Rafał Niżankowski

The effect of pain-free treadmill training on fibrinogen, haematocrit, and lipid profile in patients with claudication

Objective: To assess the effect of pain-free treadmill training on changes of plasma fibrinogen, haematocrit, lipid profile, and walking ability in patients with claudication. Design: Randomized control trial. Methods: Sixty-eight patients with peripheral obstructive arterial disease and intermittent claudication (Fontaine stage II) were randomly assigned into the treadmill training (repetitive intervals to onset of claudication pain, three times a week) or a control group (no change in physical activity) over 3 months. Both groups performed treadmill test to assess pain-free walking time (PFWT) and maximal walking time (MWT) and had blood analyses [for haematocrit, fibrinogen, triglycerides, and cholesterol: total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL)] done at baseline and after 6 and 12 weeks of the study. Results: Total and LDL cholesterol levels in the training group decreased (p < 0.05) by 14.8% and 20,5%, respectively. Significant (p < 0.05) HDL cholesterol increased (14.6%) and triglycerides decreased (19%) in the training group but changes of all these lipids were insignificant in the control group over the 3 months. Haematocrit and fibrinogen changes were insignificant in both groups. PFWT was prolonged by 109% and MWT increased by 54% in the training group (p < 0.01), but not in the control group. Conclusion: The improvement in walking time over 3 months of pain-free treadmill training parallels with progressive normalization of lipid profiles in patients with claudication.

Effects of simvastatin on angiogenic growth factors released at the site of microvascular injury

Effects of simvastatin on angiogenic growth factors released at the site of microvascular injury -

Comprehensive assessment of vascular health in patients; towards endothelium-guided therapy

Endothelial function has diagnostic, prognostic and therapeutic significance. A number of non-invasive techniques were introduced for its assessment, including flow-mediated dilation (FMD), finger plethysmography (RH-PAT) and digital thermal monitoring (DTM). All these methods can be performed simultaneously. In addition, various methods for measuring arterial wall stiffness are available such as: pulse wave analysis (PWA), pulse wave velocity (PWV), pulse contour analysis (PCA) and carotid wall distensibility coefficient (DC). Finally, carotid intima-media thickness (cIMT) and ankle brachial index (ABI) are used as surrogate read-outs of atherosclerosis. Here, we briefly describe the advantages, limitations and interrelationships of various methods used for the assessment of endothelial function, arterial stiffness, and present the concept of an integrated evaluation of vascular health based on multiple methods. This strategy may be useful to stratify cardiovascular risk and represents a step towards multiparametric assessment of endothelium for effective endothelium-guided therapy in patients with cardiovascular diseases.

Comparison of the Effect of Verapamil and Propranolol on Response of Coronary Vasomotion to Cold Pressor Test in Symptomatic Patients with Hypertrophic Cardiomyopathy

Impaired endothelium-dependent vasodilatation of coronary resistance vessels has been demonstrated in patients with hypertrophic cardiomyopathy (HC). The aim of this study was to compare the effect of verapamil and propranolol on the response of diastolic coronary blood flow velocity (CBFV) and coronary vascular resistance index to the cold pressor test (CPT) in symptomatic HC patients. In 15 patients with HC, the CBFV was measured in the distal portion of the left anterior descending coronary artery using high-sensitivity transthoracic Doppler echocardiography. Peak diastolic CBFV and coronary vascular resistance index (calculated as ratio of mean aortic pressure/CBFV ratio) were measured at baseline and after CPT. Changes of these parameters induced by the CPT (expressed as percentage of baseline values) were compared after verapamil and propranolol treatment in a crossover study. The same measurements were obtained in nine healthy control subjects. CPT induced an increasing pattern of CBFV during verapamil therapy, which was absent in CPT after propranolol administration (10.1 ± 5.6% vs. −0.9 ± 4.1%, P < 0.01). In healthy controls CBFV increased in response to CPT more than in HC patients receiving verapamil or propranolol (23.1±12.8% P < 0.01 and P < 0.05, respectively). The coronary vascular resistance index increased during the CPT significantly less on verapamil than on propranolol treatment (3.5 ± 9.2% vs. 18.1 ± 13.5%, P < 0.01). In healthy controls the coronary vascular resistance index decreased during CPT −4.5 ± 8.5% (P < 0.05 vs. verapamil and P < 0.01 vs. propranolol). Verapamil improved the coronary vasomotor response to CPT in relation to propranolol. Verapamil blunted the increase of the coronary vascular resistance index to the CPT in comparison with its change at CPT after propranolol. Thus, coronary endothelial dysfunction in symptomatic HC patients may be partially reduced by verapamil in comparison with propranolol treatment.

Verapamil improves the response of coronary vasomotion to cold pressor test in asymptomatic and mildly symptomatic patients with hypertrophic cardiomyopathy.

