with HH erythrocytes, isolated hamster retractor muscle arterioles perfused with DM2 erythrocytes constricted in response to low extraluminal PO(2). However, in the presence of cilostazol (100 μM), DM2 erythrocytes induced vessel dilation not different from that seen with HH erythrocytes. Thus rescue of low O(2)-induced ATP release from DM2 erythrocytes by cilostazol restored the ability of erythrocytes to participate in the regulation of perfusion distribution in skeletal muscle.

472 Improved angiogenic capacity of endothelial progenitor cells in patients undergoing nocturnal hemodialysis versus conventional hemodialysis

End stage renal disease (ESRD) is associated with an increased risk of coronary and peripheral vascular disease (PVD). While endothelial progenitor cells (EPCs) from non-ESRD individuals demonstrate potent angiogenic effects in PVD models, the uremic milieu impairs EPC functionality in vitro. Nocturnal hemodialysis (NHD) is a dialytic modality that greatly increases uremic clearance, and is associated with improved cardiovascular outcomes. Whether NHD improves the in vivo angiogenic capacity of uremic EPCs is unknown. Peripheral blood mononuclear cells from age- and gender-matched conventional hemodialysis (CHD, 12 hrs/week, n = 10) and nocturnal hemodialysis (NHD, 30 - 50 hrs/week, n = 8) patients were plated on fibronectin-coated flasks and cultured for 10 days in EGM-2 medium (Lonza) to generate EPCs. EPCs from healthy individuals (n = 5) served as controls. Chronic unilateral hindlimb ischemia was induced by left common iliac artery ligation in athymic nude rats. On day 1 post-ligation, 5 x 105 EPCs were injected intramuscularly at 5 sites in the ischemic hindlimb. Saline was injected as a negative control (n = 10). Hindlimb perfusion was assessed on day 28 via contrast-enhanced ultrasound (CEU). Hindlimb capillary density was assessed using lectin immunostaining and expression of the proangiogenic cytokines VEGF and SDF-1α via qPCR. While injection of CHD EPCs had no effect compared with saline, injection of NHD EPCs significantly improved perfusion of the ischemic hindlimb to levels similar to that achieved with healthy control EPCs (ischemic/nonischemic limb perfusion ratio: saline vs. healthy vs. CHD vs. NHD: 0.46 ± 0.05 vs. 0.78 ± 0.11 vs. 0.61 ± 0.06 vs. 0.85 ± 0.04, P < 0.05). Similarly, while capillary density was low in saline and CHD EPC-treated ischemic limbs, a robust capillarization response was noted in both NHD EPC and healthy control EPC-treated hindlimbs. Levels of angiogenic cytokines activated early in the angiogenic response (VEGF, SDF-1α) were not different 28 days post-ischemia induction across all 4 treatment groups. Nocturnal hemodialysis is associated with a significantly improved ability of EPCs to restore perfusion in ischemic skeletal muscle, as compared to conventional hemodialysis in a clinically relevant model of peripheral vascular disease.

Direct oxymetric peripheral tissue perfusion monitoring during open heart surgery with the use of cardiopulmonary bypass: preliminary experience

Regional hypoperfusion has been associated with the development of postoperative organ dysfunction in cardiac surgery involving cardiopulmonary bypass (CPB). Direct tissue oxymetry is a potentially new method for monitoring the quality of the peripheral tissue perfusion during CPB. The aim of this study was to assess the effects of CPB in skeletal muscle oxygenation when measured in the deltoid muscle by direct oxymetry during perioperative period. Seven patients underwent on-pump coronary artery bypass grafting. Direct oxymetry was performed by an optical cathether introduced into the deltoid muscle. Continuous measurement was made during the surgical procedure and the postoperative period. Mean arterial blood pressure, blood flow during CPB, laboratory markers of tissue hypoperfusion, blood gases and body temperature were also recorded. Interstitial muscle tissue oxygen tension (pO(2)) decreased after the introduction to anaesthesia and, more significantly, during CPB. After the disconnection from CPB at the end of the operation, the pO(2) returned to pre-anaesthetic values. During the first hours after admission of the patients to the intensive care unit, the pO(2) progressively decreased, reached a minimum value after four hours, and increased slowly thereafter. There was a significant correlation of pO(2) with mean arterial blood pressure and blood flow during that time. The result of this first measurement seems to demonstrate that the standard technique of conducting cardiopulmonary bypass produces low muscle oxygen tension and, thus, little perfusion of skeletal muscle. The data also indicate that both high mean arterial blood pressure and high flow are necessary during CPB to ensure skeletal muscle perfusion. The investigation is continuing.

