Cardiac Hemodynamics Research Articles

Admission rate-pressure product as an early predictor for in-hospital mortality after aneurysmal subarachnoid hemorrhage.

Early prediction of in-hospital mortality in aneurysmal subarachnoid hemorrhage (aSAH) is essential for the optimal management of these patients. Recently, a retrospective cohort observation has reported that the rate-pressure product (RPP, the product of systolic blood pressure and heart rate), an objective and easily calculated bedside index of cardiac hemodynamics, was predictively associated with in-hospital mortality following traumatic brain injury. We thus wondered whether this finding could also be generalized to aSAH patients. The current study aimed to examine the association of RPP at the time of emergency room (ER) admission with in-hospital mortality and its predictive performance among aSAH patients. We retrospectively included 515 aSAH patients who had been admitted to our ER between 2016 and 2020. Their baseline heart rate and systolic blood pressure at ER presentation were extracted for the calculation of the admission RPP. Meanwhile, we collected relevant clinical, laboratory, and neuroimaging data. Then, these data including the admission RPP were examined by univariate and multivariate analyses to identify independent predictors of hospital mortality. Eventually, continuous and ordinal variables were selected from those independent predictors, and the performance of these selected predictors was further evaluated and compared based on receiver operating characteristic (ROC) curve analyzes. We identified both low (< 10,000; adjusted odds ratio (OR) 3.49, 95% CI 1.93-6.29, p < 0.001) and high (> 15,000; adjusted OR 8.42, 95% CI 4.16-17.06, p < 0.001) RPP on ER admission to be independently associated with in-hospital mortality after aSAH. Furthermore, after centering the admission RPP by its median, the area under its ROC curve (0.761, 95% CI 0.722-0.798, p < 0.001) was found to be statistically superior to any of the other independent predictors included in the ROC analyzes (all p < 0.01). In light of the predictive superiority of the admission RPP, as well as its objectivity and easy accessibility, it is indeed a potentially more applicable predictor for in-hospital death in aSAH patients.

Dapagliflozin protects against doxorubicin-induced cardiotoxicity by restoring STAT3.

Doxorubicin (Dox), an effective therapy in different types of cancer, is known to exhibit cardiotoxic effects. Despite previous studies indicating the benefits of dapagliflozin (DAPA) in patients experiencing heart failure, it remains uncertain whether DAPA exerts a protective effect on Dox-induced cardiac dysfunction. Signal transducer and activator of transcription 3 (STAT3) participates in various mechanisms of cardioprotection. Herein, we aimed to investigate the effects of DAPA on Dox-induced cardiotoxicity and the role of STAT3. Sprague-Dawley rats were pretreated with oral DAPA for 6weeks followed by Dox for 4weeks. Sequential echocardiography was applied to assess cardiac function. For in vitro analysis, cardiomyocytes were treated with 10μM DAPA and subsequently exposed to 1μM Dox. The expression of reactive oxygen species- and apoptosis-related proteins was measured. Using STAT3 siRNA, we further examined the effects of STAT3 effect on DAPA-associated protection against Dox-induced apoptosis. In rats treated with Dox, DAPA significantly reduced cardiac fibrosis and improved cardiac function and hemodynamics. Additionally, DAPA effectively inhibited Dox-induced apoptosis and reactive oxygen species (ROS) in cardiomyocytes. Mechanistically, we showed that DAPA decreased cardiac expression of Bax and cleaved caspase 3 but increased Bcl-2 expression. DAPA also significantly rescued Dox-suppressed STAT3 expression. Conversely, knocking down STAT3 in cardiomyocytes reversed the DAPA-related protective effects on Dox-induced cell apoptosis and ROS. Collectively, our findings indicate that DAPA could be useful for preventing Dox-induced cardiotoxicity by restoring STAT3.

New Evidence About Aortic Valve Stenosis and Cardiovascular Hemodynamics.

