Effect of microparticles derived from bone marrow mesenchymal stem cells on cardiomyocyte hypertrophy and its mechanism / 中国生物制品学杂志

@#Objective To investigate the effect of microparticles(MPs)derived from bone marrow mesenchymal stem cells(BMSCs) on myocardial hypertrophy and its mechanism.Methods The osteogenic differentiation and adipogenic differentiation of mesenchymal stem cells(MSCs) were induced. After isolation and purification,the morphological characteristics were observed by transmission electron microscope,and the MPs surface antigen was identified by flow cytometry. Myocardial hypertrophy model was induced by using isoprenaline(ISO)in rats,which were measured for the cardiac structure and function by echocardiography,and then detected for various indexes of the heart and isolated left ventricle. Single ventricular myocytes of rats were acutely isolated and divided into control group(Control group),cardiomyocyte hypertrophy group(ISO group),MPs group(MPs group),and MPs supernatant group(Supernatant group). The mRNA expressions of atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP)were detected by qRTPCR. The expression levels of calmodulin-dependent protein kinaseⅡ（CaMKⅡ）and phosphorylated calmodulin-dependent protein kinaseⅡ（p-CaMKⅡ）were detected by ELISA. The L-type calcium current(LCa-L)in single ventricular myocyte of various groups was recorded by whole-cell patch clamp.Results The bone nodules of MSCs osteogenic differentiation turned red after alizarin red staining,and lipid droplets of adipogenic differentiation turned red after oil red O staining;Under transmission electron microscope,MPs membrane had a complete structure,a clear outline and a diameter of about200 nm;The positive rates of CD29 and CD90 on the surface of MPs were(98. 24 ± 0. 82)% and(97. 69 ± 1. 83)%,respectively. Compared with Control group,the left ventricular end diastolic dimension(LVEDD)reduced signifi-cantly(t =5. 065,P < 0. 05),while the interventricular septum end-diastolic dimension(IVSd),left ventricular posterior wall dimension(LVPWd),heart weight to body weight ratio(HW/BW),and heart weight to tibial length ratio(HW/Tibia)significantly increased in ISO group(t = 4. 013,2. 368,4. 392,5. 043 and 6. 120,respectively,each P < 0. 05),indicating that the hypertrophic model was successfully established. The expression levels of ANP and BNP mRNA in hypertrophic cardiomyocytes of rats in ISO group were significantly higher than those in Control group(t = 25. 120 and18. 261,respectively,each P < 0. 01);While the expression levels of ANP and BNP mRNA in MPs group significantly reduced after incubation with 48 μg/mL MPs for 48 h compared with ISO group(t = 12. 110 and 3. 526,respectively,each P < 0. 05);The expression levels of CaMK Ⅱand p-CaMKⅡ in ISO group were significantly higher than those in Control group(t = 3. 278 and 4. 181,respectively,each P < 0. 05),while the expression of p-CaMK Ⅱ in MPs group decreased significantly(t = 5. 420,P < 0. 05);The calcium current density in ISO group was significantly higher than that in Control group(t = 15. 261,P < 0. 01),while that in MPs group was significantly lower than that in ISO group(t =6. 216,P < 0. 05).Conclusion MSC-MPs can significantly inhibit ISO-induced cardiomyocyte hypertrophy in rats,which is related to its down-regulation of cardiomyocyte CaMKⅡ and inhibition of L-type calcium channel.

Clinical Efficacy of Qihuang Jianpi Zishen Granules in Treating Cardiac Involvement in Systemic Lupus Erythematosus / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy and safety of Qihuang Jianpi Zishen granules in the treatment of cardiac involvement in systemic lupus erythematosus （SLE）. MethodA total of 62 SLE patients with cardiac involvement treated in the Department of Rheumatology and Immunology， the First Affiliated Hospital of Anhui University of Chinese Medicine from June 2021 to December 2022 were randomized into control and observation groups （n=31）. The control group was treated with methylprednisolone tablets and hydroxychloroquine sulfate tablets， and the observation group with Qihuang Jianpi Zishen granules on the basis of the therapy in the control group. After 12 weeks of treatment， the two groups were compared in terms of the therapeutic effect， cardiac function indicators ［left atrial end-diastolic diameter （LADd）， left ventricular end-diastolic diameter （LVDd）， left ventricular posterior wall thickness （LVPWTd）， peak blood flow velocity in early diastolic period （peak E）， peak blood flow velocity in late diastolic period （peak A）， E/A ratio， stroke volume （SV）， left ventricular ejection fraction （LVEF）， left ventricular short axis shortening rate （LVFS）， and B-type natriuretic peptide （BNP）］， vascular damage indicators ［nitric oxide （NO）， endothelin-1 （ET-1）， vascular endothelial growth factor （VEGF）， and homocysteine （Hcy）］， inflammation indicators ［erythrocyte sedimentation rate （ESR） and hypersensitive C-reactive protein （Hs-CRP）］， anti-double-stranded DNA （dsDNA） antibodies， disease activity index （SLEDAI） score， mitigation of symptoms and signs， and occurrence of adverse reactions. ResultThe total response rate in the observation group was 87.09%， which was higher than that （67.74%） in the control group （P<0.01）， and the incidence of adverse reactions had no significant difference between the two groups. After treatment， the control group showed lowered LVDd， LVPWTd， BNP， ET-1， VEGF， and Hcy （P<0.05） and increased E peak， E/A ratio， SV， LVEF， and LVFS （P<0.05）. In the observation group， LADd， LVDd， LVPWTd， peak A， BNP， NO， ET-1， VEGF， and Hcy decreased （P<0.05）， while peak E， E/A ratio， SV， LVEF and LVFS increased （P<0.05） after treatment. The treatment in both groups decreased the scores of palpitation， chest tightness， dyspnea， and edema （P<0.05）， reduced ESR， Hs-CRP， ds-DNA， and SLEDAI （P<0.05）. After treatment， the observation group had lower LADd， LVDd， LVPWTd， peak A， BNP， and scores of palpation， chest tightness， dyspnea， and edema （P<0.05） and higher peak E， E/A ratio， SV， LVEF， and LVFS （P<0.05） than the control group. In addition， the observation group had lower NO， ET-1， VEGF， Hcy， ESR， Hs-CRP， ds-DNA， and SLEDAI than the control group （P<0.05）. ConclusionQihuang Jianpi Zishen granules combined with hydroxychloroquine sulfate and methylprednisolone can improve multiple indicators and mitigate the symptoms and signs of SLE patients with cardiac involvement， demonstrating a clinical application value.