Spatial heterogeneity in skeletal muscle microvascular blood flow distribution is increased in the metabolic syndrome

Previous studies have demonstrated that the metabolic syndrome is associated with impaired skeletal muscle arteriolar function, although integrating observations into a conceptual framework for impaired perfusion in peripheral vascular disease (PVD) has been limited. This study builds on previous work to evaluate in situ arteriolar hemodynamics in cremaster muscle of obese Zucker rats (OZR) to integrate existing knowledge into a greater understanding of impaired skeletal muscle perfusion. In OZR cremaster muscle, perfusion distribution at microvascular bifurcations (γ) was consistently more heterogeneous than in controls. However, while consistent, the underlying mechanistic contributors were spatially divergent as altered adrenergic constriction was the major contributor to altered γ at proximal microvascular bifurcations, with a steady decay with distance, while endothelial dysfunction was a stronger contributor in distal bifurcations with no discernible role proximally. Using measured values of γ, we found that simulations predict that successive alterations to γ in OZR caused more heterogeneous perfusion distribution in distal arterioles than in controls, an effect that could only be rectified by combined adrenoreceptor blockade and improvements to endothelial dysfunction. Intravascular (125)I-labeled albumin tracer washout from in situ gastrocnemius muscle of OZR provided independent support for these observations, indicating increased perfusion heterogeneity that was corrected only by combined adrenoreceptor blockade and improved endothelial function. These results suggest that a defining element of PVD in the metabolic syndrome may be an altered γ at microvascular bifurcations, that its contributors are heterogeneous and spatially distinct, and that interventions to rectify this negative outcome must take a new conceptual framework into account.

Kontrastverstärkter Ultraschall der Skelettmuskulatur

Functional imaging can increase the role of imaging in muscular diseases, as alterations of muscle morphology alone are non-specific for a particular disease. A good example for these functional imaging techniques is to use contrast-enhanced ultrasound (CEUS) to visualize and quantify in vivo (patho-) physiological information about the skeletal muscle microcirculation. Perfusion, i.e. the blood flow per tissue unit including capillary flow, is an important functional parameter. Pathological changes of skeletal muscle perfusion can be found in various clinical conditions, such as degenerative or inflammatory myopathy or peripheral arterial disease (PAD). This article reviews the theoretical basics of functional radiological techniques for assessing skeletal muscle perfusion and focuses on applications of microvascular imaging by CEUS which has improved the diagnosis of these muscular disorders. For evaluation of myositis, CEUS is more efficient in the diagnostic work-up than routine b-mode ultrasound because CEUS can detect inflammation-induced muscular hyperperfusion in acute myositis. This has already been demonstrated by high-mechanical index techniques using a first generation ultrasound contrast agent. Low-mechanical index CEUS techniques that require the use of a second generation contrast agent allow real-time quantification of muscular microcirculation at rest and during exercise. Using this CEUS method, the influence of different exercise intensities on the microcirculation of the exercising muscle becomes detectable. Moreover, the arterial perfusion reserve in PAD can be adequately examined using low-mechanical index CEUS. Initial findings have shown that the arterial perfusion reserve in patients suffering from PAD is reduced in comparison to healthy volunteers. In conclusion, modern CEUS techniques can offer deeper insights in muscular (patho-) physiology than just illustrating unspecific myopathic manifestations using conventional diagnostic imaging, such as edematous or lipomatous changes, hypertrophy or atrophy.

