Abstract: The DNA content was determined in 30 human hearts from different age groups and of different weight classes. Among these cases were included 4 hearts of children and 5 hearts of adults who had been treated with cytostatics. The total DNA content was determined biochemically and the nuclear DNA content was measured by means of Feulgen cytophotometry. By combining both methods, the total number of heart muscle cells was determined. We obtained the following results: (1) The DNA concentration remained the same in all the hearts, while the total amount of DNA rose up to three-fold with increasing heart weights. (2) Cytophotometric DNA measurements revealed that, in hearts of infants up to the age of 7, a diploid DNA content is found in 80% of the muscle nuclei. In children of higher ages and in adults, 60% of the muscle nuclei are tetraploid. In hypertrophied hearts, there occurs an increased polyploidization of the muscle nuclei, with up to 8% of 32-ploid nuclei. Thus, polyploidisation is caused by chronic hyperfunction of the heart. In atrophic hearts, on the other hand, no regression of polyploidisation was observed. (3) The number of connective tissue cells in a given heart increases from 1 x 10(9) just after birth to 5 x 10(9) in adults, reaching its maximum of 10 x 10(9) in extremely hypertrophied hearts. The number of heart muscle cells is 2 x 10(9) in normal hearts of children and adults, and may rise to 4 x 10(9) in excessively hypertrophied hearts. (4) During treatment with cytostatics, the DNA content of the myocardium is reduced only in hearts of children; in adult hearts, no decrease of DNA is observed. Cytostatics prevent polyploidisation of the heart muscle nuclei and exhibit no other influence upon the DNA content of the heart muscle cell nuclei. (5) Cytostatics cause a decrease in the number of connective tissue and heart muscle cells of up to 57% of the original value in hearts of children. The cell number of adult hearts remains the same under cytostatic treatment.

Abstract: Skeletal and heart muscle fibers undergo severe functional and structural alterations, resulting in necrotization as soon as extracellular Ca ions penetrate excessively into the sarcoplasm, so that the capacities of the Ca binding or extrusion processes become insufficient. In mechanically injured skeletal muscle fibers, this necrotization process begins in the neighborhood of the membrane lesion where a large Ca inward transport takes place. Accordingly, elimination of Ca from the Ringer solution or an outward electric current which blocks the influx of extracellular Ca prevents the onset of necrotization, whereas additional Ca or an inward electric current which augments the influx of Ca potentiates the course of degradation. The crucial reaction in the production of necroses in skeletal and heart muscle fibers is a high energy phosphate deficiency which results (a) from excessive activation of Ca-dependent intracellular ATPases, and (b) from Ca-induced mitochondrial destruction. This applies especially to myocardial fiber damage caused by large doses of beta-adrenergic catecholamines such as isoproterenol. The number and size of the isoproterenol-induced cardiac lesions are obviously determined by the extent and, particularly, by the duration of the Ca-mediated high energy phosphate penury. Substances which sensitize the myocardium to catecholamine-induced necrotization (9-alpha-fluorocortisol, dihydrotachysterol, NaH2PO4) act by potentiating intracellular Ca overload and high energy phosphate breakdown. Conversely, verapamil D 600, and other Ca-antagonistic compounds protect the structural integrity of the heart muscle fibers by restricting transmembrane Ca influx and, consequently, ATP and creatine phosphate exhaustion.

Abstract: The relationship between coronary flow and adenosine triphosphate ATP production was determined in isolated rat hearts and in situ pigs hearts. The major source of ATP in ischemic hearts was oxidative phosphorylation. Oxidation of glucose accounted for most of the residual oxygen consumption in ischemic hearts when the concentration of fatty acids was low, but at 1.2 mM palmitate fatty acids were oxidized in preference to carbohydrate, as in aerobic hearts. The rates of ATP production from both glycolysis and oxidative metabolism were decreased in proportion to the reduction in coronary flow in oxygen-deficient hearts. Glycolysis was reduced to below aerobic rates when coronary flow was about 0.5 ml/min/g tissue in both rat hearts perfused with bicarbonate buffer and blood-perfused pig hearts. Tissue level of high energy phosphates reflected the rates of ATP production and declined in proportion to the reduction in coronary flow. In addition, tissue lactate and H+ accumulated in proportion to the restriction in flow.

