Effects of modified Wenjing decoction on microcirculation in reproductive organs in rats with symptom patterns of cold coagulation and blood stasis.

OBJECTIVE: To investigate the relationship between symptom patterns of cold coagulation and blood stasis (CCBS) and microcirculation disturbance. In addition, we determined the efficacy of modified Wenjing decoction (WJD) for the treatment of CCBS. METHODS: CCBS was induced in rats with an ice-water bath treatment. The ovarian function, microvascular and circulatory status of reproductive organs, and function of local microvascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) were evaluated. RESULTS: Ovarian dysfunction was observed in the rats with CCBS. It was characterized by the presence of an estrous cycle disorder and a decrease in reproductive hormone levels. Microvascular circulation disorders were associated with an imbalance in vasoconstriction, relaxation substances, nitric oxide, abnormal blood flow in whole blood, and decreased blood flow in the auricle and uterus. VECs were damaged, and VSMCs contracted and proliferated in ovarian and uterine tissues. CONCLUSION: Our findings suggest that the dysfunctional reproductive organs observed in gynecological CCBS may be closely related to the microcirculation disturbance of local tissues, microvascular contraction, and vascular remodeling. Modified WJD can be used to treat CCBS by improving microcirculation in reproductive organs.

Dietary Flaxseed Reduces Central Aortic Blood Pressure Without Cardiac Involvement but Through Changes in Plasma Oxylipins.

UNLABELLED: In the year-long FlaxPAD clinical trial (Flaxseed for Peripheral Artery Disease), dietary flaxseed generated a powerful reduction in brachial systolic and diastolic blood pressure in patients with peripheral artery disease. Oxylipins were implicated as potential mechanistic mediators. However, the ability of flaxseed to impact central aortic hypertension, arterial stiffness, or cardiac performance was not investigated. Additionally, the relationship between central blood pressure (cBP) and oxylipins was not elucidated. Therefore, radial tonometry and pulse wave analysis were used to measure cBP and cardiac function in the FlaxPAD population (n=62). Plasma oxylipins were analyzed with high-performance liquid chromatography mass spectrometry. In patients with high blood pressure at baseline, the average decrease in central systolic and diastolic blood pressures versus placebo was 10 and 6 mm Hg, respectively. Flaxseed did not significantly impact augmentation index or other cardiac function indices. Alternatively, the data support several specific oxylipins as potential mediators in the antihypertensive properties of flaxseed. For example, every 1 nmol/L increase in plasma 16-hydroxyeicosatetraenoic acid increased the odds of higher central systolic and diastolic blood pressures by 12- and 9-fold, respectively. Every 1 nmol/L increase in plasma thromboxane B2 and 5,6-dihydroxyeicosatrienoic acid increased the odds of higher cBP by 33- and 9-fold, respectively. Flaxseed induced a decrease in many oxylipins, which corresponded with a reduced risk of elevated cBP. These data extend the antihypertensive properties of flaxseed to cBP without cardiac involvement but rather through oxylipins. This study provides further support for oxylipins as therapeutic targets in hypertension. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00781950.

Acupuncture in subjects with cold hands sensation: study protocol for a randomized controlled trial.

BACKGROUND: Cold hands sensation is a common disorder within the Korean population. Many Korean family physicians believe that it is a mild early manifestation of Raynaud's phenomenon (RP), or may be related to RP. RP is characterized by reversible digital vasospasm provoked by cold temperatures and/or emotional stress, and doctors often prescribe medications that are used in treatment of RP for subjects with cold hands. However, this has not shown a clear benefit, and these medications can cause unwanted side effects. It is also reported that traditional Korean medicine, including acupuncture, is widely used to treat cold hands, although the current level of evidence for this approach is also poor and to date, there have been no published randomized controlled clinical trials (RCTs) evaluating the efficacy and safety of acupuncture for cold hands. We have therefore designed a pilot RCT to obtain information for the design of a further full-scale trial. METHODS/DESIGN: The proposed study is a five-week pilot RCT. A total of 14 subjects will be recruited and randomly allocated to two groups: an acupuncture plus medication group (experimental group) and a medication-only group (control group). All subjects will take nifedipine (5 mg once daily) and beraprost (20 mg three times daily) for three weeks. The experimental group will receive additional treatment with three acupuncture sessions per week for three weeks (nine sessions total). The primary outcome will be measured using a visual analogue scale. Secondary outcomes will be measured by blood perfusion in laser Doppler perfusion imaging of the hands, frequency and duration of episodes of cold hands, and heart rate variability. Assessments will be made at baseline and at one, three, and five weeks thereafter. DISCUSSION: This study will provide an indication of the feasibility and a clinical foundation for a future large-scale trial. TRIAL REGISTRATION: This study was registered at Korean Clinical Research Information Service (CRIS) registry on 5 August 2013 with the registration number #KCT0000817.