Long-term VEGF-A expression promotes aberrant angiogenesis and fibrosis in skeletal muscle

Vascular endothelial growth factor A (VEGF-A) induces strong angiogenesis and it has been widely used in proangiogenic gene therapy studies. However, little is known about long-term effects of VEGF-A expression in skeletal muscle. Here the long- term effects of adeno-associated virus (AAV) encoding human VEGF-A(165) (AAV-VEGF-A) gene transfer in normal and ischemic rabbit hindlimb skeletal muscles were studied. AAV-LacZ was used as a control. In one-year follow-up, a remarkable increase in skeletal muscle perfusion compared with AAV-LacZ was observed measured with Doppler and contrast pulse sequence ultrasound. Angiogenesis was also seen in histology as enlarged and sprouting capillaries. In addition to favorable angiogenic effects, aberrant vascular structures with CD31 positive cell layers were seen inside muscle fibers after AAV-VEGF-A gene transfer. Importantly, we found increased amounts of extracellular matrix with a high number of macrophages and fibrosis in AAV-VEGF-A transduced muscles. No changes in skeletal muscle morphology were detected in AAV-LacZ transduced muscles. Our results indicate that local AAV-VEGF-A gene transfer efficiently promotes long-term angiogenesis in large animal model. However, non-regulated expression of VEGF-A causes unfavorable changes in muscle morphology, which suggests the need for regulation of the transgene expression in long-term AAV-mediated VEGF-A gene transfer applications.

The Feasibility of Measuring Phosphocreatine Recovery Kinetics in Muscle Using a Single-shot 31P RARE MRI Sequence

Heterogeneity of skeletal muscle structure, composition, and perfusion results in spatial differences in oxidative function between muscles and muscle regions. The simultaneous measurement of the postexercise phosphocreatine (PCr) recovery rate across all muscles of a human limb cross-section may provide new insights into normal physiology and disease states. The objective of this work was to assess the feasibility of acquiring PCr rapid acquisition with relaxation enhancement (RARE) images with sufficient temporal and spatial resolution to accurately measure PCr recovery kinetics in a cross-section of a human limb. One normal subject performed a finger exercise until fatigued. At cessation of exercise surface coil localized pulse-and-acquire phosphorus-31 MR spectra ((31)P- magnetic resonance spectroscopy [MRS]) of the forearm were acquired at 6 S intervals for 4 minutes. The exercise protocol was repeated 7 days later and axial PCr RARE images of the forearm were acquired following exercise with 5.6 cm(3) voxels at 6-second intervals for 4 minutes. The PCr recovery time constants for the PCr RARE and (31)P-MRS measurements were 91.0 and 91.1 seconds, respectively, based on a monoexponential fit. A Pearson correlation test showed that the PCr recovery data that resulted from the RARE PCr imaging were highly correlated with the data resulting from the (31)P-MRS (r = 0.91, P < .0001). Data from selected regions of RARE PCr images acquired at 6-second intervals compare well to those acquired using surface coil (31)P MR spectroscopy and can provide an accurate assessment of PCr recovery kinetics.

DIVERGENCE BETWEEN ARTERIAL PERFUSION AND FATIGUE RESISTANCE IN SKELETAL MUSCLE IN THE METABOLIC SYNDROME

The obese Zucker rat (OZR) exhibits many vascular alterations, although the integrated impact on active hyperemia remains unclear. Pressor responses and skeletal muscle perfusion were assessed in lean Zucker rats (LZR) and OZR during adrenergic stimulation (phenylephrine), challenge with thromboxane (U46619) and endothelium‐dependent dilation (methacholine). OZR were hypertensive vs. LZR, but this was abolished by adrenoreceptor blockade (phentolamine); pressor responses to U46619 were similar and were abolished by the PGH2/TxA2 receptor antagonist, SQ‐29548. Depressor responses to methacholine were impaired in OZR, but improved by the antioxidant TEMPOL. Active hyperemia to gastrocnemius muscle was restrained by adrenergic constriction in OZR, although this diminished with increased VO2. O2 extraction, reduced in OZR across levels of metabolic demand, was improved by TEMPOL or SQ‐29548; phentolamine did not impact extraction and neither TEMPOL nor SQ‐29548 improved perfusion. While VO2 and muscle performance were reduced in OZR, treatment with all three agents improved outcomes; individual agents were less effective. These data suggest that contributions of vascular dysfunction to perfusion, VO2 and muscle performance are spatially distinct, with adrenergic constriction impacting proximal resistance and endothelial dysfunction impacting distal exchange. (NIH DK64668, RR2865AR)

