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1. Questions concerning coronary heart disease have been raised for more than 200 years, but the concept of coronary insufficiency is only 50 years old. 2. The pathological anatomy of coronary insufficiency is variable, unexpectedly rich and stratified, and full of pecularities. 3. "Coronary insufficiency" is the superimposed concept; "cardiac infarcts" and "inner myocardial layer damage" are subordinate. 4. The logical connection linking all the morphological consequences of so-called coronary insufficiency is the elective necrosis of the parenchyma. The anatomically demonstrable equivalents of coronary insufficiency are, from the point of view of coronary perfusion, the result of an inadequate "vis a tergo". 5. This principle is enshrined in a complex of conditions which has to be disentangled if an individual case is to be analysed. The complex comprises three sets of factors: (a) the critical narrowing of the lumen of the coronary arteries and all their branches leading to a given territory; (b) the weight of the functioning mass of the cardiac muscle; (c) cardiac effort required of the heart during the critical period of damage. 6. The presence of anastomoses between the coronary arteries is no proof of their functional efficiency or readiness in an emergency. The conditions which determine their responsiveness, particularly as far as time is concerned, are at the moment still not adequately known. 7. The behaviour of ions at the membranes of living cells, particularly of muscle fibres, is a fundamental phenomenon, fascinating in its primitive aspects. A disturbance of cellular respiration, produced in the cardiac muscle "regularly" by the "inadequate vis a tergo" of coronary perfusion, leads to an exhaustion of energy stores, and to an increased influx of calcium ions. This activates the ATP-ase of the myofibrils, and thereby reduces the level of adenin nucleotides. This loss of energy-rich substances not only militates against the function of the muscle fibres, it also initiates their necrosis. 8. The cardiac infarct is a phenomenon of a disturbed circulation-- a "dyscirculatory" change. It is found in certain sites of predilection, whose choice becomes intelligible only through an understanding of the developmental history of the coronary arteries. The cardiac infarct is "coronary-dependent"! There are, however, also other forms of, and possibilities leading to, the development of myocardial necrosis. The nosology of the cardiac infarct clearly distinguishes the latter from these other forms. In damage of the inner layers of the myocardium infarcts do not develop by the confluence of necroses of individual fibres or of groups of fibres. Infarcts are not a phenomenon of addition, they do not have the "character of a mosaic". 9. As in other tissues, in the human myocardium also there are lysosomes. They are found in hypertrophied muscle fibres. Topical relations to zones of necrosis have not been found. 10...
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PMID:The pathogenesis of cardiac infarction. A few comments on some unanswered questions. 14 May 3

Exposure of human body to high altitude environment initiate reaction which could be result whether of adaptation or of exhaustion. The purpose is to establish the human body environment which enables regeneration of own cells. Therefore, mechanism of reestablishment of prevention and recognition of symptoms and signs of insufficient adaptability on high altitude are of great interest for clinical and other medical investigators. Special position in research refers on cardiovascular system. Results show, according to effect of only one factor-catecholamines, that in course of physical training on high altitude, could be expected, cardiac muscle hypertrophy. It is proved, that under special circumstances catecholamines stimulate synthesis of proteins what enables faster regeneration of the cells. However, under conditions of myocardial ischemia, uncontrolled loading of these patients could lead to deterioration of heart function appearance of cardiac insufficiency.
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PMID:[Aspects of acclimatization of the human body to acute and chronic high-altitude hypoxia]. 209 85

Since their discovery in cardiac muscle, ATP-sensitive K+(KATP) channels have been identified in pancreatic beta-cells, skeletal muscle, smooth muscle and central neurons. The activity of KATP channels is inhibited by the presence of cytosolic ATP. Their wide distribution indicates that they could have important physiological roles that may vary between tissues. In muscle cells the role of K+ channels is to control membrane excitability and the duration of the action potential. In anoxic cardiac ventricular muscle KATP channels are believed to be responsible for shortening the action potential, and it has been proposed that a fall in ATP concentration during metabolic exhaustion increases the activity of KATP channels in skeletal muscle, which may reduce excitability. But the intracellular concentration of ATP in muscle is buffered by creatine phosphate to 5-10 mM, and changes little, even during sustained activity. This concentration is much higher than the intracellular ATP concentration required to half block the KATP-channel current in either cardiac muscle (0.1 mM) or skeletal muscle (0.14 mM), indicating that the open-state probability of KATP channels is normally very low in intact muscle. So it is likely that some additional means of regulating the activity of KATP channels exists, such as the binding of nucleotides other than ATP. Here I present evidence that a decrease in intracellular pH (pHi) markedly reduces the inhibitory effect of ATP on these channels in excised patches from frog skeletal muscle. Because sustained muscular activity can decrease pHi by almost 1 unit in the range at which KATP channels are most sensitive to pHi, it is likely that the activity of these channels in skeletal muscle is regulated by intracellular protons under physiological conditions.
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PMID:Modulation of ATP-sensitive K+ channels in skeletal muscle by intracellular protons. 215 36

