Maximum Rate Of Pressure Development Research Articles

Age-Dependent Changes in Calcium Regulation after Myocardial Ischemia–Reperfusion Injury

During aging, heart structure and function gradually deteriorate, which subsequently increases susceptibility to ischemia–reperfusion (IR). Maintenance of Ca2+ homeostasis is critical for cardiac contractility. We used Langendorff’s model to monitor the susceptibility of aging (6-, 15-, and 24-month-old) hearts to IR, with a specific focus on Ca2+-handling proteins. IR, but not aging itself, triggered left ventricular changes when the maximum rate of pressure development decreased in 24-month-olds, and the maximum rate of relaxation was most affected in 6-month-old hearts. Aging caused a deprivation of Ca2+-ATPase (SERCA2a), Na+/Ca2+ exchanger, mitochondrial Ca2+ uniporter, and ryanodine receptor contents. IR-induced damage to ryanodine receptor stimulates Ca2+ leakage in 6-month-old hearts and elevated phospholamban (PLN)-to-SERCA2a ratio can slow down Ca2+ reuptake seen at 2–5 μM Ca2+. Total and monomeric PLN mirrored the response of overexpressed SERCA2a after IR in 24-month-old hearts, resulting in stable Ca2+-ATPase activity. Upregulated PLN accelerated inhibition of Ca2+-ATPase activity at low free Ca2+ in 15-month-old after IR, and reduced SERCA2a content subsequently impairs the Ca2+-sequestering capacity. In conclusion, our study suggests that aging is associated with a significant decrease in the abundance and function of Ca2+-handling proteins. However, the IR-induced damage was not increased during aging.

Non-invasive assessment of fatigue and recovery of inspiratory rib cage muscles during endurance test in healthy individuals.

Fatigue is defined as loss of capacity to develop muscle force and/or velocity that is reversible at rest. We assessed non-invasively the fatigue and recovery of inspiratory rib cage muscles during two respiratory endurance tests in healthy individuals. The sniff nasal inspiratory pressure (SNIP) was assessed before and after two respiratory endurance tests: normocapnic hyperpnea (NH) and inspiratory pressure threshold loading (IPTL). Contractile (maximum rate of pressure development and time to peak pressure) and relaxation parameters (maximum relaxation rate [MRR], time constant of pressure decay [τ], and half relaxation time) obtained from sniff curves and shortening velocity and mechanical power estimated using optoelectronic plethysmography were analyzed during SNIP maneuvers. Respiratory muscle activity (electromyography) and tissue oxygenation (near-infrared spectroscopy-NIRS) were obtained during endurance tests and SNIP maneuvers. Fatigue development of inspiratory rib cage muscles was assessed according to the slope of decay of median frequency. Peak pressure during SNIP decreased after both protocols (p <0.05). MRR, shortening velocity, and mechanical power decreased (p <0.05), whereas τ increased after IPTL (p <0.05). The median frequency of inspiratory rib cage muscles (i.e., sum of sternocleidomastoid, scalene, and parasternal) decreased linearly during IPTL and exponentially during NH, mainly due to the sternocleidomastoid. Fatigue development behaved differently between protocols and relaxation properties (MRR and τ), shortening velocity, and mechanical power changed only in the IPTL.

Effects of diaphragmatic control on multiparametric analysis of the sniff nasal inspiratory pressure test and inspiratory muscle activity in healthy subjects.

BackgroundWe investigated the influence of diaphragmatic activation control (diaphC) on the relaxation rate, contractile properties and electrical activity of the inspiratory muscles of healthy subjects. Assessments were performed non-invasively using the sniff inspiratory pressure test (SNIP) and surface electromyography, respectively.MethodsTwenty-two subjects (10 men and 12 women) performed 10 sniff maneuvers in two different days: with and without diaphC instructions. For the SNIP test with diaphC, the subjects were instructed to perform intense activation of the diaphragm. The tests with the best SNIP values were used for analysis.ResultsThe maneuver with diaphC when compared to the maneuver without diaphC exhibited significant lower values for: SNIP (p <0.01), maximum relaxation rate (MRR) (p <0.01), maximum rate of pressure development (MRPD) (p <0.01), contraction times (CT) (p = 0.02) and electrical activity of the sternocleidomastoid (SCM) (p <0.01), scalene (SCL) (p = 0.01) and intercostal (CI) (p = 0.03) muscles. In addition, the decay constant (tau, τ) and relaxation time (½ RT) did not present any changes.ConclusionThe diaphragmatic control performed during the SNIP test influences the inspiratory pressure and the contractile properties of inspiratory muscles. This occurs due to changes in the pattern of muscle recruitment, which change force velocity characteristics of the test. Thus, instruction on diaphC should be encouraged for better performance of the SNIP test and for evaluation targeting the diaphragm muscle activity.

