Mechanisms of adaptation to physical exertion and the effect of carbon dioxide excess on their formation

4% CO2 addition to normoxic gas medium increased the activity, mass and functional capacity of the left ventricular myocardium, enhanced the stability of acetylcholine (AC) and noradrenaline (NA) storage in the myocardial tissues and stimulated myocardial response to these mediators during physical training of rats (swimming for 2 months). When the duration of the training period was prolonged to 3 months, CO2 had a decreasing effect on the myocardial activity, AC concentration and storage stability, as well as on the myocardial response to AC. The possibility of reducing signal and increasing metabolic CO2 effects during physical training is considered. The importance of intensified heart regulation by sympathetic and parasympathetic mechanisms during adaptation and the role of mechanism dissociation with the decrease in the degree of adaptation are discussed.     

Altered single cell force-velocity and power properties in exercise-trained rat myocardium.

Myocardial function is enhanced by endurance exercise training, but the cellular mechanisms underlying this improved function remain unclear. The ability of the myocardium to perform external work is a critical aspect of ventricular function, but previous studies of myocardial adaptation to exercise training have been limited to measurements of isometric tension or unloaded shortening velocity, conditions in which work output is zero. We measured force-velocity properties in single permeabilized myocyte preparations to determine the effect of exercise training on loaded shortening and power output. Female Sprague-Dawley rats were divided into sedentary control (C) and exercise trained (T) groups. T rats underwent 11 wk of progressive treadmill exercise. Myocytes were isolated from T and C hearts, chemically skinned, and attached to a force transducer. Shortening velocity was determined during loaded contractions at 15 degrees C by using a force-clamp technique. Power output was calculated by multiplying force times velocity values. We found that unloaded shortening velocity was not significantly different in T vs. C myocytes (T = 1.43 muscle lengths/s, n = 46 myocytes; C = 1.12 muscle lengths/s, n = 43 myocytes). Training increased the velocity of loaded shortening and increased peak power output (peak power = 0.16 P/P(o) x muscle length/s for T myocytes; peak power = 0.10 P/P(o) x muscle length/s for C myocytes, where P/P(o) is relative tension). We found no effect of training on myosin heavy chain isoform content. These results suggest that training alters power output properties of single cardiac myocytes and that this adaptation may improve the work capacity of the myocardium.     

The impact of increased physical exertion on the state of adrenal cortex and pubertal development in boys

The study of the functional state of the adrenal cortex (AC) in young athletes aged 11 to 15 years, which was assessed by daily free (C_f) and bound (C_b) cortisol excretion levels, and the comparison of these levels with those of the boys from the control group made it possible to conclude that the increased physical exertion in the form of regular athletic training had a dominating effect on the age-related changes in the AC and pubertal development in the young athletes. It was found that the 12- to 14-year-old athletes had stably high C_f excretion levels, which were significantly decreased by the age of 15 years on the background of high C_b levels, as compared to the nonathletes, whose urinary cortisol levels were significantly lower (p < 0.05) and were progressively increased (p < 0.05) from 13 to 15 years of age. It was found that pubertal development (the development of secondary sex characteristics) was relatively delayed in the athletes, and pubertal changes in the glucocorticoid function of the AC reflected mainly its adaptive responses providing the increased resistance of the child’s body to increased physical exertion.     

Catecholamine content in the adrenals of rats developing under hypokinesia and muscle training

The effect of muscle training and hypokinesia on the content of catecholamines in the adrenals of rats in the postnatal ontogenesis has been studied. A systematic swimming training promotes the process of catecholamine accumulation in the adrenals, while hypokinesia slows down that process. An unitary carrying-out of maximum swimming exertion causes a sharp decrease of total content and concentration of catecholamines, at this their minimum concentration in the adrenals of developing animals does not depend on the adaptation to the locomotive regime.     

