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Elasticity of the human red cell membrane skeleton. Effects of temperature and denaturants.

The molecular basis for the elasticity of the human erythrocyte membrane was explored. Skeletons were released from ghosts in Triton X-100 and their dimensions followed by dark-field microscopy and packed volume. The rest size of skeletons was assumed to reflect the balance point between expansion (deformation) driven by electrostatic repulsions among the excess of fixed negative charges on the proteins and contraction (recovery) driven by their elasticity. The size of skeletons decreased with increasing temperature. This finding suggests that entropy drives elasticity. The requisite entropy change could be associated with either the configurational freedom of flexible protein chains or with the solvation of side chains exposed during protein dissociation (hydrophobic effects). To distinguish between these two alternatives, we tested the impact of two weak denaturants, 10% ethanol and 20 nM lithium 3,5-diiodosalicylate. Both agents reversibly promoted the expansion of skeletons, presumably by reducing their elasticity. Since the conformation of random coils and globular proteins should not be significantly altered by these mild treatments, this finding strongly suggests a role for weak interdomain and/or interprotein associations. We conclude that the elasticity of the red cell membrane skeleton may not derive from the configurational entropy of flexible coils. Rather, the elastic energy may arise from reversible dissociations of weak but specific intramolecular and/or intermolecular contacts, presumably within deformed spectrin filaments.

Detergents↗

Is the surface area of the red cell membrane skeleton locally conserved?

The incompressibility of the lipid bilayer keeps the total surface area of the red cell membrane constant. Local conservation of membrane surface area requires that each surface element of the membrane skeleton keeps its area when its aspect ratio is changed. A change in area would require a flow of lipids past the intrinsic proteins to which the skeleton is anchored. in fast red cell deformations, there is no time for such a flow. Consequently, the bilayer provides for local area conservation. In quasistatic deformations, the extent of local change in surface area is the smaller the larger the isotropic modulus of the skeleton in relation to the shear modulus. Estimates indicate: (a) the velocity of relative flow between lipid and intrinsic proteins is proportional to the gradient in normal tension within the skeleton and inversely proportional to the viscosity of the bilayer; (b) lateral diffusion of lipids is much slower than this flow; (c) membrane tanktreading at frequencies prevailing in vivo as well as the release of a membrane tongue from a micropipette are fast deformations; and (d) the slow phase in micropipette aspiration may be dominated by a local change in skeleton surface.

Biomechanical Phenomena↗

Remodeling the shape of the skeleton in the intact red cell.

The role of the membrane skeleton in determining the shape of the human red cell was probed by weakening it in situ with urea, a membrane-permeable perturbant of spectrin. Urea by itself did not alter the biconcave disk shape of the red cell; however, above threshold conditions (1.5 M, 37 degrees C, 10 min), it caused an 18% reduction in the membrane elastic shear modulus. It also potentiated the spiculation of cells by lysophosphatidylcholine. These findings suggest that the contour of the resting cell is not normally dependent on the elasticity of or tension in the membrane skeleton. Rather, the elasticity of the skeleton stabilizes membranes against deformation. Urea treatment also caused the projections induced both by micropipette aspiration and by lysophosphatidylcholine to become irreversible. Furthermore, urea converted the axisymmetric conical spicules induced by lysophosphatidylcholine into irregular, curved and knobby spicules; i.e., echinocytosis became acanthocytosis. Unlike controls, the ghosts and membrane skeletons obtained from urea-generated acanthocytes were imprinted with spicules. These data suggest that perturbing interprotein associations with urea in situ allowed the skeleton to evolve plastically to accommodate the contours imposed upon it by the overlying membrane.

Biomechanical Phenomena↗

Effect of calcium stress on the skeleton mass of intact and ovariectomized rats.

