PeerJ Preprints: Anatomy and Physiologyhttps://peerj.com/preprints/index.atom?journal=peerj&subject=3400Anatomy and Physiology articles published in PeerJ PreprintsSeven myths on crowding and peripheral visionhttps://peerj.com/preprints/273532019-12-062019-12-06Hans Strasburger
Crowding has become a hot topic in vision research and some fundamentals are now widely agreed upon. For the classical crowding task, one would likely agree with the following statements. (1) Bouma’s law can, succinctly and unequivocally, be stated as saying that critical distance for crowding is about half the target’s eccentricity. (2) Crowding is predominantly a peripheral phenomenon. (3) Peripheral vision extends to at most 90° eccentricity. (4) Resolution threshold (the minimal angle of resolution, MAR) increases strongly and linearly with eccentricity. Crowding increases at an even steeper rate. (5) Crowding is asymmetric as Bouma has shown. For that inner-outer asymmetry, the peripheral flanker has more effect. (6) Critical crowding distance corresponds to a constant cortical distance in primary visual areas like V1. (7) Except for Bouma’s seminal paper in 1970, crowding research mostly became prominent starting in the 2000s. I propose the answer is ‘not really’ or ‘not quite’ to these assertions. So should we care? I think we should, before we write the textbook chapters for the next generation.
Crowding has become a hot topic in vision research and some fundamentals are now widely agreed upon. For the classical crowding task, one would likely agree with the following statements. (1) Bouma’s law can, succinctly and unequivocally, be stated as saying that critical distance for crowding is about half the target’s eccentricity. (2) Crowding is predominantly a peripheral phenomenon. (3) Peripheral vision extends to at most 90° eccentricity. (4) Resolution threshold (the minimal angle of resolution, MAR) increases strongly and linearly with eccentricity. Crowding increases at an even steeper rate. (5) Crowding is asymmetric as Bouma has shown. For that inner-outer asymmetry, the peripheral flanker has more effect. (6) Critical crowding distance corresponds to a constant cortical distance in primary visual areas like V1. (7) Except for Bouma’s seminal paper in 1970, crowding research mostly became prominent starting in the 2000s. I propose the answer is ‘not really’ or ‘not quite’ to these assertions. So should we care? I think we should, before we write the textbook chapters for the next generation.Bone morphogenetic protein 15 induces differentiation of mesenchymal stem cell derived from human follicular fluid to oocyte like cellhttps://peerj.com/preprints/280062019-10-072019-10-07Mahin Taheri MoghadamAli Reza Eftekhari MoghadamGhasem SakiRoshan Nikbakht
Background. To study the effect of Bone morphogenetic protein 15 on differentiation potential of mesenchymal stem cell derived from human follicular fluid to oocyte like cell. Methods. Human FF derived cells were collected from 78 women in assisted fertilization program, and cultured in differentiation medium containing human recombinant BMP15 for 21 days. Mesenchymal stem cells and OLCs were characterized by real-time PCR and immunocytochemistry (ICC) staining. Results. MSCs expressed germ line stem cell markers, such as OCT4 and NANOG. After 15 days, OLCs formed and expressed zona pellucida markers (ZP2, ZP3), and reached 20 – 30 µm in diameters. Ten days after induction with BMP15, round cells remarkably developed, and the maximum size of OLCs reached 115 µm. Finally, a decrease ranging from 0.04 to 4.5 in the expression of pluripotency and oocyte specific markers was observed in the cells cultured in BMP15 supplemented medium. Our work demonstrates, FF derived MSCs have an innate potency to differentiate into OLCs, and BMP15 is effective in stimulating the differentiation of these cells, which may give an in vitro model to examine human germ cell development.