Study on the effect of spinal anesthesia on ventricular arrhythmias in acute myocardial ischemia-reperfusion in rats / 中国临床药理学与治疗学

AIM: To explore the effect of spinal anesthesia on ventricular arrhythmia and involved mechanisms in myocardial ischemia-reperfusion (MIR) rats. METHODS: The rat MIR model was made by occlusion the left anterior descending coronary artery for 30 minutes and reperfusion for 45 minutes. Bupivacaine (0.05 mL / 100 g, 1 mg / kg) was injected slowly via intrathecal for spinal anesthesia. The electromyelogram at T2 thoracic spinal cord was recorded. Ventricular arrhythmias, cardiac function, myocardial damage were assessed by electrocardiography, echocardiography and TTC or HE staining. RESULTS: MIR reduced left ventricular short-axis shortening (LVFS) and left ventricular ejection fraction (LVEF), caused myocardial histological damage and ventricular arrhythmias, promoted spinal electrical discharge frequency and amplitude in T2 dorsal horn. Spinal injection of bupivacaine could significantly reduce spinal cord electrical activities and eliminate MIR-induced arrhythmias. Moreover, bupivacaine also significantly improved MIR-induced myocardial histological damage and cardiac function inhibition. CONCLUSION: Spinal anesthesia can reduce ventricular arrhythmias induced by MIR. The mechanism may be related to the effect of abolishing spinal nerve excitability.

ZLY18 protects against angiotensin II-induced cardiac fibrosis via inhibiting TGF-β1/Smads pathway / 中国药理学通报

Aim To explore the effect of ZLY18 on angiotensin II-induced cardiac fibrosis and the underlying mechanism. Methods Ang II was used to induce cardiac fibrosis in vitro and in vivo. Cardiac fibroblasts were divided into blank control group, model group and medicine group. The medicine group was subdivided into ZLY18(L)group, ZLY18(M)group and ZLY18(H)group. Compound ZLY18 was given 1, 2, 5 μmol·L-1 respectively. C57BL/6 mice were randomly divided into control group, model group and medicine group. The medicine group were subdivided into ZLY18(L)group, ZLY18(M)group and ZLY18(H)group. Compound ZLY18 was given 10,20 and 50 mg·kg-1 respectively. Both the model group and the medicine group were given with Ang II to induce cardiac fibrosis. The changes of protein levels were detected by Western blot and immunofluorescence. The changes of cardiac function indexes in C57BL/6 mice were detected by small animal echocardiography. The morphology, cell arrangement and collagen fibers of cardiac fibroblasts were observed by tissue section staining and other methods. Results The model of Ang II-induced myocardial fibrosis was successfully established at the cell and animal levels, and ZLY18 treatment improved the elevated fibrosis-related protein caused by Ang II and abnormal cardiac function in mice. Moreover, ZLY18 was able to inhibit the increased phosphorylation of TGF-1 and Smad3 caused by Ang II and increased Smad2/3 nuclear entry, suggesting that the antifibrotic effect of ZLY18 might be related to the activation of TGF-1/Smads signaling pathway. Conclusions ZLY18 has a protective effect on Ang II-induced cardiac fibrosis. ZLY18 may inhibit TGF-β/Smads signaling pathway activation to exert anti-fibrotic effects.

Effect of Gualou Xiebai Decoction on type II cardiorenal syndrome based on endothelial/epithelial-to-mesenchymal transition and its mechanism / 中国药理学通报

Aim To investigate the protective effects of different doses Gualou Xiebai Decoction (GXD) on type II cardiorenal syndrome (type II CRS) and explore its preliminary mechanisms. Methods The type II cardiorenal syndrome rat model was replicated by li-gating the left anterior descending coronary artery. After 10 weeks of intragastric administration, the cardiac function of the rats in each group was evaluated by echocardiography; serum were collected for biochemical testing; heart and kidney tissue samples were stained with HE and Masson to observe pathological changes. The hydroxyproline content in the heart and kidney was detected. The expression levels of endothelial/epitheli-al-to-mesenchymal transition (EndMT/EMT) related proteins in heart and kidney tissues were detecterd by immunofluorescence double staining

Therapy of Dispelling Stasis， Removing Toxin， and Promoting Urination （Xuebijing Injection Combined with Modified Linggui Zhugantang） Affects Prognosis of Sepsis-induced Cardiomyopathy / 中国实验方剂学杂志

