Fatty Acid Supplementation Affects Skin Wound Healing in a Rat Model.

Polyunsaturated fatty acids (PUFA) play an important role in reparative processes. The ratio of PUFAs n-3 to n-6 may affect wound healing. The study aimed to evaluate the effect of dietary supplementation with n-3 and n-6 PUFA in two proportions on skin wounds in laboratory rats. Adult male Wistar rats received 20% fat emulsion with a ratio of 1.4:1 (group A) or 4.3:1 (group B) for n-3:n-6 PUFAs at a daily dose of 1 mL/kg. The control group received water under the same conditions. The animals were supplemented a week before and a week after the skin excision performed on the back. The level of wound closure, various parameters of oxidative stress, and plasma fatty acids composition were evaluated. Wound tissue samples were examined by electron microscopy. The administration of fat emulsions led to significant changes in plasma polyunsaturated fatty acid composition. The increased production of reactive nitrogen species, as well as more numerous newly formed blood vessels and a greater amount of highly organized collagen fibrils in both groups A and B may indicate more intensive healing of the skin wound in rats supplemented with polyunsaturated fatty acids in high n-3:n-6 ratio.

Secondary Metabolites of Plants as Modulators of Endothelium Functions.

According to the World Health Organization, cardiovascular diseases are the main cause of death worldwide. They may be caused by various factors or combinations of factors. Frequently, endothelial dysfunction is involved in either development of the disorder or results from it. On the other hand, the endothelium may be disordered for other reasons, e.g., due to infection, such as COVID-19. The understanding of the role and significance of the endothelium in the body has changed significantly over time-from a simple physical barrier to a complex system encompassing local and systemic regulation of numerous processes in the body. Endothelium disorders may arise from impairment of one or more signaling pathways affecting dilator or constrictor activity, including nitric oxide-cyclic guanosine monophosphate activation, prostacyclin-cyclic adenosine monophosphate activation, phosphodiesterase inhibition, and potassium channel activation or intracellular calcium level inhibition. In this review, plants are summarized as sources of biologically active substances affecting the endothelium. This paper compares individual substances and mechanisms that are known to affect the endothelium, and which subsequently may cause the development of cardiovascular disorders.

Calcium signaling affects migration and proliferation differently in individual cancer cells due to nifedipine treatment.

Several papers have reported that calcium channel blocking drugs were associated with increased breast cancer risk and worsened prognosis. One of the most common signs of breast tumors is the presence of small deposits of calcium, known as microcalcifications. Therefore, we studied the effect of dihydropyridine nifedipine on selected calcium transport systems in MDA-MB-231 cells, originating from triple negative breast tumor and JIMT1 cells that represent a model of HER2-positive breast cancer, which possesses amplification of HER2 receptor, but cells do not response to HER2 inhibition treatment with trastuzumab. Also, we compared the effect of nifedipine on colorectal DLD1 and ovarian A2780 cancer cells. Both, inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) and type 1 sodium calcium exchanger (NCX1) were upregulated due to nifedipine in DLD1 and A2780 cells, but not in breast cancer MDA-MB-231 and JIMT1 cells. On contrary to MDA-MB-231 and JIMT1 cells, in DLD1 and A2780 cells nifedipine induced apoptosis in a concentration-dependent manner. After NCX1 silencing and subsequent treatment with nifedipine, proliferation was decreased in MDA-MB-231, increased in DLD1 cells, and not changed in JIMT1 cells. Silencing of IP3R1 revealed increase in proliferation in DLD1 and JIMT1 cells, but caused decrease in proliferation in MDA-MB-231 cell line after nifedipine treatment. Interestingly, after nifedipine treatment migration was not significantly affected in any of tested cell lines after NCX1 silencing. Due to IP3R1 silencing, significant decrease in migration occurred in MDA-MB-231 cells after nifedipine treatment, but not in other tested cells. These results support different function of the NCX1 and IP3R1 in the invasiveness of various cancer cells due to nifedipine treatment.