Exocrine function of the pancreas in regularly swimming rats

The exocrine function of the pancreas was investigated in the course of adaptation to regular physical activity. In albino rats exercized by swimming for six weeks it has been observed that - in response to an identical physiological stimulation (liquid food via gastric tube) and under ad libitum feeding the rate of secretion and enzyme activity exceeded control values by 100 to 150%; - in pair-fed rats the values of the exercized animals were 50 to 70% higher, and - vagotomy suspended this effect even when food was offered ad libitum. On the basis of these results adaptation to regular exercise involves the exocrine function of the pancreas. In this functional increase both the increased food intake after training sessions and the direct effect of muscular work have a share. For adaptation an intact innervation is necessary.     

Myocardial contraction in the reverse development of adaptation to short-term exposure to stress

Contractile function of an isolated right atrium was studied in short-term stressor effects-adapted male Wistar rats at different times after adaptation was completed. Adaptation to short-term stressor effects was shown to produce a restricted decrease of myocardial contractility shortly after adaptation was completed. At the 3d day another decrease of contractile function was noted. However, contractile function returned to the control level by the 5th day. At the same time adaptation completely prevented the impairment of myocardial contractility, induced by prolonged stress. The protective effect was seen immediately after adaptation, by days 3 and 5 after it, being reduced by day 10. It is assumed that at the 5th day after adaptation, the animals experience the post-adaptation state marked by disappearance of the negative adaptation effect and by remarkable protective effect of adaptation. As a result, all the characteristics of myocardial contractility evaluated after prolonged stress experienced by the animals at the 5th day following short-term stressor effects do not differ from control parameters.     

Effects of exercise training on cardiac function, gene expression, and apoptosis in rats

This study determined the effects of exercise training on cardiac function, gene expression, and apoptosis. Rats exposed to a regimen of treadmill exercise for 13 wk had a significant increase in cardiac index and stroke volume index and a concomitant decrease in systemic vascular resistance compared with both age-matched and body weight-matched sedentary controls in the conscious state at rest. In exercise-trained animals, there was no change in the expression of several marker genes known to be associated with pathological cardiac adaptation, including atrial natriuretic factor, beta-myosin heavy chain, alpha-skeletal and smooth muscle actins, and collagens I and III. Exercise training, however, produced a significant induction of alpha-myosin heavy chain, which was not observed in rats with myocardial infarction. No histological features of cardiac apoptosis were observed in the treadmill-trained rats. In contrast, apoptotic myocytes were detected in animals with myocardial infarction. In summary, exercise training improves cardiac function without evidence of cardiac apoptosis and produces a pattern of cardiac gene expression distinct from pathological cardiac adaptation.     

Increased level of immunoreactive opioid peptides in the brain and adrenals of rats as affected by adaptation to physical loading

The effect of long-term (7 weeks) swimming training on the content of beta-endorphin, met- and leu-enkephalins in various brain regions and adrenal glands has been studied in Wistar rats. It has been shown that the adaptation to exercise induced an increase in the content of opioid peptides in most of the brain regions and in adrenal glands. This increase in the level of opioid peptides seems to play an important role in the increase of the resistance to stress.     

The serum levels of growth factors: PDGF, TGF-beta and VEGF are increased after strenuous physical exercise.

Strenuous physical exercise induces muscle fibers damage and non-specific inflammatory response. Activated by inflammatory process cells may serve as the source of wide spectrum of inflammatory mediators and growth factors. Namely Platelet Derived Growth Factor (PDGF), Transforming Growth Factor-beta (TGF-beta) and Vascular Endothelial Growth Factor (VEGF) could be released. The aim of present study was to assess the impact of physical exercise on growth factors generation in healthy young people. 14 young sportsmen were enrolled into the study. They performed strenuous physical exercise. Blood samples were drawn before, immediately after, and 2 hours after the exercise bout. Serum PDGF, TGF-beta and VEGF concentrations were measured using commercially available ELISA kit based on immunoenzimatic method. Serum level of PDGF increased significantly from 1.7 ng/ml before to 4.64 ng/ml (2.73-fold) immediately after, and to 3.3 ng/ml (1.94-fold) 2 hours after exertion. Serum level of TGF-beta increased significantly from 20.58 ng/ml before to 55.37 ng/ml (2.7-fold) immediately after, and to 40.03 ng/ml (1.95-fold) 2 hours after exertion. Serum level of VEGF increased significantly from 91.83 pg/ml before to 165.61 pg/ml (1.8-fold) immediately after the exercise. Two hours after the exertion serum level of VEGF was 137.22 pg/ml, what is 1.49-fold above the basal level; however not being significantly different. In summery, observed increased level of growth factors could be involved in the process of adaptation of human organism to physical training. In addition, in the context of the role of inflammation in the pathogenesis of various diseases, our results point to the potentially deleterious effect of strenuous physical exercise.     