Aortic stenosis (AS) is the most common degenerative valvular disease in western word. In patients with severe AS, small changes in aortic valve area can lead to large changes in hemodynamics. The correct understanding of cardiac hemodynamics and its interaction with vascular function is of paramount importance for correct identification of severe AS and to plan effective strategies for its treatment. In the current review with highlight the importance of pressure recovery phenomenon and valvular arterial impedance as novel tools in the evaluation of patients with aortic stenosis.

Investigation of Beraprost Sodium on Cardiac Function and Hemodynamics in Canine Models of Chronic Pulmonary Hypertension.

Pulmonary hypertension (PH) is a life-threatening disease in dogs characterized by increased pulmonary arterial pressure (PAP) and/or pulmonary vascular resistance. No study has evaluated the utility of Beraprost sodium (BPS) in dogs with PH. This study aimed to evaluate the effect of BPS on cardiac function and hemodynamics and examine the optimal dose of BPS in canine models of chronic embolic PH. In this prospective crossover study, three doses of BPS (5, 15, and 25 μg/kg, twice a day) were examined in eight canine models of chronic embolic PH. All model dogs underwent invasive PAP measurement, echocardiography, and non-invasive systemic blood pressure measurement before and after continuous administration of oral BPS for 1 week. No side effects of BPS were observed in any dog during the study. All doses of BPS significantly decreased systolic PAP and pulmonary vascular impedance. Additionally, systemic vascular impedance significantly decreased with 15 and 25 μg/kg of BPS. The right ventricular stroke volume and longitudinal strain significantly decreased with all doses of BPS. The left ventricular stroke volume and circumferential strain decreased with 15 μg/kg BPS. BPS was well-tolerated in this study. A dose-dependent vasodilating effect on pulmonary vessels was observed in canine models of chronic PH. Additionally, 15 μg/kg BPS showed a balanced vasodilating effect on systemic and pulmonary vessels. Furthermore, with a decrease in systemic and pulmonary vascular impedance, the left and right ventricular functions were significantly improved. Our results suggest that BPS may be useful in the treatment of canine PH.

Evolution of Kidney Disease in Single Ventricle Patients After Cardiac Transplantation

<h3>Purpose</h3> Unlike Fontan-associated liver disease, the impact of heart transplant (HT) on Fontan associated kidney disease has not been well described. In this single center study, we sought to characterize the natural history of chronic kidney disease in a small cohort of Fontan patients from listing to follow up after HT. <h3>Methods</h3> We conducted a retrospective review of pediatric patients at our institution with prior Fontan palliation that underwent HT between 2000-2020. We collected demographic information, data regarding baseline renal function/anatomic abnormalities, presence of protein losing enteropathy/liver disease/renal insufficiency/diabetes, and cardiac hemodynamics. Estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine (Cr) using the Cr-based "Bedside Schwartz" formula which was used to determine the stage of kidney disease. We trended data at listing, at transplant, and then at post-transplant follow-up visits (90 days, 180 days, then annually). <h3>Results</h3> Fourteen patients with prior Fontan palliation who underwent HT were identified. At listing, 10 out of 14 patients were noted to have a normal eGFR (GFR ≥ 90). By transplant, four of these patients declined to Stage 2 kidney disease (GFR 60 - 90, not inclusive). All four normalized by 1 year follow-up. The <b>4</b> patients with eGFR < 90 at listing all had further decline in renal function by the time of HT. Post-transplant, 2 normalized, 1 remained with eGFR <90, and 1 required dialysis. The progression of eGFR of all the patients is summarized in the figure below. <h3>Conclusion</h3> In this small single center series, Cr based eGFR at listing and at transplant appear to be risk factors for progressive renal insufficiency in Fontan patients undergoing HT. The predictive value of other pre-transplant variables is limited by our population size. Cr-based eGFR calculations may help identify Fontan patients at increased risk for a decline in renal function post HT who may benefit from enhanced longitudinal renal surveillance.

