Sports activities and cardiovascular system change.

Sports activity is generally considered to be beneficial to health. The World Health Organization (WHO) recommends physical activity as part of a healthy lifestyle. Sports activities significantly affect the cardiovascular system. A number of studies show that they significantly reduce the risk of cardiovascular disease as well as decrease cardiovascular mortality. This review discusses changes in various cardiovascular parameters in athletes - vagotonia/bradycardia, hypertrophy of heart, ECG changes, blood pressure, and variability of cardiovascular parameters. Because of its relationship to the cardiovascular system, VO2max, which is widely used as an indicator of cardiorespiratory fitness, is also discussed. The review concludes with a discussion of reactive oxygen species (ROS) and oxidative stress, particularly in relation to changes in the cardiovascular system in athletes. The review appropriately summarizes the above issues and points out some new implications.

Metformin therapy and risk of cancer in patients after heart transplantation.

BACKGROUND: Diabetes mellitus (DM) and malignancy are recognized among the most common complications increasing mortality in patients after heart transplantation (HTx). Clinical trials have shown a higher risk for different types of tumours in diabetic patients. This risk is potentiated by immunosuppressive therapy in transplant patients. Biguanide metformin has been shown to exhibit anti-tumour activity and we tried to find out whether this effect is valid for heart transplant patients. METHODS: We retrospectively analysed a group of 497 patients, who undergone HTx in our centre between 1998 and 2019. The primary outcome was any malignancy during the 15-year follow-up period and patient's survival. RESULTS: Out of the 497 patients enrolled in the study, 279 (56 %) had diabetes and 52 (19 %) were treated with metformin. Fifteen-year survival in treated patients without malignancy was 93 %, the remainder for the DM patients was 56 %, with survival in non-DM patients being 74 %. Untreated diabetic patients had 4.7 times higher chance of malignancy than those on metformin (p = 0.01). Fifteen-year survival in metformin treated patients was 53 %, in other DM patients 44 %, and in non-DM patients 51 %. CONCLUSION: Our study showed a significantly lower incidence of malignancies in metformin-treated patients and slightly better overall survival (Tab. 2, Fig. 3, Ref. 19) Keywords: biguanide, heart graft, malignancy, diabetes mellitus, survival.

[Combined exercise training in men with metabolic syndrome after acute coronary event]. / Kombinovaný trénink u muzu s metabolickým syndromem po akutní koronární príhode.

INTRODUCTION: Favourable effect of exercise training on cardiovascular prognosis in patients with metabolic syndrome have been documented in lot of studies. Less information exist about results of cardiovascular rehabilitation in patients with different forms of coronary heart disease and associated diseases and abnormalities within metabolic syndrome. METHODS: The present article evaluates a benefit of combined, aerobic-resistance training in two groups of patients after percutaneous coronary intervention for acute coronary syndrome: with [group MS(+), n = 42] and without [group MS(-), n = 53] metabolic syndrome. The changes in aerobic capacity (VO2 peak, VO2 peak . kg(-1)), physical performance (W peak, W peak . kg(-1)), blood pressure, BMI and waist circumference after 12 weeks of cardiovascular rehabilitation are evaluated. RESULTS: Significant improvement in aerobic capacity and physical performance were found out both in group MS(+) and MS(-) (p < 0.01, resp. p < 0.001). Decrease of systolic blood pressure was significant in MS(+), whereas in MS(-) together with decrease of diastolic BP in both groups were not significant. The increase in aerobic capacity and physical performance in patients of MS(+) is comparable with those in MS(-); the decrease in systolic BP was more intensive in MS(+) compared to MS(-). The changes in waist circumference and BMI were not significant in both groups. CONCLUSION: The results show, that in patients with high number of risk factors associated with metabolic syndrome was demonstrated at least comparable benefit from cardiovascular rehabilitation compared with those without metabolic syndrome.

The effect of regular physical activity on the left ventricle systolic function in patients with chronic coronary artery disease.