Further experimental results concerning the relationship of muscular exercise and adrenal function.

The relationship between muscular work and adrenal function was investigated by using daily swimming exercise in the rat. 1. Adrenal in vitro sensitivity to ACTH was found to have increased after six weeks of swimming training 2. In the development of adaptation the main part was played by muscular exercise itself, since a conditioning of the animals merely to the circumstances of swimming failed to stimulate such adaptive changes as seen in the course of regular physical training. 3. Plasma steroid response to certain stressor agents, such as histamine or acute exhaustion (decrease), respectively to ACTH administration (increase) was similar in ACTH-pretreated and regularly exercised animals. 4. In the 6th to 12th weeks of exercise the trained animals developed a lower plasma steroid content at rest than the controls. This feature was retained even four weeks after the cessation of training sessions. Experimental physical training reduced post-exercise steroidemia in the period of adaptation, that is, after the 6th week. After a pause of 4 weeks, however, the post-exercise steroidemia approached again the control values.     

Nutritional, cardiac and adrenergic changes induced by swimming training in rats (author's transl)

The effects of training were investigated in male Sprague Dawley rats group (N), fed ad libitum, by measuring the weight increase and food intake of the animals, biochemical parameters (myocardial triglycerides and glycogen levels), mechanical and metabolic properties of the heart, and adrenergic reactions to swimming stress. An other group of rats remaining sedentary served as control (T). Conditioned rats had been submitted to a one hour test swim 6 days a week for 9 weeks. Gradually additional weights were fixed to the thorax. At the end of training, the load reached 6% of the body weight. Both groups were sacrified by decapitation at the same time, thirty hours after the last swimming session. The study of mechanical performances and metabolic properties was achieved with isolated working heart preparation. Adrenergic reactions of swimming stress were evaluated from plasma, heart and adrenal catecholamine concentrations.     

Participation of the prostacyclin-thromboxane system in the mechanisms of prevention of arrhythmia caused by occlusion of the coronary artery in adapted rats]

It was found, that adaptation of rats to cold and physical exercise prevented ventricular fibrillation, caused by the occlusion of the left anterior coronary artery. An adaptation to cold only or to physical exercise do not prevent ventricular arrhythmias. An significant increase of prostacyclin/thromboxane index in plasma and heats was estimated in rats adapted to cold and physical exercise in relation to control non-adapted group in condition of functional rest or acute myocardial ischemia. It was assumed that an increase of prostacyclin/thromboxane ratio has a significant role in antiarrhythmic action of adaptation.     

Effect of sympathectomy on the heart pump function in rats during postnatal ontogenesis

The influence of guanetidine sympathectomy (30 mg/kg) on the heart pump function in rats during 3 weeks in postnatal ontogenesis has been investigated. Sympathectomy restrains age-dependent establishment of stroke volume, cardiac output and heart rate. The adaptation effects of regular physical training do not develop in the animals with sympathectomy, i.e. heart rate does not decrease and stroke volume does not increase. The initial stage of adaptation of the sympathectomized animals to physical training is accompanied by decrease in stroke volume and remarkable increase in heart rate which indicates the reduction of contractile activity in the myocardium.     