Home-based training using neuromuscular electrical stimulation in patients on continuous ambulatory peritoneal dialysis: A pilot study.

There is ample evidence that maintenance of basic physical fitness through exercise training is crucial for patients with chronic renal insufficiency. Rehabilitation based on neuromuscular electrical stimulation (NMES) of thigh muscles has been shown to have many beneficial effects in patients with chronic diseases. It is likely that NMES could have beneficial effects also in patients on chronic ambulatory peritoneal dialysis (CAPD). NMES was applied for 20 weeks to 14 patients on CAPD, mean age 61.9 (8.7) years, using battery-powered stimulators (CEFAR-REHAB X2; Sweden) and self-adhesive electrodes 80 × 130 mm (PALS Platinum; Denmark). Stimulation characteristics: biphasic current, pulse width 400 µs, 8 seconds contraction-12 seconds relaxation, frequency modulation 40-60 Hz, and maximal intensity 60 mA. NMES was home-based and applied simultaneously to quadriceps muscles of both legs (2 × 30 min/day). Functional performance, muscle power (Fmax ), arterial stiffness (assessed by cardio-ankle vascular index-CAVI), and quality of life by KDQOL-SF evaluation was done at baseline and at the end of program. Home NMES improved significantly the main functional parameters: VO2peak /kg increased by +2.2 (1.6) mL O2 /kg/min (P < 0.002), peak workload by +0.1 (0.1) W/kg (P < 0.005), and distance walked in 6 MWT by +44.7 (58.4) m (P < 0.008). Only insignificant changes were observed in CAVI and Fmax . KDQOL-SF analysis showed significant improvement in seven parameters of QoL (P < 0.012-0.049). This pilot study is the first clinical report dealing with the use of NMES in patients on CAPD. The results demonstrate that an improvement of exercise capacity and QoL can be achieved by home-based NMES in CAPD patients.

Effect of increased left ventricle mass on ischemia assessment in electrocardiographic signals: rabbit isolated heart study.

BACKGROUND: Detailed quantitative analysis of the effect of left ventricle (LV) hypertrophy on myocardial ischemia manifestation in ECG is still missing. The associations between both phenomena can be studied in animal models. In this study, rabbit isolated hearts with spontaneously increased LV mass were used to evaluate the effect of such LV alteration on ischemia detection criteria and performance. METHODS: Electrophysiological effects of increased LV mass were evaluated on sixteen New Zealand rabbit isolated hearts under non-ischemic and ischemic conditions by analysis of various electrogram (EG) parameters. To reveal hearts with increased LV mass, LV weight/heart weight ratio was proposed. Standard paired and unpaired statistical tests and receiver operating characteristics analysis were used to compare data derived from different groups of animals, monitor EG parameters during global ischemia and evaluate their ability to discriminate between unchanged and increased LV as well as non-ischemic and ischemic state. RESULTS: Successful evaluation of both increased LV mass and ischemia is lead-dependent. Particularly, maximal deviation of QRS and area under QRS associated with anterolateral heart wall respond significantly to even early phase (the 1st-3rd min) of ischemia. Besides ischemia, these parameters reflect increased LV mass as well (with sensitivity reaching approx. 80%). However, the sensitivity of the parameters to both phenomena may lead to misinterpretations, when inappropriate criteria for ischemia detection are selected. Particularly, use of cut-off-based criteria defined from control group for ischemia detection in hearts with increased LV mass may result in dramatic reduction (approx. 15%) of detection specificity due to increased number of false positives. Nevertheless, criteria adjusted to particular experimental group allow achieving ischemia detection sensitivity of 89-100% and specificity of 94-100%, respectively. CONCLUSIONS: It was shown that response of the heart to myocardial ischemia can be successfully evaluated only when taking into account heart-related factors (such as LV mass) and other methodological aspects (such as recording electrodes position, selected EG parameters, cut-off criteria, etc.). Results of this study might be helpful for developing new clinical diagnostic strategies in order to improve myocardial ischemia detection in patients with LV hypertrophy.

Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts.

Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.

Exercise training combined with electromyostimulation in the rehabilitation of patients with chronic heart failure: A randomized trial.

AIM: Both aerobic training (AT) and electromyostimulation (EMS) of leg muscles improve exercise tolerance in patients suffering from chronic heart failure (CHF). It was speculated that combination of both methods might have an additive effect. This study was performed to evaluate the effects of a combination of AT and EMS in rehabilitation (RHB) of CHF patients. PATIENTS AND METHODS: Patients (n=71; age 59 ± 10.2 yrs, NYHA II/III, EF 32 ± 7.1%) were randomized into 3 groups: a) group AT, b) group EMS, and c) group AT+EMS. AT protocol included standard activity on bicycle 3x a week at the level of individual anaerobic threshold. EMS (10 Hz, mode 20s "on"/20s "off") was applied to leg extensors for 2 h/day. Total time of given type of RHB was 12 weeks. RESULTS: Data analysis revealed statistically significant improvements of patients in all experimental groups (averaged difference after 12 weeks of exercise as related to initial value: ∆VO2peak: +12.9%, ∆VO2AT: +9.3%, ∆Wpeak: +22.7%). No statistically significant difference among experimental groups was found. Quality of life (Minnesota Living with Heart Failure - MLHF) global score was significantly improved in all 3 groups: AT (∆MLHF: -27.9%; P=0.001), AT+EMS (∆MLHF: -29.1%; P=0.002), and EMS (∆MLHF: -16.6%; P=0.008). MLHF score in EMS group showed the smallest time-related improvement compared to AT and AT+EMS groups, and this difference in improvement between the groups was statistically significant (P=0.021). CONCLUSION: No significant difference was found between the two types of exercise training.and nor did, their combination have any significant additional improvement.

Effects of neuromuscular electrical stimulation and aerobic exercise training on arterial stiffness and autonomic functions in patients with chronic heart failure.

Neuromuscular electrical stimulation (NMES) of leg muscles has been introduced in clinical practice as a rehabilitation (RHB) method in patients with chronic heart failure (CHF); however, the role of NMES on the reduction of arterial stiffness and autonomic disbalance in these patients has not yet been studied. Sixty-one patients with stable CHF (mean age 58.9 [2.1] years; mean ejection fraction 31 [4.2]%, New York Heart Association II-III) were randomly assigned into two groups. Patients in (i) exercise training group (ET; n = 30) underwent 12 weeks of bicycle ET (3 × 40 min/week); (ii) group NMES (n = 31) performed 12 weeks of NMES of quadriceps and calf muscles (frequency 10 Hz, mode "20 s on-20 s off," intensity 60 mA), 2 × 60 min/day. Noninvasive assessment of arterial stiffness was done using the cardio-ankle vascular index (CAVI). CAVI and heart rate variability (HRV) and ·VO(2peak) were evaluated before and after RHB program. Both types of RHB reduced significantly CAVI (ET from 9.6 [0.2] to 8.9 [0.2], P < 0.012; NMES from 9.3 [0.2] to 8.7 [0.2], P < 0.013), increased high frequency (HF) component of HRV (+65.6%; P = 0.001) and decreased ratio of low frequency (LF) component with HF component (LF/HF ratio) in group ET (-39.8%; P < 0.001). Changes of HRV parameters in group NMES were not significant; however, a marked tendency to autonomic stabilization was present. Both types of RHB led also to significant increase of ·VO(2peak) (ET from 18.7 [0.7] to 20.8 [0.7] mL/kg/min, P < 0.004; NMES from 17.3 [0.7] to 19.0 [0.7] mL/kg/min, P < 0.001). ET or NMES has been shown to improve significantly arterial stiffness and to stabilize autonomic balance.