Assessment of the respiratory muscles strength at patients with chronic obstructive pulmonary disease with various forms of comorbidity

To evaluate the RM power of COPD patients with various variants of comorbidity and to determine the role of comorbidity in the development of respiratory muscle dysfunction. RM strength of 64 men with exacerbation of COPD was studied. The severity of comorbidity was assessed by the Charlson index. Depending on the prevalence of comorbidity, patients were divided into 3 groups: cardiovascular, cerebrovascular and metabolic. Maximum inspiratory (MIP) and expiratory (MEP) pressures in the oral cavity, maximum rate of pressure development (MRPD), sniff nasal inspiratory pressure (SNIP), MEP/MIP and SNIP/MIP indexes were determined with MicroRPM device (UK). Measured values of MIP, MEP and SNIP were compared with the proper ones. The most noticeable decrease of RM strength was defined in the group of patients with severe comorbidity. In case of a mild comorbidity MEP and SNIP values were 68 and 78% of the predicted values and MIP value corresponded to the personified standard. RM strength of patients with COPD depended on the clinical variant of comorbidity. Thus, in the group of patients with cardiovascular variant of comorbidity auxiliary inspiratory muscles strength decreased. In the group of patients with cerebrovascular variant of comorbidity the expiratory muscles dysfunction predominated. In the group of patients with metabolic variant of comorbidity diaphragm dysfunction predominated. The pathogenetic significance of various factors of COPD comorbidity in the development of RM dysfunction was confirmed by the results of the correlation analysis.

Comparative analysis of the strength of the respiratory muscles in community-acquired pneumonia with different severity of endogenous intoxication

To assess the strength of the respiratory muscles in patients with community-acquired pneumonia (CAP) with varying severity of endogenous intoxication. In the hospital, 78 men aged 1826 years with CAP were examined. СAP was diagnosed in 56 (72%) patients, severe CAP in 22 (28%). The severity of endogenous intoxication was verified using intoxication indices: hematological index of intoxication (HII), leukocyte index of intoxication (LII), nuclear index of intoxication (NII) and Krebs index. Middleweight molecules (MWM) was determined by spectrophotometry in the serum and the concentration of interleukin (IL)-10 and tumor necrosis factor  (TNF-) by ELISA. The strength of the respiratory muscles was measured on the device Micro RPM (Care Fusion, Great Britain). The maximum expiratory pressure (МЕР), inspiratory pressure (MIP) in the oral cavity, the Maximal Rate of Pressure Development (MRPD) during inhalation (MRPDin) and exhalation (MRPDex), and intranasal test (SNIP) were determined. Statistical processing was performed using descriptive statistics, MannWhitney test, correlation and cluster analysis. Three clusters of endogenous intoxication corresponding to mild, moderate and severe degree were identified. The first cluster was represented only by patients with mild CAP, the second-mild CAP and severe CAP, and the third severe CAP. Dysfunction of the expiratory respiratory muscles prevailed during the height of the disease in patients with the first cluster, and in the second and third inspiratory, including the diaphragm. The level of actually measured values of MIP and SNIP was 68% and 58% of those due to severe endogenous intoxication. Significant negative correlations were established LII, HII, MWM, TNF-, IL-10 с MEP, MRPDex, MIP и SNIP. Respiratory muscle dysfunction remained only expiratory respiratory muscles in convalescents of the first cluster, and expiratory and inspiratory muscles of the second and third cluster. The development of respiratory muscle dysfunction in CAP is associated with the influence of endogenous intoxication factors. The results can be used in personalized programs of rehabilitation.

