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PubMed1981

Immunoelectron and immunofluorescence localization of desmin in mature avian muscles.

Antisera or affinity-purified antibodies shown to be specific for avian gizzard desmin antigen by double immunodiffusion, antigen-blocking, and immunoautoradiography experiments have been used in indirect immunofluorescence and indirect immunoelectron microscopy to demonstrate localization of desmin in myofibrils from mature avian muscles. The light microscope results agree with the work of others in that they suggest that desmin is primarily at or near the periphery of Z-lines of striated muscle myofibrils. Immunoperoxidase labelling more clearly shows that the reactive desmin antigen is located almost entirely between Z-lines of adjacent parallel myofibrils and that there is no obvious correlation between locations of T-tubules and desmin structures. The electron-dense reaction product often followed an approximately linear course between Z-lines of adjacent myofibrils and indicated the desmin antibodies had decorated a small number of filaments spanning this region. These results suggest that the desmin found in close association with myofibrils of mature striated muscle is in the aggregated form of 10-nm filaments.

Animals↗
PubMed1992

Incorporation of fluorescently labeled contractile proteins into freshly isolated living adult cardiac myocytes.

When fluorescently labeled contractile proteins are injected into embryonic muscle cells, they become incorporated into the cells' myofibrils. In order to determine if this exchange of proteins is unique to the embryonic stage of development, we isolated adult cardiac myocytes and microinjected them with fluorescently labeled actin, myosin light chains, alpha-actinin, and vinculin. Each of these proteins was incorporated into the adult cardiomyocytes and was colocalized with the cells' native proteins, despite the fact that the labeled proteins were prepared from noncardiac tissues. Within 10 min of injection, alpha-actinin was incorporated into Z-bands surrounding the site of injection. Similarly, 30 sec after injection, actin was incorporated into the entire I-bands at the site of injection. Following a 3-h incubation, increased actin fluorescence was noted at the intercalated disc. Vinculin exchange was seen in the intercalated discs, as well as in the Z-bands throughout the cells. Myosin light chains required 4-6 h after injection to become incorporated into the A-bands of the adult muscle. Nonspecific proteins, such as fluorescent BSA, showed no association with the myofibrils or the former intercalated discs. When adult cells were maintained in culture for 10 days, they retain the ability to incorporate these contractile proteins into their myofibrils. T-tubules and the sarcoplasmic reticulum could be detected in periodic arrays in the freshly isolated cells using the membrane dye WW781 and DiOC6[3], respectively. In conclusion, the myofibrils in adult, as in embryonic, muscle cells are dynamic structures, permitting isoform transitions without dismantling of the myofibrils.

Actinin↗
PubMed1989

Immunofluorescent, immunogold, and electrophoretic studies for desmin in embryonic hearts of normal and cardiac mutant Mexican axolotls, Ambystoma mexicanum.

Recessive mutant gene c for "cardiac nonfunction" in axolotls results in an absence of normal heart contractions in affected embryos due to a failure of myofibril formation. In the present study, the intermediate filament protein, desmin, is compared in developing normal and mutant hearts by means of two-dimensional gel electrophoresis, immunofluorescent microscopy, and immunoelectron microscopy. Tissues were fixed in periodate-lysine-paraformaldehyde or paraformaldehyde-glutaraldehyde solutions and rapidly frozen or embedded in Lowicryl resin. Frozen sections stained with FITC-conjugated antibodies by an indirect approach revealed that desmin is localized in the I-band regions of adult cardiac myofibrils. In normal embryonic hearts at stage 32 (preheartbeat) desmin is localized as "spots" or amorphous collections in the cells. As development progresses to stage 35, staining for desmin in normal hearts becomes more intense with localization being most pronounced at the cell peripheries. By stage 41 most of the desmin in normal hearts is localized in the I band areas of the organized myofibrils and the staining of amorphous areas is much less prominent. During early development, the distribution of desmin in mutant hearts is similar to normal. However, while most of the desmin in normal organs at stage 41 is associated with myofibrils, the staining remains diffuse in mutants. Two-dimensional gel electrophoresis reveals comparable patterns for desmin from normal and mutant hearts. Immunogold staining shows desmin localization to be between the myofibrils and around the I-band regions in adult cardiac muscle and in stage 41 normal embryonic hearts. Immunogold staining confirms a diffuse distribution of desmin in mutant hearts.

Ambystoma mexicanum↗
PubMed1994

Immunofluorescent studies on titin and myosin in developing hearts of normal and cardiac mutant axolotls.