Noninvasive Assessment Of Cardiovascular Hemodynamics During Exercise Using Systolic Time Intervals

Noninvasive Assessment Of Cardiovascular Hemodynamics During Exercise Using Systolic Time Intervals

Comparison of fibrosing mediastinitis patients with vs. without markedly increased systolic pulmonary arterial pressure: a single-center retrospective study

IntroductionFibrosing mediastinitis (FM) complicated with pulmonary hypertension (PH) has been considered as an important cause of morbidity and mortality. This study was designed to observe the possible effects of abnormal hemodynamics on patients by conducting a between-group comparison according to the presence of markedly increased systolic pulmonary arterial pressure (SPAP), so as to provide more information for clinical management.Materials and methodsFifty-one patients with clinically diagnosed FM were divided in two groups (SPAP < 50 mmHg group; SPAP ≥ 50 mmHg group) and retrospectively included in the study. Data mainly including demographic factors, echocardiographic data, results of right heart catheter and computed tomography (CT) examination were retrieved from the medical database. Echocardiographic parameters pre- and post- balloon pulmonary angioplasty (BPA) treatment were also collected in 8 patients.ResultsSignificant changes in cardiac structure, hemodynamics and cardiac function were detected in patients complicated with markedly increased SPAP. Patients in the SPAP ≥ 50 mmHg group had increased right heart diameter, right heart ratio and velocity of tricuspid regurgitation (VTR) (p < 0.05). Deteriorated right heart function was also observed. There was no significant difference in CT findings between the two groups, except that more patients in the SPAP ≥ 50 mmHg group had pleural effusion (p < 0.05). After primary BPA in 8 patients, improvement in the right atrium proportion was observed.ConclusionsChanges due to significantly increased SPAP in patients with FM include adverse structure and function of the right heart, but differences in CT findings were not significant. Echocardiography has advantages as a noninvasive tool for the evaluation of cardiac structure, function and hemodynamics in patients with FM.

Thyroid dysfunction and its relation to myocardial performance among patients with acute myocardial infarction

Background: The cardiovascular system is one of the most important targets on which thyroid hormones act, thyroid hormone has a major role in the cardiovascu­lar system function and cardiac hemodynamics. Objectives: The primary aim of our study was to evaluate the prevalence of thyroid dysfunction in patients with acute myocardial infarction and to study the impact of these dysfunctions on in-hospital morbidity and mortality among those subjects. Patients and Methods: This study was conducted on one hundred critically ill patients admitted to the critical care department with the diagnosis of acute myocardial infarction in the period from April 2017 to January 2019. Results: According to thyroid profile, 78 patients (78%) had euthyroid status and the remaining 22 patients (22%) had thyroid dysfunctions which include: 12 patients (54.54%) were euthyroid sick syndrome, 7 patients (13.81%) had subclinical hypothyroidism, 3 patients (13.63%) had subclinical hyperthyroidism. Conclusion: Thyroid dysfunction in association with acute myocardial infarction affect the myocardial performance and this was evident in our study by lower ejection fraction, higher initial killip class, higher wall motion score index, and increased myocardial performance index compared to those with normal thyroid status but it has no impact on the in-hospital mortality.

High Density Lipoprotein Reduces Blood Pressure and Protects Spontaneously Hypertensive Rats Against Myocardial Ischemia-Reperfusion Injury in an SR-BI Dependent Manner.