Background. To study the effect of Bone morphogenetic protein 15 on differentiation potential of mesenchymal stem cell derived from human follicular fluid to oocyte like cell. Methods. Human FF derived cells were collected from 78 women in assisted fertilization program, and cultured in differentiation medium containing human recombinant BMP15 for 21 days. Mesenchymal stem cells and OLCs were characterized by real-time PCR and immunocytochemistry (ICC) staining. Results. MSCs expressed germ line stem cell markers, such as OCT4 and NANOG. After 15 days, OLCs formed and expressed zona pellucida markers (ZP2, ZP3), and reached 20 – 30 µm in diameters. Ten days after induction with BMP15, round cells remarkably developed, and the maximum size of OLCs reached 115 µm. Finally, a decrease ranging from 0.04 to 4.5 in the expression of pluripotency and oocyte specific markers was observed in the cells cultured in BMP15 supplemented medium. Our work demonstrates, FF derived MSCs have an innate potency to differentiate into OLCs, and BMP15 is effective in stimulating the differentiation of these cells, which may give an in vitro model to examine human germ cell development.What do we mean by the directions “cranial” and “caudal” on a vertebra?https://peerj.com/preprints/274372019-09-302019-09-30Michael P TaylorMatthew J Wedel
In illustrating vertebrae, it is important to consistently depict their orientation, so we can objectively assess and compare the slope of the neural arch, neural canal, or articular surfaces. However, differing vertebral shapes across taxa and across regions of the spinal column make it difficult to maintain consistency, or even define what we mean by the directions “cranial” and “caudal”. Consequently, characters such as “Neural arch slopes cranially 30° relative to the vertical” are disputable rather than objective measurements. Cranial and caudal are defined as directed along the horizontal axis, but several different notions of “horizontal” are possible:
1. Long axis of centrum is horizontal. This is appealing for elongate vertebrae such as sauropod cervicals, but is not always well defined, and is difficult to determine for craniocaudally short vertebrae such as most caudals.
2. Articular surfaces of centrum are vertical. Difficult to determine when dealing with facets that are concave or (worse) convex; and ambiguous for “keystoned” vertebrae in which the facets are not parallel.
3. Neural canal is horizontal. Anatomically informative, but difficult to determine in vertebrae that have not been fully prepared or CT-scanned, and impossible to see in lateral view. Ambiguous for vertebrae where the dorsal and ventral margins of the canal are not straight or not parallel.
4. Similarity in articulation (“horizontal” is defined as a line joining the same point on two similarly oriented copies of the same vertebra when optimally articulated). This is less intuitive than definitions 1–3, but takes the entire vertebra into account.
We advocate explicitly stating a definition and using it consistently. In most cases, definition 3 (“Neural canal is horizontal”) best reflects anatomical and developmental realities, and it is therefore preferred. Low-tech techniques can be used to determine neural canal orientation with adequate precision for most purposes.
In illustrating vertebrae, it is important to consistently depict their orientation, so we can objectively assess and compare the slope of the neural arch, neural canal, or articular surfaces. However, differing vertebral shapes across taxa and across regions of the spinal column make it difficult to maintain consistency, or even define what we mean by the directions “cranial” and “caudal”. Consequently, characters such as “Neural arch slopes cranially 30° relative to the vertical” are disputable rather than objective measurements. Cranial and caudal are defined as directed along the horizontal axis, but several different notions of “horizontal” are possible:1. Long axis of centrum is horizontal. This is appealing for elongate vertebrae such as sauropod cervicals, but is not always well defined, and is difficult to determine for craniocaudally short vertebrae such as most caudals.2. Articular surfaces of centrum are vertical. Difficult to determine when dealing with facets that are concave or (worse) convex; and ambiguous for “keystoned” vertebrae in which the facets are not parallel.3. Neural canal is horizontal. Anatomically informative, but difficult to determine in vertebrae that have not been fully prepared or CT-scanned, and impossible to see in lateral view. Ambiguous for vertebrae where the dorsal and ventral margins of the canal are not straight or not parallel.4. Similarity in articulation (“horizontal” is defined as a line joining the same point on two similarly oriented copies of the same vertebra when optimally articulated). This is less intuitive than definitions 1–3, but takes the entire vertebra into account.We advocate explicitly stating a definition and using it consistently. In most cases, definition 3 (“Neural canal is horizontal”) best reflects anatomical and developmental realities, and it is therefore preferred. Low-tech techniques can be used to determine neural canal orientation with adequate precision for most purposes.How to make new discoveries in (human) anatomyhttps://peerj.com/preprints/279802019-09-242019-09-24Mathew John Wedel
Despite the perception that human anatomy is a completed science, new discoveries continue to be reported. Some merely expand the previously known range of human variation, but others are gross structures present in most people, which simply escaped detection until recently. An analysis of recent discoveries suggests several avenues along which new discoveries might be sought:
1. Anatomically complex regions with multiple potential distractors: the anterolateral ligament of the knee escaped widespread appreciation until 2013, probably because the human knee is a forbiddingly complex structure that is rarely dissected completely, and several superficially similar structures are present in the same area.