Female rats were ovariectomized (Ovx) or sham-operated (control) at 18 weeks and the entire skeleton obtained at 24 weeks (baseline) or after an additional 31 day (28 week) interval on a normal (1.0%) or deficient (0.02%) calcium diet. Ovx rats showed a 42% increase in whole body bone resorption (3H-tetracycline loss) in the absence of calcium stress (1.0% calcium diet) and a 70% increase in resorption with morphological evidence of dramatic loss of cancellous bone mass when placed on calcium-deficient (0.02%) diets. Ovx rats kept on the 1.0% calcium diet showed a significant increase in both their body weight (30.2%) and total bone mass (11.6%) compared to baseline sham-operated controls. However, the total skeleton mass of these animals was significantly reduced (-20%) from that predicted by calculations based on body weight. Maintaining animals on calcium-deficient diets had no significant effect on the total skeleton mass of either control or Ovx rats in comparison with age-matched controls on 1.0% diets. It was further determined that an increase in bone mass between 24 and 28 weeks in rats receiving 1.0% dietary calcium occurred in both the axial and appendicular skeleton and was proportionately similar between control and Ovx groups. However, in animals subjected to dietary calcium stress during this interval, the decreased skeletal growth noted was confined primarily to the axial skeleton. The data indicate that ovariectomy or ovariectomy plus calcium stress does not result in loss of total bone mass during the interval of dramatically increased resorption and rapid loss of cancellous bone. The results suggest that the deterioration in individual bone structural and mechanical integrity due to ovariectomy or dietary calcium deficiency may not be attributed to overt loss in total bone mass but may involve a redistribution of bone mass.

Animals↗

Effects of wavelength and intensity of light in initiation of body fattening and gonadal growth in a migratory bunting under complete and skeleton photoperiods.

A series of experiments investigated the effects of wavelength and intensity of light in initiation of body fattening (gain in body weight) and gonadal growth in migratory blackheaded bunting under complete and skeleton photoperiods. Using fluorescent light at an intensity approximately 700 lx, the first experiment compared the inductiveness of a complete (13 h continuous light coupled with 11 h darkness; 13L:11D) and a skeleton (two light pulses of 6 and 1 h at 6 h apart; 6L:6D:1L:11D) photoperiod. Observations at the beginning and after 3, 8, 10, and 13 weeks of the treatment indicated that both photoperiods were fully inductive but that birds under 13L photoperiod fattened and lost body weight significantly earlier than birds under skeleton photoperiod. In the second experiment, bunting were subjected to 13L:11D (L = 100 lx; D = 0 lx) of white, green (528 nm), and red (654 nm) light for a period of 5 weeks. Birds gained weight and testes grew in all groups except for an inconsistent fattening response in the white light group. The third experiment tested if the inductive effects of 1-h light pulse in a skeleton photoperiod were intensity dependent. Groups of bunting were exposed to 6L:6D:1L:11D (intensity of 1-h white light pulse = 2, 10, 50, or 100 lux) and examined at the beginning and after 3 and 8 weeks of the treatment. Photoinduction occurred at a slower rate and only at 50- and 100-lx intensities. The fourth experiment was similar to the third in design but it employed 1-h light pulse of two different wavelengths (green = 528 nm, and red = 654 nm) at 50- and 100-lx intensities. Birds fattened and testes grew only under red light. The last experiment varied the wavelength and intensity of the first (6 h) light pulse of the skeleton photoperiod (6L:6D:1L:11D): 6-h entraining light pulse of white, green (528 nm), or red (654 nm) colour at 10- or 50-lx intensity was used with 1-h inducing light pulse of white light at approximately 700-lx intensity. Testes grew in all groups but significant fattening occurred only in birds entrained to 50-lx light intensity. These results indicate i) the dissociation of body weight and gonadal responses, in the sense that the timing of photostimulation and/or magnitude of photoperiod-induced body weight and testicular responses differed under various photoperiodic manipulations, and ii) the circadian processes involved in photoperiod-induced responses have differential spectral and intensity sensitivity.

Animals↗

Clinical disorders of the red cell membrane skeleton.

The lipid bilayer of the adult red cell is supported on its inner surface by a complex arrangement of proteins known as the membrane skeleton. This filamentous network, a major component of which is a multifunctional protein called spectrin, has an essential role in determining the shape, structural integrity, and deformability of the red cell. A significant achievement of modern biochemistry and hematology has been the elucidation of the organization of the components of the membrane skeleton and their relationship to other membrane proteins and lipids. This article reviews current concepts of membrane skeleton structure and function and emphasizes recent advances which have been made in characterizing and classifying molecular defects of the skeleton which manifest clinically with changes in the shape and stability of the red cell. The pathobiology of hereditary skeletal defects associated with hereditary spherocytosis (HS), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP) are comprehensively discussed. Secondary defects of the membrane skeleton occurring in glucose-6-phosphate dehydrogenase deficiency and sickle cell anemia are also briefly considered.