Homozygous recessive cardiac mutant gene c in the axolotl, Ambystoma mexicanum, results in a failure of the embryonic heart to initiate beating. Previous studies show that mutant axolotl hearts fail to form sarcomeric myofibrils even though hearts from their normal siblings exhibit organized myofibrils beginning at stage 34-35. In the present study, the proteins titin and myosin are studied using normal (+/+) axolotl embryonic hearts at stages 26-35. Additionally, titin is examined in normal (+/c) and cardiac mutant (c/c) embryonic axolotl hearts using immunofluorescent microscopy at stages 35-42. At tailbud stage 26, the ventromedially migrating sheets of precardiac mesoderm appear as two-cell-layers. Myosin shows periodic staining at the cell peripheries of the presumptive heart cells at this stage, whereas titin is not yet detectable by immunofluorescent microscopy. At preheartbeat stages 32-33, a myocardial tube begins to form around the endocardial tube. In some areas, periodic myosin staining is found to be separated from the titin staining; other areas in the heart at this stage show a co-localization of the two proteins. Both titin and myosin begin to incorporate into myofibrils at stage 35, when normal hearts initiate beating. Additionally, areas with amorphous staining for both proteins are observed at this stage. These observations indicate that titin and myosin accumulate independently at very early premyofibril stages; the two proteins then appear to associate closely just before assembly into myofibrils. Staining for titin in freshly frozen and paraffin-embedded tissues of normal embryonic hearts at stages 35, 39, and 41 reveals an increased organization of the protein into sarcomeres as development progresses. The mutant siblings, however, first show titin staining only limited to the peripheries of yolk platelets. Although substantial quantities of titin accumulate in mutant hearts at later stages of development (39 and 41), it does not become organized into myofibrils as in normal cells at these stages.

Aging↗
PubMed1995

The unique amino-terminal peptide of cardiac troponin I regulates myofibrillar activity only when it is phosphorylated.

Protein kinase A (PKA) dependent phosphorylation of C-protein and cardiac troponin I (cTnI) is known to be associated with a reduced sensitivity to Ca2+. We have investigated the relative importance of each of these sites of phosphorylation in this effect by use of extraction/reconstitution experiments and mutagenesis of recombinant cTnI. Conditions developed for extraction of troponin (Tn) complex also resulted in extraction of C-protein. A truncated cTnI (cTnI/NH2) lacking the 32 amino acids in the unique amino terminal extension of cTnI was engineered and expressed. In contrast to native cTnI, cTnI/NH2, which lacks Ser23 and Ser24, was not phosphorylated by PKA either in pure form or after incorporation into the myofilament lattice. The relation between pCa (-log molar free Ca2+ concentration) and MgATPase activity of non-phosphorylated native myofibrils or non-phosphorylated myofibrils reconstituted with cTnI, but lacking C-protein, was the same and could not be distinguished from that of control or PKA-treated myofibrils into which we exchanged cTnI with cTnI/NH2. However, PKA-dependent phosphorylation of either native myofibrils or reconstituted myofibrils containing cTnI but lacking C-protein resulted in an identical and significant rightward shift of pCa50 (half-maximally activating pCa) in the pCa-activity relationship. Our results strongly indicate that phosphorylation of cTnI at Ser residues in the unique amino terminal extension of the molecule is both necessary and sufficient for the decrease in myofilament Ca(2+)-sensitivity associated with PKA-dependent phosphorylation.

Animals↗
PubMed1994

The role of extracellular ions in the pathogenesis of myonecrosis induced by a myotoxin isolated from Broad-Banded copperhead (Agkistrodon contortrix laticinctus) venom.

Pathological changes in murine skeletal muscle cells induced by ACL (Agkistrodon contortrix laticinctus, Broad-Banded Copperhead) myotoxin in vivo were compared to pathological changes induced by an influx of Ca2+ and other ions into cut skeletal muscle cells in vitro in the absence of myotoxin. In vivo, ACL myotoxin induced a rapid myonecrosis characterized by densely clumped myofibrils in the cytoplasm. In vitro, this pathological change was not produced by incubating skeletal muscle cells in Ca2+ concentrations as high as 200 mM, whereas skeletal muscle cells incubated in concentrations of 150 mM and 300 mM NaCl contained densely clumped myofibrils similar in morphology to muscle cells damaged by ACL myotoxin in vivo. Treatments of 300 mM KCl did not produce densely clumped myofibrils in muscle cells. These results suggest that an influx of Na+, possibly through disrupted regions of sarcolemma, may be primarily responsible for the pathological changes, including clumped myofibrils, induced by ACL myotoxin in vivo. However, an influx of extracellular Ca2+ which has been proposed to produce densely clumped myofibrils in muscle cells damaged by other snake venom myotoxins, may not be responsible for this pathological change since extracellular Ca2+ concentrations much higher than physiological levels did not produce this change in skeletal muscle cells in vitro.