2. Common characters of other taxa expressed as rare variants in humans: vagus nerve fibers to the trachea and esophagus are typically incorporated into the recurrent laryngeal nerve in humans, but form a separate pararecurrent nerve in some other mammals, and rarely in humans.
3. Replaced peripheral nerves: nerve fibers from the 4th lumbar spinal level to the leg are usually incorporated into the femoral nerve, but in rare cases become part of the obturator nerve. In such cases, the posterior branch of the saphenous nerve appears to have been replaced by the obturator nerve. Similar replacements in other regions of the body are underexplored.
Most recent discoveries fall into a perceptual blind spot: medical students dissecting human cadavers have the opportunity to find these structures, but usually lack the expertise to recognize or preserve them. In contract, surgeons have the necessary expertise, but rarely have the opportunity to open people up sufficiently to identify or trace these structures.
If new discoveries remain to be made even in the well-trod ground of human anatomy, then many more surely await discovery in extant and extinct non-humans, and these guidelines may prove useful in other taxa as well.
Despite the perception that human anatomy is a completed science, new discoveries continue to be reported. Some merely expand the previously known range of human variation, but others are gross structures present in most people, which simply escaped detection until recently. An analysis of recent discoveries suggests several avenues along which new discoveries might be sought:1. Anatomically complex regions with multiple potential distractors: the anterolateral ligament of the knee escaped widespread appreciation until 2013, probably because the human knee is a forbiddingly complex structure that is rarely dissected completely, and several superficially similar structures are present in the same area.2. Common characters of other taxa expressed as rare variants in humans: vagus nerve fibers to the trachea and esophagus are typically incorporated into the recurrent laryngeal nerve in humans, but form a separate pararecurrent nerve in some other mammals, and rarely in humans.3. Replaced peripheral nerves: nerve fibers from the 4th lumbar spinal level to the leg are usually incorporated into the femoral nerve, but in rare cases become part of the obturator nerve. In such cases, the posterior branch of the saphenous nerve appears to have been replaced by the obturator nerve. Similar replacements in other regions of the body are underexplored.Most recent discoveries fall into a perceptual blind spot: medical students dissecting human cadavers have the opportunity to find these structures, but usually lack the expertise to recognize or preserve them. In contract, surgeons have the necessary expertise, but rarely have the opportunity to open people up sufficiently to identify or trace these structures.If new discoveries remain to be made even in the well-trod ground of human anatomy, then many more surely await discovery in extant and extinct non-humans, and these guidelines may prove useful in other taxa as well.Neural canal ridges: A novel osteological correlate of post-cranial neurology in dinosaurshttps://peerj.com/preprints/279672019-09-172019-09-17Jessie AtterholtMathew J Wedel
Bony ridges occur on the walls of the neural canal in caudal vertebrae of numerous sauropod dinosaurs. These neural canal ridges (NCRs) are anteroposteriorly elongated but do not extend to the ends of the canal. To date, we have observed NCRs in caudal vertebrae of Alamosaurus, Apatosaurus, Astrophocaudia,Brontomerus, Camarasaurus, and Diplodocus.