Perinatal L-arginine and antioxidant supplements reduce adult blood pressure but not ameliorate the altered vascular function in spontaneously hypertensive rats

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Spontaneously hypertensive rat (SHR) offspring from L-arginine- and antioxidant-supplemented SHR dams had persistent lower blood pressure in adulthood. We investigated the influence of vascular mechanism in this effect. We analyzed response to acetylcholine and phenylephrine in aorta and superior mesenteric arteries from Wistar–Kyoto (WKY), SHR, and SHR perinatally supplemented with L-arginine and 4-hydroxy-2,2,6,6-tetramethylpiperidinoxyl (TEMPOL; SHR-suppl). Supplements reduced blood pressure persistently in SHR. Relaxation to acetylcholine was greater in WKY than SHR and remained unmodified in SHR-suppl compared with SHR. Acute TEMPOL did not alter relaxation to acetylcholine in WKY but increased it similarly in SHR and SHR-suppl. Phenylephrine contraction was increased in SHR compared to WKY. In SHR-suppl, this response was similar to SHR. Endothelium removal or N-nitro-L-arginine methyl ester (L-NAME) increased contraction to phenylephrine more in WKY than SHR. In SHR-suppl, this was similar to SHR. In both SHR and SHR-suppl, TEMPOL similarly reduced phenylephrine response. This effect was prevented by L-NAME. Results exposed reinforce the concept that oxidative stress during perinatal period is a contributing factor to the development of hypertension in SHR. Results also reveal that the beneficial effect of this supplementation does not appear to be related to improved endothelial function, suggesting that other regulatory mechanisms of blood pressure may be involved (AU)

Eficacia de un programa de masaje y ejercicio sobre el índice tobillo/brazo y presión sanguínea en pacientes con diabetes mellitus tipo 2 y enfermedad arterial periférica: ensayo clínico aleatorizado / Efficacy of a massage and exercise programme on the ankle-brachial index and blood pressure in patients with diabetes mellitus type 2 and peripheral arterial disease: a randomized clinical trial

Fundamento y objetivo: La diabetes mellitus tipo 2 es una enfermedad con una elevada prevalencia y puede favorecer la aparición de enfermedad arterial periférica. El objetivo del presente estudio fue analizar la eficacia de un programa de ejercicios y masaje reflejo del tejido conjuntivo sobre el índice tobillo/brazo y los valores de presión arterial de pacientes con diabetes mellitus tipo 2 y enfermedad arterial periférica. Pacientes y método: Se realizó un estudio experimental con grupo control placebo. Se asignaron de forma aleatorizada 66 pacientes diabéticos tipo 2 con enfermedad arterial periférica en estadio II-b de Leriche-Fontaine a un grupo de intervención (ejercicio y masaje) y a un grupo control placebo (programa de magnetoterapia simulada). Las dimensiones de medida fueron la presión arterial e índice tobillo/brazo. Resultados: Finalizadas las 10 semanas de tratamiento, en el grupo de intervención se obtuvieron diferencias significativas (p<0,05) en el índice tobillo/brazo derecho e izquierdo y en la presión arterial sistólica y diastólica en el miembro inferior derecho e izquierdo. Conclusiones: Un programa combinado de ejercicios y masaje mejora la presión arterial y el índice tobillo/brazo en pacientes diabéticos tipo 2 con enfermedad arterial periférica (AU)

