Decrease In Contractile Function Research Articles

Diaphragm Voluntary Activation After Inspiratory Pressure Threshold Loading In Healthy Humans

Inspiratory pressure threshold loading (IPTL) elicits a reduction in diaphragm contractile function (transdiaphragmatic twitch pressure; PDI,TW). It is unknown if diaphragm fatigability after IPTL is also mediated by neural mechanisms (diaphragm voluntary activation; D-VA) or if it differs on the basis of sex. PURPOSE: We sought to determine if D-VA decreases after IPTL and whether this was different between sexes. METHODS: Healthy participants (11F; 10 M) performed IPTL to task failure with an inspired duty cycle of 0.7 at 60% PDI,MAX. Cervical magnetic stimulation of the phrenic nerves was used to assess PDI,TW and D-VA. The relationship between fatigability outcomes (PDI,TW and D-VA), time to task failure, and cumulative diaphragm work were tested to explore how each factor contributes to diaphragm fatigability. RESULTS: Main effects of time (p < 0.001) and sex (p = 0.030), along with an interaction effect (p = 0.007) were observed when examining the changes in PDI,TW after IPTL. Specifically, immediately following IPTL, the decrease in PDI,TW was greater in males compared to females (24 ± 17 vs. 13 ± 15%points; p = 0.016). D-VA was 91 ± 8%baseline in males and 88 ± 11%baseline in females immediately following IPTL. We observed main effects of time, (p < 0.001) but neither the effect of sex (p = 0.177) nor the interaction between sex and time (p = 0.304) were significant, suggesting that D-VA decreases after IPTL similarly in males and females. The decrease in PDI,TW correlated with both the total cumulative diaphragm work (R2 = 0.43; p = 0.021) and time to task failure (R2 = 0.40; p = 0.030), whereas the decrease in D-VA was significantly correlated with time to task failure (R2 = 0.24; p = 0.041) and not cumulative diaphragm work (R2 = 0.19; p = 0.079). CONCLUSION: Our results indicate that neural mechanisms contribute to diaphragm fatigability and this contribution is similar between females and males after IPTL. A decrease in contractile function can be partially explained by both the amount of work performed and the total time of the IPTL task. Decreases in D-VA appear to be influenced primarily by the total time spent performing the IPTL task rather than the amount of work performed. Moreover, these contributing factors appear to be independent of sex. Supported by the Natural Sciences and Engineering Research Council of Canada.

Роль та місце кардіопротекції з використанням сучасних інфузійних препаратів у періопераційному періоді

Кардіальні ускладнення не тільки є найчастішою причиною післяопераційної летальності, але й істотно збільшують тривалість і вартість лікування, створюють передумови для розвитку поліорганної недостатності. Саме профілактика й своєчасне адекватне лікування кардіальних ускладнень при позасерцевих оперативних втручаннях є важливим тактичним і стратегічним завданням лікаря-анестезіолога. Можливості радикально знизити ризик ускладнень досить обмежені. Лікарські засоби, до складу яких входять амінокислоти L-аргінін та L-карнітин, можуть бути ефективно використані як кардіо- та ендотеліопротективні препарати. Упровадження таких підходів у клінічну практику в найближчому майбутньому буде мати велике значення для підвищення ефективності та безпечності періопераційної інфузійної терапії пацієнтів із супутніми серцево-судинними захворюваннями.

Intramuscular adipose tissue: a cause for concern.

Intramuscular adipose tissue: a cause for concern.

Atrial Function and Its Role in the Non-invasive Evaluation of Diastolic Function in Congenital Heart Disease.

Diastolic dysfunction has correlated with adverse outcomes in various forms of unrepaired and repaired or palliated congenital heart disease (CHD). The non-invasive assessment of diastolic function in pediatric and adult patients with CHD remains challenging. Atrial size has a pivotal role in the evaluation of diastolic function; however, a growing body of evidence supports the additional role of atrial function as a more sensitive parameter of ventricular diastolic dysfunction. While the importance of atrial function is becoming clearer in adult acquired heart disease, it remains ambiguous in those with CHD. In this review we set the stage with the current understanding of diastolic function assessment in CHD, followed by insight into atrial form and function including its non-invasive assessment, and conclude with the current knowledge of atrial function in CHD. A general pattern of decrease in reservoir and conduit function with compensatory increase followed by decompensatory decrease in contractile function seems to be the common pathway of atrial dysfunction in most forms of CHD.