Effects of caffeine on inspiratory muscle function

Research suggests that caffeine can enhance measures of muscular strength in the upper and lower extremities, although the literature is somewhat equivocal. Little is known on whether or not caffeine will improve maximal inspiratory pressure (MIP), a surrogate measure of inspiratory muscle strength. The purpose of the study was to determine the effects of a moderate dose of caffeine on inspiratory muscle function. Fifteen (8 male, 7 female) healthy adults (mean ± SD: age = 24.3 ± 6.4 years; height = 1.75 ± 0.11 m; body mass = 78.8 ± 16.5 kg) volunteered to participate in the study which used a double-blind, placebo-controlled, cross-over design. During the initial visit, baseline data was collected and participants were familiarized with inspiratory muscle measurements. For the second and third visits, participants ingested either a 5 mg kg−1 dose of caffeine (CAF) or placebo capsule (PL). After one hour, they completed at least 12 maximal inspiratory manoeuvres with 1 min rest between each attempt. MIP, maximal inspiratory peak pressure (PP), and maximal rate of pressure development (MRPD) were recorded. The CAF trial resulted in significantly higher MIP (154.7 ± 35.8 vs. 146.6 ± 37.6 cmH2O; p = 0.02) and PP (165.8 ± 36.8 vs. 158.3 cmH2O; p = 0.01) compared to the PL condition. No significant difference was observed in MRPD (p = 0.18). MIP and PP improved after ingestion of caffeine compared to the placebo condition. The findings from the study further establish caffeine’s potential ergogenic benefit on measures of muscular strength.

Pressure and Volume Characteristics of the Left Ventriclе in Its Diastolic and Systolic Dysfunction

Cardiomyopathy in rats has been developed after 4 weeks doxorubicin administration(2 mg / kg weekly). Echocardiographic study of rats in 8 weeks from onset of doxorubicin administration showed preponderanceof systolic dysfunction (67 %) with decrease of left ventricular (LV) ejection fraction (EF) by 30 %. Simultaneous registration of LV pressureand volume showed that diastolic LV volume was preserved in doxorubicin-treated rats due to considerable lengthening of the diastole,the heart rate was reduced by 22 %. These hearts also showed slowing of relaxation, reduced maximal rate of pressure development andstroke work, as well as significant reduction in peripheral arterial resistance. Diastolic dysfunction differed from the systolic one by normalsystolic EF and preserved LV contractility index as well as lower diastolic LV pressure throughout the diastole. Based on thesedata, four compensatory mechanisms associated with cardiomyopathy were distinguished - 1) slowing of myocardial relaxation, prolongingmyofibrillar active state, 2) reduction of peripheral arterial resistance for easier LV ejection, 3) heart rate reduction, prolonging diastolicpause and thus facilitating better LV filling and 4) increased pressure in the small circle, also contributing to the LV rapid filling.

Assessment of the respiratory muscles strength at various stages of ischemic stroke

To assess the power of RM in patients with IS at different stages of the disease. Power characteristics of RM of 56 patients with IS with different severity of the disease were examined after 2-4, 5-6 and 13-14 months of IS onset. Maximum inspiratory (MIP) and expiratory (MEP) pressures in the oral cavity, maximum rate of pressure development (MRPD) and sniff nasal inspiratory pressure (SNIP) were determined. A decrease in expiratory and inspiratory RM strength was shown in the early and late periods of IS, severity of which was depended on the severity of neurologic disorders. The bronchial obstruction resulted in RM dysfunction. Expiratory muscles weakness only was observed in the remote period while one third of patients had obstructive disorders of breathing. The functional activity of different RM at different IS stages was correlated with the smoking index, forced expiratory volume in the first second, forced vital capacity, skeletal muscles mass and severity of dyspnea, asthenia and disturbances of vital functions. These differences were the most obvious in elderly group of people. RM power examination of IS patients is an important mechanism of early diagnosis and rehabilitation.

Embryonic developmental oxygen preconditions cardiovascular functional response to acute hypoxic exposure and maximal β-adrenergic stimulation of anesthetized juvenile American alligators (Alligator mississippiensis).

