Post-resistance exercise hypotension in patients with intermittent claudication

OBJECTIVE:

To verify the acute effects of resistance exercise on post‐exercise blood pressure in patients with intermittent claudication.

METHODS:

Eight patients randomly underwent two experimental sessions: a session of resistance exercise (R: 6 exercises, 3 sets of 12, 10 and 8 reps with a perceived exertion of 11 to 13 on the 15‐grade Borg scale) and a control session (C: resting on exercise machines).

RESULTS:

Before and for 60 min following an intervention, auscultatory blood pressure was measured while subjects rested in a sitting position. After the C session, systolic, diastolic and mean blood pressures did not change from the pre‐intervention values, while these values decreased significantly after the R session throughout the entire recovery period (greatest decreases  =  ‐14±5, ‐6±5, and ‐9±4 mmHg, respectively, P < 0.05).

CONCLUSION:

After a single bout of resistance exercise patients with intermittent claudication exhibited reduced systolic, diastolic and mean blood pressures, suggesting that acute resistance exercise may decrease cardiovascular load in these patients.     

Excretion of thromboxane A2 and prostacyclin metabolites during treadmill exercise in patients with intermittent claudication

Platelet activation, with subsequent formation of thromboxane A2 (TxA2), is thought to play a role in the development of arterial occlusion. In patients with severe atherosclerosis of the lower limbs, characterized by leg ulcers and rest pain, the basal formation of TxA2 and prostacyclin (PGI2) is increased. Corresponding data in patients with more moderate atherosclerosis of the lower limbs have not been reported. Since the capacity to physical exercise is not blunted in such patients proper evaluation of their TxA2-PGI2 synthesis should comprise not only assessment of the basal formation, but also TxA2/PGI2 biosynthesis during conditions of elevated cardiovascular activity. To address this, we analysed these eicosanoids in patients with a history of intermittent claudication. Urinary dinor-metabolites of TxB2 and PGI2 (Tx-M and PGI-M, respectively) were estimated by gas chromatography/negative ion-chemical ionization mass spectrometry in samples collected prior to, during and immediately after 20 min of severe treadmill exertion. The basal excretion of Tx-M was 105 +/- 26 pg/mg creatinine. It was not changed during exercise, but increased to 176 +/- 48 pg/mg creatinine (P less than 0.05) during the recovery. The basal excretion of PGI-M was 142 +/- 25 pg/mg creatinine. The PGI-M response to exercise varied from no change at all to a 30-fold increase, without any obvious correlation to experienced leg pain, walking distance or other recorded variables. During the recovery period the outflow of PGI-M was significantly higher than at rest (482 +/- 145 pg/mg creatinine; P less than 0.01). We conclude that in patients with intermittent claudication due to atherosclerosis (1) platelet activation does not occur during the course of the exercise, and (2) vascular prostacyclin formation can be dissociated from of TxA2 synthesis. The observed increase in PGI-M in some of the patients is suggested to reflect tissue ischaemia induced by the lack of adequate hyperaemia during exercise.     

Exercise prescription using the heart of claudication pain onset in patients with intermittent claudication

OBJECTIVE:

To assess the acute metabolic and cardiovascular responses to walking exercise at an intensity corresponding to the heart rate of claudication pain onset and to investigate the effects of a 12-week walking training program at this intensity on walking capacity.

METHODS:

Twenty-nine patients with intermittent claudication were randomly allocated to the walking training (n = 17) or control (CO, n = 12) group. The walking training group performed an acute exercise session comprising 15×2-min bouts of walking at the heart rate of claudication pain onset, with 2-min interpolated rest intervals. The claudication symptoms and cardiovascular and metabolic responses were evaluated. Walking training was then performed at the same intensity twice each week for 12 weeks, while the control group engaged in twice weekly stretching classes. The claudication onset distance and total walking distance were evaluated before and after the interventions. Brazilian Registry Clinical Trials: RBR-7M3D8W.

RESULTS:

During the acute exercise session, the heart rate was maintained within tight limits. The exercise intensity was above the anaerobic threshold and >80% of the heart rate peak and VO_2peak. After the exercise training period, the walking exercise group (n = 13) showed increased claudication onset distance (309±153 vs. 413±201m) and total walking distance (784±182 vs. 1,100±236m) compared to the control group (n = 12) (p<0.05).

CONCLUSION:

Walking exercise prescribed at the heart rate of claudication pain onset enables patients with intermittent claudication to exercise with tolerable levels of pain and improves walking performance.     