Pathogenetic role of the autonomic nervous system in arterial hypotension cardiac remodeling in young women

Aim. To study the features of cardiac remodeling on condition of the autonomic nervous system (ANS) in young women with idiopathic arterial hypotension (IAH).Material and methods. A comparative analysis of the echocardiography data in women with IAH aged 18-25 years with a predominance of sympathetic (n=150) and parasympathetic (n=60) parts of the ANS was performed. The level of systolic blood pressure ≤98 mm Hg worked as the criterion of IAH. The activity of the ANS was evaluated by the I. Kérdö index.Results. It has been shown that women with IAH with sympathicotonia are characterized by a significant decrease in the structural parameters of the heart: the size of all chambers and the aortic ostium, contractile function decrease and a slower relaxation of the left ventricle (LV). Acceleration of intracardiac hemodynamics was observed: an increase in blood flow rates and pressure gradients on the mitral, tricuspid and pulmonary artery valves, an increase in the rates of early and late diastolic LV filling. Changes in early LV diastole are associated with an increase of pressure in the left atrium. We identified a restrictive type of diastolic dysfunction in women with parasympathicotonia.Conclusion. Sympathicotonia and parasympathicotonia in young women with IAH are associated with different heart remodeling variants. Cardiac hypotrophy, decrease of contractile function and impaired LV relaxation during hypotension are associated with low sympathetic activity against the background of parasympathicotonia. The restrictive type of diastolic dysfunction during hypotension is associated with parasympathicotonia. Use of cholinolytics and anticholinesterase reactivators are the potential way of correction of ANS dysfunction, IAH regression and cardiac remodeling.

Simulation of swallowing dysfunction and mechanical ventilation after a Montgomery T-tube insertion

The Montgomery T-tube is used as a combined tracheal stent and airway after laryngotracheoplasty, to keep the lumen open and prevent mucosal laceration from scarring. It is valuable in the management of upper and mid-tracheal lesions, while invaluable in long and multisegmental stenting lesions. Numerical simulations based on real-patient-tracheal geometry, experimental tissue characterization, and previous numerical estimation of the physiological swallowing force are performed to estimate the consequences of Montgomery T-tube implantation on swallowing and assisted ventilation: structural analysis of swallowing is performed to evaluate patient swallowing capacity, and computational fluid dynamics simulation is carried out to analyze related mechanical ventilation. With an inserted Montgomery T-tube, vertical displacement (Z-axis) reaches 8.01 mm, whereas in the Y-axis, it reaches 6.63 mm. The maximal principal stress obtained during swallowing was 1.6 MPa surrounding the hole and in the upper contact with the tracheal wall. Fluid flow simulation of the mechanical ventilation revealed positive pressure for both inhalation and exhalation, being higher for inspiration. The muscular deflections, considerable during normal breathing, are nonphysiological, and this aspect results in a constant overload of the tracheal muscle. During swallowing, the trachea ascends producing a nonhomogeneous elongation. This movement can be compromised when prosthesis is inserted, which explains the high incidence of glottis close inefficiency. Fluid simulations showed that nonphysiological pressure is established inside the trachea due to mechanical ventilation. This may lead to an overload of the tracheal muscle, explaining several related problems as muscle thinning or decrease in contractile function.

Radiation-associated degenerative cardiovascular risks during normal aging and after adverse CV event 10 months post-initial exposure