The purpose of this study was to assess the influence of aerobic training on the left ventricular (LV) systolic function. Thirty patients with stable coronary artery disease, who had participated in the conducted 3-month physical training, were retrospectively divided into 2 cohorts. While patients in the cohort I (n=14) had continued training individually for 12 months, patients in the cohort II (n=16) had stopped training after finishing the conducted program. Rest and stress dobutamine/atropine echocardiography was performed in all patients before the training program and 1 year later. The peak systolic velocities of mitral annulus (Sa) were assessed by tissue Doppler imaging for individual LV walls. In addition, to determine global LV systolic longitudinal function, the four-site mean systolic velocity was calculated (Sa glob). According to the blood supply, left ventricular walls were divided into 5 groups: A- walls supplied by nonstenotic artery; B- walls supplied by coronary artery with stenosis ≤50 %; C- walls supplied by coronary artery with stenosis 51-70 %; D- walls with stenosis of supplying artery 71-99 %; and E- walls with totally occluded supplying artery. In global systolic function, the follow-up values of Sa glob in cohort I were improved by 0.23±0.36 as compared with baseline values at rest, and by 1.26±0.65 cm/s at the maximal load, while the values of Sa glob in cohort II were diminished by 0.53±0.22 (p=NS), and by 1.25±0.45 cm/s (p<0.05), respectively. Concerning the resting regional function, the only significant difference between cohorts in follow-up changes was found in walls E: 0.37±0.60 versus -1.76±0.40 cm/s (p<0.05). At the maximal load, the significant difference was found only in walls A (0.16±0.84 versus -2.67±0.87 cm/s; p<0.05). Patients with regular 12-month physical activity improved their global left ventricle systolic function mainly due to improvement of contractility in walls supplied by a totally occluded coronary artery.

[Differentiated approach to prescription of physical activity in patients with left ventricular dysfunction]. / Diferencovaný prístup k preskripci fyzické aktivity u nemocných s dysfunkcí levé komory srdecní.

Correctly indicated physical exercise performed and controlled on a regular basis is an inseparable part of treatment and rehabilitation of patients with left ventricular dysfunction. In order to guarantee the best effect and safety of physical exercise, it is necessary to adopt a differential approach to its prescription to patients with different degrees of functional damage. In addition, a number of conditions should be fulfilled, among which, in the first place, the determination of functional classification of patients used in practice and described in the relevant literature (NYHA, AMA, Goldman, Weber). Physical exercise cannot be differentiated only with respect to the degree of dysfunction; other conditioning factors should be taken into consideration, too, among which the relative contraindication of physical strain, somatic condition, physical exercise anamnesis and others (i.e. sex, age, motivation, etc.), causing a high degree of patient heterogeneity. Also described are additional conditions for differentiation and correct application of physical training, which involve the selection of suitable types of exercise and their energetic demands, adequate intensity, frequency and duration; it is also important to determine the available effective and safe methods, programmes and means of training. The article contains examples of the above conditions, as well as classification of physical exercise into functional classes NYHA I-IV. In conclusion, the authors point out the necessity of differentiation of physical training and of cooperation of the cardiologist with the physiotherapist in its indication, implementation and monitoring.

Melatonin protects against ischemia-reperfusion injury and inhibits apoptosis in isolated working rat heart.