Abstract: The mitochondrial respiratory chain has been shown to produce H2O2 under certain conditions (Loschen, Flohe, and Chance, 1971; Boveris, Oshino, and Chance, 1972; Loschen, Azzui, and Flohe, 1973; Boveris and Chance, 1973) At least 1 percent of the total oxygen uptake in State 4 (Chance and Williams, 1956) in the presence of succinate is caused by H2O2 formation (Boveris et al, 1972) It was shown that the component responsible for mitochondrial H2O2 formation is located between the sites of the antimycin and rotenone inhibition (Loschen et al, 1971; Boveris et al, 1972) The possible physiological consequences of a respiratory chain-linked H2O2 formation is not yet understood It would therefore be of significance to know whether oxygen radicals are involved in this process or not It was recently suggested by Rotilio et al (1973) that enzyme systems producing H2O2 via oxygen radicals are always closely associated with a superoxide dismutase Thus, the existence of a mitochondrial superoxide dismutase located in the matrix space (Weisiger and Fridovich, 1973) prompted us to look for oxygen radicals as possible intermediates in the mechanism of the formation of mitochondrial H2O2 In the present communication we show that, under the same conditions in which H2O2 is formed in the mitochondrial respiratoy chain, oxygen radical formation can be demonstrated also A possible relationship of this finding with lipid peroxidation and the toxic effects of hyperbaric oxygen is likely

Abstract: In the myocardium of 30 human hearts of all age groups quantitative deoxyribonucleic acid (DNA) measurements were performed and the results of the measurements were correlated with the pure myocardium weight. By means of the diphenylamine reaction the total amount of DNA (DNA concentration and DNA amount) in the myocardium was estimated. By means of Feulgen cytophotometry the DNA amount exclusively in the heart muscle cell nuclei was measured. With the use of myocardial tissue spread on slides, the nuclear areas of the heart muscle nuclei were planimetrically measured. After preparation with DNase and staining with gallocyanine chromalumn the nucleoli in heart muscle nuclei were specifically presented and their number per nucleus as well as their area values were demonstrated. From the biochemical and cytophotometric results of the myocardial DNA content it was possible to estimate the absolute cell number of the hearts, keeping the pure myocardium weight in consideration. The investigations led to the following results. In growing childrens' hearts the DNA concentration decreases to a constant level of 0.3-0.4 mg/g. The amount of DNA rises with increasing heart weight. During the growth of the heart of a child between the ages of 8 and 12 the DNA amount doubles in the heart muscle nuclei, and most of the muscle nuclei of an adult have a tetraploid DNA content. In pathological heart hypertrophy a further polyploidization of the heart muscle nuclei occurs. The areas of the nuclei increases with growing polyploidization. The nuclear areas form the same grouping as the ploidy classes. With growing nuclear areas, the total areas of the nucleoli and their number per nucleus also increase. Right after birth an increase in the number of connective tissue and heart muscle cells follows. A normal heart contains about 2 x 10(9) muscle cells. In hypertrophic hearts the number of muscle cells can double.

Abstract: Morphological aspects of cardiac myocytes during neonatal growth were studied in isolated cell preparations from 23 dog hearts (newborn to 38 weeks old) Additional hearts were perfused with glutaraldehyde for electron microscopic study At least 200 isolated cells in stained smears of each ventricle were examined for nuclear number, and at least 25 cells were measured with an eyepiece micrometer to calculate cell volume At birth, 96-100% of myocytes contained a single nucleus By 2 weeks, 15% of cells contained two to four nuclei; multiple nuclei were present in 55% of myocytes at 4 weeks, in 85% at 6-10 weeks, and in 55-60% at 15, 28, and 38 weeks Although left ventricular weight increased lenearly from birth, there was no increase in single nucleated cell size until 4-6 weeks, indicating cellular hyperplasia; by 38 weeks single nucleated cells were 9 times the volume at birth Double nucleated cells steadily increased in size, reaching a volume at 38 weeks 19 times that of newborn myocytes At birth, myocytes were small and spindle-shaped; intercalated discs were poorly developed, but lateral connections between cells were common As the cells increased in size, the lateral attachment areas appeared to move to the cell ends to form the intercalated discs Myofibrils appeared to be assembled at the lateral connections and at the intercalated discs Hyperplasia is the prevalent means of cell growth at birth in the dog and is gradually replaced by cell hypertrophy from 2 to 6 weeks of age Double nucleated cells occur in hypertrophying cells by karyokinesis without subsequent cytokinesis, perhaps in response to the intense protein synthetic demands of normal growth