Background: During the future exploration-type space missions, astronauts will be exposed to ionizing radiation (IR) for more than 1–2 years. The effect of cosmic IR during and after space flights on the cardiovascular (CV) system is unknown. Therefore, it is important to evaluate space IR effects on the CV system and determine potential post-mission degenerative excess relative risks (ERR) to the heart as a function of normal aging (IR + AGING model) as well as determine whether space IR may affect the processes of recovery after an adverse CV event (i.e. acute myocardial infarct, AMI) during normal aging (IR + AGING + AMI model).Methods: Nine-month-old C57BL6N male mice were IR once with proton (50 cGy, 1 GeV/n) or (56Fe 15 cGy, 1 GeV/n). IR-induced alterations in cardiac function were assessed by echocardiography (ECHO) and hemodynamic measurements (HEMO). AMI was induced by ligation of left anterior descending (LAD) coronary artery 10 months post-IR. Mice were monitored over 28 days post-AMI.Results: Compared with control, in the IR + AGING study group, left ventricular end-systolic pressure (LVESP) was significantly decreased in both 1H- and 56Fe-IR (P < 0.03, both), suggesting IR-associated decrease in contractile function 10 month post-IRs. However, compared with age-matched control mice (18 months), the LV end-diastolic pressure (LVEDP) was significantly increased (P < 0.05) and minimum LV pressure change (dP/dt min, mmHg/sec) was significantly decreased (P < 0.02) in 1H-IR but not 56Fe-IR mice, suggesting that a single 50 cGy full body 1H-IR decreases considerably the relaxation function of the heart 10 months post-AMI. Of note, an increase in LVEDP and a decrease in dP/dt min are indicators that heart is not pumping blood well and is an early independent prognostic CV risk factor for development of cardiac de-compensation.In all three IR + AGING + AMI study groups, in average, there was 10–15% mortality up to 3 days post-AMI surgery with ∼90% survival rate in all groups 28 days post-AMI. This is rather very good survival rate for 18- to 20-month-old mice after permanent LAD ligation. In the IR + AGING + AMI study group, the most harmful effects on myocardial recovery 10 months post-IR and 28 days post-AMI were observed in the 56Fe-IR group. LVESP was significantly decreased in 56Fe-IR vs control and 1H-IR mice (P < 0.04 and <0.02, respectively). LVEDP was 3-fold higher in 56Fe-IR vs 1H-IR mice (P < 0.004) but was only slightly higher (P = n.s.) compared with control mice. However, dP/dt max and dP/dt min were significantly decreased in 56Fe-IR vs control (P < 0.007 and <0.05, respectively) and 1H-IR mice (P < 0.0004 and <0.0015, respectively), suggesting that 56Fe-AMI hearts developed cardiac de-compensation.Summary: Our data in the IR + AGING study group strongly suggest that 10 months post-IR low-dose high-energy 1H-IR but not low-dose HZE (56Fe) particle IR affects considerably contractile and relaxation functions during normal aging. Conversely, our data in the IR + AGING + AMI study group at 10 months post-IR taken together with our previously reported data for AMI recovery 3 month after a single 50 cGy 1H-IR and 15 cGy 56Fe-IR indicate that 3 months and as long as 10 months after a single full-body IR, the 56Fe-IR is detrimental, whereas 1H-IR does not have negative effects on post-AMI recovery. In fact, single 1H-IR, at this dose, was considerably beneficial for post-AMI recovery at 3 months, as well as at 10 months post-IR.Major conclusions: Our longitudinal 1, 3 and 10 months studies in the IR + AGING and IR + AGING + AMI groups reveal that a single full-body low-dose 1H and HZE particle radiation (56Fe) have long-lasting negative effect on heart homeostasis during normal aging (predominantly 56Fe and at 10 months 1H-IR, as well), and present a significant CV risk for recovery after adverse CV event (exclusively 56Fe-IR, whereas 1H-IR at this dose could beneficial). Further, the divergent effects of low dose 1H-IR vs 56Fe-IR on heart function during normal aging vs after adverse CV event suggest significantly different biological responses responsible for this ion-dependent dichotomy over 10 months post-IR and necessitate further in-depth studies into underlying molecular mechanisms.

Abstract 042: Radiation-Associated Cardiovascular Risks for Future Deep-Space Missions