Numerous similar structures occur in extant vertebrates: (1) Neurocentral joints are ventral to NCRs in sauropod caudal vertebrae, and NCRs occur in unfused juvenile arches. Hypothesis rejected. (2) Attachment scars from ligamentum flavum occur at the ends of the dorsal roof of the canal, not the midpoint of the lateral edges, and this mammalian ligament was probably absent in dinosaurs. Hypothesis rejected. (3) Smooth ridges separate the spinal cord from the dorsal spinal vein and paramedullary airways in some crocodilians and birds, respectively. However, these septa persist to the ends of the canal, giving it an 8-shape, unlike the discrete NCRs of dinosaurs. Hypothesis rejected. (4) Bony attachments for denticulate ligaments occur in some non-mammalian vertebrates. The dura mater around the spinal cord fuses to the periosteum of the neural canal in non-mammals, so the denticulate ligaments that support the spinal cord can leave ossified attachment scars. These spinal cord supports have been identified in teleosts, salamanders, and a juvenile lizard, and they are the best match for the morphology of the NCRs in sauropod vertebrae.
Functions of NCRs remain obscure. Denticulate ligaments are largest in regions of the vertebral column that experience strong lateral flexion. The hypothesis that NCRs supported the spinal cord of sauropods during lateral tail-whipping is attractive, but inconsistent with our recent discovery of NCRs in a hadrosaur caudal. NCRs are a new osteological correlate of the peripheral nervous system in dinosaurs, and highlight the need for more study in this area.
Bony ridges occur on the walls of the neural canal in caudal vertebrae of numerous sauropod dinosaurs. These neural canal ridges (NCRs) are anteroposteriorly elongated but do not extend to the ends of the canal. To date, we have observed NCRs in caudal vertebrae of Alamosaurus, Apatosaurus, Astrophocaudia,Brontomerus, Camarasaurus, and Diplodocus.Numerous similar structures occur in extant vertebrates: (1) Neurocentral joints are ventral to NCRs in sauropod caudal vertebrae, and NCRs occur in unfused juvenile arches. Hypothesis rejected. (2) Attachment scars from ligamentum flavum occur at the ends of the dorsal roof of the canal, not the midpoint of the lateral edges, and this mammalian ligament was probably absent in dinosaurs. Hypothesis rejected. (3) Smooth ridges separate the spinal cord from the dorsal spinal vein and paramedullary airways in some crocodilians and birds, respectively. However, these septa persist to the ends of the canal, giving it an 8-shape, unlike the discrete NCRs of dinosaurs. Hypothesis rejected. (4) Bony attachments for denticulate ligaments occur in some non-mammalian vertebrates. The dura mater around the spinal cord fuses to the periosteum of the neural canal in non-mammals, so the denticulate ligaments that support the spinal cord can leave ossified attachment scars. These spinal cord supports have been identified in teleosts, salamanders, and a juvenile lizard, and they are the best match for the morphology of the NCRs in sauropod vertebrae.Functions of NCRs remain obscure. Denticulate ligaments are largest in regions of the vertebral column that experience strong lateral flexion. The hypothesis that NCRs supported the spinal cord of sauropods during lateral tail-whipping is attractive, but inconsistent with our recent discovery of NCRs in a hadrosaur caudal. NCRs are a new osteological correlate of the peripheral nervous system in dinosaurs, and highlight the need for more study in this area.Broad similarities in shoulder muscle architecture and organization across two amniotes: Implications for reconstructing non-mammalian synapsidshttps://peerj.com/preprints/279502019-09-102019-09-10Philip Fahn-LaiAndrew A BiewenerStephanie E Pierce
The evolution of upright limb posture in mammals may have enabled modifications of the forelimb for diverse locomotor ecologies. A rich fossil record of non-mammalian synapsids holds the key to unraveling the transition from “sprawling” to “erect” limb function in the precursors to mammals, but a detailed understanding of muscle functional anatomy is a necessary prerequisite to reconstructing postural evolution in fossils. Here we characterize the gross morphology and internal architecture of muscles crossing the shoulder joint in two morphologically-conservative extant amniotes that form a phylogenetic and morpho-functional bracket for non-mammalian synapsids: the Argentine black and white tegu Salvator merianaeand the Virginia opossum Didelphis virginiana. By combining traditional physical dissection of cadavers with non-destructive three-dimensional digital dissection, we find striking similarities in muscle organization and architectural parameters. Despite the wide phylogenetic gap between our study species, distal muscle attachments are notably similar, while differences in proximal muscle attachments are driven by modifications to the skeletal anatomy of the pectoral girdle that are well-documented in transitional synapsid fossils. Further, correlates for force production (PCSA, physiological cross-sectional area), muscle gearing (pennation), and working range (fascicle length) are statistically indistinguishable for an unexpected number of muscles. Functional tradeoffs between force production and working range reveal muscle specializations that may facilitate increased girdle mobility, weight support, and active stabilization of the shoulder in the opossum—a possible signal of postural transformation. Together, these results create a foundation for reconstructing the musculoskeletal anatomy of the non-mammalian synapsid pectoral girdle with greater confidence, as we demonstrate by inferring shoulder muscle PCSAs in the fossil non-mammalian cynodont Massetognathus pascuali.
