Inspiratory Muscle Training Improves Blood Flow to Resting and Exercising Limbs in Patients With Chronic Heart Failure

ObjectivesWe tested the hypothesis that inspiratory muscle loading could result in exaggerated peripheral vasoconstriction in resting and exercising limbs and that inspiratory muscle training (IMT) could attenuate this effect in patients with chronic heart failure (CHF) and inspiratory muscle weakness.BackgroundInspiratory muscle training improves functional capacity of patients with CHF, but the mechanisms of this effect are unknown.MethodsEighteen patients with CHF and inspiratory muscle weakness (maximal inspiratory pressure <70% of predicted) and 10 healthy volunteers participated in the study. Inspiratory muscle loading was induced by the addition of inspiratory resistance of 60% of maximal inspiratory pressure, while blood flow to the resting calf (CBF) and exercising forearm (FBF) were measured by venous occlusion plethysmography. For the patients with CHF, blood flow measurements as well as ultrasound determination of diaphragm thickness were made before and after a 4-week program of IMT.ResultsWith inspiratory muscle loading, CHF patients demonstrated a more marked reduction in resting CBF and showed an attenuated rise in exercising FBF when compared with control subjects. After 4 weeks of IMT, CHF patients presented hypertrophy of the diaphragm and improved resting CBF and exercise FBF with inspiratory muscle loading.ConclusionsIn patients with CHF and inspiratory muscle weakness, inspiratory muscle loading results in marked reduction of blood flow to resting and exercising limbs. Inspiratory muscle training improves limb blood flow under inspiratory loading in these patients

New insights into the physiologic basis for intermittent pneumatic limb compression as a therapeutic strategy for peripheral artery disease

The capability for externally applied rhythmic limb compressions to improve the outcomes of patients with peripheral artery disease has been recognized for nearly a century. Modern technology has permitted the development of portable and cost-effective intermittent pneumatic compression (IPC) systems to be made readily available for affordable at-home use. Mounting clinical evidence attests to the effectiveness of this strategy, with improvements in claudication distance rivaling those seen with exercise training or pharmacologic interventions, or both. However, owing to a lack of mechanistic knowledge, whether current application protocols are optimized for clinical outcomes is unknown. Traditional thinking has suggested that IPC transiently elevates blood flow, which is purported to relieve ischemia, improve vascular function, and promote vascular remodeling. Surprisingly, much ambiguity exists regarding the physiologic stimuli and adaptations that are responsible for the clinical effectiveness of IPC treatment. This review presents and critically discusses emerging evidence that sheds new light on the physiologic and molecular responses to IPC therapy. These novel findings highlight the importance of characterizing the phasic changes in the hemodynamic profile during IPC application. Further, these studies indicate that factors other than the elevation in blood flow during this therapy should be taken into account when designing an optimal IPC device. Lastly, we advance the hypothesis that manipulation of IPC stimulation characteristics could potentially magnify the documented clinical benefits associated with this therapy. in conclusion, recent evidence challenges the physiologic basis on which current IPC systems were designed, and further research to elucidate the basic and clinical outcomes of alternate stimulation characteristics is necessary.American College of Sports Medicine Research EndowmentFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Missouri, Dept Nutr & Exercise Physiol, Columbia, MO 65211 USAUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilUniv Missouri, Dept Biomed Sci, Columbia, MO 65211 USACalif State Univ San Marcos, Dept Kinesiol, San Marcos, CA 92096 USAUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilFAPESP: 2011/18197-0Web of Scienc

Acute Thermotherapy Prevents Impairments in Cutaneous Microvascular Function Induced by a High Fat Meal

We tested the hypothesis that a high fat meal (HFM) would impair cutaneous vasodilation, while thermotherapy (TT) would reverse the detrimental effects. Eight participants were instrumented with skin heaters and laser-Doppler (LD) probes and tested in three trials: control, HFM, and HFM + TT. Participants wore a water-perfused suit perfused with 33°C (control and HFM) or 50°C (HFM + TT) water. Participants consumed 1 g fat/kg body weight. Blood samples were taken at baseline and two hours post-HFM. Blood pressure was measured every 5–10 minutes. Microvascular function was assessed via skin local heating from 33°C to 39°C two hours after HFM. Cutaneous vascular conductance (CVC) was calculated and normalized to maximal vasodilation (%CVCmax). HFM had no effect on initial peak (48 ± 4 %CVCmax) compared to control (49 ± 4 %CVCmax) but attenuated the plateau (51 ± 4 %CVCmax) compared to control (63 ± 4 %CVCmax, P < 0.001). Initial peak was augmented in HFM + TT (66 ± 4 %CVCmax) compared to control and HFM (P < 0.05), while plateau (73 ± 3 % CVCmax) was augmented only compared to the HFM trial (P < 0.001). These data suggest that HFM negatively affects cutaneous vasodilation but can be minimized by TT