During the future Moon and Mars missions astronauts will be exposed to space radiation (IR) for extended time. The effect of cosmic IR during and after space flights on cardiovascular (CV) system is unknown. Nine-month old C57BL/6N male mice were IR once with proton 50 cGy or 56Fe 15 cGy, both at 1 GeV/nucleon. We evaluated IR-induced biological responses - underlying molecular mechanisms, calcium handling, signal transduction and gene expression. Cardiac function was assessed by echocardiography and hemodynamic measurements. Left ventricular end diastolic pressure (LVEDP) was increased in 56Fe mice 1 and 3 months post-IR (p&lt;0.001). One month post-IR, compared to control, proton- and 56Fe-IR sarcolemmal Na+-Ca2+ exchanger (NCX) (p&lt;0.007) and sarco(endo)plasmic reticulum calcium-ATPase (SERCA2a, p&lt;0.02) were both increased more than 200% and p-p38 was decreased 400% (p&lt;0.05), suggesting activation of compensatory mechanisms in [Ca2+]i handling in these hearts. By 3 months, compared to control, proton- and 56Fe-IR hearts SERCA2a and p-Creb1 was decreased 200-500% (p&lt;0.02), suggesting reduced capacity in intracellular [Ca2+]i handling, suggesting that [Ca2+]i handling dysfunction combined with LVEDP increase in 56Fe-IR may be due to prolonged activation of compensatory mechanisms that lead to changes in SERCA2a and p-Creb1 levels. By 10 months, compared to control, LVESP was decreased in proton- and 56Fe-IR (p&lt;0.03), suggesting IR-associated decrease in contractile function. However, compared to age-matched controls (18 months), the LVEDP was increased (p&lt;0.05) and dP/dt Min was decreased (p&lt;0.02) in proton-IR but not 56Fe-IR mice. This data suggests that after 10 months proton- but not 56Fe-IR affects considerably contractile and relaxation functions during aging. Our longitudinal 1, 3 and 10 months studies reveal that a single full body low dose proton- and 56Fe-IR have long-lasting negative effect on heart homeostasis during aging. The divergent effects of low dose proton vs. 56Fe-IR on heart function during aging suggest significantly different biological mechanisms responsible for this ion-dependent dichotomy over 10 months post-IR and necessitate further studies into underlying molecular mechanisms.

Metabolic imaging of acute and chronic infarction in the perfused rat heart using hyperpolarised [1‐13C]pyruvate

Hyperpolarised (13)C MRI can be used to generate metabolic images of the heart in vivo. However, there have been no similar studies performed in the isolated perfused heart. Therefore, the aim of this study was to develop a method for the creation of (13)C metabolite maps of the perfused rat heart and to demonstrate the technique in a study of acute and chronic myocardial infarction. Male Wistar rat hearts were isolated, perfused and imaged before and after occlusion of the left anterior descending (LAD) coronary artery, creating an acute infarct group. In addition, a chronic infarct group was generated from hearts which had their LAD coronary artery occluded in vivo. Four weeks later, hearts were excised, perfused and imaged to generate metabolic maps of infused pyruvate and its metabolites lactate and bicarbonate. Myocardial perfusion and energetics were assessed by first-pass perfusion imaging and (31)P MRS, respectively. In both acute and chronically infarcted hearts, perfusion was reduced to the infarct region, as revealed by reduced gadolinium influx and lower signal intensity in the hyperpolarised pyruvate images. In the acute infarct region, there were significant alterations in the lactate (increased) and bicarbonate (decreased) signal ratios. In the chronically infarcted region, there was a significant reduction in both bicarbonate and lactate signals. (31)P-derived energetics revealed a significant decrease between control and chronic infarcted hearts. Significant decreases in contractile function between control and both acute and chronic infracted hearts were also seen. In conclusion, we have demonstrated that hyperpolarised pyruvate can detect reduced perfusion in the rat heart following both acute and chronic infarction. Changes in lactate and bicarbonate ratios indicate increased anaerobic metabolism in the acute infarct, which is not observed in the chronic infarct. Thus, this study has successfully demonstrated a novel imaging approach to assess altered metabolism in the isolated perfused rat heart.

FGF23 is a novel regulator of intracellular calcium and cardiac contractility in addition to cardiac hypertrophy

Fibroblast growth factor 23 (FGF23) is a hormone released primarily by osteocytes that regulates phosphate and vitamin D metabolism. Recent observational studies in humans suggest that circulating FGF23 is independently associated with cardiac hypertrophy and increased mortality, but it is unknown whether FGF23 can directly alter cardiac function. We found that FGF23 significantly increased cardiomyocyte cell size in vitro, the expression of gene markers of cardiac hypertrophy, and total protein content of cardiac muscle. In addition, FGFR1 and FGFR3 mRNA were the most abundantly expressed FGF receptors in cardiomyocytes, and the coreceptor α-klotho was expressed at very low levels. We tested an animal model of chronic kidney disease (Col4a3(-/-) mice) that has elevated serum FGF23. We found elevations in common hypertrophy gene markers in Col4a3(-/-) hearts compared with wild type but did not observe changes in wall thickness or cell size by week 10. However, the Col4a3(-/-) hearts did show reduced fractional shortening (-17%) and ejection fraction (-11%). Acute exposure of primary cardiomyocytes to FGF23 resulted in elevated intracellular Ca(2+) ([Ca(2+)](i); F/F(o) + 86%) which was blocked by verapamil pretreatment. FGF23 also increased ventricular muscle strip contractility (67%), which was inhibited by FGF receptor antagonism. We hypothesize that although FGF23 can acutely increase [Ca(2+)](i), chronically this may lead to decreases in contractile function or stimulate cardiac hypertrophy, as observed with other stress hormones. In conclusion, FGF23 is a novel bone/heart endocrine factor and may be an important mediator of cardiac Ca(2+) regulation and contractile function during chronic kidney disease.