Abstract: The evolutive histological stages, the frequency, and the eventual association of the different types of myocardial cell death have been studied in the following human material: acute infarction, sudden "coronary" death, accidental death, pheochromocytoma, transplanted hearts, "stone" heart syndrome, thrombotic thrombocytopenic purpura, and alcoholic cardiomyopathy. Three distinct main histological types of myocardial cell death are recognizable: Coagulation necrosis, the fundamental lesion in infarcts in which the myocardial cell loses its capability to contract and dies in an atonic state with overdistension due to the intraventricular pressure. No early myofibrillar damage is seen. Coagulative myocytolysis, found in all the present cases, always seen in the outer zone of an early infarct and in the surrounding normal myocardium at any stage of the repair process in most of the acute infarcts and in most cases of sudden death. The myocardial cell dies in a hypercontracted state, with early myofibrillar rhexis, and anomalous irregular cross-band formations. This tetanic death is similar to that seen in pheochromocytoma and in experimental catecholamine-induced necrosis. Colliquative myocytolysis, in which edematous vacuolization with dissolution of myofibrils is the main early finding, without hypercontraction, anomalous bands, and myofibrillar rhexis. This pattern, likely related to the low-output syndrome, was often seen in the preserved subendocardial and perivascular muscle fibers of acute infarct cases, in some transplanted hearts, and in all the alcoholic hearts. The different clear-cut morphological patterns of these three types of myocardial necrosis suggest a different pathogenesis and that different pathogenetic mechanisms may act in the same disease.

Abstract: Closed aorta working hearts perfused with 1 mM pyruvate were subjected to a 4-fold increase in work load by raising the left atrial filling pressure. Citric acid cycle flux, pyruvate uptake, and oxygen consumption rose 3-fold when cardiac output was increased. In the first 40 sec after the transition tissue glutamate and citrate fell by 22 and 45%, respectively, and there were reciprocal decreases in malate and aspartate. The ratio of creatine phosphate/creatine declined by 50% within 30 sec, with a corresponding increase in inorganic phosphate, but the fall in the ATP/ADP ratio was only 10%. During the first 10 sec the surface fluorescence from cardiac pyridine nucleotides fell by 30% and this change was synchronous with a sharp decline in the calculated adenine nucleotide phosphate potential. This suggests that heart mitochondrial respiration is controlled by the cytosolic phosphate potential, and that a state 4 to state 3 transition occurs when cardiac output is increased. Apparent disequilbrium of creatine phosphokinase can be explained by the compartmentation of most of the cardiac ADP within the mitochondria. Citric acid cycle flux was coordinated by activational interactions at citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase, but a transient imbalance between the individual cycle steps leads to a sharp peak of lactate production shortly after the work transition.

Abstract: Studies with a sarcolemma preparation from guinea pig hearts revealed two classes of Ca2+ binding sites: high affinity sites (Km' of 16 muM) and a 10-fold greater number of low affinity sites (Km' of 800 muM). Low affinity Ca2+ binding was inhibited by ruthenium red and verapamil, suggesting that these sites are located on the external side of the membrane. However, clear-cut competition between H+ and Ca2+ could not be demonstrated with isolated sarcolemma.

Abstract: Isolated isometric ventricular muscle of frogs and cats was studied. Perfusing solutions were played directly on the muscle to permit rapid exchange of the extracellular space. Developed force and maximal rate of rise of force were measured in all studies and action potentials (AP) were recorded in some. For both species low concentrations of ethanol (75 degrees mg/l) potentiate contraction. Higher concentrations ( greater than or equal to 750 mg/l) depress contraction progressively with increasing concentration. Concentrations which depress contraction, e.g., 3-4.5 gm/l, usually shorten AP duration. The shortening of AP duration can occur even though contractile force does not fall and, conversely, force may fall while AP duration is unaffected. When 10 mM caffeine is added to the perfusate of either species, AP duration is prolonged and contraction is potentiated. If both ethanol (4.5 gm/l) and 10 mM caffeine are added simultaneously to the perfusate, there is a rapid (within 4 beats) increase in AP duration and an initial depression of contraction, followed by a further increase in AP duration and a significant potentiation of contraction. The steady state contraction is less than with caffeine alone. These preliminary studies suggest that ethanol may depress contraction both by shortening AP duration and by a direct effect upon the contractile apparatus.