INTRODUCTION: Melatonin (MEL), a pineal hormone, is well known as a potent antioxidant in a variety of ischemia-reperfusion models. Recent studies have assumed a pivotal role of reactive oxygen species (ROS) in the development of apoptosis. There are few pieces of information concerning a possible protective role of MEL against apoptosis in ischemia-reperfusion injury of myocardium. METHODS: We conducted an in vitro experiment: (1) to study the effect of MEL in the model of isolated and perfused working rat heart; (2) to evaluate the antioxidant capacity of MEL by a simple fluorescence test; and (3) to analyze the extent of apoptosis inhibition by MEL. Four groups of male Wistar rat were used: (a) group 'MEL 50 muM' (n=8); (b) group 'ischemia 30 min' (n=8); (c) group 'controls' (n=8); and (d) group 'controls+MEL 50 muM' (n=8). The perfusion medium was an oxygenated Krebs-Henseleit buffer (KHB). Hearts in groups (a) and (b) underwent 30 min of global normothermic ischemia and 45 min of reperfusion; 3 min before ischemia the hearts of group (a) received KHB with MEL 50 muM (and MEL 50 muM was also present in KHB solution during reperfusion). Hearts of group (c) were only perfused by KHB, and hearts of group (d) perfused by KHB+MEL 50 muM throughout the experiment. Registered were basic hemodynamic parameters: coronary, aortic, cardiac output and heart rate. At the end of each experiment, a left ventricle samples were taken for in situ detection of apoptosis using a TUNEL in-situ detection kit (POD) and quantitative analysis was performed. Malonedialdehyde concentrations were evaluated from heart homogenate to determine the severity of oxidative damage. To study the antioxidant capacity of MEL, a fluorescence test with allophycocyanin as an indicator was performed. A peroxyl radical generator, 2,2'-azobis(2-amidinopropan)-4-hydrochloride (AAPH) was used, and the antioxidant effect of MEL was expressed in oxygen-radical absorbing capacity (ORAC) units. RESULTS: Treatment by MEL resulted in a significant improvement of hemodynamic parameters and reduction of postischemic arrhythmias during reperfusion. All hearts in group 'ischemia 30 min' developed fatal ventricular fibrillations. MEL significantly reduced the incidence of apoptotic cells (14+/-4.3%; **P<0.01) vs. group 'ischemia 30 min' (58+/-2.1%). No apoptotic cells were detected in both control groups (c) and (d). In the fluorescence test, MEL exhibited a significant dose-dependent protective effect against peroxyl radical; MEL also reduced significantly the level of lipoperoxidation (MDA; *P<0.05). Analysis of hemodynamic parameters in both control groups (c) and (d) did not show any significant differences; the presence of MEL 50 muM in KHB solution did not have any important influence on cardiac performance in this type of experiment. CONCLUSION: We confirmed the previously reported beneficial effects of MEL against ischemia-reperfusion injury, presumably via its antioxidant properties. A significant suppression of apoptosis and the peroxyl radical scavenging properties of MEL in our study could contribute to the hypothesis of a close link between oxidative stress and apoptosis promotion.

[Combined training in patients with systolic left ventricular dysfunction]. / Kombinovaný trénink u nemocných se systolickou dysfunkcí levé komory srdecní.

The objective of the work was to evaluate the effect of eight-week combined training on the performance, aerobic capacity and basic haemodynamic parameters in patients with systolic dysfunction of the left ventricle and to assess its safety. The investigation comprised 26 patients, men mean age (x +/- SD) 61.8 +/- 11.1 years with coronarographically verified chronic ischaemic heart disease and with a left ventricular ejection fraction lower than 40% (EF 35 +/- 4%). Before the beginning and after completion of the rehabilitation programme (eight weeks) a spiroergometric examination was made, up to the symptom-limited maximum. Fitness elements were included after 2 weeks of aerobic training. The lesson lasted 60 mins. and included warming up (10 mins.), aerobic load on an ergometer with an intensity of the load at the level of the anaerobic threshold (20 mins.), the stage of fitness training on a combined training machine (20 mins) and the relaxation stage (10 mins). In the fitness stage the patients started to exercise at the 30% level, after two weeks at the 60% level 1-RM (one repetition maximum) The results showed after eight-week combined training a significant (p < 0.05) increase of the maximum achieved performance (from 104 +/- 27 to 132 +/- 32 W) in patients with systolic left ventricular dysfunction. There was a significant increase in the capacity of the transport system expressed by the value of the maximum oxygen uptake (from 1545 +/- 312 to 1740 +/- 359 ml.min-1) and MET (from 5.3 +/- 1.3 to 6.0 +/- 1.4). There was a significant decrease of the blood pressure at rest, systolic and diastolic, and of the baseline value of the heart rate at rest and of the "product rate, pressure"--RPP. Changes in the EF were not significant.