Viral-mediated expression of desmin mutants to create mouse models of myofibrillar myopathy

BackgroundThe clinical features of myofibrillar myopathies display a wide phenotypic heterogeneity. To this date, no studies have evaluated this parameter due to the absence of pertinent animal models. By studying two mutants of desmin, which induce subtle phenotypic differences in patients, we address this issue using an animal model based on the use of adeno-associated virus (AAV) vectors carrying mutated desmin cDNA.MethodsAfter preparation of the vectors, they were injected directly into the tibialis anterior muscles of C57BL/6 mice to allow expression of wild-type (WT) or mutated (R406W or E413K) desmin. Measurements of maximal force were carried out on the muscle in situ and then the injected muscles were analyzed to determine the structural consequences of the desmin mutations on muscle structure (microscopic observations, histology and immunohistochemistry).ResultsInjection of AAV carrying WT desmin results in the expression of exogenous desmin in 98% of the muscle fibers without any pathological or functional perturbations. Exogenous WT and endogenous desmin are co-localized and no differences were observed compared to non-injected muscle. Expression of desmin mutants in mouse muscles induce morphological changes of muscle fibers (irregular shape and size) and the appearance of desmin accumulations around the nuclei (for R406W) or in subsarcolemmal regions of fibers (for E413K). These accumulations seem to occur and disrupt the Z-line, and a strong regeneration was observed in muscle expressing the R406W desmin, which is not the case for E413K. Moreover, both mutants of desmin studied here induce a decrease in muscle force generation capacity.ConclusionsIn this study we show that AAV-mediated expression of desmin mutants in mouse muscles recapitulate the aggregation features, the decrease in contractile function and the morphological changes observed in patients with myofibrillar myopathy. More importantly, our results suggest that the R406W desmin mutant induces a robust muscle regeneration, which is not the case for the E413K mutant. This difference could help to explain the phenotypic differences observed in patients. Our results highlight the heterogeneous pathogenic mechanisms between different desmin mutants and open the way for new advances in the study of myofibrillar myopathies.

Prevascularization of self-organizing engineered heart tissue by human umbilical vein endothelial cells abrogates contractile performance

Establishing vascularization is a critical obstacle to the generation of engineered heart tissue (EHT) of substantial thickness. Addition of endothelial cells to the formative stages of EHT has been demonstrated to result in prevascularization, or the formation of capillary-like structures. The detailed study of the effects of prevascularization on EHT contractile function is lacking. Here, we evaluated the functional impact of prevascularization by human umbilical vein endothelial cells (HUVECs) in self-organizing EHT. EHT fibers were generated by the self-organization of neonatal rat cardiac cells on a fibrin hydrogel scaffold with or without HUVECs. Contractile function was measured and force-length relationship and rate of force production were assessed. Immunofluorescent studies were used to evaluate arrangement and distribution of HUVECs within the EHT fibers. RT-PCR was used to assess the transcript levels of hypoxia inducible factor-1a (Hif-1α). EHT with HUVECs manifested tubule-like structures at the periphery during fiber formation. After fiber formation, HUVECs were heterogeneously located throughout the EHT fiber and human CD31+ tubule-like structures were identified. The expression level of Hif-1α did not change with the addition of HUVECs. However, maximal force and rate of force generation were not improved in HUVECs containing EHT as compared to control EHT fibers. The addition of HUVECs may result in sparse microvascularization of EHT. However, this perceived benefit is overshadowed by a significant decrease in contractile function and highlights the need for perfused vascularization strategies in order to generate EHT that approaches clinically relevant dimensions.