The effects of the embryonic environment on juvenile phenotypes are widely recognized. We investigated the effect of embryonic hypoxia on the cardiovascular phenotype of 4-year-old American alligators (Alligator mississippiensis). We hypothesized that embryonic 10% O2 preconditions cardiac function, decreasing the reduction in cardiac contractility associated with acute 5% O2 exposure in juvenile alligators. Our findings indicate that dobutamine injections caused a 90% increase in systolic pressure in juveniles that were incubated in 21% and 10% O2, with the 10% O2 group responding with a greater rate of ventricular relaxation and greater left ventricle output compared with the 21% O2 group. Further, our findings indicate that juvenile alligators that experienced embryonic hypoxia have a faster rate of ventricular relaxation, greater left ventricle stroke volume and greater cardiac power following β-adrenergic stimulation, compared with juvenile alligators that did not experience embryonic hypoxia. When juveniles were exposed to 5% O2 for 20 min, normoxic-incubated juveniles had a 50% decline in left ventricle maximal rate of pressure development and maximal pressure; however, these parameters were unaffected and decreased less in the hypoxic-incubated juveniles. These data indicate that embryonic hypoxia in crocodilians alters the cardiovascular phenotype, changing the juvenile response to acute hypoxia and β-adrenergic stimulation.

Study on the expression and roles of nucleolin in cardiac injury in septic mice

Objective: To explore the expression and roles of nucleolin in cardiac injury in septic mice. Methods: C57BL/6 mice (WT mice) and myocardium-specific expression of nucleolin transgenic mice (TG mice) were randomly divided into sham group (n=10, sham-operated) and sepsis group (n=15, animal model). Cecal ligation and puncture (CLP) was adopted to produce animal models of sepsis. The expression of nucleolin was detected by Western blotting analysis at 0, 12, 24, 48 hours after the operation. The 7-day survival rate, haemodynamic measurement, levels of isoenzyme of creatinekinase-MB (CK-MB) and cardiac troponin I (cTnI) in serum and levels of reactive oxygen species (ROS) and malondlaldehyde (MDA) in myocardium were evaluated 24 hours after the operation. The data were compared between groups with t test. Results: The expression of nucleolin in myocardium up-regulated significantly in WT+CLP group when compared with that in the WT+Sham group(2.57±0.34 vs 1.00±0.15, t=7.468, P<0.01). Compared with those in the WT+Sham group, the survival rate decreased (33.3% vs 100%, χ(2)=13.375, P<0.01), maximal rate of pressure development (+dp/dtmax) declined (t=4.993, P<0.01), but the serum levels of CK-MB and cTnI and the levels of ROS and MDA in myocardium increased in the WT+CLP group(t=5.031, 4.335, 3.365, 2.375, all P<0.05). Compared with that in WT+CLP group, the 7-day survival rate of mice increased in TG+CLP group (60.0% vs 33.3%, χ(2)=8.227, P=0.004), and the cardiac function improved (t=2.337, P=0.019), but the serum levels of CK-MB and cTnI and the levels of ROS and MDA in myocardium in TG+CLP group reduced significantly (t=2.127, 3.347, 2.115, 2.224,P<0.05). Conclusion: The expression of nucleolin is up-regulated in the myocardium of septic mice, and the overexpression of nucleolin can inhibit oxidative stress injury, attenuate the cardiac injury and dysfunction, and reduce mortality in septic mice.

Effects of Calorie Restriction and Voluntary Exercise on Doxorubicin-Induced Cardiotoxicity.