ObjectiveTo evaluate the effect of the therapy of dispelling stasis， removing toxin， and promoting urination （modified Linggui Zhugantang combined with Xuebijing injection） on the prognosis of sepsis-induced cardiomyopathy （SICM）. MethodA total of 96 patients were randomly assigned into an observation group and a control group， with 48 patients in each group. The patients in the control group received sepsis bundle， and those in the observation group additionally received the therapy of dispelling stasis， removing toxin， and promoting urination （intravenous drip of Xuebijing injection and oral administration of modified Linggui Zhugantang）. The course of treatment in both groups was 7 days. The disease and prognosis indicators ［28-day mortality， intensive care unit （ICU） length of stay， major adverse cardiac events （MACE）， acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ）， sequential organ failure assessment （SOFA） score， and mortality in emergency department sepsis （MEDS） score］， cardiac function indicators ［left ventricular ejection fraction （LVEF）， E/A ratio of peak velocity blood flow from left ventricular relaxation in early diastole （the E wave） to peak velocity flow in late diastole caused by atrial contraction （the A wave）， E/e′ ratio of mitral peak velocity of early filling （E） to early diastolic mitral annular velocity （e′）， and afterload-corrected cardiac performance （ACP）］， myocardial injury markers ［high-sensitivity cardiac troponin T （hs-cTnT）， N-terminal pro-brain natriuretic peptide （NT-proBNP）， heart-type fatty acid-binding protein （H-FABP）， and high mobility group box-1 （HMGB-1）］， hemodynamic indicators ［extravascular lung water index （EVLWI）， global end-diastolic volume index （GEDVI）， cardiac index （CI）， and systemic vascular resistance index （SVRI）］， and TCM syndrome scores were assessed and compared between the two groups. ResultThe 28-day mortality and the incidence of MACE in the observation group were slightly lower than those in the control group. The ICU length of stay in the observation group was shorter than that in the control group （P<0.05）. After treatment， APACHE Ⅱ， SOFA， MEDS， syndrome score of stasis-caused internal obstruction， E/e′ ratio， hs-cTnT， NT-proBNP， H-FABP， and HMGB1 decreased compared with those before treatment （P<0.05）， while LVEF， E/A ratio， and ACP increased （P<0.05）. Moreover， the changes were more significant in the observation group （P<0.05）. On days 3， 5， and 7 after treatment， the EVLWI and SVRI in the observation group were lower than those in the control group （P<0.05）， while CI showed an opposite trend （P<0.05）. The observation group had higher GEDVI than the control group on days 3 and 5 after treatment （P<0.05）. ConclusionOn the basis of conventional bundle therapy， modified Linggui Zhugantang combined with Xuebijing injection with the effect of dispelling stasis， removing toxin， and promoting urination can inhibit the generation of myocardial injury markers and improve hemodynamics to shorten the length of ICU stay， mitigate the TCM syndrome， and reduce the risk of death， thereby improving the prognosis of SICM.

Functional effect of aerobic combined with resistance exercise on old patients with coronary heart disease and hypertension using WHO-FICs framework / 中国康复理论与实践

ObjectiveTo analyze the effect of moderate intensity aerobic combined with low intensity resistance exercise on old patients with coronary heart disease and hypertension. MethodsFrom November, 2021 to May, 2022, 16 patients with coronary heart disease and hypertension in Wuhan Donghu Hospital were divided into control group (n = 8) and experimental group (n = 8). Based on the World Health Organization Family of International Classification (WHO-FICs), the exercise intervention program was constructed. The control group accepted routine treatment, and the experimental group accepted moderate intensity aerobic combined with low intensity resistance exercise in addition, for eight weeks. They were measured lung function and cardiac function with cardiopulmonary exercise test system, and assessed with Timed 'Up and Go' Test, 6-Minute Walk Distance, 2-Minute Step Test, 30-Second Sit to Stand Test and grip strength before and after intervention. ResultsThe vital capacity, forced vital capacity, forced expiratory volume in the first second, forced expiratory volume in the one second as percentage of predicted volume, peak expiratory flow and maximal voluntary ventilation improved in the experimental after intervention (|t| > 2.391, P < 0.05), and the vital capacity, force vital capacity and maximal voluntary ventilation were more in the experimental group than in the control group (|t| > 2.207, P < 0.05). Peak oxygen uptake, anaerobic subthreshold oxygen uptake, metabolic equivalents, oxygen pulse, maximum work load and exercise load time improved in the experimental group after intervention (|t| > 2.823, P < 0.05), and they all were better in the experimental group than in the control group (|t| > 2.295, P < 0.05). Systolic blood pressure improved in both the groups (|t| > 4.608, P < 0.01), and diastolic blood pressure improved in the experimental group (t = 5.964, P < 0.01); while systolic blood pressure was less in the experimental group than in the control group (t = -3.654, P < 0.01). The performances of Timed 'Up and Go' Test, 6-Minute Walk Distance, 2-Minute Step Test, 30-Second Sit to Stand Test and grip strength improved in the experimental group after intervention (|t| > 2.996, P < 0.05), and all the performances were better in the experimental group than in the control group (|t| > 2.220, P < 0.05). ConclusionThe moderate intensity aerobic combined with low resistance exercise developed based on WHO-FICs can improve the cardiac function, lung function, cardiac load and motor function of old patients with coronary heart disease and hypertension.

Effects of electroacupuncture on cardiac function and local field potential of sensory and motor cortices in mice with stress cardiomyopathy / 中国针灸