Intra-dialytic electrostimulation of leg extensors may improve exercise tolerance and quality of life in hemodialyzed patients.

Hemodialyzed (HD) patients with end-stage renal disease (ESRD) exhibit lower fitness as a consequence of chronic uremic changes that trigger various structural, metabolic, and functional abnormalities in skeletal muscles. The aim of this randomized study was to compare the effect of rehabilitation (RHB) training on a bicycle ergometer and electromyostimulation (EMS) of leg extensors in HD patients with ESRD. Thirty-two HD patients (18 men/14 women; mean age 61.1 ± 8.8 years) were randomized into three groups: (i) exercise training (ET; n = 11) on bicycle ergometer 2 × 20 min; (ii) EMS (n = 11) where stimulation (10 Hz) of leg extensors was applied for 60 min; and (iii) controls (CON; n = 10) without exercise. Exercising was performed between the 2nd and the 3rd hour of HD, three times a week, 20 weeks in total. Ergometric test was performed in order to evaluate peak workload (W(peak)), 6-min corridor walking test (CWT) to evaluate the distance walked, and dynamometry of leg extensors to assess muscle power (F(max)). Urea clearance was monitored and expressed as standard parameters: spKt/V, spKt/V equilibrated (spKt/V-e), and the urea removal ratio (URR). Quality of life (QoL) was assessed by the questionnaire SF-36. A significant increase of F(max) (P = 0.040 in group ET; P = 0.032 in group EMS), of 6-min CWT (P < 0.001 in ET group; P = 0.042 in EMS group), and of W(peak) (P = 0.041 in ET group) was observed. In both exercising groups, significant increase of spKt/V, spKt/V-e, and URR was found as compared with initial values (P < 0.05). In both exercising groups, highly significant changes in summarized mental functions were found (P = 0.001); in summarized physical components, significant improvement was observed in the ET group (P = 0.006). Intradialytic RHB showed comparable positive effects on functional parameters, urea clearance, and QoL. Intradialytic EMS might represent wide therapeutic possibility in the near future.

Electrical stimulation of skeletal muscles. An alternative to aerobic exercise training in patients with chronic heart failure?

The aim of this study was to investigate whether electrical stimulation of skeletal muscles could represent a rehabilitation alternative for patients with chronic heart failure (CHF). Thirty patients with CHF and NYHA class II-III were randomly assigned to a rehabilitation program using either electrical stimulation of skeletal muscles or bicycle training. Patients in the first group (n = 15) had 8 weeks of home-based low-frequency electrical stimulation (LFES) applied simultaneously to the quadriceps and calf muscles of both legs (1 h/day for 7 days/week); patients in the second group (n = 15) underwent 8 weeks of 40 minute aerobic exercise (3 times a week). After the 8-week period significant increases in several functional parameters were observed in both groups: maximal VO2 uptake (LFES group: from 17.5 +/- 4.4 mL/kg/min to 18.3 +/- 4.2 mL/kg/min, P < 0.05; bicycle group: from 18.1 +/- 3.9 mL/kg/min to 19.3 +/- 4.1 mL/kg/min, P < 0.01), maximal workload (LFES group: from 84.3 +/- 15.2 W to 95.9 +/- 9.8 W, P < 0.05; bicycle group: from 91.2 +/- 13.4 W to 112.9 +/- 10.8 W, P < 0.01), distance walked in 6 minutes (LFES group: from 398 +/- 105 m to 435 +/- 112 m, P < 0.05; bicycle group: from 425 +/- 118 m to 483 +/- 120 m, P < 0.03), and exercise duration (LFES group: from 488 +/- 45 seconds to 568 +/- 120 seconds, P < 0.05; bicycle group: from 510 +/- 90 seconds to 611 +/- 112 seconds, P < 0.03). These results demonstrate that an improvement of exercise capacities can be achieved either by classical exercise training or by home-based electrical stimulation. LFES should be considered as a valuable alternative to classical exercise training in patients with CHF.