Introduction: Doxorubicin (DOX) is a widely used chemotherapeutic agent with known cardiotoxic properties, while calorie restriction (CR) and exercise have well-documented cardioprotective effects. No studies have investigated the effects of CR alone or the combined effects of CR and exercise on DOX cardiotoxicity. Methods: Rats were divided into 4 groups based on their food intake (ad libitum or CR) and activity (sedentary or voluntary wheel running [WR]). After completing a 16-week treatment, animals received either DOX (15 mg/kg) or saline (SAL) and cardiac function was measured 5 days after treatment. Chromatography was used to quantify left ventricular DOX accumulation. Results: Left ventricular developed pressure (LVDP), end systolic pressure (ESP), and left ventricular maximal rate of pressure development (dP/dtmax) were significantly higher in the CR + DOX group when compared with DOX. Fractional shortening, LVDP, ESP, dP/dtmax, and dP/dtmin were significantly higher in the CR + WR + DOX group compared with the DOX group. In addition, the CR + WR + DOX group showed significantly higher LVDP and ESP compared with the WR + DOX group. DOX accumulation in the heart was 5-fold lower (P < .05) in the CR + WR + DOX group compared with the DOX group. Conclusion: This is the first study to demonstrate that CR can reduce cardiac DOX accumulation, and confirms the protective role of CR against DOX-induced cardiac dysfunction. Our data also show that combining a known cardioprotective intervention, exercise training, with CR results in additive benefits in the protection against DOX cardiotoxicity.

Cardioprotection of salvianolic acid B and ginsenoside Rg1 combination on subacute myocardial infarction and the underlying mechanism

BackgroundFollowing myocardial infarction (MI), a series of structural and functional changes evolves in the myocardium, collectively defined as cardiac remodeling. PurposeThe aim of present study was to investigate the cardioprotection of salvianolicacid B (SalB) and ginsenoside Rg1 (Rg1) combination against cardiac remodeling in a rat model at the subacute phase of MI and further elucidate the underlying mechanism. MethodsRat heart was exposed via a left thoracotomy at the fourth intercostal space and MI was induced by a ligature below the left descending coronary artery. Hemodynamic assay was conducted using a Mikro-tipped SPR-320 catheter which was inserted through the right carotid artery into left ventricle.Myocardial infarct size was detected using 3,5-triphenyltetrazolium chloride (TTC) staining. Haematoxylin and eosin (HE) stain and picric sirius red stain were conducted for histopathological detection. Immunohistochemistry was used to detect the expression of α-smooth muscle actin (α-SMA) and gelatin zymography was used to evaluate the activities of matrix metalloproteinase-9 (MMP-9). ResultsComparing with MI rats, 30 mg/kg SalB-Rg1 improved cardiac function verified by maximum rate of pressure development for contraction (+dp/dtmax, p < 0.01) and maximum rate of pressure development for relaxation (−dp/dtmax, p < 0.05); reduced myocardial infarct size (p < 0.05) verified by TTC staining, improved cardiac structure based on HE stain; decreased collagen volume fraction (p < 0.05) and collagen I/III ratio (p < 0.05) according picrosirius red staining. The underlying mechanism of SalB-Rg1 against cardiac remodeling was associated with its down-regulation on α-SMA expression according immunohistochemistry (p < 0.01) and inhibition on MMP-9 activity based on in-gel zymography (p < 0.05). ConclusionAll above study indicated the potential therapeutic effects of SalB-Rg1 on heart.

MicroRNA-1249 regulates the apoptosis of myocardial cells in rats with chronic intermittent hypoxia by autophagy

Objective: To investigate the regulation and possible mechanism of microRNA (miR)-1249 on myocardial apoptosis in chronic intermittent hypoxia rats. Methods: A total of 16male SD rats aged 8 weeks were randomly divided into 2 groups by the random number table: normoxia control group and chronic intermittent hypoxia group (CIH) (n=8 each). The CIH group was exposed to intermittent hypoxia every day from 9: 00 to 17: 00 for 8 consecutive weeks, while the control group received the same frequency of pulse air. Hemodynamic values were measured via a cannula inserted into right common carotid artery. The expressions of miR-1249 and microtubule-associated protein light chain 3 (LC3) mRNA were observed by real-time PCR. The expressions of LC3 and Cleaved Caspase-3 were detected by Western bolt. TUNEL staining was performed to detect myocardial apoptosis. The rat cardiomyocyte cell H9C2 was divided into normoxia group, intermittent hypoxia (IH) group and miR-1249 inhibitor transfected and IH treatment group (inhibitor group). At the end of the experiment, the activation of LC3 protein in each group of cells was determined. Results: Compared with normoxia control group, left ventricle end diastolic pressure (LVEDP) increased [(4.6±0.4) vs (2.2±0.1) mmHg (1 mmHg=0.133 kPa)], left ventricular systolic pressure (LVSP) , maximal rate of pressure decline (-dp/dtmax), and maximal rate of pressure development (+ dp/dtmax) decreased in CIH group [(92.7±4.1) vs (135.3±3.2) mmHg, (4 247±108) vs (7 626±235) mmHg/s, and (3 168±105) vs (6 028±81) mmHg/s] (all P<0.001). The expression of miR-1249 and LC3 mRNA were significantly higher in CIH group than that in normoxia control group (all P<0.001), and a positive correlation was found between the expression of LC3 mRNA and miR-1249. The expression of LC3 and Cleaved Caspase-3 protein in myocardial tissue of CIH rats were significantly higher than that of the normoxia control group (all P<0.001). The proportion of myocardial cell apoptosis in CIH rats was significantly higher than that in the normoxia control group [(23.84±4.94)% vs (2.93±0.73)%] (P<0.001). The activation of LC3 in myocardial cells of inhibitor group was significantly lower than that of IH group, but higher than that in normoxia group. Conclusions: CIH could induce LC3 by raising the expression of miR-1249, and then induce the activation of apoptosis protein Caspase3. It ultimately induces myocardial apoptosis.