Effect of preliminary adaptation to short-term stress exposure on the resistance of the spontaneously contracting myocardium to a lipid peroxidation inducer

Contractile function of the isolated right atrium was studied in male Wistar rats adapted to short-term stressor exposures at varying times after adaptation was completed. Adaptation to short-term stressor exposures induced a limited decrease in myocardial contractility immediately after adaptation was over. On the 3d day an additional reduction in the characteristics of contractile function was still observed. However, by the 5th day the characteristics recovered to the control level. At the same time adaptation completely prevented the derangement of myocardial contractility, induced by exposure to a prolonged stress. That protective effect was observed as early as adaptation was completed, on days 3 and 5 after adaptation, and became lessened on the 10th day. It is assumed that on the 5th day after adaptation the animals are in a postadaptation state where the untoward effect of adaptation disappears whereas the protective effect is demonstrable to a full extent. As a result all the characteristics of myocardial contractility following a prolonged stress on the 5th day after completion of short-term stressor exposures differed in no way from the control parameters.     

Effects of plasma norepinephrine elevation on the heart's adaptation to chronic aortic constriction in rats

Chronically elevated plasma norepinephrine has the potential for supporting function of diseased hearts, yet may also initiate harmful biochemical and (or) structural changes in the myocardium. The present study investigated the dosage-related effects of chronic norepinephrine infusion on markers of myocardial damage and then tested the influence of a relatively low norepinephrine infusion rate (0.05 microgram X kg-1 X min-1) on the heart's adaptation to pressure overload in aortic constricted rats. Norepinephrine infusion at 0.50 microgram X kg-1 X min-1 led to significantly increased myocardial hydroxyproline concentration and significant mortality. A rate of 0.25 microgram X kg-1 X min-1 increased myocardial hydroxyproline concentration and mortality in aortic constricted rats but had no such effects on sham-operated rats. The lowest rate tested (0.05 microgram X kg-1 X min-1) significantly increased mean arterial pressure and lung weight of aortic constricted rats, without affecting the degree of left ventricular hypertrophy. This infusion rate and aortic constriction each increased plasma norepinephrine and impaired cardiac performance during rapid preloading, although their combination did not cause further impairment. Thus, it appears that even modest plasma norepinephrine elevation has a negative effect on the heart's adaptation to sustained pressure overload.     

Effects of insulin perfusion and altered glucose concentrations on heart function in 3-day and 6-week diabetic rats

Diabetes is known to result in depression of myocardial function, whereas hearts from insulin-treated diabetic rats exhibit functional characteristics similar to controls. In the present study, we have studied the effect of insulin perfusion on cardiac performance of 3-day and 6-week streptozotocin (STZ) diabetic rats. Three days of diabetes did not result in depressed cardiac performance when the hearts were isolated and perfused in the working heart mode. Increasing the concentration of glucose from 5 to 10 mM in the perfusion fluid did not alter the function in either control or in diabetic rat hearts. However, when regular insulin or glucagon-free insulin (Humulin) (5 mU/mL) was included in the perfusion medium, the ventricular function of hearts from control rats was significantly enhanced, while diabetic myocardial function remained unaffected. When the study was repeated on hearts from 6-week diabetic animals, cardiac function of diabetic rats was significantly depressed as compared with controls. As in the 3-day study, contractility was not affected in either group by increasing glucose concentration in the perfusion medium. Again, inclusion of insulin in the medium enhanced cardiac contractility only in control hearts. These results suggest that diabetes results in a loss of myocardial sensitivity to insulin which seems to occur as early as 3 days after induction of diabetes with STZ. The study also demonstrates that the beneficial effects of in vivo insulin treatment on myocardial alterations induced by diabetes are not due to its direct myocardial effects.     