BackgroundHypertension is a key risk factor in the development of cardiovascular diseases. Elevation in blood pressure alters high density lipoprotein (HDL) function and composition. The exact role of HDL in cardiovascular complications observed in hypertension is however not clearly understood. HDL protected against myocardial ischemia/reperfusion (I/R) injury in normotensive rats. Nonetheless, it's not clear if restoration of HDL function and/or composition protects against myocardial I/R injury in spontaneously hypertensive rats (SHR).ObjectivesIn this study we tested the effect of HDL treatment on I/R injury in Wistar Kyoto rats (WKY) and SHR and investigated the possible underlying mechanism(s).MethodsHDL (900 ng/kg/min) or vehicle were continuously administered to 11-week old WKY and SHR for 1 week (chronic treatment). Blood pressure was measured before and after treatment. Hearts were subjected to I/R injury using a modified Langendorff system. Another set of rats were treated with HDL administered at reperfusion (acute treatment) in the presence or absence of scavenger receptor class B type-I (SR-BI) blocking antibody. Cardiac hemodynamics were computed and cardiac enzyme release and infarct size were measured. Total cholesterol (TC) and HDL-cholesterol (HDL-C) were enzymatically assayed. Markers of autophagy and inflammation were detected by immunoblotting and ELISA, respectively.ResultsHDL treatment did not increase TC or HDL-C levels in SHR or WKY, yet it significantly (P < 0.01) reduced systolic and diastolic blood pressure in SHR. Chronic and acute HDL treatment significantly (P < 0.05) protected WKY and SHR against myocardial I/R injury. Chronic HDL treatment was significantly (P < 0.05) more protective in SHR whereas acute HDL treatment induced significantly (P < 0.05) greater protection in WKY. The extent of HDL induced protection was proportional to the expression levels of cardiac SR-BI and blockage of SR-BI completely abolished HDL mediated protection in SHR. Chronic HDL treatment significantly (P < 0.05) reduced markers of autophagy and inflammation in hypertensive rats.ConclusionsWe demonstrate a novel anti-hypertensive and a cardioprotective effect of HDL against myocardial I/R injury in SHR, the magnitude of which is directly related to the expression levels of cardiac SR-BI. Mechanistically, chronic HDL treatment protected SHR hearts by reducing autophagy and inflammation.

Impact of perinatal management on neurodevelopmental outcomes in congenital heart disease

With advancements in cardiopulmonary bypass technique and perioperative care, there has been a progressive decline in mortality associated with neonatal surgical correction of congenital heart disease (CHD). Thus, there is now increased focus on improving neurodevelopmental outcomes in CHD survivors. While the cause of these neurodevelopmental impairments is multifactorial, there is increasing evidence that structural and functional cerebral abnormalities are present before cardiac corrective repair. This suggests that in addition to patient specific risk factors, underlying cardiac physiology and clinical hemodynamics are critical to brain health and development. Prenatal diagnosis of CHD and subsequent optimization of perinatal care may therefore be important modifiable factors for long-term neurodevelopmental outcome.This article reviews the impact that prenatal diagnosis of CHD has on perinatal care and the preoperative clinical status of a neonate, as well as the potential influence this may have on lessening the degree of cerebral injury and long-term neurodevelopmental impairments.

Effects of a New Form of Resistance-Type High-Intensity Interval Training on Cardiac Structure, Hemodynamics, and Physiological and Performance Adaptations in Well-Trained Kayak Sprint Athletes.

This study examined the effects of a resistance-type high-intensity interval training (RHIIT) matched with the lowest velocity that elicited O2peak (100% vO2peak) in well-trained kayak sprint athletes. Responses in cardiac structure and function, cardiorespiratory fitness, anaerobic power, exercise performance, muscular strength, and hormonal adaptations were examined. Male kayakers (n = 24, age: 27 ± 4 years) were randomly assigned to one of three 8-wk conditions (N = 8): (RHIIT) resistance training using one-armed cable row at 100% vO2peak; paddling-based HIIT (PHIIT) six sets of paddling at 100% vO2peak; or controls (CON) who performed six sessions including 1-h on-water paddling/sessions at 70–80% maximum HR per week. Significant increases (p < 0.05) in O2peak, vO2peak, maximal cardiac output, resting stroke volume, left ventricular end-systolic dimension, 500-m paddling performance were seen pre- to post-training in all groups. Change in O2peak in response to PHIIT was significantly greater (p = 0.03) compared to CON. Also, 500-m paddling performance changes in response to PHIIT and RHIIT were greater (p = 0.02, 0.05, respectively) than that of CON. Compared with pre-training, PHIIT and RHIIT resulted in significant increases in peak and average power output, maximal stroke volume, end-diastolic volume, ejection fraction, total testosterone, testosterone/cortisol ratio, and 1,000-m paddling performance. Also, the change in 1,000-m paddling performance in response to PHIIT was significantly greater (p = 0.02) compared to that of CON. Moreover, maximum strength was significantly enhanced in response to RHIIT pre- to post-training (p < 0.05). Overall, RHIIT and PHIIT similarly improve cardiac structure and hemodynamics, physiological adaptations, and performance of well-trained kayak sprint athletes. Also, RHIIT enhances cardiorespiratory fitness and muscular strength simultaneously.