The evolution of upright limb posture in mammals may have enabled modifications of the forelimb for diverse locomotor ecologies. A rich fossil record of non-mammalian synapsids holds the key to unraveling the transition from “sprawling” to “erect” limb function in the precursors to mammals, but a detailed understanding of muscle functional anatomy is a necessary prerequisite to reconstructing postural evolution in fossils. Here we characterize the gross morphology and internal architecture of muscles crossing the shoulder joint in two morphologically-conservative extant amniotes that form a phylogenetic and morpho-functional bracket for non-mammalian synapsids: the Argentine black and white tegu Salvator merianaeand the Virginia opossum Didelphis virginiana. By combining traditional physical dissection of cadavers with non-destructive three-dimensional digital dissection, we find striking similarities in muscle organization and architectural parameters. Despite the wide phylogenetic gap between our study species, distal muscle attachments are notably similar, while differences in proximal muscle attachments are driven by modifications to the skeletal anatomy of the pectoral girdle that are well-documented in transitional synapsid fossils. Further, correlates for force production (PCSA, physiological cross-sectional area), muscle gearing (pennation), and working range (fascicle length) are statistically indistinguishable for an unexpected number of muscles. Functional tradeoffs between force production and working range reveal muscle specializations that may facilitate increased girdle mobility, weight support, and active stabilization of the shoulder in the opossum—a possible signal of postural transformation. Together, these results create a foundation for reconstructing the musculoskeletal anatomy of the non-mammalian synapsid pectoral girdle with greater confidence, as we demonstrate by inferring shoulder muscle PCSAs in the fossil non-mammalian cynodont Massetognathus pascuali.Internal sensation of pleasure can be explained as a specific conformation of semblance: Inference from electrophysiological findingshttps://peerj.com/preprints/278862019-08-062019-08-06Kunjumon Vadakkan
Semblance hypothesis was able to find a solution for the generation of first- person internal sensation of memory along with provisions for behavioral motor actions. The derived inter-postsynaptic functional LINK (IPL) mechanism was able to explain a large number of findings from different levels of the system ranging from perception to sleep. It was possible to explain long-term potentiation (LTP) as the effect of experimental scaling-up of the changes occurring during natural learning. By keeping the latter relationship as a baseline, it was possible to explain long-term depression (LTD) observed in the nucleus accumbens (NAc), a scaled-up change of a mechanism responsible for inducing internal sensation of pleasure. This mechanism provides inter-connectable explanations for the attenuation of postsynaptic potentials, reduced ring of medium spiny neurons and the finding that LTD induced by stimulation of one pathway to NAc occludes the LTD induction by another pathway.
Semblance hypothesis was able to find a solution for the generation of first- person internal sensation of memory along with provisions for behavioral motor actions. The derived inter-postsynaptic functional LINK (IPL) mechanism was able to explain a large number of findings from different levels of the system ranging from perception to sleep. It was possible to explain long-term potentiation (LTP) as the effect of experimental scaling-up of the changes occurring during natural learning. By keeping the latter relationship as a baseline, it was possible to explain long-term depression (LTD) observed in the nucleus accumbens (NAc), a scaled-up change of a mechanism responsible for inducing internal sensation of pleasure. This mechanism provides inter-connectable explanations for the attenuation of postsynaptic potentials, reduced ring of medium spiny neurons and the finding that LTD induced by stimulation of one pathway to NAc occludes the LTD induction by another pathway.Modelling the effect of curves on distance running performancehttps://peerj.com/preprints/278842019-08-062019-08-06Paolo TabogaRodger Kram
Background On a curve, the average axial leg force (Fa) of a runner is increased due to the need to exert centripetal force. The increased Fa presumably requires a greater rate of metabolic energy expenditure than straight running at the same velocity. We propose a model that explains the velocity reduction on curves, compared to straight running, assuming that runners maintain a constant metabolic rate.