Multiparametric Analysis of Sniff Nasal Inspiratory Pressure Test in Middle Stage Amyotrophic Lateral Sclerosis.

The relaxation rates and contractile properties of inspiratory muscles are altered with inspiratory muscle weakness and fatigue. This fact plays an important role in neuromuscular disorders patients and had never been extensively studied in amyotrophic lateral sclerosis (ALS). In this cross-sectional study, these parameters were investigated non-invasively through nasal inspiratory sniff pressure test (SNIP) in 39 middle stage spinal onset ALS subjects and compared with 39 healthy controls. ALS patients were also divided into three subgroups according to a decline in their percentage of predicted forced vital capacity (FVC%pred) as well as a decline in the ALS functional rating scale score and its respiratory subscore (R-subscore) in order to determine the best parameter linked to early respiratory muscle weakness. When compared with healthy subjects, middle stage ALS subjects exhibited a significantly lower (p < 0.0001) maximum relaxation rate and maximum rate of pressure development (MRPD), as well as a significantly higher (p < 0.0001) tau (τ), contraction time, and half-relaxation time. The results from receiver operating characteristic curves showed that MRPD (AUC 0.735, p < 0.001) and FVC%pred (AUC 0.749, p = 0.009) were the best discriminator parameters between ALS patients with ≤30 and >30 points in the ALS functional rating scale. In addition, 1/2RT (AUC 0.720, p = 0.01), FVC%pred (AUC 0.700, p = 0.03), τ (AUC 0.824, p < 0.0001), and MRPD (AUC 0.721, p = 0.01) were the parameters more sensitive in detecting a fall of three points in the R-subscore. On the other hand, MRPD (AUC 0.781, p < 0.001), τ (AUC 0.794, p = 0.0001), and percentage of predicted of SNIP (AUC 0.769, p = 0.002) were the parameters able to detect a fall in 30% of the FVC%pred in middle stage ALS patients. The contractile properties and relaxation rates of the diaphragm are altered in middle stage spinal onset ALS when compared with healthy subjects. These parameters are able to discriminate between those middle stage ALS subjects with early decline in inspiratory muscle function and those who not.

Effect of omentin on cardiovascular functions and gene expressions in isolated rat hearts.

Objective:Omentin is a recently identified novel adipocytokine mainly expressed in the epicardial adipose tissue. Although it has favorable effects on cardiovascular disease, the impact of omentin on the hearts is still an understudied issue. The aim of the present study was to investigate the possible effects of omentin on isolated rat heart.Methods:Using the Langendorff method, 28 adult male Sprague–Dawley rat hearts were isolated and perfused with modified Krebs–Henseleit solution (mK–Hs). Concentrations of 100, 200, and 400 ng/mL omentin were given to the hearts for 30 min. The control group (n=7) was perfused with mK–Hs alone. Gene expressions in the left ventricle tissue were determined by real-time polymerase chain reaction. Left ventricular cyclic adenosine monophosphate and cyclic guanosine monophosphate (cGMP) concentrations were determined by using enzyme-linked immunosorbent assay.Results:All concentrations of omentin significantly decreased left ventricular developed pressure and maximal rate of pressure development that are the indexes of cardiac contractility. At the same time, omentin decreased both phosphoinositide 3-kinase γ (PI3Kγ) and sarcolemmal L-type Ca2+ channel (CaV1.2) mRNA levels. Moreover, this peptide at concentrations of 200 and 400 ng/mL increased endothelial nitric oxide synthase (eNOS) mRNA. Furthermore, concentrations of 200 and 400 ng/mL omentin increased the amount of cGMP.Conclusion:We conclude that acute omentin treatment decreases cardiac contractility. Elevated eNOS mRNA and cGMP levels with reduced CaV1.2 mRNA are likely to lead to negative inotropy.