Background and Objective: Type 2 diabetes mellitus is a highly prevalent disease that can favour the development of peripheral arterial disease. The objective of this study was to analyse the efficacy of a massage and exercise programme on the ankle-brachial index and arterial pressure of patients with diabetes mellitus type 2 and peripheral arterial disease. Material and Methods: An experimental study with placebo control group was performed. Sixty-six type 2 diabetes patients with Leriche-Fontaine stage II peripheral arterial disease were randomly assigned to an intervention (exercise and massage) or placebo control (simulated magnetotherapy) group. Study variables were arterial pressure and ankle-brachial index. Results: After 10 weeks of treatment, significant (P<0.05) differences between the intervention and placebo groups were found in right and left ankle-brachial index values and in systolic and diastolic pressures in right and left lower extremities. Conclusions: A combined programme of exercise and massage improves arterial blood pressure and ankle brachial index values in type 2 diabetics with peripheral arterial disease (AU)

Waon therapy for cardiovascular disease: innovative therapy for the 21st century.

Waon therapy is a form of thermal treatment in a dry sauna maintained at a temperature of 60 degrees C, which differs from the traditional sauna. Waon therapy reportedly improves the hemodynamics, cardiac function, ventricular arrhythmias, vascular endothelial function, neurohormonal factors, sympathetic nervous system function, and symptoms in patients with chronic heart failure (CHF). It has also been demonstrated that the molecular mechanism by which Waon therapy improves vascular flow and endothelial function involves increased expression of endothelial nitric oxide synthase (eNOS). Furthermore, in a mouse model of hindlimb ischemia, repeated Waon therapy increased eNOS protein expression, blood flow, and capillary density. Moreover, Waon therapy did not increase blood flow and capillary density in eNOS-deficient mice, indicating that eNOS is a critical regulator of the angiogenesis induced by this therapy. Moreover, repeated Waon therapy is effective for patients with severe peripheral arterial disease (PAD), as evidenced by substantial decrease in pain scores, increases in both ankle-brachial pressure index and blood flow assessed by laser Doppler perfusion imaging, and by formation of new collateral vessels on angiography. In addition, ischemic ulcers heal or improve markedly. In conclusion, Waon therapy is an innovative and highly promising strategy for treating CHF and PAD.

Efficacy of keishibukuryogan, a traditional Japanese herbal medicine, in treating cold sensation and numbness after stroke: clinical improvement and skin temperature normalization in 22 stroke patients.

Cold sensation and numbness have been reported as post-stroke sensory sequelae attributable to distal axonopathy, which is caused by chronic ischemia of diseased limbs resulting from dysfunction of vasomotor regulatory systems. Keishibukuryogan is a traditional herbal medicine used to treat symptoms of peripheral ischemia such as cold extremities. This study investigated clinical improvement and skin temperature in peripheral ischemia patients to determine the efficacy of keishibukuryogan in alleviating post-stroke cold sensation and numbness. Twenty-two stroke patients with cold sensation and/or numbness were enrolled in this study. Subjective cold sensation and numbness, evaluated using the visual analogue scale, were found in 21 and 31 limbs, respectively. The skin temperature of diseased and healthy limbs was recorded. We observed all patients for 4 weeks and 17 patients for 8 weeks after administration of keishibukuryogan. The skin temperature of diseased limbs was significantly higher than baseline at 4 weeks and 8 weeks, whereas that of healthy limbs did not change significantly. Cold sensation and numbness were significantly improved at 4 weeks and 8 weeks compared to baseline. Keishibukuryogan administration resulted in warming of diseased limbs and improved cold sensation and numbness, probably by increasing peripheral blood flow.