Methods We combined published equations to estimate the change in the rate of gross metabolic energy expenditure as a function of Fa, where Fa depends on curve radius and velocity, with an equation for the gross rate of oxygen uptake as a function of velocity. We compared performances between straight courses and courses with different curve radii and geometries.
Results The differences between our model predictions and the actual indoor world records, are between 0.45 % in 3000 m and 1.78 % in the 1500 m for males, and 0.59 % in the 5000 m and 1.76 % in the 3000 m for females. We estimate thata 2:01:39 marathon on a 400 m track, corresponds to 2:01:32 on a straight path and to 2:02:00 on a 200 m track.
Conclusion Our model predicts that compared to straight racecourses, the increased time due to curves, is notable for smaller curve radii and for faster velocities. But, for larger radii and slower speeds, the time increase is negligible and the general perception of the magnitude of the effects of curves on road racing performance is not supported by our calculations.
Background On a curve, the average axial leg force (Fa) of a runner is increased due to the need to exert centripetal force. The increased Fa presumably requires a greater rate of metabolic energy expenditure than straight running at the same velocity. We propose a model that explains the velocity reduction on curves, compared to straight running, assuming that runners maintain a constant metabolic rate.Methods We combined published equations to estimate the change in the rate of gross metabolic energy expenditure as a function of Fa, where Fa depends on curve radius and velocity, with an equation for the gross rate of oxygen uptake as a function of velocity. We compared performances between straight courses and courses with different curve radii and geometries.Results The differences between our model predictions and the actual indoor world records, are between 0.45 % in 3000 m and 1.78 % in the 1500 m for males, and 0.59 % in the 5000 m and 1.76 % in the 3000 m for females. We estimate thata 2:01:39 marathon on a 400 m track, corresponds to 2:01:32 on a straight path and to 2:02:00 on a 200 m track.Conclusion Our model predicts that compared to straight racecourses, the increased time due to curves, is notable for smaller curve radii and for faster velocities. But, for larger radii and slower speeds, the time increase is negligible and the general perception of the magnitude of the effects of curves on road racing performance is not supported by our calculations.Characteristics of effective home-based resistance training exercise in patients with chronic disease: a scoping review protocolhttps://peerj.com/preprints/276792019-04-242019-04-24Thomas WilkinsonRoseanne BillanyCourtney J LightfootMatthew Graham-BrownAlice C Smith
Regular exercise, principally resistance training, is an effective method to promote muscle hypertrophy and attenuate muscle atrophy during various atrophic conditions . There is growing interest in the evaluation of home-based resistance training programmes. These programmes have the potential to overcome common barriers to participation, such as accessibility and affordability. The objective of the scoping review is to map the available evidence to provide an overview of what characteristics, principles, and components are required for an effective home-based resistance training programme in patients with chronic disease. The four specific objectives of the scoping review will be to: 1) conduct a systematic search of the published and grey literature for studies reporting on home-based resistance training in patients with chronic disease; 2) map out the characteristics and range of methodologies (including exercise protocols and outcome measures) used in effective home-based resistance training; 3) examine reported challenges and limitations of home-based resistance training; and 4) propose recommendations for optimizing home-based resistance training protocols in this population.