Histochemical changes in striated muscle in patients with intermittent claudication

Biopsy specimens from the gastrocnemius or rectus femoris muscle of 20 patients with intermittent claudication were studied using fresh frozen cryostat sections and histochemical reactions for adenosine triphosphatase, nicotinamide adenine nucleotide dehydrogenase reductase and phosphorylase and modified Gomori trichrome staining. Neuropathic changes, such as fibertype grouping and small group atrophy, were present to some extent in all of the biopsy specimens. Myogenic muscle changes such as necrosis and phagocytosis were seen in approximately one third and various forms of myofibrillar disorganization in approximately two thirds of the specimens. The amount and size of the type I aerobic fibers increased with the increasing severity of the ischemic disease.     

Platelet inhibition with Ticlopidine in atherosclerotic intermittent claudication.

Fifty-one men with atherosclerotic intermittent claudication and haemorheological abnormalities completed a double-blind, one-year randomised trial of Ticlopidine (500 mg/day), a new antiplatelet agent. Ticlopidine caused significant inhibition of platelet aggregation but did not fully correct abnormalities of coagulation, viscosity, and fibrinolysis. There was no significant improvement in walking ability, Doppler ankle-pressure indices, or calf blood flow. Sustained platelet inhibition for 12 months was insufficient to correct the prothrombotic abnormality of extensive atherosclerosis.     

Measurement of ischaemia-reperfusion in patients with intermittent claudication using NMR-based metabonomics

Intermittent claudication has proved to be a good in vivo model for ischaemia-reperfusion. For assessment of ischaemia-reperfusion damage, the known biochemical markers all have disadvantages with respect to sensitivity and interference with other physiological events. In this work, we studied the metabolic effects of ischaemia-reperfusion in patients with intermittent claudication, and the effects of vitamin C and E intervention, using both traditional biochemical measurements and 1H-NMR-based metabonomics on urine and plasma. The 1H-NMR spectra were subjected to multivariate modelling using principal components discriminant analysis, and the observed clusters were validated using joint deployment of univariate analysis of variance and Tukey-Kramer honestly significant difference (HSD) testing. The study involved 14 patients with intermittent claudication and three healthy volunteers, who were monitored during a walking test, before and after a vitamin C/E intervention, and after a washout period. The effect of exercise was only observable for a limited number of biochemical markers, whereas 1H NMR revealed an effect in line with anaerobic ATP production via glycolysis in exercising (ischaemic) muscle of the claudicants. Thus, the beneficial effect of vitamins C and E in claudicants was more pronounced when observed by metabonomics than by traditional biochemical markers. The main effect was more rapid recovery from exercise to resting state metabolism. Furthermore, after intervention, claudicants tended to have lower concentrations of lactate and glucose and several other citric acid cycle metabolites, whereas acetoacetate was increased. The observed metabolic changes in the plasma suggest that intake of vitamin C/E leads to increased muscle oxidative metabolism.     

Factors of prognostic importance for subsequent rest pain in patients with intermittent claudication

The risk of developing rest pain during a six-year period was studied in 224 non-diabetic patients with intermittent claudication. Both smoking and multiple arterial stenoses in the leg were significantly correlated with an increased risk of developing rest pain. In non-smokers and in those who had stopped smoking within one year after the initial examination, the cumulative percentage of patients without rest pain after six years was 92, and in smokers and those who stopped smoking after more than one year it was 79 (p less than 0.03 after adjustment for differences in the presence of multiple stenoses). In patients with single stenosis the cumulative percentage of patients without rest pain was 86, and in those with multiple stenoses 70 (p less than 0.05 after adjustment for differences in smoking habits). The results emphasize how important it is that patients with intermittent claudication do not smoke. The increased risk of rest pain associated with the presence of multiple arterial stenoses in the leg should be considered when making decisions concerning vascular surgery.     

Effect of physical training on different categories of patients with intermittent claudication

The effect of supervised training was studied in 68 patients with intermittent claudication. Maximal walking distance was measured on a treadmill. Eight of the patients had resting pain in the leg when recumbent (group A), 25 had an initial walking distance of less than 500 m (group B), 11 had an initial walking distance of 500--1 000 m (group C), 24 had coronary insufficiency (group D). The study shows that training should be undertaken for at least three months. In some patients with resting pain, training led to relief of pain and surgical treatment was not necessary. Almost all patients without signs of coronary insufficiency increased their walking distance, compared to only 14 of the 24 patients with coronary insufficiency. Walking distance increased significantly in groups B and C and no significant difference was found between patients and proximal or distal arterial stenosis.     