[Efficacy of a massage and exercise programme on the ankle-brachial index and blood pressure in patients with diabetes mellitus type 2 and peripheral arterial disease: a randomized clinical trial]. / Eficacia de un programa de masaje y ejercicio sobre el índice tobillo/brazo y presión sanguínea en pacientes con diabetes mellitus tipo 2 y enfermedad arterial periférica: ensayo clínico aleatorizado.

BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus is a highly prevalent disease that can favour the development of peripheral arterial disease. The objective of this study was to analyse the efficacy of a massage and exercise programme on the ankle-brachial index and arterial pressure of patients with diabetes mellitus type 2 and peripheral arterial disease. MATERIAL AND METHODS: An experimental study with placebo control group was performed. Sixty-six type 2 diabetes patients with Leriche-Fontaine stage II peripheral arterial disease were randomly assigned to an intervention (exercise and massage) or placebo control (simulated magnetotherapy) group. Study variables were arterial pressure and ankle-brachial index. RESULTS: After 10 weeks of treatment, significant (P<0.05) differences between the intervention and placebo groups were found in right and left ankle-brachial index values and in systolic and diastolic pressures in right and left lower extremities. CONCLUSIONS: A combined programme of exercise and massage improves arterial blood pressure and ankle brachial index values in type 2 diabetics with peripheral arterial disease.

The impact of oral L-arginine supplementation on acute smoking-induced endothelial injury and arterial performance.

BACKGROUND: Smoking is associated with endothelial dysfunction and increased inflammatory status. The amino acid L-arginine, improves endothelial function in patients with cardiovascular risk factors. We investigated the effect of L-arginine on vascular function and inflammatory process in healthy smokers at rest and after acute smoking. METHODS: We studied the effect of L-arginine and/or placebo in 12 healthy young smokers on three occasions (day 0, day 1, and day 3). The study was carried out on two separate arms, one with L-arginine (3 x 7 g/day) and one with placebo, according to a randomized, placebo-controlled, double-blind, cross-over design. Measurements were carried out before, immediately after, and 20 min after cigarette smoking. Endothelial function was evaluated by flow-mediated dilation (FMD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) and as a measure of arterial wave reflections. Serum soluble intercellular adhesion molecule-1 (sICAM-1) was measured. RESULTS: Compared to placebo, L-arginine improved FMD (P < 0.01 at day 1 and P < 0.05 at day 3). L-Arginine reduced PWV and AIx at both days 1 and 3 (P < 0.05 vs. baseline). L-Arginine blunted the acute smoking-induced increase of AIx at both day 1 (P < 0.05) and day 3 (P < 0.01), and prevented the smoking-induced elevation of PWV at day 3 (P < 0.05). Importantly, L-arginine reduced sICAM-1 at days 1 and 3 (P < 0.05 for both vs. baseline). CONCLUSIONS: Oral L-arginine improves endothelial function and vascular elastic properties of the arterial tree during the acute phase of smoking, an effect accompanied by reduced sICAM-1 levels in these subjects.

Serum phosphorus concentrations and arterial stiffness among individuals with normal kidney function to moderate kidney disease in MESA.

BACKGROUND AND OBJECTIVES: Higher phosphorus levels are associated with cardiovascular disease (CVD) events and mortality. Whether vascular stiffness may be responsible is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study examined the cross-sectional associations of serum phosphorus with ankle brachial index (ABI), pulse pressure, and large and small artery elasticity by radial artery waveform analysis among 1370 individuals (440 with moderate chronic kidney disease) who did not have clinical CVD and participated in the Multi-Ethnic Study of Atherosclerosis. RESULTS: Fifty-nine (4%) individuals had high ABI (>1.30), a marker of peripheral arterial stiffness. Participants with phosphorus levels >4 mg/dl had greater than four-fold risk for high ABI compared with participants with phosphate levels <3 mg/dl (relative risk 4.6; 95% confidence interval 1.6 to 13.2; P = 0.01) after adjustment for demographics, traditional CVD risk factors, and kidney function. Higher phosphorus levels were also associated with greater pulse pressure and lesser large and small artery elasticity in unadjusted models, but these associations were attenuated after adjustment. CONCLUSIONS: Higher phosphorus levels are strongly associated with high ABI but not pulse pressure or large or small artery elasticity. If confirmed in future studies, then the association of higher phosphorus concentrations with CVD events may be partially mediated through peripheral arterial stiffness.