Total artificial heart: the adaptation and pathophysiological deviations in the recipient.

In the short historical review the principal technical and pathophysiological approaches of the Czech total artificial heart (TAH) research are emphasized. Survival was endangered by arterial and venous hypertension, especially the central venous pressure (CVP) increase, mineralization of driving diaphragms, thromboembolization, and infection. By the appropriate combination of antihypertensive, antimineralization, and anticoagulation treatment and of measures against infection, the survival of the experimental calves was increased (the longest one was 314 days of pumping). Technical and constructional improvement of the blood pumps was another cause of successful experiments. All details are issued in the references.

Microvessels of bulbar conjunctiva in UPTAH goats.

Aiming to observe directly the microcirculation after total artificial heart (TAH) implantation, we performed a long-term follow-up in 2 goats using conjunctival angioscopy. A short segment of parallel arteriole and venule was photographed and analyzed on computer picture program (magnification 40x). Three main parameters were measured: arteriole diameter, venule diameter, and arteriovenous ratio (A/V ratio). The intrathoracically implanted TAH was the undulation pump total artificial heart (UPTAH) with cardiac output of 100 ml/kg/min. To stabilize the peripheral hemodynamics a 1/R biofeedback control system was used. Our results provided only elementary data about morphology of bulbar microvessels. The main finding was the tendency to general vasoconstriction, more intensive on the venous side (*P < 0.05 in one goat). We did not observe any pathological shapes (e.g., tortuosities, varicosities, or sludge); this result could be attributed to the high effectivity of 1/R control method. These preliminary results should be considered only as an attempt to apply the widely used clinical method of conjunctival angioscopy to the conditions of TAH.

Electronmicroscopic changes in selected vital organs after long-term total artificial heart pumping in animal experiments.

Electronmicroscopic (EM) evaluation of selected vital organs (liver, kidney, lung) informs us about otherwise hardly detectable changes during total artificial heart (TAH) pumping. In our experiments, we compared 2 groups of long-surviving animals in which the TAH TNS-BRNO pneumatic device was implanted (TNS-BRNO-II and VII in 45 experiments, TNS-BRNO-III in 1 experiment, and TNS-BRNO-VIII in 1 experiment). In 4 experiments, the Rostock TAH (NABEL, TAH Research Center, Rostock, Germany) was implanted. One group of 22 animals with an average survival of 162 days (the longest, 293 days) was submitted to an antihypertensive treatment; another 1 of 29 calves with an average survival of 98 days (the longest, 173 days) was untreated. The evaluation was performed using a scale (0 to 3) based on very precisely fixed criteria. EM pathologic changes documented various stages of ischemic damage. Except for the liver, no significant difference was found between both groups, despite the substantially prolonged survival in the treated group. Very important was the general state of mitochondria, endoplasmic reticulum, and nucleus. Further, the state of glomerular podocytes in the kidney and the state of interalveolar septa and of pneumocytes constituting the air-blood barrier for gas exchange in the lungs are especially important. In some animals of both groups, the EM findings were completely normal, especially in the lung.

Antioxidative properties of pyruvate and protection of the ischemic rat heart during cardioplegia.