OBJECTIVE@#To observe the effects of electroacupuncture (EA) on cardiac function and local field potential (LFP) in sensory and motor cortices in mice with stress cardiomyopathy (SC), and to explore the possible mechanism of EA in improving SC.@*METHODS@#Twenty-seven female C57BL/6 mice were randomized into a blank group, a model group and an EA group, 9 mice in each group. In the model group and the EA group, SC model was established by continuous intraperitoneal injection of isoproterenol (ISO) for 14 days. At the same time of modeling, EA was applied at "Neiguan" (PC 6) and "Shenmen" (HT 7) in the EA group, with disperse-dense wave, in frequency of 2 Hz/15 Hz, 15 min each time, once a day for 14 days. After intervention, the total movement distance, the number of crossing grid and the number of crossing central grid of open field test within 5 minutes were observed; the left ventricular function indexes (left ventricular diameter of end-diastole [LVIDd], left ventricular diameter of end-systole [LVIDs], left ventricular volume of end-diastole [LVEDV], left ventricular volume of end-systole [LVESV], ejection fraction [EF] and fraction shortening [FS]) were detected by echocardiography; the changes in ST-segment amplitude and PR interval of electrocardiogram were observed; the morphology of myocardial tissue was observed by HE staining; the serum levels of cortisol (CORT), cardiac troponin T (cTnT) and brain natriuretic peptide (BNP) were detected by ELISA; the changes of LFP in sensory and motor cortices were recorded by Plexon multi-channel acquisition system.@*RESULTS@#Compared with the blank group, in the model group, the total movement distance, the number of crossing grid and the number of crossing central grid of open field test were decreased (P<0.05); LVIDd, LVIDs, LVEDV and LVESV were increased (P<0.05), EF and FS were decreased (P<0.05); ST-segment amplitude was increased (P<0.05) and PR interval was prolonged (P<0.05); irregular myocardial fiber arrangement, interstitial edema and inflammatory cell infiltration were observed; the serum levels of CORT, cTnT and BNP were increased (P<0.05); in the sensory cortex, the ratios of delta, theta, alpha and beta frequency bands were increased (P<0.05), the maximum energy spectrum of theta and beta frequency bands was increased (P<0.05), the power spectral density (PSD) of delta, theta, alpha, beta and gamma frequency bands was increased (P<0.05); in the motor cortex, the ratios of delta, theta, alpha and beta frequency bands were increased (P<0.05), the maximum energy spectrum as well as PSD of delta, theta, alpha, beta and gamma frequency bands were increased (P<0.05). Compared with model group, in the EA group, the total movement distance, the number of crossing grid and the number of crossing central grid of open field test were increased (P<0.05); LVIDd, LVIDs, LVEDV and LVESV were decreased (P<0.05), EF and FS were increased (P<0.05); ST-segment amplitude was decreased (P<0.05), and the PR interval was shortened (P<0.05); myocardial fiber injury and inflammatory cell infiltration were reduced; the serum levels of CORT, cTnT and BNP were decreased (P<0.05); in the sensory cortex, the ratios of theta, alpha and beta frequency bands were decreased (P<0.05), the ratio of gamma frequency band was increased (P<0.05), the maximum energy spectrum of theta frequency band as well as the PSD of theta, alpha, beta and gamma frequency bands were decreased (P<0.05); in the motor cortex, the ratios of theta, alpha and beta frequency bands were decreased (P<0.05) and the ratio of gamma frequency band was increased (P<0.05), the maximum energy spectrum of delta frequency band was increased (P<0.05), the maximum energy spectrum of theta frequency band as well as the PSD of theta and gamma frequency bands were decreased (P<0.05).@*CONCLUSION@#EA can improve cardiac function in mice with stress cardiomyopathy, and its mechanism may be related to the regulation of local field potentials in sensory and motor cortices.

Effect of MG53 on Cardiac Function Affected by Acute Doxorubicin-Induced Cardiotoxicity in Mice and Its Mechanism / 中山大学学报(医学科学版)

ObjectiveThis study was designed to explore the effect of MG53 on cardiac function affected by acute doxorubicin （DOX）-induced cardiotoxicity （DIC） in mice and its possible mechanism. MethodsIn vivo， C57BL/6 mice were injected intraperitoneally with twenty mg/kg DOX for one week to induce the acute DIC. In vitro， neonatal rat cardiomyocytes （NRCs） were treated with 1 μmol/L DOX to induce DIC. A small animal ultrasound imaging system was used to evaluate cardiac function， and the left ventricular changes in ejection fraction （EF） and fraction shortening （FS） were measured. qPCR technology was used to evaluate cardiac remodeling related factors ANP， BNP and α-MHC， autophagy-related factors Beclin1 and LC3， and apoptosis-related factor CASPASE3. Autophagy-related protein levels of Beclin1， LC3 and apoptosis-related protein levels of caspase3 were assessed by Western Blot. Transmission electron microscopy （TEM） was used to detect autophagosomes in heart tissues. TUNEL assay kit was used to detect apoptosis in neonatal murine cardiomyocytes. ResultsThe small animal ultrasound imaging revealed cardiac function was significantly reduced by doxorubicin in the DOX group and DOX+AAV9-NC group compared with the sham group （EF： Sham： 86.06 ± 2.08 vs. DOX：58.97 ± 1.62， P < 0.000 1； Sham： 86.06 ± 2.08 vs. DOX+AAV9-NC： 59.00 ± 1.86， P < 0.000 1. FS： Sham： 45.47 ± 1.95 vs. DOX：30.68 ± 1.21， P < 0.000 1； Sham： 45.47 ± 1.95 vs. DOX+AAV9-NC： 30.79 ± 1.13， P < 0.000 1）. However， the overexpression of MG53 with adeno-associated virus9 （AAV9） ameliorated cardiac dysfunction （EF： DOX+AAV9-MG53： 66.93 ± 1.78 vs. DOX+AAV9-NC： 59.00 ± 1.86， P < 0.000 1. FS： DOX+AAV9-MG53： 36.35 ± 1.33 vs. DOX+AAV9-NC： 30.79 ± 1.13， P < 0.000 1）. TEM showed autophagosomes were increased in the DOX+AAV9-MG53 group compared with the DOX group and DOX+AAV9-NC. qPCR results suggested that MG53 down-regulated the mRNA expression of cardiac remodeling related genes. Additionally， Western blot results confirmed that the protein level of caspases3 was decreased and Beclin1 and LC3 expression was increased in the DOX+AAV9-MG53 group compared with those in the DOX group and DOX+AAV9-NC group （caspase： DOX+AAV9-MG53： 1.49 ± 0.13 vs. DOX+AAV9-NC： 2.49 ± 0.46， P = 0.000 2； Beclin-1： DOX+AAV9-MG53：0.82 ± 0.02 vs. DOX+AAV9-NC： 0.62 ± 0.05， P < 0.000 1； LC3： DOX+AAV9-MG53： 0.83 ± 0.04 vs. DOX+AAV9-NC： 0.40 ± 0.05， P < 0.000 1）. In contrast， knockdown of MG53 significantly up-regulated the protein level of Caspase3 and significantly down-regulated the protein level of Beclin1 and LC3 （caspase： DOX+si-MG53： 4.52 ± 0.28 vs. DOX+si-NC： 3.37 ± 0.08， P < 0.000 1； Beclin-1： DOX+si-MG53： 0.34 ± 0.06 vs. DOX+si-NC： 0.54 ± 0.07， P = 0.026 2； LC3： DOX+si-MG53： 0.41 ± 0.12 vs. DOX+si-NC： 0.70 ± 0.07， P = 0.001 5）. TUNEL analysis showed overexpression of MG53 significantly inhibited the apoptosis of cardiomyocytes （DOX+Ad-MG53： 9.41 ± 0.53 vs. DOX+Ad-NC： 29.34 ± 7.29， P < 0.000 1）， and knockdown of MG53 significantly facilitate the apoptosis of cardiomyocytes （DOX+si-MG53： 71.34 ± 5.90 vs. DOX+si-NC： 32.19 ± 9.91， P < 0.000 1）. ConclusionMG53 inhibits cardiac apoptosis and enhances autophagy， which delays cardiac remodeling and ameliorates cardiac dysfunction.

Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction (CODE-AAMI): Protocol for a Randomized Placebo-Controlled Trial / 中国结合医学杂志

BACKGROUND@#Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction.@*OBJECTIVE@#This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale.@*METHODS@#This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment.@*DISCUSSION@#This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).

Echocardiographic Evaluation of Patients with Goiter in a Nigerian Tertiary Hospital

Background: Goiter is endemic in iodine deficient areas of the world including Nigeria. Cardiovascular disorder is a cause of morbidity in patients with thyroid diseases. These cardiovascular disorders are more likely to be found in patients with hypothyroid or hyperthyroid goiter. Large euthyroid goiter can potentially compromise respiration with potentials for secondary cardiac changes. Despite these, echocardiography is not a routine assessment of these patients. This study set out to determine the baseline cardiac function in a cohort of patients with endemic goiter using echocardiography. Materials and Methods: A comparative study of One hundred goiter patients presenting consecutively at the out-patient clinic of a tertiary hospital and 50 age and gender matched healthy non-goitrous control subjects. They all had thyroid function tests, cardiovascular evaluation and echocardiography done. Results: The mean ages of the goiter and the control groups were 46.92 + 13.85 and 46.58 + 11.62 years respectively (P=0.8510). The goiter population comprised 12 males and 88 females while the control group had 6 males and 44 females. 47% of the goiter subjects were hyperthyroid, while 44% and 9% were euthyroid and hypothyroid respectively. All the control subjects were euthyroid. Systolic and diastolic dysfunction were seen in 18% and 24% of the goiter group respectively, compared to 2% and 5% of the control group (P<0.0001). Hyperthyroid and hypothyroid subgroups had higher rates of both systolic and diastolic dysfunction. Systolic dysfunction was seen in 6.4%, 4.5% and 100% of the hyperthyroid, euthyroid and hypothyroid subgroups respectively while diastolic dysfunction was seen in 23.4%, 9.2 and 100% of the subgroups. Prevalence of systolic and diastolic dysfunction in the euthyroid and control subjects were 4.5% vs 2% (P=0.1228) and 9.2% vs 5% (P=0.2018). Conclusion: This study concluded that cardiac dysfunction is common in both hypothyroid and hyperthyroid goiter population while the prevalence of cardiac dysfunction in the euthyroid population is not influenced by the presence of goiter. This may suggest that routine echocardiography is unnecessary in patient with euthyroid goiter

Evaluation of the effect of 2-aminoethoxydiphenyl-borate on cardiac dysfunction in arsenic poisoning rats by stratified strain technique / 中华超声影像学杂志

Objective:To evaluate the effect of 2-aminoethoxydiphenyl-borate (2-APB) on cardiac dysfunction in arsenic poisoning rats by stratified strain technique.Methods:Thirty-two 12-week-old SD rats were randomly divided into control group ( n=8) and arsenic exposure group ( n=24). After 12 weeks of arsenic exposure, arsenic exposure group was divided into three groups: natural recovery group ( n=8), low-dose intervention group (n=8) and high-dose intervention group ( n=8). The rats were treated with 2-APB for 21 days. After the last administration, the routine parameters and the layered strain parameters were measured by ultrasonic instrument. Then the rats were killed and their blood and myocardial samples were obtained. The levels of serum creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH) were tested, and the morphological changes of cardiomyocytes were observed by HE staining. Results:Left ventricular ejection fraction (LVEF), left ventricular short axis shortening (LVFS), global circumferential strain of subendocardial myocardium (GCS-endo), global circumferential strain of middle myocardium (GCS-mid), global circumferential strain of subepicardial myocardium (GCS-epi) and circumferential strain rate of left ventricular segments (SrC) in the natural recovery group were lower than those in the control group ( P<0.05), while serum CK-MB and LDH were higher than those in the control group ( P<0.05). Some ultrasonic parameters and biochemical indexes in the low and high dose intervention groups were improved in varying degrees compared with the natural recovery group ( P<0.05). The correlation between GCS-endo and CK-MB was the highest ( r=-0.931, P<0.05). Myocardial HE staining showed that the degree of myocardial cell swelling and necrosis were reduced, and erythrocyte exudation was reduced in the low and high dose intervention groups compared with the natural recovery group. Conclusions:The stratified strain technique can be used to evaluate the protective effect of 2-APB on cardiac dysfunction in arsenic poisoning rats, and GCS-endo may be one of its sensitive indexes.