Thermotherapy reduces blood pressure and circulating endothelin-1 concentration and enhances leg blood flow in patients with symptomatic peripheral artery disease

Leg thermotherapy (TT) application reduces blood pressure (BP) and increases both limb blood flow and circulating levels of anti-inflammatory mediators in healthy, young humans and animals. The purpose of the present study was to determine the impact of TT application using a water-circulating garment on leg and systemic hemodynamics and on the concentrations of circulating cytokines and vasoactive mediators in patients with symptomatic peripheral artery disease (PAD). Sixteen patients with PAD and intermittent claudication (age: 63 ± 9 yr) completed three experimental sessions in a randomized order: TT, control intervention, and one exercise testing session. The garment was perfused with 48°C water for 90 min in the TT session and with 33°C water in the control intervention. A subset of 10 patients also underwent a protocol for the measurement of blood flow in the popliteal artery during 90 min of TT using phase-contrast MRI. Compared with the control intervention, TT promoted a significant reduction in systolic (∼11 mmHg) and diastolic (∼6 mmHg) BP (P < 0.05) that persisted for nearly 2 h after the end of the treatment. The serum concentration of endothelin-1 (ET-1) was significantly lower 30 min after exposure to TT (Control: 2.3 ± 0.1 vs. TT: 1.9 ± 0.09 pg/ml, P = 0.026). In addition, TT induced a marked increase in peak blood flow velocity (∼68%), average velocity (∼76%), and average blood flow (∼102%) in the popliteal artery (P < 0.01). These findings indicate that TT is a practical and effective strategy to reduce BP and circulating ET-1 concentration and enhance leg blood flow in patients with PAD

Effects of N-acetylcysteine on skeletal muscle structure and function in a mouse model of peripheral arterial insufficiency

Objective: Abnormalities in skeletal muscle structure and function are important contributors to exercise intolerance and functional decline in peripheral arterial disease. in this study, we tested the hypothesis that administration of N-acetylcysteine (NAC) would improve fatigue resistance and ameliorate the histopathological changes in skeletal muscle in a mouse model of peripheral arterial disease. We also anticipated that NAC treatment would lower the levels of biomarkers of oxidative damage in the ischemic muscle.Methods: Male Balb/c mice were subjected to bilateral ligation of the femoral artery and, after 2 weeks of recovery, received daily intraperitoneal injections of either NAC (150 mg/kg) or saline for 15 days. At the end of the treatment, the extensor digitorium longus (EDL) and soleus muscles were excised for assessment of contractile function in vitro and histological analysis. Free malondialdehyde and protein carbonyl levels were measured in the gastrocnemius muscle.Results: in the soleus muscle, force after 10 minutes of submaximal tetanic stimulation (60 Hz, 300 ms trains, 0.3 trains/s) was higher (P <.05) in NAC-treated animals (45% +/- 3% of the initial value; n = 7) when compared with controls (30.3% +/- 3%; n = 8). No differences were found in fatigue development between groups in the EDL muscle (ligated NAC, 35.7% +/- 1.9%; ligated saline, 37.5% +/- 1.1%). in addition, there was a tendency for lower levels of connective tissue deposition in the soleus of animals treated with NAC (n = 6) when compared with those that received only saline (n = 9) (ligated NAC, 16% +/- 2% vs ligated saline, 24% +/- 2%; P = .057). No differences were found in lipid peroxidation or protein carbonyl levels between ligated saline and ligated NAC groups.Conclusions: Taken together, these results indicate that treatment with NAC improves fatigue resistance in the soleus but not the EDL muscle in a model of peripheral arterial insufficiency.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Postdoctoral FellowshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, BR-04044010 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, Escola Paulista Med, Sect Nat Prod, BR-04044010 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, BR-04044010 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, Escola Paulista Med, Sect Nat Prod, BR-04044010 São Paulo, SP, BrazilFAPESP: 2010/51344-3FAPESP: 2011/00859-6Postdoctoral Fellowship: Fapesp 2011/18197-0Web of Scienc