Abstract: The methodology for use of the mass spectrometer for the measurement of intramyocardial gas tensions in the canine preparation is described. Baseling studies were carried out initially in 36 animals, and control levels for myocardial oxygen tension and myocardial carbon dioxide tension were 19 mm Hg (S.D. 6 mm Hg) and 43 mm Hg (S.D. 10 mm Hg), respectively. Myocardial oxygen tension was not altered significantly by varying the arterial oxygen tension between 65 and 300 mm Hg. However, myocardial carbon dioxide tension increased linearly with increased arterial carbon dioxide tension. In 15 dogs placed on total cardiopulmonary bypass, a perfusion pressure 40-60 mm lower than the control mean arterial pressure resulted in myocardial ischemia with a decrease in myocardial oxygen tension and an increase in myocardial carbon dioxide tension. A subsequent increase in perfusion pressure to control levels resulted in resolution of ischemia and return of myocardial oxygen and carbon dioxide tensions to their control level. In another series of open-chest dogs on cardiopulmonary bypass, a proximal constriction applied to the left coronary circumflex artery resulted in a marked decrease in myocardial oxygen tensions and a marked increase in myocardial carbon dioxide tensions in the region supplied by the constricted vessel. In yet another series of open-chest dogs, it was found that incremental decreases in coronary flow established by constriction of the circumflex artery resulted in an exponential increase in both myocardial carbon dioxide tensions and ST-segment elevation as determined by a 25-gauge multi-contact plunge electrode placed in the posterior left ventricular wall. It appears that mass spectrometry techniques for evaluating myocardial ischemia have several advantages over myocardial biopsy techniques for assay of ATP and lactate, and also over the technique of coronary sinus lactate determination.

Abstract: Degeneration and fibrosis of the atrioventricular nodal tissue and left bundle branch, associated with cartilage of bone in the central fibrous body and fibrosis of the interventricular septal crest, were observed in 63 cats with cardiomyopathy. The cardiac lesions consisted of endocardial and myocardial fibrosis or organized endomyocarditis. Electrocardiographic, radiographic, angiocardiography, and hemodynamic changes were also observed in the cats.

Abstract: The effect of 40- or 90-min periods of temporary myocarardial ischemia on the distribution of coronary flow and capillary structure were assessed in groups of mongrel dogs. Thioflavin S. a fluorescent dye which stains vascular endothelium when injected intravenously, was used to demonstrate the distribution of microvascular perfusion at 10 sec, 5 min, or 20 min following release of a 40-or 90min circumflex coronary artery occlusion. Hearts which demonstrated perfusion defects were sampled for electron microscopy. Following 40 min of occlusion, thioflavin S was distributed uniformly throughout the myocardium. In contrast, following 90-min periods of coronary occlusion, perfusion defects always were present in the subendocardial half of the posterolateral left ventricular wall. Several morphological features in these areas of no reflow were observed by electron microscopy, including decreased endothelial pinocytotic vesicles, endothelial gaps and bleb formation, capillaries packed with erythrocytes, occasional intraluminal thrombi, and extravascular erythrocytes and fibrin. Myocardial cells showing severe injury always were seen within but also extended beyond the areas of poor perfusion. These results demonstrate that areas of no reflow occur following 90-min periods of ischemic injury in the dog, but that primary myocardial cell injury occurs during the ischemic period and not as a function of the "no-reflow" phenomenon.

Abstract: A review is presented of morphological aspects of myofibrillar alterations which occur in cardiac muscle cells following various types of injury. Emphasis is placed on the association between specific patterns of alterations involving the structure or the orientation of myofibrils and diverse forms of myocardial injury.

Abstract: Rabbits were crowded 4 to a cage for 2 weeks, then released for 1 week, crowded again for 2 weeks, and so on. Of 44 rabbits subjected to intermittent crowding, only 9 survived for longer than 10 months, 20 died during the 1st month, and 15 died between the 2nd and 9th month of the experiment. Histological sections of the myocardium showed myocytolysis, intersititial edema, and an increased amount of acid mucopoly saccharides in rabbits surviving for 2 weeks and more. The accumulations of acid mucopolysaccharides were apparently unrelated to necrotic foci. Long-term survivors frequently showed myocardial fibrosis and endocardial fibroelastosis, as well as basophilic degeneration of myocardial fibers. The lesions observed were similar to those described in idiopathic endomyocardiopathy in Southern Africa. Therefore, the rabbit may be of some value for research in cardiomyopathies.