Evaluation of cardiac function and systolic dyssynchrony of fetuses exposed to maternal anti-SSA and anti-SSB antibodies using two-dimensional speckle tracking imaging / 中华超声影像学杂志

Objective:To evaluate the cardiac function and systolic dyssynchrony of fetuses exposed to maternal autoimmune antibodies (anti-SSA/Ro60, anti-SSA/Ro52 and anti-SSB/La) by using two-dimensional speckle tracking imaging (2D-STI).Methods:A total of 52 pregnant women with singleton pregnancy in the Affiliated Hospital of Inner Mongolia Medical University from July 2018 to November 2020 were selected. Eighteen fetuses of mothers with autoimmune antibodies were enrolled as autoimmune disease (AD) group and 34 fetuses of healthy mothers without antibodies were included as control group. Maternal baseline characteristics, fetoplacental Doppler parameters, and conventional echocardiographic data of two groups were prospectively collected. The systolic global and regional longitudinal strain of left and right ventricles (LV and RV) and the time to peak strain of regional myocardium were measured using 2D-STI. The differences in time to peak strain between the LV free wall and RV free wall (two-chamber dyssynchrony, 2C-DYS) and between the septum and LV free wall (one-chamber dyssynchrony, 1C-DYS) were also calculated.Results:There were no significant differences between the two groups in conventional systolic and diastolic functional parameters for the LV and RV(all P>0.05). The myocardial deformation parameters and 2C-DYS obtained by 2D-STI showed no statistical differences between two groups(all P>0.05). However, 1C-DYS was significantly more prolonged in the AD group than control group[28.50(13.50, 39.25)ms vs 19.50(8.00, 29.25)ms, P=0.042]. Conclusions:LV systolic mechanical dyssynchrony in fetuses of mothers with autoimmune antibodies suggests in-utero subclinical damage of the cardiac conduction system.

Qishen Taohong Granule () as Adjuvant Therapy for Improving Cardiac Function and Quality of Life in Patients with Chronic Heart Failure: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To confirm the improvement of cardiac function and quality of life (QOL) in patients with chronic heart failure (CHF) via Chinese medicine (CM) Qishen Taohong Granule (, QTG).@*METHODS@#This study was a single-center, prospective, randomized, controlled clinical trial. Seventy-six patients from 27 to 84 years old diagnosed with CHF New York Heart Association (NYHA) class II or III in stage C were enrolled and randomly assigned at a 1:1 ratio to receive QTG or trimetazidine (TMZ), in addition to their standard medications for the treatment of CHF. The study period was 4 weeks. The primary outcomes included cardiac function evaluated by NYHA classification and left ventricular ejection fraction (LVEF), as well as QOL evaluated by CHF Integrated Chinese and Western Medicine Survival Scale (CHFQLS). The secondary outcomes included 6-min walking test (6MWT), CM syndrome score, symptom and sign scores and N-terminal pro-B-type natriuretic peptide (NT-proBNP). All indices were measured at baseline and the end of the trial.@*RESULTS@#At the 4-week follow-up period, the effective rate according to NYHA classification in the QTG group was better than that in the TMZ group (74.29% vs. 54.29%, P<0.05). But there was no significant difference in post-treatment level of LVEF between the two groups (P>0.05). The CHFQLS scores improved by 13.82±6.04 vs. 7.49±2.28 in the QTG and TMZ groups, respectively (P<0.05). Subgroup analysis of the CHFQLS results showed that physiological function, role limitation and vitality were significantly higher in the QTG group than in the TMZ group (15.76±7.85 vs. 7.40±3.36, P<0.05; 16.00±8.35 vs. 10.53±4.64, P<0.05; 15.31±8.09 vs. 7.89±4.60, P<0.05). Compared with TMZ group, treatment with QTG also demonstrated superior performance with respect to 6MWT, CM syndrome, shortness of breath, fatigue, gasping, general edema and NT-proBNP level. No significant adverse reactions or adverse cardiac events occurred during treatment in either group.@*CONCLUSION@#In addition to conventional treatments, the use of QTG as an adjuvant therapy significantly improved cardiac function and QOL in patients with CHF class II or III in stage C. [Registration No. ChiCTR1900022036 (retrospectively registered)].

The protective effect of Dexrazoxane on onco-Cardiology induced by anticancer agents other than anthracyclines / 中国药理学通报

Aim To evaluate the protective effect of Dexrazoxane(Dex)on onco-Cardiology caused by chemotherapeutic drugs other than anthracycline antitumor drugs using zebrafish embryos, including:cisplatin, paclitaxel, vincristine sulfate, 5-fluorouracil and cyclophosphamide. Methods Zebrafish embryos at 24 hpf(hours post-fertilization)were exposed to different concentrations of drugs. The survival rate and the overall animal morphology at 48 hpf, 72 hpf and 96 hpf were observed with a microscope. Heart rate, ventricular contraction fraction, ventricular volume, and cardiac output were measured and calculated by video recordings made with a VCD system. The protective effect of Dex was evaluated using the established model of onco-Cardiology induced by anti-tumor drugs other than anthracyclines. Results In terms of acute toxicity, cisplatin, vincristine sulfate, 5-fluorouracil and cyclophosphamide all significantly reduced the survival rate of zebrafish embryos. The LC50 value was 437.655, 25.538, 65.606 and 19.021 mmol·L-1, respectively. In addition to paclitaxel, the other four anti-tumor drugs all showed significant changes in overall animal morphology and cardiac function indicators. In the study of the protective effect of Dex on four kinds of tumor heart diseases except anthracyclines, only cisplatin had a significant protective effect, which could improve the cardiotoxicity caused by cisplatin. The optimal concentration of Dex was 80 μmol·L-1. Conclusions Zebrafish models of drug toxicity caused by cisplatin, vincristine sulfate, 5-fluorouracil, and cyclophosphamide is established, which proves that Dex only has a protective effect on the toxicity caused by cisplatin.

doxorubicin induces chronic heart failure in rats by regulating mitochondrial dynamics via drp1/fundc1 pathway / 中国药理学通报