Actins↗

Interaction of IgG immunoglobulins with the guinea pig peritoneal macrophage Fc gamma receptors. Effect on the association of the receptors with the membrane skeleton and the cytoskeleton.

Binding of ligands to cell surface receptors may induce an interaction of the receptors with the cytoskeleton and/or membrane skeleton and decrease the solubility of the receptors in nonionic detergents. Cytochalasins, reagents affecting the structure of microfilaments, inhibit some cell functions induced by cross-linking of the receptors with ligands. Information concerning the function of the cytoskeleton in insolubilization of Fc gamma receptors (Fc gamma R) and in Fc gamma R-mediated signal transmission is rather limited. The aim of this work was to investigate the effect of binding of homologous (guinea pig IgG1 and IgG2) and heterologous (rabbit IgG) immunoglobulins to guinea pig peritoneal macrophages on association of the macrophage Fc gamma receptors with the membrane skeleton and cytoskeleton. Cross-linking the macrophage Fc gamma receptors with immunoglobulin ligands induced insolubilization of the receptors in nonionic detergents suggesting association of the receptors with the membrane skeleton and the cytoskeleton. The ligands showed differential effects depending on a subclass and origin of the IgG used. The process of association of the Fc gamma receptors with the skeletons was fast and did not depend on temperature. Treatment of insoluble complexes with cytochalasin D, DNAse I or colchicine showed that actin microfilaments and microtubules play a role, at least partially, in insolubilization of the cross-linked macrophage Fc gamma receptors. Inhibition of insolubilization of the macrophage Fc gamma receptors by genistein indicated that tyrosine kinases are involved in the process of insolubilization. The association with the skeletons might be a part of the process of transduction of a signal which depended on the subclass and origin of IgG used and on the type of the Fc gamma receptor.

Actin Cytoskeleton↗

Experimental validation of the tetrahedral skeleton model pressure drop correlation for silica monoliths and the influence of column heterogeneity.

This paper describes the use of computational fluid dynamics for the calculation of the flow resistance through computer-generated models resembling silica monoliths. This study was undertaken to determine the effect of skeleton heterogeneity on the flow resistance and, more precisely, to test the hypothesis that increased skeleton heterogeneity decreases the flow resistance. To evaluate the proposed model, 24 real silica monoliths have been prepared using the same method, covering a wide range of skeleton sizes (2.2 microm < d(s) < 8 microm) and porosities (0.47 < epsilon < 0.66). The permeability of these monoliths was determined by pressure drop measurements, and structural information was obtained by image analysis of laser scanning confocal microscopy-generated 3D images of the skeleton structure. The results indicate that the presence of preferential flow paths due to an increased heterogeneity of the flow through pore space reduces the flow resistance of monolithic media. It is also shown that the pore size is hence a much better suited scaling dimension than the skeleton size to reduce the permeability of monolithic columns.

Journal Article↗

Simple method for identification of skeletons of aporphine alkaloids from 13C NMR data using artificial neural networks.

This paper describes the use of artificial neural networks as a theoretical tool in the structural determination of alkaloids from (13)C NMR chemical shift data, aiming to identify skeletal types of those compounds. For that, 162 aporphine alkaloids belonging to 12 different skeletons were codified with their respective (13)C NMR chemical shifts. Each skeleton pertaining to aporphine alkaloid type was used as output, and the (13)C NMR chemical shifts were used as input data of the net. Analyzing the obtained results, one can then affirm the skeleton to which each one of these compounds belongs with high degree of confidence (over 97%). The relation between the correlation coefficient and the number of epochs and the architecture of net (3-layer MLP or 4-layer MLP) were analyzed, too. The analysis showed that the results predicted by the 3-layer MLP networks trained with a number of the epochs higher than 900 epochs are the best ones. The artificial neural nets were shown to be a simple and efficient tool to solve structural elucidation problems making use of (13)C NMR chemical shift data, even when a similarity between the searched skeletons occurs, offering fast and accurate results to identification of skeletons of organic compounds.

Alkaloids↗

Bones in the heart skeleton of the otter (Lutra lutra).