Spinal cord stimulation for the treatment of angina and peripheral vascular disease.

Spinal cord stimulation has been shown to be an effective and well-established treatment for failed back surgery syndrome, complex regional pain syndrome, and other neuropathic pain states. Recent advances in this therapy have led to its use in enhancing blood flow and reducing ischemic pain patterns. The application of spinal cord stimulation to treat angina and improve outcomes in patients suffering from peripheral vascular disease is now becoming a part of the algorithmic standard of care. This article examines the selection of patients, application of the therapy, outcomes, and future uses of stimulation for patients afflicted with these diseases. This article also examines possible study protocols to further examine the overall outcome of these therapies.

Effect of Ginkgo biloba (EGb 761) on treadmill walking time among adults with peripheral artery disease: a randomized clinical trial.

PURPOSE: Medical therapies for treatment of peripheral artery disease (PAD) are limited. Ginkgo biloba has been reported to increase maximal and pain-free walking distance among patients with PAD; however, the evidence is inconsistent. The objective of this study was to compare the effects of 300 mg/d of Ginkgo biloba (EGb 761) versus placebo on treadmill walking time and related cardiovascular measures among patients with PAD. METHODS: A double-blind, placebo-controlled, parallel design trial with a 4-month duration was used. Participants were 62 adults, aged 70 +/- 8 years (mean +/- SD), with claudication symptoms of PAD. The primary study outcomes were maximal and pain-free walking time on a treadmill. Secondary outcomes included flow-mediated vasodilation, a measure of antioxidant status as assessed by determining antibody levels to epitopes of oxidized low-density lipoprotein, and questionnaires addressing walking impairment and quality of life. RESULTS: Maximal treadmill walking time increased by 20 +/- 80 and 91 +/- 242 seconds in the placebo and the EGb 761 groups, respectively (P = .12). Pain-free walking time increased by 15 +/- 31 and 21 +/- 43 seconds, respectively (P = .28). No significant differences were detected between groups for any of the secondary outcomes. CONCLUSIONS: In older adults with PAD, Ginkgo biloba produced a modest but insignificant increase in maximal treadmill walking time and flow-mediated vasodilation. These data do not support the use of Ginkgo biloba as an effective therapy for PAD, although a longer duration of use should be considered in any future trials.

Omega-3 polyunsaturated fatty acid in peripheral arterial disease: effect on lipid pattern, disease severity, inflammation profile, and endothelial function.

BACKGROUND & AIMS: Peripheral arterial disease (PAD) is strongly associated with endothelial dysfunction and inflammation, which portend a high cardiovascular risk. Accordingly, we investigated the effects of omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on endothelial function and inflammatory status in affected individuals. METHODS: PAD patients were randomly divided into two groups. In Group I (n=16) pre-enrollment therapy was not modified, while in Group II (n=16) n-3 PUFAs 1 g b.i.d. for 3 months were added to the previous treatment. Endothelial function was assessed by measuring plasma soluble thrombomodulin (sTM) and brachial artery flow-mediated dilation (FMD), and the inflammatory status by measuring high-sensitivity C-reactive protein and myeloperoxidase. RESULTS: In Group II, n-3 PUFAs reduced sTM levels from the median value of 33.0 ng/mL (interquartile range 16.7, 37.2) to 17.0 ng/mL (11.2, 33.7) (p=0.04), and improved FMD from 6.7% (3.7, 8.7) to 10.0% (6.2, 14.2) (p=0.02). Conversely, these markers did not change in Group I. After 3 months, the levels of inflammatory markers remained unmodified in both groups. CONCLUSIONS: In PAD, n-3 PUFAs induced a marked improvement in endothelial function. Conversely, they did not affect the inflammatory status. In future, large, prospective studies are needed to investigate whether n-3 PUFAs, by improving endothelial function, would reduce the incidence of ischemic events in a population at high risk.