The activation characteristics of Mg-ATP and Ca2+ on cardiac and skeletal muscle myofibril ATPase activity were studied in rats following a run to exhaustion. In addition, the effect of varying ionic strength was determined on skeletal muscle from exhausted animals. The exhausted group (E) ran at a speed of 25 m min-1 with an 8% incline. Myofibril ATPase activities for control (C) and E were determined with 1, 3 and 5 mM Mg-ATP and 1 and 10 microM Ca2+ at pH 7.0 and 30 degrees C. For control skeletal muscle, at 1 and 10 microM Ca2+, there was an increase in ATPase activity from 1 to 5 mM Mg-ATP (P less than 0.05). For E animals the myofibril ATPase activities at 10 microM Ca2+ and all Mg-ATP concentrations were similar to C (P greater than 0.05). At 1.0 microM Ca2+ and all Mg-ATP concentrations were similar to C (P greater than 0.05). At 1.0 microM Ca2+ the activities at 3 and 5 mM Mg-ATP were greater for the E animals (P less than 0.05). Increasing KCl concentrations resulted in greater inhibition for E animals. With cardiac muscle, the myofibril ATPase activities at 1.0 microM free Ca2+ were lower for E at all Mg-ATP levels (P less than 0.05). In contrast, at 10 microM Ca2+, the E group exhibited an elevated myofibril ATPase activity. The results indicate that Mg-ATP and Ca2+ activation of cardiac and skeletal muscle myofibril ATPase is altered with exhaustive exercise.
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PMID:Myofibril ATPase activity of cardiac and skeletal muscle of exhaustively exercised rats. 623 Feb 76

Previous studies have established that older (16 wk) and more obese rats conserve body protein during prolonged starvation. This adaptation is due in part to a curtailment of muscle proteolysis. To determine whether this response occurs also in younger rats and whether protein is conserved at sites other than muscle, studies were conducted in young 6-wk-old rats previously fed either a chow or a high-fat diet before starvation. Fat feeding caused a marked increase in adipose mass and prolonged survival. Whereas chow-fed rats survived the fast for approximately 5 days, fat-fed rats lived for 10 days and diminished their excretion of nitrogen for at least 6 days, indicative of protein conservation. Despite the ability of fat-fed rats to survive the fast longer, protein was conserved in only a few organs. The timing and magnitude of protein loss from liver, kidney, intestine, and lung was similar to that in chow-fed rats, and little protein was lost during the fast from brain, stomach, skin, and soleus muscle in either group. In fat-fed rats, cardiac and skeletal muscle were the principle tissues in which protein was conserved, and this adaptation was lost when body fat stores were nearing exhaustion. In both groups nitrogen excreted in the urine early in the fast was derived mainly from protein lost from muscle, liver, and to a lesser extent intestine. Later in the fast, the principal source was muscle. These findings indicate that during starvation in the rat the conservation of protein occurs principally in skeletal and cardiac muscle. They also suggest that the ability of the rat to conserve protein is dependent on the size of its lipid stores.
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PMID:Sites of protein conservation and loss during starvation: influence of adiposity. 672 Sep 43

Acid hydrolase activities in skeletal and cardiac muscle were studied 5, 10 and 20 days after exhaustive intermittent running by untrained and endurance-trained mice. Exhaustion increased the activities of cathepsin D, beta-glucuronidase and ribonuclease, but not that of p-nitrophenylphosphatase in skeletal muscle of untrained mice. Activities were highest on the fifth day after exhaustion and decreased during the following two weeks. More intensive loading produced no changes in acid hydrolytic capacity in skeletal muscle of endurance-trained mice. Acid hydrolase activities in cardiac muscle of both untrained and trained mice were unaffected by exhaustive running. It is suggested that exhaustive running causes both lethal and sublethal hypoxic fiber injuries in the skeletal muscle of untrained mice but not in that of endurance-trained mice or in the cardiac muscle of animals of either group. These injuries manifest themselves as fiber necrosis (lethal) and as increased acid hydrolytic capacity in surviving fibers (sublethal).
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PMID:Acid hydrolase activities in mouse cardiac and skeletal muscle following exhaustive exercise. 719 24