Protection against skeletal muscle hypoperfusion by adenosine and nitric oxide: together alone?

regulation of vasomotor tone in the microcirculation is essential to ensure adequate tissue oxygenation, particularly when oxygen demand is high, i.e., in skeletal or cardiac muscle during exercise and/or when supply is compromised, i.e., during hypoxia or in the presence of a flow-limiting stenosis

Rehabilitation bei Herzinsuffizienz – gibt es eine Behandlung jenseits von Pharmakologie, Chirurgie und Device-Therapie?

The reduced exercise capacity of patients with chronic heart failure cannot be explained solely on the basis of cardiac dysfunction. It seems to be the case that within the frame of the disease progression the importance of peripheral factors steadily increases. Chronic diminished perfusion of skeletal muscles, inactivity as well as harmful neuro-humoral activation leads to myopathy with loss of mitochondria and capillaries and to increased fibrosis. A systematic, controlled and properly dosed training improves in heart failure patients their cardiac symptoms like dyspnoe and exercise capacity. In addition an improved quality of life, augmented ejection fraction, diminished enddiastolic dimensions, improved respiratory efficiency will be achieved and the incidence of rehospitalization decreased. In the European guidelines there is a "class I recommendation" that is of the same class as the recommendation for a pharmacological standard therapy. The exact mechanism of the training of patients with heart failure is not known. In patients with ischemic heart failure training improves the myocardial perfusion due to a reduction of the endothelial dysfunction, and furthermore the training promotes collateralisation due to intermittend ischemic stimuli. The training is counteracting peripheral myopathy and it diminishes or even reverses the development of cardiac cachexia. In comparison of the prevalence of heart failure as well as the importance of training the referral pattern of some 500 patients per year encompasing all Swiss rehabilitation centers is considerably less than one would wish for. Heart failure exercise training should be started in a properly equipped center and evidenced with the advantage that it could be continued at home as a life long procedure.

Divergence between arterial perfusion and fatigue resistance in skeletal muscle in the metabolic syndrome

The metabolic syndrome is associated with elevated peripheral vascular disease risk, characterized by mismatched blood flow delivery/distribution and local metabolism. The obese Zucker rat (OZR) model of the metabolic syndrome exhibits myriad vascular impairments, although their integrated impact on functional hyperaemia remains unclear. In this study, arterial pressor responses and skeletal muscle perfusion were assessed in lean Zucker rats (LZRs) and OZRs during adrenergic stimulation (phenylephrine), challenge with thromboxane (U46619) and endothelium-dependent dilatation (methacholine). The OZRs were hypertensive compared with the LZRs, but this was abolished by adrenoreceptor blockade (phentolamine); pressor responses to U46619 were similar between strains and were abolished by blockade with the prostaglandin H(2)/thromboxane A(2) receptor antagonist, SQ-29548. Depressor reactivity to methacholine was impaired in OZRs, but was improved by antioxidant treatment (TEMPOL). Across levels of metabolic demand, blood flow to in situ gastrocnemius muscle was restrained by adrenergic constriction in OZRs, although this diminished with increased demand. Oxygen extraction, reduced in OZRs compared with LZRs across levels of metabolic demand, was improved by TEMPOL or SQ-29548; treatment with phentolamine did not impact extraction, and neither TEMPOL nor SQ-29548 improved muscle blood flow in OZRs. While oxygen uptake and muscle performance were consistently reduced in OZRs versus LZRs, treatment with all three agents improved outcomes, while treatment with individual agents was less effective. These results suggest that contributions of vascular dysfunction to perfusion, oxygen uptake and muscle performance are spatially distinct, with adrenergic constriction impacting proximal resistance and endothelial dysfunction impacting distal microvessel-tissue exchange. Further, these data suggest that increasing skeletal muscle blood flow in OZRs is not sufficient to improve performance, unless distal perfusion inhomogeneities are rectified.