A longitudinal study on BIO14.6 hamsters with dilated cardiomyopathy: micro-echocardiographic evaluation

BackgroundIn recent years, several new technologies for small-animal imaging have been developed. In particular, the use of ultrasound in animal imaging has focused on the investigation of accessible biological structures such as the heart, of which it provides a morphological and functional assessment. The purpose of this study was to investigate the role of micro-ultrasonography (μ-US) in a longitudinal study on BIO14.6 cardiomyopathic hamsters treated with gene therapy.MethodsThirty hamsters were divided into three groups (n = 10): Group I, untreated BIO 14.6 hamsters; Group II, BIO 14.6 hamsters treated with gene therapy; Group III, untreated wild type (WT) hamsters. All hamsters underwent serial μ-US sessions and were sacrificed at predetermined time points.Resultsμ-US revealed: in Group I, progressive dilation of the left ventricle with a change in heart morphology from an elliptical to a more spherical shape, altered configuration of the mitral valve and subvalvular apparatus, and severe reduction in ejection fraction; in Group II, mild decrease in contractile function and ejection fraction; in Group III, normal cardiac chamber morphology and function. There was a negative correlation between the percentage of fibrosis observed at histology and the ejection fraction obtained on μ-echocardiography (Spearman r: -0.839; p < 0.001).ConclusionsAlthough histological examination remains indispensable for a conclusive diagnosis, high-frequency μ-echocardiography, thanks to the high spatial and contrast resolution, can be considered sufficient for monitoring therapeutic efficacy and/or the progression of dilated cardiomyopathy, providing an alternative tool for repeatable and noninvasive evaluation.

The effect of repeated ischaemic periods on left ventricular dynamics during percutaneous coronary intervention

To study online left ventricular (LV) dynamic effects of transmural ischaemia and reperfusion during consecutive balloon coronary occlusions in the setting of percutaneous coronary intervention (PCI). In 10 consecutive unselected patients with stable angina (seven males, mean age 62 ± 3 years) who underwent elective PCI, LV dynamics were continuously recorded using a pressure-conductance catheter to simultaneously measure pressure and volume (PV-loop). The effects of a prolonged balloon coronary occlusion (148 ± 19 s) and a second occlusion on various LV function parameters were studied, as well as recovery of these parameters after reperfusion. Ischaemia caused an immediate (<5 s) decrease in diastolic function, followed by a decrease in contractile function, indicated by a rightward shift of the PV-loop, and a decreased dP/dtmax and ejection fraction. All parameters recovered within two minutes after reperfusion. The second occlusion caused a more rapid and more pronounced decrease in systolic and global LV function, while the 12-lead ECG showed less ST-segment deviation. Online LV pressure-volume measurements during elective PCI show that prolonged balloon coronary occlusion causes a phased ischaemic response of diastolic dysfunction, and then systolic dysfunction with more pronounced deterioration during a consecutive ischaemic period, paradoxical to the ischaemic electrocardiographic signs.

Reduced Expression of Alpha MHC in Failing, Pre-LVAD Human Myocardium Contributes to Depressed Rates of ATP Utilization

The ventricles of human myocardium normally express low levels of α myosin heavy chain (MHC) on a predominately β MHC background. However, in heart failure the distribution changes to ∼100% β MHC with virtually undetectable levels of α MHC. While it has been known for some time that α MHC exhibits greater rates of ATP utilization and maximal shortening velocity (Vmax), we have recently shown that the low level of α MHC normally present in the ventricles of larger mammals increases the rate of rise of force compared to myocardium expressing 100% β MHC. Here, we tested the hypothesis that the loss of α MHC in human heart failure impairs contraction kinetics and contributes to mechanical dysfunction by measuring the rate of ATP utilization and isometric force in normal donor hearts and in failing myocardium excised from patients prior to the implantation of a left ventricular assist device (LVAD). Permeabilized multicellular preparations from normal myocardium yielded maximal rates of ATP turnover approximately 3-fold greater than in pre-LVAD failing myocardium, while maximal isometric force between the two groups was similar. This equates to a nearly 3-fold greater tension cost in normal human myocardium, and it is possible that the lower tension cost observed in failing myocardium would enhance the efficiency of contraction under conditions of impaired energetics. Furthermore, SDS-PAGE indicated a reduction in α MHC content in pre-LVAD, failing myocardium compared to normal myocardium. These results suggest that a loss of α MHC in human heart failure would be at least partly responsible for the decrease in contractile function and would contribute to lower rates of pressure development (dP/dt) in vivo, ultimately impairing both systole and diastole. This work supported by NIH RO1-HL61635 (RLM).