Duchenne muscular dystrophy (DMD) is a debilitating X-linked disorder that is fatal. DMD patients lack the expression of the structural protein dystrophin caused by mutations within the DMD gene. The absence of functional dystrophin protein results in excessive damage from normal muscle use due to the compromised structural integrity of the dystrophin associated glycoprotein complex. As a result, DMD patients exhibit ongoing cycles of muscle destruction and regeneration that promote inflammation, fibrosis, mitochondrial dysfunction, satellite cell (SC) exhaustion and loss of skeletal and cardiac muscle function. The nuclear receptor REV-ERB suppresses myoblast differentiation and recently we have demonstrated that the REV-ERB antagonist, SR8278, stimulates muscle regeneration after acute injury. Therefore, we decided to explore whether the REV-ERB antagonist SR8278 could slow the progression of muscular dystrophy. In mdx mice SR8278 increased lean mass and muscle function, and decreased muscle fibrosis and muscle protein degradation. Interestingly, we also found that SR8278 increased the SC pool through stimulation of Notch and Wnt signaling. These results suggest that REV-ERB is a potent target for the treatment of DMD.
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PMID:Pharmacological inhibition of REV-ERB stimulates differentiation, inhibits turnover and reduces fibrosis in dystrophic muscle. 2921 66

To investigate whether high-intensity interval training (HIIT) and continuous moderate-intensity training (CMT) have different impacts on exercise performance and cardiac function and to determine the influence of these exercise protocols on modulating basal autophagy in the cardiac muscle of rats. Rats were assigned to three groups: sedentary control (SC), CMT, and HIIT. Total exercise volume and mean intensity were matched between the two protocols. After a 10-week training program, rats were evaluated for exercise performance, including exercise tolerance and grip strength. Blood lactate levels were measured after an incremental exercise test. Cardiac function and morphology were assessed by echocardiography. Western blotting was used to evaluate the expression of autophagy and mitochondrial markers. Transmission electron microscopy was used to evaluate mitochondrial content. The results showed that time to exhaustion and grip strength increased significantly in the HIIT group compared with the SC and CMT groups. Both training interventions significantly increased time to exhaustion, reduced blood lactate level (after an incremental exercise test) and induced adaptive changes in cardiac morphology, but without altering cardiac systolic function. The greater improvements in exercise performance with the HIIT than with the CMT protocol were related to improvement in basal autophagic adaptation and mitochondria function in cardiac muscle. Mitochondria markers were positively correlated with autophagy makers. This study shows that HIIT is more effective for improving exercise performance than CMT and this improvement is related to mitochondrial function and basal autophagic adaptation in cardiac muscle.
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PMID:Cardiac basal autophagic activity and increased exercise capacity. 2934 13

The effects of high-intensity interval (HIIT) and moderate-intensity continuous training (MICT) on basal autophagy and mitochondrial function in cardiac and skeletal muscle and plasma metabolic phenotypes have not been clearly characterized. Here, we investigated how 10-weeks HIIT and MICT differentially modify basal autophagy and mitochondrial markers in cardiac and skeletal muscle and conducted an untargeted metabolomics study with proton nuclear magnetic resonance (1H NMR) spectroscopy and multivariate statistical analysis of plasma metabolic phenotypes. Male Sprague-Dawley rats were separated into three groups: sedentary control (SED), MICT, and HIIT. Rats underwent evaluation of exercise performance, including exercise tolerance and grip strength, and blood lactate levels were measured immediately after an incremental exercise test. Plasma samples were analyzed by 1H NMR. The expression of autophagy and mitochondrial markers and autophagic flux (LC3II/LC3-I ratio) in cardiac, rectus femoris, and soleus muscle were analyzed by western blotting. Time to exhaustion and grip strength increased significantly following HIIT compared with that in both SED and MICT groups. Compared with those in the SED group, blood lactate level, and the expression of SDH, COX-IV, and SIRT3 significantly increased in rectus femoris and soleus muscle of both HIIT and MICT groups. Meanwhile, SDH and COX-IV content of cardiac muscle and COX-IV and SIRT3 content of rectus femoris and soleus muscle increased significantly following HIIT compared with that following MICT. The expression of LC3-II, ATG-3, and Beclin-1 and LC3II/LC3-I ratio were significantly increased only in soleus and cardiac muscle following HIIT. These data indicate that HIIT was more effective for improving physical performance and facilitating cardiac and skeletal muscle adaptations that increase mitochondrial function and basal autophagic activities. Moreover, 1H NMR spectroscopy and multivariate statistical analysis identified 11 metabolites in plasma, among which fine significantly and similarly changed after both HIIT and MICT, while BCAAs isoleucine, leucine, and valine and glutamine were changed only after HIIT. Together, these data indicate distinct differences in specific metabolites and autophagy and mitochondrial markers following HIIT vs. MICT and highlight the value of metabolomic analysis in providing more detailed insight into the metabolic adaptations to exercise training.
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PMID:Beneficial Autophagic Activities, Mitochondrial Function, and Metabolic Phenotype Adaptations Promoted by High-Intensity Interval Training in a Rat Model. 2987 83