Abstract: Contractile performance of ischemic feline myocardium was evaluated under conditions of selective changes in perfusate in pH and pCO2. A substantial increase in myocardial performance was noted when the pCO2 was lowered at constant pH, and depression of performance was noted when the pCO2 was increased at constant pH. Perfusate acidosis at constant pCO2 resulted in depression of performance and decreased performance only after 20 min of exposure. Alkalosis did not increase performance and decreased performance transiently during mild ischemia. These studies suggest that performance of myocardium during ischemia is closely related to tissue pCO2 and is minimally related to the level of extracellular pH.

Abstract: The crucial point in the pathogenesis of isoproterenol-induced myocardial necrotization is an abundant intracellular Ca accumulation leading to high energy phosphate exhaustion. Accordingly, in the early stage of the isoproterenol-induced necrotization process, the onset of ATP and creatine phosphate breakdown strictly parallels the acute Ca gain. In this type of necrosis, the Mg losses from the myocardium appear as a concomitant phenomenon. The hearts can be protected against the deleterious Ca overload and necrotization by increasing the plasma concentration of Mg, K, or H ions in order to counterbalance Ca according to the ration (see article). On the other hand, if Mg, K, or H ion concentrations are too low, isoproterenol-induced Ca uptake and myocardial lesions are potentiated.

Abstract: During development the total mass of collagen increases to the same degree in each ventricle independently of the mass of muscle. At birth the concentration of collagen is the same in each ventricle. Thereafter a greater quantity of muscle is developed in the left ventricle than in the right ventricle, so that the concentration of collagen in the right ventricle comes to exceed that in the left. In the mature rabbit the concentration of collagen is higher in the atria than in the ventricles, higher in the right ventricle than in the left ventricle, and higher in the epicardium than in the endocardium. Beta blockade has no effect on the content of myocardial collagen.

Abstract: The electron microscopic aspects of myocardial cells in several types of mechanically overloaded heart are reviewed. Alterations which may be interpreted as degenerative changes are all the more frequent as the load is more severe. They seem to be the cause of the interstitial fibrosis which often accompanies hypertrophy. Their mechanism is dubious: swelling of mitochondria and intracellular lipidosis, which could signify cellular hypoxia, are rarely present. Other changes are characteristic of an increase of proteosynthesis and of the active growth of the main structures of the cell: myofibrils, mitochondria, T- and L-tubules. Some pictures of myofibrillar growth are not always easily distinguished from those of myofibrillar lesions. The mitochondria/myofibril ratio may be modified or not. The apparent volume of the mitochondria may remain normal while their density increases, which implies a decrease of their average size. In severe and long-lasting overloads, hypertrophy and hyperplasia of the Golgi apparatus and multiplication of granules of the auricular type evoke a regression of the cell toward its fetal type.

Abstract: A morphological study of the sudanophilic lipids in dog and human hearts was carried out. The hearts of 5 mongrel dogs and 20 auricular appendices of human patients were utilized. The dog hearts were fixed in situ by perfusion with 2% glutaraldehyde, and the human tissue was fixed by immersion. For the ultrastructural study, some blocks of every portion of the specimen were postfixed in osmium and embedded in Epon. The topographical and quantitative study was done on frozen 20-mu sections of tissue stained with Sudan IV in propylene glycol and counterstained with hematein (Geigy). The results indicate that a significant quantity of visible triglycerides is extracellular and located in the interstitial spaces of the heart. The dimensions of these lipid droplets vary from 0.5 mu to more than 20 mu. The highest concentration was found in the epicardial region of the left ventricle, but a significant amount was found in the endocardium and in the middle portion of the myocardium. These observations indicate that a sizable portion of the heart interstitium is occupied by free droplets of triglycerides. This substrate pool is probably mobile and readily available as a source of energy.