Increased entropy production in diaphragm muscle of PPAR α knockout mice

Peroxisome proliferator activated receptor alpha (PPAR α) regulates fatty acid β-oxidation (FAO) and plays a central role in the metabolic and energetic homeostasis of striated muscles. The thermodynamic consequences of the absence of PPAR α were investigated in diaphragm muscle of PPAR α knockout mice (KO). Statistical mechanics provides a powerful tool for determining entropy production, which quantifies irreversible chemical processes generated by myosin molecular motors and which is the product of thermodynamic force A/ T (chemical affinity A and temperature T) and thermodynamic flow (myosin crossbridge (CB) cycle velocity υ). The behavior of both wild type (WT) and KO diaphragm was shown to be near-equilibrium and in a stationary state, but KO was farther from equilibrium than WT. In KO diaphragm, a substantial decrease in contractile function was associated with an increase in both A/ T and υ and with profound histological injuries such as contraction band necrosis. There were no changes in PPAR δ and γ expression levels or myosin heavy chain (MHC) patterns. In KO diaphragm, a marked increase in entropy production ( A/ T× υ) accounted for major thermodynamic dysfunction and a dramatic increase in irreversible chemical processes during the myosin CB cycle.

Effect of β-hydroxy-β-methylglutaryl coenzyme a reductase inhibitor atorvastatin on contractility of the isolated rat heart under normal conditions and during oxidative stress

Long-term administration of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor atorvastatin to rats was accompanied by an increase in the relative weight of the heart and decrease in the rate of pressure development in the isovolumic heart. During oxidative stress induced by addition of 100 microM H2O2 to the perfusate, the decrease in contractile function was more pronounced that in the control. Our results indicate that administration of atorvastatin is accompanied by a decrease in myocardial contractility, which becomes more pronounced under conditions of oxidative stress.

Microgravity and cardiac atrophy: no sex discrimination

mans’ continued initiative in space exploration will tax the human body, including the cardiovascular system. This system is exquisitely sensitive to loading conditions and neurohormonal stimuli and is adapted to function in normal gravitational environments (1 G). Both mechanical (muscle and

The role of protective effects of proline-containing peptides (PGP, PG, and GP) in contractile dysfunction of mesenteric lymphatic vessels in rats with experimental acute peritonitis

The development of acute peritonitis in rats induced by intraperitoneal injection of thioglycollate was accompanied by a decrease in contractile function of mesenteric lymphatic vessels and impaired response to norepinephrine. Administration of proline-containing peptides after induction of inflammation significantly decreased the severity of these disorders. Our results attest to the possibility of using peptides for the correction of mesenteric microcirculatory disturbances during inflammation.

Effects of a vitamin D3 analogue in a rat model of bladder outlet obstruction

To explore the effect of the vitamin D3 analogue, BXL-628, on some of the consequences of bladder outlet obstruction (BOO), e.g. hypertrophy and loss of contractile function, as vitamin D3 and BXL-628 inhibit prostate and bladder cell growth in vitro, and there are receptors for vitamin D in rat and human bladder. In female rats, BOO was produced by a standardized method; one group received daily BXL-628 (150 microg/kg per day) and the remaining rats received vehicle. Sham-operated rats received BXL-628 or vehicle. After 2 weeks, the conscious rats were assessed by cystometry. Plasma calcium levels were determined and in vitro contractility assessed at the end of the experiments. There was a significant increase in bladder weight, micturition interval and volume, and in bladder capacity in both the obstructed groups compared to sham controls, but no difference between the obstructed groups. On plotting the micturition pressure against bladder weight within the obstructed groups, there was a clear correlation in the vehicle-treated group, indicating a decrease in contractile function with increasing bladder weight. There was no such correlation in the treatment group. In vitro, there was a strong correlation of increasing bladder weights vs decrease in response to KCl and electrical-field stimulation in strips from obstructed vehicle-treated rats, but no correlation in those from drug-treated rats. Treatment increased the plasma calcium level by 12%. The vitamin D(3) analogue used did not prevent bladder hypertrophy, but appeared to reduce some of the negative functional changes of the bladder smooth muscle, which occurs with BOO-induced increases in bladder weight.