Skeletal muscle capillaries in intermittent claudication

The ultrastructural dimensions and density of capillaries in 23 gastrocnemius or rectus femoris muscles in patients with intermittent claudication due to arteriosclerosis obliterans (ASO) were studied. Constant ultrastructural alterations that were not seen in the control patients were thickening, replication, and remnants of the capillary basement membrane (BM). Compared with the control patientes, the percentual area of the BM was significantly larger (P less than .01), the lumen was significantly smaller (P less than .01), and the ratio of capillaries to muscle fiber was significantly higher (P less than .01) in patients with ASO. These changes were probably due to ASO since they increased with growing severity of claudication.     

Striated muscle ultrastructure in intermittent claudication

Twenty-four biopsy specimens from the lower leg muscles of 21 patients with intermittent claudication were studied by electron microscopy. Sixteen of the specimens contained hypertrophic, atrophic, autolytic, or phagocytic fibers, or other forms of macroscopic fiber degeneration. Of the pathological changes in the cell organelles, the most common was simple myofibrillar degeneration, followed by slightly pathological mitochondria and excessive accumulations of glycogen and lipofuscin. Different types of basement membrane alterations and central nuclei were present in 16 of the biopsy specimens. Most of the pathological changes were the same as those previously reported by others to occur in specific diseases of muscle. There was some positive correlation of the degree of pathological changes to the estimated clinical severity of claudication.     

Calf muscle adaptation in intermittent claudication. Side-differences in muscle metabolic characteristics in patients with unilateral arterial disease

The adaptation of enzyme activities, notably in the oxidative metabolism, and of prerequisites for tissue transport of oxygen in the claudication leg was evaluated by comparing muscle biopsies from the gastrocnemius muscle of the claudication and the symptom-free leg of seven patients with unilateral claudication. The claudication leg had higher activities of a marker enzyme for mitochondrial oxidative capacity, citrate synthase (CS), as well as of the MB and the mitochondrial isoenzyme of creatine kinase (CK), which are considered to be involved in the transfer of high energy phosphate from the mitochondria to the resynthesis of ATP in the cytoplasm. The difference between claudication and healthy leg in activities of these CK isoenzymes were well correlated with the corresponding side difference in CS activity. No significant differences between claudication and healthy leg were found in distribution of muscle fibre types or fibre dimension, capillary density or myoglobin content, nor was there any side difference in phosphofructokinase or lactate dehydrogenase. Side differences tended to be greater in those patients with the most advanced obstructive arterial disease as estimated from non-invasive pressure measurements. It is concluded that in reasonably physically-active patients, the mode of ischaemia to which the claudication leg is subjected leads to a metabolic adaptation characterized by increased activities of enzymes involved in the oxidative metabolism, but no significant adaptation of either the conditions for local oxygen transport, as estimated by myoglobin content, and capillary density, or capacity for anaerobic metabolism.     

Clinical efficacy of ozonated autohemotherapy in hemodialyzed patients with intermittent claudication: an oxygen-controlled study

BACKGROUND: Hemodialyzed patients are particularly exposed to the development of peripheral arterial occlusive disease. Ozonotherapy is used as a therapeutic tool in the treatment of this atherosclerotic complication, but there are still no properly designed studies to show the clinical effectiveness of this approach. The aim of this study was to evaluate the influence of ozonated autohemotherapy on walking ability and the subjective clinical experience of hemodialyzed patients with peripheral arterial disease. METHODS: Ten subjects with intermittent claudication (Fontain II stage) received the cycle of ozonated autohemotherapy with ozone concentration of 50 microg/ml and the cycle of oxygen autohemotherapy as a control in a cross-over, single-blind manner. Pain-free distance and maximal walking distance were measured using a standardized march test on a treadmill. The efficacy of therapy was assessed subjectively by patients on a five-degree scale. RESULTS: Significant prolongation of maximal waking distance after ozonated autohemotherapy was found, as compared to the baseline (by 30.5%) and to the oxygen control (by 22.7%) (p<0.01 and p<0.03). There was also significant increase in pain-free distance after ozonated autohemotherapy, as compared to the baseline (by 71.7%) and to the oxygen control (by 62.8%) (p<0.02 and p<0.03 respectively). In a subjective assessment (questionnaires) 90% of patients reported clinical improvement relative to the baseline after ozonated autohemotherapy as compared to 40% after the oxygen-control treatment (p<0.025). CONCLUSION: We demonstrated that ozonated autohemotherapy might prolong walking ability and attenuate subjective clinical signs of ischemia in patients with peripheral arterial disease treated regularly with hemodialysis.     