In most mammalian species the cardiac skeleton is composed of coarse collagen fibres, fibrocartilage, and pieces of hyaline cartilage. Bone, the os cordis, is a regular constituent of the ruminant heart. The cardiac skeleton of the otter (Lutra lutra) has not previously been described. The skeleton in 30 otter hearts was studied by x-ray analysis and light microscopy. Serial sections were cut parallel to the atrioventricular plane and histochemical staining methods were performed to identify connective tissue fibres, glycosaminoglycans, mineral deposits, and bone. Age and sex of the animals under investigation were considered. The otter heart skeleton was composed of coarse collagen fibres with intercalated pieces of fibrous and/or hyaline cartilage, calcified cartilage, and lamellar bone with red or white marrow. Pieces of hyaline cartilage were not clearly defined: a perichondrial layer was missing and coarse connective tissue continuously transformed into fibrous and hyaline cartilage. In both sexes the amount of cartilage and bone were found to increase with age. Our results establish the presence of bony material in the heart skeleton of the otter, a small mammalian species. This finding indicates that differentiation of bone is not exclusively related to the size of the organ. Increasing amounts of calcified cartilage and bone correlated with increasing age.

Aging↗

Seasonal changes in the lower jaw skeleton in male Atlantic salmon (Salmo salar L.): remodelling and regression of the kype after spawning.

The return of Atlantic salmon (Salmon salar) to their home river for spawning coincides with drastic skeletal alterations in both sexes. Most prominent is the development of a kype (hook) at the tip of the lower jaw in males. Salmon that survive spawning have to cope with the kype throughout their life, unless it disappears after spawning, as was suggested in the early literature. To understand the fate of the kype skeleton, we compared morphological and histological features of kypes from pre-spawned mature anadromous males (grilse) with post-spawned males (kelts). The kype of male grilse is supported by fast-growing skeletal needles that differ from regular dentary bone. In kelts, growth of the kype skeleton has stopped and skeletal needles are resorbed apically by osteoclasts. Simultaneously, and despite the critical physiological condition of the animals, proximal parts of the kype skeleton are remodelled and converted into regular dentary bone. Apical resorption of the skeleton explains reports of a decrease of the kype in kelts. The conversion of basal kype skeleton into regular dentary bone contributes to the elongation of the dentary and probably also to the development of a larger kype in repetitive spawning males.

Animals↗

Early vasoreactive profile of skeletonized versus pedicled internal thoracic artery grafts.

BACKGROUND: No data are available on the early vasoreactive profile of skeletonized internal thoracic artery grafts. METHODS: Fifteen patients undergoing primary isolated coronary artery bypass grafting were randomly assigned to receive a skeletonized or pedicled internal thoracic artery graft. On the second postoperative day all patients were subjected to follow-up angiography and endovascular infusion of serotonin, acetylcholine, and isosorbide dinitrate. RESULTS: Internal thoracic artery grafts were widely patent in all cases. Mean diameters of the internal thoracic artery were 1.95 +/- 0.17 mm in the pedicled group and 2.26 +/- 0.40 mm in the skeletonized group. After serotonin challenge, mean internal thoracic artery diameters were reduced to 1.44 +/- 0.34 mm and 1.64 +/- 0.14 mm, respectively; acetylcholine challenge lead to a moderate degree of vasoconstriction (1.55 +/- 0.59 mm in the pedicled group and 1.84 +/- 0.15 mm in the skeletonized group). No statistically significant difference was evident between the two groups at any step. CONCLUSION: Skeletonization does not affect the early vasoreactive profile of internal thoracic artery grafts used for surgical myocardial revascularization.

Acetylcholine↗

Regulation of von Willebrand factor binding to the platelet glycoprotein Ib-IX by a membrane skeleton-dependent inside-out signal.

The platelet receptor for von Willebrand factor (vWF), glycoprotein Ib-IX (GPIb-IX), mediates initial platelet adhesion and activation. We show here that the receptor function of GPIb-IX is regulated intracellularly via its link to the filamin-associated membrane skeleton. Deletion of the filamin binding site in GPIb(alpha) markedly enhances ristocetin- (or botrocetin)-induced vWF binding and allows GPIb-IX-expressing cells to adhere to immobilized vWF under both static and flow conditions. Cytochalasin D (CD) that depolymerizes actin also enhances vWF binding to wild type GPIb-IX. Thus, vWF binding to GPIb-IX is negatively regulated by the filamin-associated membrane skeleton. In contrast to native vWF, binding of the isolated recombinant vWF A1 domain to wild type and filamin binding-deficient mutants of GPIb-IX is comparable, suggesting that the membrane skeleton-associated GPIb-IX is in a state that prevents access to the A1 domain in macromolecular vWF. In platelets, there is a balance of membrane skeleton-associated and free forms of GPIb-IX. Treatment of platelets with CD increases the free form and enhances vWF binding. CD also reverses the inhibitory effects of prostaglandin E1 on vWF binding to GPIb-IX. Thus, GPIb-IX-dependent platelet adhesion is doubly controlled by vWF conformation and a membrane skeleton-dependent inside-out signal.