Effect of adaptation to periodic hypoxia on the resistance of the indicators of energy metabolism and myocardial contraction in acute anoxia and reoxygenation

The effect of preliminary adaptation to intermittent (40 days, 4 hrs daily at 4000 m "altitude") on the resistance of myocardial energy metabolism and contractile function to acute anoxia and subsequent reoxygenation was studied. It was found that adaptation to hypoxia significantly accelerated the restoration of creatine phosphate, ATP and creatine phosphokinase activity in myocardium in reoxygenation following acute anoxia. On the whole, this effect reduces the competition of H+ with Ca2+ in myofibrils to improve the energy supply and to accelerate the restoration of myocardial contractile function in reoxygenation.     

Plasma epinephrine in chronically adrenodemedullated rats: lack of response to acute or chronic exercise.

Even if it is well established that epinephrine is a hormone originating from the adrenal medullae, the reappearance of circulating epinephrine has been reported in rats a few days after adrenodemedullation. To verify if the extra-adrenal tissue responsible for this epinephrine production can be stimulated, sham-operated or adrenodemedullated rats, either trained or kept sedentary, were submitted to an acute exercise stimulation test. Blood sampling was done before and after the test in precannulated rats for the determination of plasma epinephrine, norepinephrine, and corticosterone levels. Basal epinephrine levels were significantly reduced in trained and sedentary adrenodemedullated rats compared with their sham-operated counterparts. In response to exercise, there was no significant rise in epinephrine levels in both groups of adrenodemedullated rats. The norepinephrine levels in the basal state and in response to exercise were not altered by adrenodemedullation nor by physical conditioning. Basal corticosterone levels were similar between adrenodemedullated and sham-operated animals, either trained or kept sedentary. In response to exercise, corticosterone levels increased significantly in each group of rats but to a lesser extent in both groups of adrenodemedullated animals. These data indicate that the extra-adrenal epinephrine secretion that develops in the absence of adrenal medullae is not influenced by acute exercise nor by physical training.     

Effects of endurance moderate physical training on basal metabolism of young adult rats

In order to clarify the conclusion that the change of basal metabolism affected by physical training, effect of endurance training for 8 weeks on basal metabolism of young adult rats were investigated. Results are as follows. Endurance training increased significantly running ability of rats, for instance the running time at a speed of 25 m/min on the control and training groups were 53.7 +/- 18.8 min, 232.8 +/- 32.8 min, respectively. The ratio of soleus's weight to the body weight in trained rats was high significantly (p less than 0.05). The glycogen contents of trained rats under the condition of feeding have higher than the control rats. Especially, glycogen contents of the soleus and red-gastrocnemius significant increased (p less than 0.05), and liver glycogen content under the same condition increased significantly (p less than 0.02). The oxygen consumption in trained rats increased significantly compared with control rats (p less than 0.03). The basal metabolism of trained rats showed 1.24-fold increase compared with those of control (p less than 0.02). Oxygen consumption of sliced ventricle in trained rats increased significantly (p less than 0.03), it's rate was 118% of control. However those of other tissues did not change significantly.     

Running training attenuates the ACTH responses in rats to swimming and cage-switch stress.

The present study was carried out to investigate the effect of running training on adrenocorticotrophic hormone (ACTH) response in rats to swimming or cage-switch stress to determine whether, after physical training, a cross-adaptation develops in the ACTH responses induced by different types of stresses. Rats were trained by two different kinds of exercises and for two different periods of training: 1) swimming for 4 wk (4W-swimming), 2) running for 4 wk (4W-running), and 3) running for 10 wk (10W-running). Remaining rats were used for control for 4 wk (4W-control) and 10 wk (10W-control). The ACTH response induced by swimming stress was reduced after training by swimming (62.4%) or by running (13.8-16.4%). These training periods also attenuated the ACTH response induced by cage-switch stress (62.4% in the swimming group, 23.8-34.6% in the running groups). After swimming stress, the 4W-swimming and 10W-running groups showed smaller increases in blood glucose than the control groups. In addition, the increased levels of blood lactate in all the trained rats were significantly smaller than those in the control groups, suggesting that an adaptation was achieved after physical training. These results suggest that after running training, cross-adaptation is developed in the ACTH response induced by different types of physical (swimming) or psychological (cage-switch) stresses.