The impact of apelin-36 on isolated rat hearts as a member of apelin family.

Apelinis an endogenousadipocytokine thatplays an important role in the regulation of cardiovascular function. Apelin-36 is a member of apelin family. However cardiac reports related to apelin-36 are very rare. The purpose of this study is to investigate the impact of apelin-36 onhemodynamic variables of the isolated rat hearts. Twenty-eight ratswere equally divided into four groups: control, apelin-36 at the following concentrations: 1 nM, 10 nM and 100 nM. Theisolatedhearts were perfused with modified Krebs-Henseleit solution (mK-Hs) by using theLangendorffmethod. Cardiac parameters, including left ventricular developed pressure (LVDP),maximal rate of pressure development (+dP/dtmax), heartrate (HR) and coronary flow (CF) were measured. Gene expressions relevant to cardiomyocyte contractility were determined by real-time PCR. 10 and 100 nM doses of apelin-36 perfusion led topositive inotropy with an increase of LVDP and +dP/dtmax, which are the indexes of cardiac contractility. Furthermore both doses of apelin-36 increased endothelial nitric oxide synthase (eNOS), sarco/endoplasmic reticulum Ca2+-ATPase (Serca2a) andβ2-Adrenergic receptors (β2-AR) mRNA. These results showed that apelin-36 had a positive inotropic effect on the isolated rat heart and can induceeNOS,Serca2aandβ2-ARgenes activation that enhancescontractilityof theheart (Tab. 1, Fig. 2, Ref. 23).

Reduced Binding of the M-Domain of Cardiac Myosin Binding Protein C to Actin Impairs the Ability of the Heart to Respond to Chronic Stress

Cardiac myosin binding protein C (cMyBP-C) is a sarcomeric protein that regulates cross bridge cycling to control timing and strength of cardiac contraction. However, the molecular mechanisms by which cMyBP-C influences cross bridge cycling are incompletely understood. The M-domain of cMyBP-C can interact with actin and myosin, and phosphorylation of cMyBP-C in response to β-adrenergic stimulation during cardiac stress diminishes its affinity for both.In this study we determined the functional relevance of cMyBP-C binding to actin on cardiac function. Binding of cMyBP-C to actin can activate the thin filament and we hypothesize that dissociation of cMyBP-C from actin is essential for cardiac relaxation. To test our hypothesis, we created a transgenic mouse model with a mutation in the M-domain of cMyBP-C (E330K) that reduced binding affinity for actin in vitro. We then used echocardiography and pressure-volume recordings to assess cardiac function under sedentary and stress conditions.Both systolic function (e.g. stroke volume, ejection fraction and maximal rate of pressure development (+dP/dt)) and diastolic function (e.g. –dP/dt, isovolumetric relaxation time, E/A) were normal in E330K-Tg mice under sedentary conditions. Acute β-adrenergic stimulation with isoprenaline also led to normal increases in both contractility and relaxation in E330K-Tg mice. However, chronic cardiac stress by increasing preload to the heart by aortocaval fistula was fatal to all E330K-Tg mice within 10 days after surgery.Our results demonstrate that reduced interaction between the M-domain of cMyBP-C and actin did not impair cardiac function in E330K-Tg mice under sedentary conditions, but that this interaction may be essential for the heart to cope with chronic volume overload.This work is supported by NIH HL-080367 and AHA 15POST25700403.