Animals↗

Visualization of the hexagonal lattice in the erythrocyte membrane skeleton.

The isolated membrane skeleton of human erythrocytes was studied by high resolution negative staining electron microscopy. When the skeletal meshwork is spread onto a thin carbon film, clear images of a primarily hexagonal lattice of junctional F-actin complexes crosslinked by spectrin filaments are obtained. The regularly ordered network extends over the entire membrane skeleton. Some of the junctional complexes are arranged in the form of pentagons and septagons, approximately 3 and 8%, respectively. At least five forms of spectrin crosslinks are detected in the spread skeleton including a single spectrin tetramer linking two junctional complexes, three-armed Y-shaped spectrin molecules linking three junctional complexes, three-armed spectrin molecules connecting two junctional complexes with two arms bound to one complex and the third arm bound to the adjacent complex, double spectrin filaments linking two junctional complexes, and four-armed spectrin molecules linking two junctional complexes. Of these, the crosslinks of single spectrin tetramers and three-armed molecules are the most abundant and represent 84 and 11% of the total crosslinks, respectively. These observations are compatible with the presence of spectrin tetramers and oligomers in the erythrocyte membrane skeleton. Globular structures (9-12 nm in diameter) are attached to the majority of the spectrin tetramers or higher order oligomer-like molecules, approximately 80 nm from the distal ends of the spectrin tetramers. These globular structures are ankyrinor ankyrin/band 3-containing complexes, since they are absent when ankyrin and residual band 3 are extracted from the skeleton under hypertonic conditions.

Actins↗

Role of the membrane skeleton in preventing the shedding of procoagulant-rich microvesicles from the platelet plasma membrane.

The platelet plasma membrane is lined by a membrane skeleton that appears to contain short actin filaments cross-linked by actin-binding protein. Actin-binding protein is in turn associated with specific plasma membrane glycoproteins. The aim of this study was to determine whether the membrane skeleton regulates properties of the plasma membrane. Platelets were incubated with agents that disrupted the association of the membrane skeleton with membrane glycoproteins. The consequences of this change on plasma membrane properties were examined. The agents that were used were ionophore A23187 and dibucaine. Both agents activated calpain (the Ca2(+)-dependent protease), resulting in the hydrolysis of actin-binding protein and decreased association of actin with membrane glycoproteins. Disruption of actin-membrane interactions was accompanied by the shedding of procoagulant-rich microvesicles from the plasma membrane. The shedding of microvesicles correlated with the hydrolysis of actin-binding protein and the disruption of actin-membrane interactions. When the calpain-induced disruption of actin-membrane interactions was inhibited, the shedding of microvesicles was inhibited. These data are consistent with the hypothesis that association of the membrane skeleton with the plasma membrane maintains the integrity of the plasma membrane, preventing the shedding of procoagulant-rich microvesicles from the membrane of unstimulated platelets. They raise the possibility that the procoagulant-rich microvesicles that are released under a variety of physiological and pathological conditions may result from the dissociation of the platelet membrane skeleton from its membrane attachment sites.

Actins↗

The cytoskeleton of the resting human blood platelet: structure of the membrane skeleton and its attachment to actin filaments.

We used high-resolution EM and immunocytochemistry in combination with different specimen preparation techniques to resolve the ultrastructure of the resting platelet cytoskeleton. The periphery of the cytoskeleton, an electron-dense subplasmalemmal region in thin section electron micrographs, is a tightly woven planar sheet composed of a spectrin-rich network whose interstices contain GPIb/IX-actin-binding protein (ABP) complexes. This membrane skeleton connects to a system of curved actin filaments (F-actin) that emanate from a central oval core of F-actin cross-linked by ABP. The predominant interaction of the radial actin filaments with the membrane skeleton is along their sides, and the strongest connection between the membrane skeleton and F-actin is via ABP-GPIb ligands, although there is evidence for spectrin attaching to the ends of the radial actin filaments as well. Since a mechanical separation of the F-actin cores and radial F-actin-GPIb-ABP complexes from the underlying spectrin-rich skeleton leads to the latter's expansion, it follows that the spectrin-based skeleton of the resting cell may be held in a compressed form by interdigitating GPIb/IX complexes which are immobilized by radial F-actin-ABP anchors.