Formation of oxygen free radicals during heart transplantation seems to be related to the alterations occurring during ischemia and reperfusion and could explain the short preservation time of donor hearts. The aim of our study was (a) to analyze the protective effects of pyruvate during cold cardioplegia and ischemia/reperfusion sequence, and (b) to investigate in vitro the radical scavenging properties of this compound. After 30 min of perfusion, isolated working rat hearts were arrested by cardioplegic solution, stored 4 h in B21 solutions at 4 degrees C, and reperfused with Krebs-Henseleit buffer for 45 min. Pyruvate (2 mM) was added to Krebs-Henseleit, cardioplegic, and storage solutions, and functional parameters were recorded throughout the experiments. In a second part, control hearts and hearts treated with pyruvate were cannulated via the aorta and perfused for 30 min by the Langendorff method, arrested by cardioplegic solution, stored 4 h in B21 solutions at 4 degrees C, and reperfused for 45 min by the Langendorff method. Malonedialdehyde and alpha-tocopherol levels were determined on heart homogenate. In situ detection of apoptotic cells also was performed on tissue samples (left ventricle) at the end of the ischemia/reperfusion sequence. To demonstrate in vitro the antioxidant effects of pyruvate, we monitored (a) its hydroxyl radical scavenging properties by using electron paramagnetic resonance (EPR) spectroscopy, and (b) the decrease of fluorescence of allophycocyanin, in the presence of a Fenton system (H2O2/Cu2+). Ischemia for 4 h, followed by myocardial reperfusion, resulted in substantially reduced mechanical function. Hearts subjected to this ischemia and pretreated with pyruvate showed a significant improvement in the function recovery. After the ischemia/reperfusion protocol, no significant decrease of malonedialdehyde levels was shown on hearts treated with pyruvate. However, alpha-tocopherol levels were higher in the pyruvate group compared with the control group. At the end of the reperfusion period, levels of apoptotic cells were significantly lower in hearts treated with pyruvate compared with control hearts. EPR studies showed that pyruvate was an efficient hydroxyl scavenger, with a median inhibitory concentration (IC50) of 8 mM. The allophycocyanin assay also showed a dose-dependent effect of pyruvate against hydroxyl radicals. In conclusion, these findings showed that pyruvate could prevent reperfusion injuries in the isolated heart, probably by its antioxidative properties. The application of pyruvate may contribute to the preservation of hearts for organ transplantation.

[Transesophageal echocardiography in cardiac and paracardiac tumors. A multicenter study]. / Apport de l'échocardiographie transoesophagienne au cours des tumeurs cardiaques et paracardiaques. Etude multicentrique.

A multicentre study was undertaken to determine the diagnostic value of transoesophageal echocardiography (TOE) in tumours of the heart and pericardium. Forty-five cases were recensed: 24 myxomas, 1 fibroma, 1 hydatid cyst, 2 lymphomas, 3 sarcomas, 1 pleuropericardial cyst, 1 branchogenic cyst and 12 cardiac metastases. The diagnosis was made in all 45 cases by TOE but only in 35 cases by conventional transthoracic echocardiography which failed to recognise 2 myxomas, 1 hydatid cyst, 1 sarcoma, 2 paracardiac cysts and 4 cardiac metastases. The site of the tumour was identified 45 times by TOE compared with only 12 times by transthoracic echocardiography. However, the anatomical investigation of mediastinal tumours requires complementary computerised tomography. Moreover, TOE, like all other imaging techniques, is unable to predict the benign or malignant nature of the tumour, 1 leiomyosarcoma having been confused with a myxoma.

Instrumentation of ramus circumflexus compromises the innervation of coronary artery and myocardium.

A fine non-compressing methacrylate ring was implanted on the ramus circumflexus (RC) in 13 dogs. After the animals survived 7-14 days, the distribution and the rate of the Wallerian degeneration was studied in coronary arteries and myocardium by means of the formaldehyde induced fluorescence (FIF) technique and the transmission electron microscopy. The density of vasomotor innervation in the main arterial trunks was expressed as the number of transsected terminals per 1 mm2 of the transversally sectioned media; the density of adrenergic terminals in the myocardium was determined by the point-counting method. A compact scar encompassing the ring was found. The scar compressed some perivascular nerves. As a consequence, by about 40% of terminals degenerated in the RC. The innervation of the branching of this artery was compromised as well. Moreover, the density of nerve terminals in myocardium decreased around the whole circumference of the ventricles and in the septum, equally by 29%. The value was lower than that found after the instrumentation of ramus interventricularis anterior (50%). The results indicate (i) a compromise of the innervation of coronary artery and myocardium after the instrumentation of RC; (ii) the different decrease in density of nerve terminals in the myocardium suggests that majority of adrenergic nerve supply for ventricle myocardium is running along ramus interventricularis anterior.