The Effects of Beta Amyloid Peptide 1-42 on Isolated Rat Hearts and Ileum Smooth Muscle

Neurotoxic beta amyloid peptides (βAPs) are involved in the pathogenesis of Alzheimer disease. βAP_1-42 may also play a role in the regulation of cardiovascular functions. Therefore, we investigated the possible effects of βAP_1-42 on isolated rat heart and ileum. The hearts were perfused with modified Krebs-Henseleit solution. Left ventricular developed pressure (LVDP), maximal rate of pressure development of left ventricle (+dP/dt_max), heart rate, coronary flow, monophasic action potential amplitude (MAPamp), MAP duration at 90% repolarization (MAP₉₀) and contractions of ileum were measured. One, 10 and 100 nmol/l doses of βAP_1-42 significantly decreased LVDP, +dP/dt_max and heart rate. The dose of 1 nmol/l did not change coronary flow, but 10 and 100 nmol/l doses significantly reduced it. All doses of βAP_1-42 did not alter MAPamp, but increased MAP₉₀. βAP_1-42 (1, 10, 100, 1,000 nmol/l) also did not influence ileum contractions. We suggest that βAP_1-42 produces negative inotropic and negative chronotropic effects with an increase in MAP duration. Furthermore, βAP_1-42 at high doses decreases coronary flow.

Estimation of bladder contractility from intravesical pressure-volume measurements.

To describe parameters from urodynamic pressure recordings that describe urinary bladder contractility through the use of principles of muscle mechanics. Subtracted detrusor pressure and voided flow were recorded from patients undergoing filling cystometry. The isovolumetric increase of detrusor pressure, P, of a voluntary bladder contraction before voiding was used to generate a plot of (dP/dt)/P versus P. Extrapolation of the plot to the y-axis and the x-axis generated a contractility parameter, vCE (the maximum rate of pressure development) and the maximum isovolumetric pressure, P0 , respectively. Similar curves were obtained in ex vivo pig bladders with different concentrations of the inotropic agent carbachol and shown in a supplement. Values of vCE , but not P0 , diminished with age in female subjects. vCE was most significantly associated with the 20-80% duration of isovolumetric contraction t20-80 ; and a weaker association with maximum flow rate and BCI in women. P0 was not associated with any urodynamic variable in women, but in men was with t20-80 and isovolumetric pressure indices. The rate of isovolumetric subtracted detrusor pressure (t20-80 ) increase shows a very significant association with indices of bladder contractility as derived from a derived force-velocity curve. We propose that t20-80 is a detrusor contractility parameter (DCP). Neurourol. Urodynam. 36:1009-1014, 2017. © 2016 Wiley Periodicals, Inc.

Thyroid hormone reduces inflammatory cytokines improving glycaemia control in alloxan-induced diabetic wistar rats.

This study aimed at evaluating whether thyroid hormone treatment could improve glycaemia and insulin response in alloxan-induced diabetic rats by altering cytokine expression in the skeletal muscle and epididymal white adipose tissue (eWAT) as well as altering inflammatory cell infiltration in eWAT. Diabetes mellitus (DM) was induced in male Wistar rats by alloxan injection, and a subset of the diabetic rats was treated with T3 (1.5μg per 100g body weight) for a 28-day period (DT3 ). Cytokines were measured in serum (MILIplex assay kit) as well as in soleus and EDL skeletal muscles and eWAT by Western blotting. Thyroid function was evaluated by morphological, molecular and biochemical parameters. Cardiac function was assessed by measuring heart rate, blood pressure, maximal rate of pressure development (dp/dtmax ) and decline (dp/dtmin ) as well as the contractility index (CI). Sixty rats were used in the study. Diabetic rats exhibited decreased thyroid function and increased inflammatory cytokines in serum, soleus muscle and eWAT. T3 treatment decreased glycaemia and improved insulin sensitivity in diabetic animals. These alterations were accompanied by decreased TNF-alpha and IL-6 content in soleus muscle and eWAT, and inflammatory cell infiltration in eWAT. T3 treatment did not affect cardiac function of diabetic rats. The present data provide evidence that T3 treatment reduces glycaemia and improves insulin sensitivity in diabetic rats, and that at least part of this effect could result from its negative modulation of inflammatory cytokine expression.