Regular exercise, principally resistance training, is an effective method to promote muscle hypertrophy and attenuate muscle atrophy during various atrophic conditions . There is growing interest in the evaluation of home-based resistance training programmes. These programmes have the potential to overcome common barriers to participation, such as accessibility and affordability. The objective of the scoping review is to map the available evidence to provide an overview of what characteristics, principles, and components are required for an effective home-based resistance training programme in patients with chronic disease. The four specific objectives of the scoping review will be to: 1) conduct a systematic search of the published and grey literature for studies reporting on home-based resistance training in patients with chronic disease; 2) map out the characteristics and range of methodologies (including exercise protocols and outcome measures) used in effective home-based resistance training; 3) examine reported challenges and limitations of home-based resistance training; and 4) propose recommendations for optimizing home-based resistance training protocols in this population.Sex differences in the response to angiotensin II receptor blockade in a rat model of eccentric cardiac hypertrophyhttps://peerj.com/preprints/276502019-04-122019-04-12Élisabeth Walsh-WilkinsonMarie-Claude DroletCharlie Le HouillierÈve-Marie RoyMarie ArsenaultJacques Couet
Aim of study was to evaluate the development of cardiac hypertrophy (CH) in response to left ventricle (LV) volume overload (VO) caused by chronic aortic valve regurgitation (AR) in male and female rats treated or not with angiotensin II receptor blocker (ARB), valsartan. We studied 8 groups of Wistar rats: male or female, AR or sham-operated (sham) and treated or not with valsartan (30 mg/kg/day) for 9 weeks starting one week before AR surgical induction. As expected, VO from AR resulted for both male and female rats in significant LV dilation (39% vs. 40% increase of end-diastolic LV diameter, respectively; p<0.0001) and CH (53% vs. 64% increase of heart weight, respectively; p<0.0001) compared to sham. Sex differences were observed in the LV wall thickening in response to VO. In untreated AR males, relative LV wall thickness (a ratio of wall thickness to end-diastolic diameter) was reduced compared to sham, whereas this ratio in females remained unchanged. ARB treatment did not prevent LV dilation for both male and female animals but reversed LV wall thickening in females. Systolic and diastolic functions in AR animals were altered similarly for both sexes compared to sham. ARB treatment did not improve systolic function but help normalizing diastolic parameters in female AR rats. Increased LV expression of Anp and Bnp genes was normalized by ARB treatment in AR females but not in males. Other hypertrophy gene markers (Fos, Trpc6, Klf15, Myh6 and Myh7) were not modulated by ARB treatment. The same was true for genes related to LV extracellular matrix remodeling (Col1a1, Col3a1, Fn1, Mmp2, Timp1 and Lox). In summary, ARB treatment of rats with severe AR blocked the female-specific hypertrophic response characterized by LV chamber wall thickening. LV dilation, on the other hand, was not significantly decreased by ARB treatment.
Aim of study was to evaluate the development of cardiac hypertrophy (CH) in response to left ventricle (LV) volume overload (VO) caused by chronic aortic valve regurgitation (AR) in male and female rats treated or not with angiotensin II receptor blocker (ARB), valsartan. We studied 8 groups of Wistar rats: male or female, AR or sham-operated (sham) and treated or not with valsartan (30 mg/kg/day) for 9 weeks starting one week before AR surgical induction. As expected, VO from AR resulted for both male and female rats in significant LV dilation (39% vs. 40% increase of end-diastolic LV diameter, respectively; p<0.0001) and CH (53% vs. 64% increase of heart weight, respectively; p<0.0001) compared to sham. Sex differences were observed in the LV wall thickening in response to VO. In untreated AR males, relative LV wall thickness (a ratio of wall thickness to end-diastolic diameter) was reduced compared to sham, whereas this ratio in females remained unchanged. ARB treatment did not prevent LV dilation for both male and female animals but reversed LV wall thickening in females. Systolic and diastolic functions in AR animals were altered similarly for both sexes compared to sham. ARB treatment did not improve systolic function but help normalizing diastolic parameters in female AR rats. Increased LV expression of Anp and Bnp genes was normalized by ARB treatment in AR females but not in males. Other hypertrophy gene markers (Fos, Trpc6, Klf15, Myh6 and Myh7) were not modulated by ARB treatment. The same was true for genes related to LV extracellular matrix remodeling (Col1a1, Col3a1, Fn1, Mmp2, Timp1 and Lox). In summary, ARB treatment of rats with severe AR blocked the female-specific hypertrophic response characterized by LV chamber wall thickening. LV dilation, on the other hand, was not significantly decreased by ARB treatment.