Agkistrodon↗
PubMed1983

Quantitative morphologic findings of the myocardium in idiopathic dilated cardiomyopathy.

This study assesses the relation between quantitative morphologic findings and left ventricular contractile function in patients with idiopathic dilated cardiomyopathy. Left ventricular endomyocardial catheter biopsy specimens were obtained from 73 patients during diagnostic heart catheterization. All patients had normal coronary arteriograms but abnormal electrocardiograms. Twenty-six patients had normal left ventricular function (ejection fraction greater than or equal to 55%), whereas 47 patients had contractile dysfunction (ejection fraction less than or equal to 54%). Myocardial fiber diameter, volume fraction of interstitial fibrosis, and intracellular volume fraction of myofibrils were determined by light microscopic morphometry. Results of light microscopic morphometry were confirmed by electron microscopic morphometry in 12 patients. The coefficient of variation (analysis of several biopsies from the same patient) was 6% for determination of fiber diameter, 43% for interstitial fibrosis, and 3% for volume fraction of myofibrils. Fiber diameter (r = -0.32, p less than 0.01) and fibrosis (r = -0.47, p less than 0.001) showed a negative correlation, the volume fraction of myofibrils (r = 0.55, p less than 0.001) and calculated myofibrillar mass per 100 g of myocardium (r = 0.64, p less than 0.001) a positive correlation with the ejection fraction. Thus, (1) sampling error is low for determination of fiber diameter and myofibrils but high for evaluation of fibrosis, and (2) a reduction in the volume fraction of myofibrils and an increase in fibrosis are morphologic correlates of left ventricular dysfunction in patients with idiopathic dilated cardiomyopathy.

Adult↗
PubMed1999

Thick filament assembly occurs after the formation of a cytoskeletal scaffold.

The development of myofibrils involves the formation of contractile filaments and their assembly into the strikingly regular structure of the sarcomere. We analysed this assembly process in cultured human skeletal muscle cells and in rat neonatal cardiomyocytes by immunofluorescence microscopy using antibodies directed against cytoskeletal and contractile proteins. In particular, the question in which temporal order the respective proteins are integrated into developing sarcomeres was addressed. Although sarcomeric myosin heavy chain is expressed as one of the first myofibrillar proteins, its characteristic A band arrangement is reached at a very late stage. In contrast, titin, then myomesin and finally C-protein (MyBP-C) gradually form a regularly arranged scaffold on stress fiber-like structures (SFLS), on non-striated myofibrils (NSMF) and on nascent striated myofibrils (naSMF). Immediately subsequent to the completion of sarcomere cytoskeleton formation, the labeling pattern of myosin changes from the continuous staining of SFLS to the periodic staining characteristic for mature myofibrils. This series of events can be seen most clearly in the skeletal muscle cell cultures and--probably due to a faster developmental progression less well in cardiomyocytes. We therefore conclude that the correct assembly of a cytoskeletal scaffold is a prerequisite for correct thick filament assembly and for the integration of the contractile apparatus into the myofibril.

Actin Cytoskeleton↗
PubMed2001

Ultrastructure of the contractile apparatus in cardiomyocytes during regenerative and plastic insufficiency of the myocardium.

Lytic changes in cardiomyocyte myofibrils constituting the morphological basis of contractile insufficiency were found in Wistar rats with regenerative and plastic myocardial insufficiency 3 h after daunomycin administration. Myofibrils became less dense, empty spaces appeared in many sarcomeres, sometimes total lysis of myofilaments within the sarcomere was noted. These changes were most pronounced in the perinuclear zone. Intracellular regeneration of cardiomyocytes was characterized by disorientation of newly formed myofibrils in relation to the long axis of muscle fibers and preserved myofibrils. Progressive inhibition of protein synthesis, lysis of myofibrils, and focal degradation of the sarcoplasm caused apoptotic death of some cardiomyocytes.

Animals↗
PubMed1993

Kinetics of hydrolysis of cardiac S1 heavy chain isoforms and identification of light chain and actin binding sites.