Abstract: Studies with extracellular fine structural diffusion protein tracers, horseradish peroxidase and ferritin, were carried out on catecholamine-induced cardiac muscle cell injury. Epinephrine, norepinephrine, and isoproterenol were administered in a dose of 4- 6 mug/100g body weight by continuous intravenous infusion. For follow-up studies, isoproterenol was also given subcutaneously in a dose of 8.5 mg/100 g body weight as a single injection. In contrast to saline-infused controls and following epinephrine infusion, where these tracers always remained extracellular, norepinephrine- and isoproterenol-infused animals exhibited alteration of sarcoplasmic membrane permeability to macromolecules in the early stage of evolution preceding fine structural changes of cardiac muscle cells. This was reflected by the intrasarcoplasmic presence of peroxidase in some cardiac muscle cells which otherwise showed no ultrastructural alteration. Deposition upon and selective binding of the extracellular protein tracer, peroxidase, to intact myofilament was also a characteristic early change that may affect the contraction-relaxation mechanism of the myofilaments and may contribute to the evolution of necrobiotic alteration. In structurally altered cells, peroxidase showed similar affinity to contraction bands and fragmented myofilaments. Furthermore, these studies disclosed different sensitivities of various membrane components of the cardiac muscle cell. While in the early pahse of cell damage no peroxidase could be detected in various intrasarcoplasmic compartments, with increasing severity of the lesion the external and internal mitochondrial membranes as well as the sarcoplasmic reticulum were also affected. When the large molecular tracer, ferritin, was used, the sequence of events in altered cardiac muscle cells followed that outlined for peroxidase. However, free ferritin molecules could not be demonstrated in the sarcoplasm of cardiac muscle cells which exhibited normal ultrastructure.

Abstract: The effect of prolonged adminstration of ehtanol on cardiac metabolism, contractility, and ultrastructure was investigated. Dogs received 400 ml of a 25 percent solution of ethanol during a period of 3-6 months. Repeated heart muscle biopsied revealed a significant diminution in the activity of intramitochondrial NAD-linked isocitrate dehydrogenase in the animals exposed to alcohol. Oxidative, phosphorylation of mitochondria was measured polarographically using a vibrating oxygen electrode; respiratory control index and mitochondrial oxygen consumption were markedly reduced (p less than 0.001). Myocardial ATP content was significantly diminished (p less than 0.025). Electron microscopic changes observed consisted of mitochondrial degeneration, dehiscence of intercalated discs, and dilatation of intercellular spaces. The average force velocity curve was shifted downward and to the left in afterloaded contractions with a significant depression of Vmax (p less than 0.01). Both calcium binding and calcium uptake of mitochondria and sarcoplasmic reticulum were inhibited. These results suggest that a disorder in the generation of energy and a defect in calcium binding by subcellular membranes may be the determinant events leading to impaired myocardial function in the course of chronic alcoholism.

Abstract: Medical records of 12 dogs determined at necropsy as having had cardiomyopathy and of 5 live dogs with clinical, electrocardiographic and radiographic evidence of the disease were reviewed. Congestive cardiomyopathy was the most common form of the disease, affecting 15 of the 17 dogs. The dogs were primarily of large breeds and ranged in age from 2 to 8 years. Clinical findings included right and left congestive heart failure presenting as pulmonary congestion and edema, pleural effusion, hepatomegaly, and ascites. Thoracic radiographs showed moderate severe enlargement of all cardiac chambers and evidence of congestive heart failure. Atrial fibrillation was the predominant rhythmn; ventricular premature contractions and left ventricular hypertrophy were sometimes noted. At necropsy, biventricular dilation including dilation of the atrioventricular annular rings and accompanying massive atrial dilation was observed. Myocardial contractility was poor and had resulted in dilation of the heart chambers with minimal hypertrophic responses. The atrioventricular valve leaflets and chordae tendinae were usually near normal. Medical treatment included rest, digoxin, and diuretics, Medical or electrical cardioversion of atrial fibrillation to normal sinus rhythm was also attempted. Prognosis for congestive cardiomyopathy is very poor. The average survival time after onset of signs is 6-12 months; 1 dog in our study survived for 20 months. In contrast to congestive cardiomyopathy, the hypertrophic form is rare in the dog. Only two of the dogs studied had hypertrophic cardiomyopathy; one case was diagnosed at necropsy and one by angiocardiography. Both had features of idiopathic hypertrophic subaortic stenosis (IHSS) as reported in man.

Abstract: Cardiomyopathic hamsters (UM-X7.1) show clinical signs of congestive heart failure and an abnormal EKG pattern. The sarcolemmal fraction obtained from the failing hearts at advanced stages of myopathy exhibited no change in the basal adenylate cyclase activity; however, the activity of this enzyme in the presence of catecholamines or NaF was lower in the failing heart sarcolemma than that in the control. The activities of Ca2+-ATPase, Mg2+-ATPase, and Na+-K+-ATPase in the failing heart sarcolemma were also less than the control values. These results suggest an association of membrane defect with heart failure.