High-dose atorvastatin in peripheral arterial disease (PAD): effect on endothelial function, intima-media-thickness and local progression of PAD. An open randomized controlled pilot trial.

Beneficial effects of aggressive lipid-lowering with high-dose atorvastatin (80 mg/day) have been demonstrated in patients with coronary and cerebrovascular disease. The impact of such a therapy in patients with peripheral arterial disease (PAD) is less known so far. Here we studied the effects of high-dose atorvastatin on brachial artery endothelial function, common carotid intima-media thickness (IMT) and local progression of PAD in these patients. One hundred of 500 patients screened with documented PAD were randomly assigned to receive 80 mg of atorvastatin daily for six months or to continue on conventional medical treatment. Ninety-six percent of patients in the control group were on standard statin treatment. High resolution B-mode ultrasonography was used to study brachial artery flow-mediated dilation (FMD), IMT and ankle-brachial index (ABI) at baseline and at six months. FMD and IMT at baseline and at six months were 4.1 (0.06-8.6) versus 5.0 (0.76 vs. 8.1) %, p = 0.96, and 0.76 (0.66-0.82) versus 0.73 (0.63-0.81) mm, p = 0.41, respectively, in the atorvastatin group, and 2.66 (-1.9-6.9) versus 3.65 (0.0-8.6)%, p = 0.02, and 0.78 (0.71-0.90) versus 0.77 (0.70-0.90) mm, p = 0.48, in the control group. ABI at baseline and at six months was not different in either group. LDL cholesterol was reduced from 2.53 (2.21-3.28) to 1.86 (1.38-2.29) mM (p < 0.0001) in the atorvastatin group, whereas levels remained stable in the control group [2.38 (1.94-3.16) vs. 2.33 (1.82-2.84) mM, p = 0.61]. Major adverse cardiovascular events occurred in 2.1% in the atorvastatin group and 1.9% in the control group (p = 0.61). In conclusion, in this pilot trial aggressive lipid-lowering with 80 mg of atorvastatin daily for six months had no effect on brachial artery FMD in patients with PAD. IMT and ABI were also similar in patients with and without high-dose atorvastatin at six months.

Clinical, cellular, and molecular aspects of arterial calcification.

Arterial calcification is a complex and independently regulated process with risk factors similar to those for atherosclerotic occlusive disease. It may develop either within the atherosclerotic intima or in the media. When calcification is found in coronary or lower extremity arteries, it is an independent predictor of cardiovascular events and lower extremity amputation. Recent evidence suggests a role for several endogenous stimulators and inhibitors in the pathogenesis of arterial calcification. Inflammatory mediators and matrix-degrading enzymes are also thought to control the progression of calcification in humans. Current research involves efforts to define the complex interactions between cellular and molecular mediators of arterial calcification.

Amino acids stimulate leg muscle protein synthesis in peripheral arterial disease.