OBJECTIVE: A comparative study of the kinetics of proteolysis of myosin S1 heavy chain was performed using dog ventricular and atrial S1 to distinguish between protease sensitive sites in S1 isotypes and to determine the binding sites on S1 heavy chain for LC1, LC2, and actin. METHODS: Digestion of S1 as a function of actin was performed at 25 degrees C at a trypsin to S1 ratio (w/w) of 1:1500. Myofibrils were digested (trypsin/myofibrils w/w ratio = 1:300) in the presence of ATP, ADP, and under rigor conditions. Light chain and actin binding sites were identified by the gel overlay method. RESULTS: Ventricular and atrial S1 were proteolysed at 0.13 min-1 and 0.04 min-1 respectively. Actin significantly reduced the cleavage rate of both S1 heavy chains by blocking hydrolysis at the 50/20 kD site. Myofibrillar myosin heavy chains from ventricles were also hydrolysed faster than those of the atria in the presence of 4 mM MgATP. The calculated rates were 0.42-0.50 and 0.17-0.19 min-1 for ventricular and atrial myofibrils respectively. MgADP 2 mM or absence of nucleotides reduced the cleavage rates to 0.04-0.07 (ventricular myofibrils) and 0.02-0.03 min-1 (atrial myofibrils) respectively. Gel overlay experiments showed that 125I labelled LC1 and LC2 bound to the 20 kD fragment and actin mainly to the 50 and 20 kD peptides. CONCLUSIONS: The 50/20 kD site in either ventricular or atrial S1 was blocked when actin was present, while proteolysis at the 25/50 site proceeded regardless of the presence of actin. However, the 25/50 site was less accessible to trypsin in the alpha myosin heavy chain, since the roughly threefold reduction in the rates of hydrolysis of atrial S1 heavy chain was also maintained in the myofibrils in rigor or in the presence of ADP. Although actin made contact with the 70 kD and the 25 kD fragments, the 50 kD and 20 kD fragments appeared to be the central "anchor" for binding of both light chains and actin.

Actins↗
PubMed1987

Calcium-induced weakening of Z-disks in postmortem skeletal muscle.

The reaction mechanism of calcium ion in the postmortem weakening of Z-disks was studied in myofibrils prepared from fresh or stored muscles. The alpha-actinin content in myofibrils remained almost unchanged within 10 days postmortem, showing very limited proteolysis of myofibrils during postmortem storage of muscles at 10 degrees C. The postmortem weakening of Z-disks was markedly dependent on muscle pH, showing a minimum at pH 6.5. These results agree well with the calcium-induced weakening of Z-disks of freshly isolated myofibrils, indicating that no protease participates in the postmortem weakening of Z-disks. Z-Disks of myofibrils prepared from stored muscles split into halves after treatment with 0.1 N NaOH for 5 min. The identical splitting of Z-disks was induced by a calcium ion concentration of 10(-4)M, which is of the same order of magnitude as that in the sarcoplasm in postmortem muscle. We therefore conclude that the postmortem weakening of Z-disks is non-enzymatically induced by the raised sarcoplasmic calcium ion concentration of 10(-4) M. Calcium ions probably solubilize the amorphous cementing material of Z-disks, leaving unchanged the two sets of Z filaments composed of alpha-actinin.

Actinin↗
PubMed2001

Early morphological changes in the rat soleus muscle induced by tenotomy and denervation.

Early morphological changes of the rat soleus muscle induced by tenotomy were examined by scanning and thin-section electron microscopy. The potassium hydroxide (KOH) and collagenase treatment was successfully used to remove extracellular materials and to examine the surface of muscle fibres with a scanning electron microscope. Morphological changes in the fibre surface appeared as early as 12 h after tenotomy, showing wrinkling of the sarcolemma in localized areas. At 24 h post-operative, transverse folds and grooves were conspicuous along the entire length of muscle fibres. Tenotomized muscles which were denervated simultaneously or within 24 h of tenotomy did not show any appreciable changes in the fibre surface. Thin-section electron microscopy revealed that the earliest change inside muscle fibres was the occurrence of focal or segmental areas of an irregular alignment of myofibrils representing myofibril disorganization with occasional disintegrated Z lines at 24 h after tenotomy. Segmental myofibril breakdown was occasionally found to extend obliquely from the fibre periphery to the central area. Such myofibril disorganization became more conspicuous along muscle fibres, especially in the central area, at 2 days after tenotomy, showing the loss of thick filaments within myofibrils and the disintegration of Z lines. Such myofibrillar disorganization can be correlated with the morphological changes in the fibre surface in view of the clinical implication.