Summary. Impaired endothelium-dependent vasodilatation of coronary resistance vessels was previously demonstrated in patients with hypertrophic cardiomyopathy (HC). Therefore, we decided to assess the effect of verapamil administration on the response of diastolic coronary blood flow velocity (CBFV) and the coronary vascular resistance index to the cold pressor test in asymptomatic and mildly symptomatic HC patients. In 10 patients with nonobstructive HC, the CBFV was detected in the distal portion of the left anterior descending coronary artery using high-sensitivity transthoracic Doppler echocardiography. Peak diastolic CBFV, the velocity-time integral of diastolic CBF, and the coronary vascular resistance index (calculated as the mean aortic pressure/CBFV ratio) were measured at baseline and after the cold pressor test. The percentage changes from baseline to the cold pressor test of these parameters were compared before and after 1 month of verapamil therapy. Open-label verapamil changed the decrease in CBFV into an increase in response to the cold pressor test (from −4.1 ± 6.4% to +11 ± 10.9%, P < 0.01). A similar reversibility of changes in the velocity–time integral of CBF in response to the cold pressor test after verapamil therapy was observed (from −3.3 ± 8.3% to +9.6 ± 10.3%, P < 0.05). Verapamil reversed the response of coronary resistance vessels to the cold pressor test from a +12 ± 9.8% increase to a −5.2 ± 10.2% decrease in the coronary vascular resistance index (P < 0.01). We concluded that in asymptomatic and mildly symptomatic HC patients in response to the cold pressor test, treatment with open-label verapamil increased CBF parameters and decreased the coronary vascular resistance index. Verapamil reversed the abnormal vasoconstrictor to vasodilator response of coronary resistance vessels to the cold pressor test. The restoration of the vasodilator response to the by verapamil cold pressor test suggests the potential positive effect of verapamil on endothelium-dependent coronary vasodilatation in HC patients. Thus, a randomized blinded trial is now required.

Comparison of two treadmill training programs on walking ability and endothelial function in intermittent claudication

BACKGROUND In this randomized trial we compared two treadmill trainings, based on exercises performed to moderate claudication pain vs pain-free training, with respect to their effects on walking ability and endothelial function. METHODS A total of sixty patients with stable intermittent claudication were randomized to the pain-free treadmill training (repetitive intervals to onset of claudication pain) or moderate treadmill training (repetitive intervals to moderate claudication pain). In both groups exercises were performed 3 times a week for 3 months. Changes in flow mediated dilatation (FMD) and treadmill walking performance as well as plasma levels of C-reactive protein (hs-CRP) and fibrinogen were assessed before and after the program. RESULTS Fifty-two patients completed the training program. Post-training maximal walking time was prolonged by 100% (p<0.001) vs 98% (p<0.001), and pain-free walking time by 120% (p<0.001) vs 93% (p<0.001) in the moderate training group as compared to the pain-free training group, respectively. FMD increased by 56% (p<0.001) in the moderate training group and by 36% (p<0.01) in the pain-free training group. No significant changes in the levels of hs-CRP and fibrinogen were seen after treadmill program in either group. CONCLUSIONS Both pain-free treadmill training and the moderate treadmill training have similar efficacy on walking ability in patients with claudication. The improvement of post-training FMD indicates systemic effect of both treadmill programs on endothelial function. Both programs appear to be safe therapeutic modes, since none of them escalates the inflammation. Pain-free treadmill training seems useful and effective therapeutic option for patients with claudication.

Exercise training in intermittent claudication: Effects on antioxidant genes, inflammatory mediators and proangiogenic progenitor cells

Exercise training remains a therapy of choice in intermittent claudication (IC). However, too exhaustive exercise may cause ischaemic injury and inflammatory response. We tested the impact of three-month treadmill training and single treadmill exercise on antioxidant gene expressions, cytokine concentrations and number of marrow-derived proangiogenic progenitor cells (PPC) in the blood of IC patients. Blood samples of 12 patients were collected before and after training, before and 1, 3 and 6 hours after the single exercise. PPCs were analysed with flow cytometry, cytokine concentrations were checked with Milliplex MAP, while expression of mRNAs and miRNAs was evaluated with qRT-PCR. Treadmill training improved pain-free walking time (from 144 ± 44 seconds [s] to 311 ± 134 s, p=0.02) and maximum walking time (from 578 ± 293 s to 859 ± 423 s, p=0.01) in IC patients. Before, but not after training, the single treadmill exercise increased the number of circulating CD45dimCD34+CD133-KDR+ PPCs (p=0.048), decreased expression of HMOX1 (p=0.04) in circulating leukocytes, reduced tumour necrosis factor-α (p=0.03) and tended to elevate myeloperoxidase (p=0.06) concentrations in plasma. In contrast, total plasminogen activator inhibitor-1 was decreased by single exercise only after, but not before training (p=0.02). Both before and after training the single exercise decreased monocyte chemoattractant protein (MCP)-1 (p=0.006 and p=0.03) concentration and increased SOD1 (p=0.001 and p=0.01) expression. Patients after training had also less interleukin-6 (p=0.03), but more MCP-1 (p=0.04) in the blood. In conclusion, treadmill training improves walking performance of IC patients, attenuates the single exercise-induced changes in gene expressions or PPC mobilisation, but may also lead to higher production of some proinflammatory cytokines.