OBJECTIVE: Older patients with peripheral arterial disease (PAD) and intermittent claudication have impaired walking ability resulting from reduced lower extremity blood flow. Evidence suggests that leg muscle abnormalities may also contribute to walking intolerance in claudicants. In healthy elderly people, leg muscle protein synthesis can be augmented by nutritional supplementation with amino acids; preliminary data suggest that this increases muscle mass, walking ability, and functional status. In this study, we investigated whether amino acid supplementation would improve leg muscle protein synthesis in elderly PAD subjects, given that reduced leg blood flow might restrict the availability of amino acids to muscle. METHODS: Two groups participated in the study: a group of 11 claudicants (mean age, 62 years; mean ankle-brachial index, 0.62; 46% male) and a group of 9 age- and sex-matched healthy controls (mean ankle-brachial index, 1.1). Both groups underwent measurement of leg blood flow by using strain gauge plethysmography, as well as measurement of baseline and amino acid-stimulated protein synthesis in leg muscle. Protein synthesis was quantified from calf muscle biopsy samples by measurement of the fractional synthetic rate (FSR) of protein, by using the incorporation of the stable isotope l-[ring-(2)H(5)]-phenylalanine into muscle protein. Total protein was extracted from muscle samples, and gas chromatography/mass spectroscopy methodology was used to measure incorporation rates. After measurement of basal FSR, all subjects were given an oral drink of 15 g of essential amino acids, and the measurements of FSR were repeated. Data are expressed as mean +/- SD; statistical analysis of differences between the two groups (with and without amino acid supplementation) was performed by using analysis of variance with repeated measures. RESULTS: Calf blood flow was reduced in the PAD subjects compared with controls (1.44 +/- 0.53 mL/min per 100 mg of tissue vs 2.40 +/- 0.57 mL/min per 100 mg of tissue; P = .005; t test). FSR in the basal state was equivalent between the two groups (healthy, 0.060% +/- 0.025% per hour; PAD, 0.061% +/- 0.029% per hour; P = .97). Equivalent increases (P < .05) occurred in both groups in response to oral amino acid supplementation (healthy, 0.087% +/- 0.012% per hour; PAD, 0.104% +/- 0.041% per hour; P > .05; analysis of variance). CONCLUSIONS: Despite reduced leg blood flow, elderly PAD patients synthesize calf muscle protein in the basal state in a fashion similar to that in healthy elderly people. More importantly, administration of exogenous amino acids produces a significant increase in protein synthesis in these patients that is also equivalent to that in healthy elderly people. Our goal is to use these results as the basis for an intervention study to determine whether long-term oral amino acids, by augmenting calf muscle protein synthesis, increase calf muscle mass, walking ability, and functional status in elderly claudicants.

Peripheral arterial disease.

Peripheral arterial disease (PAD) in the elderly can be: 1) asymptomatic, 2) associated with intermittent claudication, or 3) cause critical limb ischemia. Persons with PAD are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from coronary artery disease (CAD). Hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism should be treated, and smoking should be stopped. Statins reduce the incidence of intermittent claudication and increase exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolemia. Antiplatelet drugs (eg, aspirin, clopidogrel, angiotensin-converting enzyme [ACE] inhibitors, statins) should be given to all persons with PAD. Beta blockers should be given if CAD is present. Exercise rehabilitation programs and cilostazol lengthen exercise time until leg pain develops. Chelation therapy has no scientific basis and should be avoided. Revascularization or amputation may be indicated in some cases.

Peripheral arterial disease in the elderly.

Smoking should be stopped and hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism treated in elderly patients with peripheral arterial disease (PAD) of the lower extremities. Statins reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in patients with PAD and hypercholesterolemia. Antiplatelet drugs such as aspirin or clopidogrel, especially clopidogrel, angiotensin-converting enzyme inhibitors, and statins should be given to all elderly patients with PAD without contraindications to these drugs. Beta blockers should be given if coronary artery disease is present. Exercise rehabilitation programs and cilostazol increase exercise time until intermittent claudication develops. Chelation therapy should be avoided. Indications for lower extremity percutaneous transluminal angioplasty or bypass surgery are (1) incapacitating claudication in patients interfering with work or lifestyle; (2) limb salvage in patients with limb-threatening ischemia as manifested by rest pain, nonhealing ulcers, and/or infection or gangrene; and (3) vasculogenic impotence.

Hyperbaric oxygen and bone marrow-derived endothelial progenitor cells in diabetic wound healing.

Endothelial progenitor cells (EPCs) are the key cellular effectors of postnatal vasculogenesis and play a central role in wound healing. In diabetes, there is a significant impairment in the number and function of circulating and wound-tissue EPC. Recent evidence indicates, that tissue-level hyperoxia achieved by therapeutic hyperbaric oxygen protocols (HBO2) can increase the mobilization of EPC from the bone marrow into peripheral blood. In this paper we review the recent reports on hyperoxia-mediated mobilization of bone marrow-derived EPC and postulate avenues of future research in this area as it applies to improving healing in chronic wounds affected by diabetes and peripheral arterial disease (PAD).