Animals↗
PubMed1987

Anesthetic depression of myocardial contractility: a review of possible mechanisms.

The bulk of experimental evidence indicates that anesthetics do not produce their negative inotropic effect via an inhibitory action on mitochondrial electron transport. Anesthetics decrease energy need, rather than energy production. Anesthetics also decrease the rate of sequestration of Ca2+ by mitochondria, but, again, this appears not to be an important cause of reduced myocardial contractility. The role played by direct anesthetic depression of the myofibrils in reducing contractility is uncertain. Most experimental evidence now available suggests that significant myofibrillar depression, measured in terms of inhibition of actomyosin ATPase activity or inhibition of force production, occurs only at anesthetic concentrations which are high compared to concentrations employed clinically. This would seem to indicate that the myofibrils are not an important target for anesthetics in regard to the production of depressed myocardial contractility. However, the experimental act of removing myofibrils from their intracellular environment, or of removing the sarcolemma or making it hyperpermeable, appears to prevent some regulatory myofibrillar phosphorylation reactions from taking place. As stated by Winegrad, "certain forms of regulation of the cardiac myofibril are fragile and can be seen only when cellular constituents and structure are maintained." It is possible that this type of regulation is susceptible to inhibition by anesthetics. Methods for preserving this regulation are available, and will need to be employed before a depressant action of anesthetics on the myofibril can be definitely dismissed as a significant cause of the inhibition of cardiac contractility. A single study, of intracellular Ca2+ levels in the intact cell (where myofibrillar regulation was presumably preserved), has indicated that halothane may decrease myofilament Ca2+ sensitivity. However, for reasons stated above, this study cannot be taken as unequivocal proof of such an action. Despite the fact that the normal action potential is little affected by anesthetics, the sarcolemma appears to play a pivotal role in the production of anesthetic-induced contractile depression. Significant depression of the rate of upstroke of the slow (Ca2+-mediated) action potential by clinical concentrations of both inhalation and intravenous anesthetics has been demonstrated by several workers. This has been interpreted to mean that anesthetics inhibit the influx of Ca2+ through the slow channel, and such has been confirmed (to date, for halothane and thiamylal) by direct measurement of the slow inward Ca2+ current using a voltage clamp technique.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthetics↗
PubMed1996

Differential assembly of cytoskeletal and sarcomeric actins in developing skeletal muscle cells in vitro.

Monoclonal antibodies (McAb) to actin were prepared to analyze the assembly of actin isoforms in developing muscle cells in vitro. One of the antibodies (SkA-06) was specific for alpha-sarcomeric actin isoforms in skeletal and cardiac muscles, while the others recognized cytoskeletal (beta, gamma) actin isoforms in smooth muscle and non-muscle tissues as well as the sarcomeric (alpha) actins. Using SkA-06 and a polyclonal antibody (PcAb) specific for cytoskeletal actins, the subcellular localization of the actin isoforms was examined by immunocytochemical methods. While in developing young myotubes, cytoskeletal and sarcomeric actins were co-localized in nascent myofibrils or stress-fiber-like structures, sarcomeric actins predominated in striated myofibrils in more developed myotubes. When FITC-labeled cytoskeletal and sarcomeric actins were introduced into young myotubes by a microinjection method, the latter became detectable in striated structures sooner than the former but they were finally incorporated into striated myofibrils. These results suggest that alpha-actin(s) as well as beta- and gamma-actins can be incorporated into myofibrils, but alpha-actin(s) is assembled preferentially into myofibrils in developing muscle cells.

Actins↗
PubMed2000

Peculiarities of intracellular regeneration of cardiomyocytes during plastic myocardial insufficiency.

We performed morphological assay of the myocardium in Wistar rats with anthracycline cardiomyopathy and SHR rats with genetically determined arterial hypertension causing hypertrophic cardiomyopathy. Both disorders were accompanied by a decrease in protein synthesis and development of plastic cardiomyocyte insufficiency. Electron microscopy revealed peculiarities of intracellular regeneration of cardiomyocytes. We observed disorientation of newly formed myofibrils lying between preserved myofibrils. These myofibrils were positioned perpendicular or at angle to the long axis of muscle fibers, or extended from the Z line (in a fan-like manner) crossing each other. Regeneration disturbances also included excessive elongation of myofibrils. These abnormalities of myofibril regeneration were related to changes in transcription and translation in cardiomyocytes, due to DNA damages caused by cardiotoxic doses of rubomycin.