Impaired response of the forearm resistance but not conductance vessels to reactive hyperemia in hypertrophic cardiomyopathy.

It has been suggested that in hypertrophic cardiomyopathy (HC), vascular abnormali ties are not restricted to the heart. Flow-mediated dilation of peripheral conductance arteries (reflecting their endothelial function) has not yet been studied in HC. Our aim was to assess both flow-dependent dilation of the brachial artery and flow responses (dependent on resistance vessels) during forearm reactive hyperemia (RH) in nontreated HC patients. The authors studied 13 HC patients and 14 age- and sex-matched healthy controls. None of them exhibited any factors known to be associated with endothelial dysfunc tion. Using 7 MHz ultrasound, brachial artery diameter and Doppler flow velocity were measured continuously at baseline and throughout 1 min of RH following 5 min of forearm ischemia induced by inflation of a blood pressure cuff. Arterial diameter and RH flow are expressed as percent changes with respect to the baseline. Flow-dependent dilation was similar in the HC patients and control subjects (7.2 ±9.5% vs 9.9 ± 10.4%, p>0.05). Compared to the control group, RH flow in HC was decreased; however, differences did not reach statistical significance until 60 sec of RH (112 ±102% vs 261 ±217%, p<0.05; HC vs controls). In HC patients, endothelial function of peripheral conductance arteries is preserved. Hence, a defect in the forearm arterial bed in HC seems to be limited to mechanisms maintaining the dilation of resistance vessels during decreasing RH flow.

Postocclusive Hyperemia Measured with Laser Doppler Flowmetry and Transcutaneous Oxygen Tension in the Diagnosis of Primary Raynaud’s Phenomenon: A Prospective, Controlled Study

The aim of this study was to measure the sensitivity and specificity of transcutaneous oxygen tension and postocclusive hyperemia testing using laser Doppler flowmetry in patients with primary Raynauds phenomenon. One hundred patients and one hundred controls were included in the study. Baseline microvascular blood flow and then time to peak flow following occlusion were measured using laser Doppler flowmetry. Afterwards, the transcutaneous oxygen tension was recorded. The sensitivities of baseline microvascular blood flow, postocclusive time to peak flow, and transcutaneous oxygen tension were 79%, 79%, and 77%, respectively. The postocclusive time peak flow had a superior specificity of 90% and area under the curve of 0.92 as compared to 66% and 0.80 for baseline microvascular flow and 64% and 0.76 for transcutaneous oxygen tension. Time to postocclusive peak blood flow measured by laser Doppler flowmetry is a highly accurate test for differentiating patients with primary Raynauds phenomenon from healthy controls.

The Effect of Verapamil on Response of Coronary Vasomotion to Handgrip Exercise in Symptomatic Patients with Hypertrophic Cardiomyopathy

AbstractObjectives. To assess the effect of verapamil on the response of diastolic coronary blood flow velocity (CBFV) and coronary vascular resistance index to handgrip exercise in symptomatic HCM patients. Design. In 13 patients with HCM, the CBFV was detected in the distal portion of left anterior descending coronary artery using high-sensitivity transthoracic Doppler echocardiography. The peak diastolic CBFV and coronary vascular resistance index (calculated as the ratio of mean aortic pressure to CBFV) was measured at baseline and during handgrip exercise. Changes of these parameters induced by the exercise (expressed as the percentage of baseline values) were compared on verapamil treatment and after verapamil withdrawal. The same measurements were obtained in 10 healthy control subject. Results. In HCM patients, the increase in CBFV during exercise was significantly higher on than off verapamil therapy (16.2 ± 5% versus 6.8 ± 3.8%, p < 0.001). In healthy controls, exercise-induced increase in CBFV was comparable to CBFV changes in HCM patients receiving verapamil (17.4 ± 5.7 versus 16.2 ± 5%, p < 0.05) and was significantly greater than the CBFV response in HCM patients off verapamil (17.4 ± 5.7% versus 6.8 ± 3.8 % p < 0.005). During exercise the coronary vascular resistance index decreased on verapamil and increased after drug withdrawal (−5.8 ± 5.6% versus 1.1 ± 5.1%, p < 0.001). In healthy controls the coronary vascular resistance index decreased during exercise −8.5 ± 4.5% to similar extent as in HCM patients on verapamil. Conclusion. In HCM symptomatic patients, verapamil improved coronary vasomotor response to physical stress. Verapamil was able to restore adequate vasodilator response to handgrip exercise.