Effect of training on the post-exercise ankle blood pressure reaction in patients with intermittent claudication

The effect of physical training on the post-exercise blood pressure reaction in the ankle was studied in 63 patients with intermittent claudication but without angina pectoris. After three months of supervised training the maximal walking distance increased by 67% and the pain-free walking distance by 73%. Compared with that after the pre-training treadmill test, the ankle blood pressure was significantly higher 2-16 min after the post-training test and more rapidly returned to the initial resting value, both with similar work loads and with a higher post-training work load. Blood pressure measurement in the ankle after exercise is useful as an objective test of the circulatory effect of training in patients with intermittent claudication.     

Delayed respiratory response to exercise of short duration in patients with severe intermittent claudication due to bilateral atherosclerotic vascular disease: normalization after aorto-bifemoral bypass operation.

To investigate the respiratory response to exercise in patients with severe intermittent claudication, eight male patients, aged 57 years (range 43-73), with bilateral multi-segment atherosclerotic vascular disease, median maximum walking distance 50 m (range 20-200) and ankle-to-arm pressure index 0.4 (range 0.3-0.6), were studied before and after aorto-bifemoral bypass operation. Ventilation, CO2 output and O2 intake were recorded in the sitting position during 20 min of rest, 1 min of leg exercise on a bicycle ergometer [4.9 kJ (500 kpm)], and 20 min of recovery and rest. Before operation, maximal ventilation and CO2 output per minute were observed 2-4 min after cessation of work, while afterwards peak values were found during the work or the first minute of recovery. Pre-operatively, the extra ventilation and CO2 output during the work and recovery period and the recovery times of the ventilation and CO2 output per minute were markedly increased. Afterwards these values were clearly reduced towards normal. It is concluded that patients with severe intermittent claudication show a characteristic delay and prolonged rise in the respiratory response to exercise of short duration, which closely corresponds to the previously described pattern of outflow of hypoxia-generated metabolites from the exercising muscles. The pattern of respiratory response after operation reflects the fact that these patients also suffer from atherosclerotic heart dysfunction.     

Changes in peripheral blood pressures after five years of follow-up in non-operated patients with intermittent claudication

Changes in the segmental blood pressures (BP) in the legs after five years of follow-up and factors related to the changes were studied in 93 non-operated non-diabetic patients with intermittent claudication. Independent variables affecting the ankle/arm BP index (ABI) in the more affected leg were the initial ABI, smoking, duration of claudication and location of the stenoses (whether single or multiple). ABI was stable in non-smokers but decreased in smokers. It also decreased in patients with multiple stenoses at the initial examination but not in those with single stenoses. The correlation between subjective changes in claudication and changes in the ankle BP was poor. In the less affected leg, ABI decreased both in smokers and non-smokers but stenoses in legs without signs of stenoses initially developed to a greater extent in smokers than in non-smokers. Smoking is an important risk factor for progression of the occlusive atherosclerotic disease in intermittent claudication. Patients with multiple stenoses seem to have a more progressive occlusive disease.     

Hepatitis B virus reactivation among hepatitis C patients treated with direct-acting antiviral therapies in routine clinical practice

BackgroundHepatitis B (HBV) reactivation in chronic hepatitis C (CHC) patients treated with IFN-free direct acting antiviral (DAA) therapies has recently emerged as a potential risk. Given the potential burden of this issue, further data are needed to establish its actual clinical impact.ObjectivesThe aim of the present study was to analyze the occurrence of HBV reactivation in a cohort of CHC patient treated with DAAs in routine clinical practice.Study designConsecutive CHC patients with different genotypes, treated with DAA between January 2015 and January 2016 were included in the study. Subjects had been tested for HBsAg and anti-HBc antibodies before antiviral therapy. HBV-DNA levels were examined in anti-HBc positive patients at baseline and 24 weeks after the end of treatment. Post-treatment HBsAg determination was performed in case of HBV-DNA positivity. Serum anti-HBs kinetics was analysed in anti-HBs and anti-HBc positive subjects.ResultsA cohort of 137 consecutive HCV patients treated with IFN-free regimens in routine clinical practice was evaluated. From this cohort, plasma samples of 44 subjects with positive serology for HBV (anti-HBc positive) were tested for HBV-DNA levels at baseline and 24 weeks after the end of treatment. Two of them were HBsAg-positive, while the others had signs of a past HBV exposure (HBsAg-negative ± HBsAb-positive). No reactivation was found in HBcAb-positive and HBsAg-negative subjects. In the two HBsAg-positive, one experienced an increase in HBV-DNA levels of ≥2 log₁₀ IU/mL during treatment. However, the reactivation was without clinical impact and, most important, was followed by HBsAg loss.ConclusionsBased on our experience, a past HBV infection seems not to be a condition predisposing to HBV reactivation. On the contrary, in HBsAg-positive subjects not in suppressive treatment with nucleos(t)ide analogs, regular monitoring of HBV-DNA during and after DAA treatment should be considered.