Aim To investigate the damage degree of doxorubicin hydrochloride( DOX )on cardiac function in rats, and to explore its possible mechanism. Methods Experiment 1: SD rats( n=48 )were randomly divided into control group( normal saline ), DOX 1 group( DOX cumulative dose 12 mg·kg-1 ;intraperitoneal injection ), DOX 2 group( 15 mg·kg-1 ;)and DOX 3 group( 18 mg·kg-1 ;). Cardiac structure and cardiac function were detected by echocardiography. B-type natriuretic peptide( BNP )was detected by ELISA. The morphological changes of myocardium were observed by Hematoxylin-eosin( HE )staining. The optimal dose group( DOX 2 group )was selected comprehensively. Experiment 2: SD rats( n=36 )were randomly divided into control group( normal saline ), DOX 2 group(15 mg·kg-1)and DOX 2+Mdivi-1 group( 15 mg·kg-1+daily abdominal injection of Mdivi-1(1 mg ·kg-1 ;)). Western blot was used to detect the protein expression of myocardial mitochondrial dynamics. Results Compared with the control group, hearts in DOX groups were enlarged and the heart function was reduced. Under the microscope, hypertrophy of cardiac cells and loose arrangement of cardiac fibers were observed in DOX group, and the higher the cumulative dose of DOX in rats, the more severe the degree of heart failure and the higher the mortality rate of rats. Compared with control group, the expression of mitochondrial dynamin-related protein 1( DRP1 )and related signaling pathway protein FUN14 domain containing 1( FUNDC1 )in DOX 2 group increased. The expression of optic atrophy 1( OPA1 )decreased, the expression of FUNDC1 and DRP1 protein decreased, and the expression of OPA1 protein was enhanced after the use of mitochondrial dynamics inhibitor(Mdivi-1). Conclusions DOX can cause chronic heart failure, and the mechanism may be related to DRP1/FUNDC1 mediated mitochondrial fission and fusion.

Effect of positive end-expiratory pressure on cardiac function in patients with early left ventricular diastolic dysfunction: a prospective cohort study / 中华危重病急救医学

Objective:To evaluate the effect of positive end-expiratory pressure (PEEP) ventilation on cardiac function in patients with early left ventricular (LV) diastolic dysfunction undergoing laparoscopic radical gastrectomy.Methods:Patients who underwent laparoscopic radical gastrectomy under elective general anesthesia from July 2021 to February 2022 at the Subei People's Hospital were enrolled [age 60-75 years old, American Society of Anesthesiologists (ASA) grade Ⅰ-Ⅱ, and left ventricular ejection fraction (LVEF) > 0.50]. Transthoracic echocardiography (TTE) was performed before operation, and the peak early diastolic velocity (E peak) and peak late diastolic velocity (A peak) at the mitral ostium were recorded and the E/A and E peak deceleration time (DT) were calculated. Then isovolumic relaxation time (IVRT) and early peak mitral annular diastolic velocity (e') were recorded and left ventricular E/e' (LVE/e') was calculated. According to the E/A, mitral e', LVE/e', DT, and IVRT, the patients were divided into early LV diastolic dysfunction group (E/A < 1, mitral e' < 7 cm/s, LVE/e' > 14, DT > 200 ms, and IVRT > 100 ms) and normal cardiac function group (1 < E/A < 2, 160 ms < DT < 240 ms, and 70 ms < IVRT < 90 ms), with 35 patients in each group. Both groups were received fixed 5 cmH 2O (1 cmH 2O≈0.098 kPa) PEEP 5 minutes after the beginning of the pneumoperitoneum until the end of the procedure. A volume controlled ventilation was used with a tidal volume (VT) of 7 ml/kg, an inspired oxygen concentration of 0.60, and an inspiratory to expiratory ratio of 1∶2. Left and right myocardial systolic and diastolic function related parameters, including LVEF, LV global longitudinal strain (LVGLS), tricuspid annulus plane systolic migration (TAPSE), the peak early diastolic velocity (E peak) at the mitral and tricuspid valve ostia and the peak early diastolic velocity (e') at the corresponding annulus were measured by transesophageal echocardiography (TEE) before tracheal intubation (T 0), 5 minutes after the pneumoperitoneum (T 1), 5 minutes after PEEP ventilation (T 2), 30 minutes after PEEP ventilation (T 3), and 5 minutes after the end of pneumoperitoneum (T 4), respectively. The left and right ventricular myocardial performance index (LVMPI/RVMPI) was calculated. Results:Finally, 60 patients were included in the analysis, including 28 patients in the early LV diastolic dysfunction group and 32 patients in the normal cardiac function group. Compared with those at T 0, mean arterial pressure (MAP), LVEF, mitral e', LVGLS, tricuspid e' and TAPSE were significantly lower in the normal cardiac function group at T 1, and the early LV diastolic dysfunction group at T 1, T 2, and T 3, and LVMPI, LVE/e', RVE/e', and RVMPI were significantly higher. At T 4, the LVE/e' and the RVE/e' were significantly higher in the early LV diastolic dysfunction group than those at T 0 (LVE/e': 16.52±1.26 vs. 14.32±1.09, and RVE/e': 18.71±1.74 vs. 16.51±1.93, respectively, both P < 0.05), Mitral e' and tricuspid e' were significantly lower than those at T 0 [mitral e' (m/s): 0.07±0.01 vs. 0.09±0.01, tricuspid e' (m/s): 0.06±0.01 vs. 0.08±0.01, both P < 0.05]. Compared with the normal cardiac function group, MAP, LVEF, mitral e', LVGLS, tricuspid e', and TAPSE at T 1, T 2, and T 3 were significantly lower in the early LV diastolic dysfunction group, while LVMPI, LVE/e', RVE/e', and RVMPI were significantly higher. At T 4, the LVE/e' and the RVE/e' were significantly higher in the early LV diastolic dysfunction group than those in the normal cardiac function group (LVE/e': 16.52±1.26 vs. 9.87±1.25, RVE/e': 18.71±1.74 vs. 10.97±1.70, both P < 0.05). Mitral e' and tricuspid e' were significantly lower in the normal cardiac function group [mitral e' (m/s): 0.07±0.01 vs. 0.11±0.02, tricuspid e' (m/s): 0.06±0.01 vs. 0.10±0.02, both P < 0.05]. Conclusions:In early LV diastolic dysfunction patients, compared with patients with normal cardiac function, 5 cmH 2O PEEP can further exacerbate left and right myocardial systolic and diastolic function in patients during pneumoperitoneum; when the pneumoperitoneum was ended, 5 cmH 2O PEEP only worsen left and right myocardial diastolic function in patients, and did not affect left and right myocardial systolic function.