Abstract: Magnesium causes a marked decrease in the initial rates of respiration-supported calcium uptake by isolated heart mitochondria. Differential responses of mitochondrial respiration and cytochrome b redox states in the presence and absence of magnesium indicate that with magnesium present, heart mitochondria retain the ability to phosphorylate ADP after calcium uptake. Electron microscopy of the isolated mitochondria after calcium accumulation revealed markedly different crystal structures within the matrix space depending on the presence or absence of magnesium. The results suggest a "protective" effect of magnesium on the phosphorylating mechanism of mitochondria during active calcium uptake. Further, magnesium appears to determine the type of crystal structure formation within the intramitochondrial compartment.

Abstract: The classic view that the resting bradycardia of exercise training is due to an increase in the tonic discharge of the vagi is no longer tenable; If it were true, full doses of atropine would accelerate the heart to a greater extent in the athletic animal. All investigators agree that the reverse is the case. Some workers report a decrease in cardiac sympathetic influence after training. This would cause a preponderance of vagal influence which may decrease to a lesser extent than the sympathetics or may not change at all. Several studies have demonstrated that training causes a distinct slowing of the intrinsic rate of the pacemaker. It is concluded that two factors operate to lower the resting heart rate after athletic training: 1) slowing of the intrinsic rate of the pacemaker, 2) Increase in cholinergic predominance on the pacemaker frequency as a result of a decrease in adrenergic influence. Vagal influence per se seems either to remain the same or to decrease slightly in the athlete compared to the nonathelete. It appears that slowing of the intrinsic rate plays a more important role, a factor that has been hitherto overlooked. The mechanisms underlying these changes remain obscure.

Abstract: Administration of isoproterenol induces changes in phospholipids of heart muscle membranes. Longer and more unsaturated fatty acids replace shorter and less unsaturated fatty acids. Dietary polyunsaturated fatty acids, i.e., C22:6, replace C18:2 and C20:4 in phospholipids of heart muscle. Increased sensitivity to isoproterenol and increased myocardial cell damage is accompanied by a relative increase in long chain polyunsaturated fatty acids in phospholipids of heart muscle. Development of myocardial necrosis increases with a progressive replacement of C18:2 and C20:4 by C22:6. Alterations in fatty acid composition of membrane phospholipids and consequent changes in membrane properties may play an important role in myocardial cell damage. Myocardial damage following administration of isoproterenol is increased when there is enhanced intramyocardial lipolysis and an increased amount of polyunsaturated fatty acids in membrane phospholipids. Mocardial damage is decreased when there is reduced intramyocardial lipolysis and the membrane response makes the membranes less permeable and more stable.

Abstract: The effects of isoproterenol, glucose, and pH on the responses of isolated rat cardiac muscle to hypoxia (95% N2, 5% CO2) were examined while the muscles were contracting isometrically 12 times a minute at 28 degrees C. In the presence of 5.5 mM glucose, 10(-5) M isoproterenol and alkaline pH (7.8) improved the performance of cardiac muscle during early hypoxia. This was followed by a premature decline in developed tension, and contracture appeared. Recovery of function following reoxygenation with 95% O2 and 5% CO2 after a 60-min period of hypoxia was poor. Acid pH (6.8) resulted in an early decline of mechanical activity during hypoxia; but contracture did not appear, and full recovery of developed tension was seen upon reoxygenation after 60 min of hypoxia. When 22 mM glucose was used as substrate, the early responses to hypoxia were not altered; but late performance was improved, contracture did not appear, and full recovery after 60 min of hypoxia was seen. If additional glucose was added to the bath after 30 min of hypoxia (concentration 22 mM), little effect on developed tension was evident; but contracture diminished and recovery after 60 min of hypoxia was improved. Addition of 22 mM glucose allowed isoproterenol to exert its inotropic effect in the absence of late deleterious changes. The data support the concept that factors tending to increase the utilization of limited stores of anaerobic substrate during hypoxia facilitate deterioration. By increasing exogenous glucose, the support of inotropic activity without late adverse effects appears possible, and recovery is improved upon reoxygenation.