Animals↗
PubMed1979

[State of the myocardial contractile structures in different areas of the heart in myocardial infarct complicated by cardiogenic shock and congestive circulatory failure].

In myocardial infarction, destructive changes develop in the contractile elements of the heart muscle in the peri-infarction zones. The degree and extent of the myofibril involvement depend on the clinical course of myocardial infarction, the drug therapy applied, and the distance from the focus of necrosis. The most marked destructive changes were in the prenecrotic zone of the myocardium in individuals with cardiogenic shock or severe congestive cardiac failure with clinical symptoms of glycoside intoxication. Gross focal contractures of myofibrils were found, which subsequently underwent fibrinoid necrosis. There were also areas of myofibril relaxation with dissociation of the actin fibers and destruction of the z-disks. The destructive changes in the myofibrils are due to a great extent to the effect of catecholamines, myocardial hypoxia, and glycoside intoxication. The disturbed orientation of the myofibril bundles in patients with recurrent myocardial infarction may play an essential role in the decrease of the myocardial contractile function and the development of extrasystolic arrhythmias.

Aged↗
PubMed1996

Local and regional variations in myofibrillar patterns in looping rat hearts.

BACKGROUND: In chickens, cytodifferentiation, right side dominance in myofibril development, and variations in myofibrillar patterns in different areas and layers of the myocardial wall exist which have been implicated in the process of heart looping. Little comparable information is available for developing myofibrillar patterns in the early development of mammalian hearts. METHODS: We have used transmission electron microscopy (TEM), confocal scanning laser microscopy (CSLM), and 3-D reconstruction techniques also present in the looping hearts of embryonic day (ED) 9.5 to 11.5 rat hearts. RESULTS: Local and regional variations and right side dominance in myofibrillar patterns were shown during looping in 9.5 through 11.5 days of development in embryonic rat heart. At 9.5 days of development, myofibrils near the lumen of the myocardial wall were primarily in circumferential bands while near the pericardial surface they were primarily in longitudinal bands. In older embryos, regional variations in myofibrillar organization was found in areas associated with the cardiac cushions, trabeculae, and myocardial wall of the developing heart chambers. Based on sarcomeric structure, myofibrils in the ventricle and outflow tract were more advanced than those found in the atrial wall. CONCLUSIONS: The local and regional patterns of myofibrils in looping rat hearts are similar to those which have been found in developing chicken hearts. This study and others indicate cytodifferentiation and development of the contractile apparatus has a crucial role in the process of heart looping.

Animals↗
PubMed1999

Quantitative electron microscopic study of the hypoxic fetal sheep heart.

In order to determine the effects of chronic, high-altitude hypoxia on the ovine fetal heart, we exposed pregnant ewes to 3,820 m beginning at 30 days gestation. We previously showed that following approximately 110 days of hypoxia the fetal heart showed significant reduction in cardiac output (76% of control) and contractility, and elevated levels of citrate synthase and lactate dehydrogenase. To investigate ultrastructural influences on these observed physiologic changes at altitude, we hypothesized that the volume densities of myofibrils and mitochondria, and glycogen content would be reduced in the ovine fetal heart and that this may contribute to contraction and cardiac output deficits in hypoxia. Mitochondria and myofibril volume density were determined by standard point-counting techniques and glycogen content was determined by biochemical analysis. The glycogen content from the hypoxic right ventricle (4.8 +/- 0.3%) was significantly lower than in control right ventricle (6.8 +/- 0.5%) and both left ventricles (hypoxia, 7.2 +/- 0.5; control, 7.8 +/- 0. 4%). Total mitochondrial volume density was also significantly reduced following hypoxia (15.5 +/- 0.7%) compared to controls (16.9 +/- 0.4%). As is common in the ovine fetal heart, the myofibril volume density of the right ventricle from both groups was significantly higher than the left ventricle (RV, 58.6 +/- 1.6; LV 54.3 +/- 0.9%). However, it was not different between control and high altitude. In support of our hypothesis, we may speculate that deficits in the quantity of myocyte glycogen and mitochondria contribute to the observed reduction in cardiac output and contractility, despite the upregulation of citrate synthase and lactate dehydrogenase. In contrast, myofibril volume density was unchanged.

Altitude↗