Clinical study of self-designed Yiqi Huoxue Huayu Decoction combined with western conventional therapy in the treatment of chronic heart failure complicated with atrial fibrillation / 国际中医中药杂志

Objective:To observe the effects of self-designed Yiqi Huoxue Huayu Decoction on cardiac function and serum endothelin (ET-1) and matrix metalloproteinase-9 (MMP-9) levels in patients with chronic heart failure (GHF) complicated with atrial fibrillation.Methods:A total of 100 patients with GHF complicated with atrial fibrillation treated in our hospital from January 2019 to June 2021 were selected as the study subjects, and divided into experimental group and control group according to random number table method, with 50 patients in each group. Patients in both groups were given cardiotonic, diuretic, vasodilator and other conventional treatment, and patients in the experimental group added self-designed Yiqi Huoxue Huayu Decoction. TCM syndrome score, left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD) and left ventricular ejection fraction (LVEF), serum ET-1 and MMP-9 levels, clinical efficacy, safety and incidence of adverse reactions were observed and compared between 2 groups before and after treatment.Results:The total response rate was 82.0% (41/50) in the observation group and 62.0% (31/50) in the control group, and the difference was statistically significant ( χ 2=4.96, P=0.026). After treatment, the symptoms scores of palpitation, shortness of breath, fatigue, chest and hypochasm pain in the observation group were significantly significantly lower than those in the control group ( t=5.28, 5.29, 5.62, 5.42, P<0.01). After treatment, the LVEDD[(51.23±6.59)mm vs. (55.65±6.17)mm, t=3.46], LVESD[(43.10±4.76)mm vs. (45.99±5.31)mm, t=2.87], serum ET-1[(65.79±8.29)μg/L vs. (79.83±10.08)μg/L, t=7.61], MMP-9 [(175.86±24.81)ng/L vs. (189.49±26.13)ng/L, t=2.68] in experimental group were significantly lower than those in the control group ( P<0.05), while LVEF [(50.01±7.6)% vs. (46.25±6.96)%, t=2.57] was significantly higher than that of the control group ( P<0.05). There were no significant differences in GPT, GOT, UA, SCr levels between both groups before and after treatment ( P>0.05). There were no obvious adverse reactions betewwn both groups. Conclusion:The self-designed Yiqi Huoxue Huayu Decoction can relieve the clinical symptoms, improve the heart function and serum ET-1 and MMP-9 levels in patients with GHF complicated with atrial fibrillation safely.

Effect of Auditory Stimulation by Upbeat Music on Radial Pulse

@#Introduction: Music of varying tempo or beats have physiological as well as adverse effects on the body. This study throws light on the influence of upbeat music on properties of radial pulse, in healthy young adults. Methods: One hundred and seventy-five students between the age of nineteen and twenty-four years were included in this study. The experiment was conducted in a room, devoid of any external disturbances. Subjects were made to listen the chosen upbeat music for 4 minutes using a headphone. The radial pulse was measured before and immediately after the experiment. Data analysis was done by using SPSS software version 16.0.Results: In this study we observed that normal mean pulse rate was 76 per minute in males and 72 per minute in female young adults. Following the auditory stimulation with upbeat music, rise in pulse rate was observed in more than 70% of subjects. Whilst, 24% showed a decrease pulse rate and 5% showed no change in pulse rate. Increased pulse rate was associated with decrease in amplitude of pulse wave but no change in rhythm and character of the pulse when compared to resting state. Conclusion: This study indicates that the music can increase the pulse rate in the majority of the subjects but also decreases the pulse rate in few individuals. This study provides the preliminary evidence to promote the music therapy in many preventive programs for patients with depression, patients with depressed cardiac functioning and useful in improving daily performances.

Effects of an intradialytic cardiovascular rehabilitation program on functional capacity and cardiac function: ICRP trial

Abstract Introduction: Chronic kidney disease (CKD) is a worldwide public health problem associated with an increased risk of death from cardiovascular complications. Although previous studies have described significant improvements in exercise in functional capacity and quality of life in patients with end-stage kidney disease (ESKD), there is a lack of studies that propose to assess its impact on cardiac function using transthoracic echocardiogram (ECHO). In addition, most of the intradialytic exercise protocols are inconsistent, and incomplete regarding their intensity prescription, time of intervention, and monitoring. Methods: The present study aims to evaluate the effects of an intradialytic cardiovascular rehabilitation protocol (ICRP) using medium intensity aerobic exercises, for 30 min. on cardiac function and functional capacity. In this 6-month longitudinal study, heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure, peripheral oxygen saturation (SpO2) and modified Borg scale will be analyzed in all HD sessions. The cardiac function will be evaluated by left ventricular ejection fraction (LVEF) through ECHO; functional capacity by the six-minute walk test (6MWT); quality of life through the SF-36 questionnaire and routine laboratory tests and KT/Vsp calculation before and after the ICRP. Conclusion: ICRP protocol will be examined and is expected to improve cardiac function, functional capacity, and quality of life in ESKD patients on hemodialysis.