Actins↗

Association of the crosslinked IgE receptor with the membrane skeleton is independent of the known signaling mechanisms in rat basophilic leukemia cells.

Crosslinking of the IgE receptor on the surface of rat basophilic leukemia (RBL) cells by multivalent antigen induces an association of these receptors with the detergent-insoluble membrane skeleton. Detergent insolubility of the receptor can also be induced on purified plasma membranes isolated from RBL cells by the use of either IgE oligomers or IgE monomers plus multivalent antigen. The critical event in initiating this interaction between the receptor and the membrane skeleton is cross-linking of the receptor. This association is rapid, and, when triggered by multivalent antigen, it is quickly reversed by the addition of excess monovalent antigen. The fact that this association occurs with the use of purified plasma membranes indicates that all of the components necessary for this interaction are present in the plasma membrane and that intracellular components are not required. Although crosslinking of the receptor activates phospholipase C and phospholipase A2 leading to the generation of several second messengers, none of these signaling mechanisms appears to be involved in IgE receptor interaction with the membrane skeleton. This interaction cannot be induced by phorbol 12-myristate 13-acetate (PMA), ionomycin, or a combination of these two reagents, although this will result in degranulation. Furthermore, receptor detergent insolubility is temperature independent when triggered by multivalent antigen, thus indicating that enzyme-catalyzed reactions are not important. This was verified by the fact that a variety of inhibitors that block phosphatidylinositol metabolism, arachidonic acid metabolism, Ca2+ influx, and protein kinase C (PKC) activation had no effect on antigen-induced association of the receptor with the membrane skeleton. These results indicate that the signaling mechanisms leading to the degranulation response are not involved in the association of the crosslinked receptor with the membrane skeleton.

Animals↗

Sternal wound infections in patients after coronary artery bypass grafting using bilateral skeletonized internal mammary arteries.

OBJECTIVES: This study evaluated the risks of sternal wound infections in patients undergoing myocardial revascularization using bilateral skeletonized internal mammary arteries (IMAs). BACKGROUND: The skeletonized IMA is longer than the pedicled one, thus providing the cardiac surgeon with increased versatility for arterial myocardial revascularization without the use of vein grafts. It is isolated from the chest wall gently with scissors and silver clips, and no cauterization is employed. Preservation of collateral blood supply to the sternum and avoidance of thermal injury enable more rapid healing and decrease the risk of sternal wound infection. METHODS: From April 1996 to August 1997, 545 patients underwent arterial myocardial revascularization using bilateral skeletonized IMAs. The right gastroepiploic artery was used in 100 patients (18%). The average age of the patients was 65 years; 431 (79%) were men and 114 (21%) were women; 179 (33%) were older than 70 years of age; 166 (30%) were diabetics. The average number of grafts was 3.2 per patient. RESULTS: The 30-day operative mortality rate was 2% (n = 11). There were six perioperative infarcts (1.1%) and six strokes (1.1%); 9 patients had sternal infection (1.7%) and 15 (2.8%) had superficial infection. Risk factors for sternal infection were chronic obstructive pulmonary disease and emergency operation. Superficial sternal wound infections were more common in women and in patients with chronic obstructive pulmonary disease, renal failure, or peripheral vascular disease. The 1-year actuarial survival rate was 97%. Two of the six late deaths were not cardiac-related. Late dehiscence occurred in three patients (0.6%). The death rate (early and late) of patients with any sternal complication was higher than that of patients without those complications (33% vs. 2.7%). CONCLUSIONS: Routine arterial myocardial revascularization using bilateral skeletonized IMAs is safe, and postoperative morbidity and mortality rates are low, even in elderly patients and those with diabetes. Chronic obstructive pulmonary disease and emergency operations were found to be associated with an increased risk of sternal infections, and the authors recommend avoiding the use of bilateral skeletonized IMAs in patients with these preoperative risk factors.

Aged↗