LncRNA LINC00461 exacerbates myocardial ischemia\u2013reperfusion injury via microRNA-185-3p/Myd88

ObjectiveLong non-coding RNAs (lncRNAs) play critically in the pathogenesis of myocardial ischemia–reperfusion (I/R) injury. Thus, it was proposed to investigate the mechanism of LINC00461 in the disease through mediating microRNA-185-3p (miR-185-3p)/myeloid differentiation primary response gene 88 (Myd88) axis.MethodsmiR-185-3p, LINC00461 and Myd88 expression in mice with I/R injury was measured. Mice with I/R injury were injected with the gene expression-modified vectors, after which cardiac function, hemodynamics, myocardial enzyme, oxidative stress, and cardiomyocyte apoptosis were analyzed.ResultsI/R mice showed LINC00461 and Myd88 up-regulation and miR-185-3p down-regulation. Down-regulating LINC00461 or up-regulating miR-185-3p recovered cardiac function, reduced myocardial enzyme levels, and attenuated oxidative stress and cardiomyocyte apoptosis in mice with I/R. miR-185-3p overexpression rescued the promoting effect of LINC00461 upregulation on myocardial injury in I/R mice.ConclusionLINC00461 knockdown attenuates myocardial I/R injury via elevating miR-185-3p expression to suppress Myd88 expression.

Leptin Alleviates Inflammatory Response in Myocardial Ischemia Reperfusion Injury.

Objective To investigate the role of leptin in regulating cell inflammation and protecting myocardium after myocardial ischemia-reperfusion injury in rats through signaling pathway at tissue and molecular protein levels. Methods Healthy female SD rats were randomly divided into 4 groups, which were sham, I/R group, leptin low-dose intervention group, and high-dose intervention group (40 μg/kg and 80 μg/kg, respectively). Cardiac hemodynamics, myocardial enzymology, inflammatory indices, and pathological changes were observed. Western blot was used to observe the expression of PI3K, AKT, and NFκB protein by leptin. Results Leptin can improve the hemodynamics of cardiac ischemia-reperfusion rats, improve the expression of myocardial enzymology, reduce the release of cardiac and serum inflammatory factors, increased PI3k, AKT, and NFκB expression, and reduce the occurrence of inflammation from the perspective of gross pathology, thus protecting the body. Conclusion Leptin pretreatment can reduce MIRI injury, and the protective mechanism may be that leptin upregulates PI3K-AKT-NFκB expression in myocardial tissue to reduce inflammation and promote repair of I/R injury.

Association of triglyceride-glucose with cardiac hemodynamics in type 2 diabetes

PurposeTriglyceride-glucose (TyG) index is a reliable and inexpensive alternative indicator of insulin resistance. Previous studies have shown that elevated TyG index increases the risk of diabetes, coronary heart disease, and other diseases, but the relationship between TyG index and cardiac hemodynamics in patients with type 2 diabetes mellitus (T2DM) is not clear. This study was conducted in patients with T2DM to assess the relationship between TyG and cardiac hemodynamics and its predictive ability for T2DM.MethodsA total of 647 individuals (348 males and 299 females) were enrolled in this study, including 446 T2DM patients and 201 healthy controls. The clinical data and related laboratory variables were assessed and recorded, and TyG index was calculated. Cardiac hemodynamics was measured by echocardiography. Pearson or Spearman correlation analysis and linear regression analysis were conducted to explore the association between TyG and cardiac hemodynamics. The receiver operating characteristics (ROC) curve was used to evaluate the efficacy of TyG index in the diagnosis of T2DM.ResultsCompared with healthy controls, the systolic blood pressure (SBP), body weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), HOMA-IR, and TyG levels were higher in patients with T2DM. With the increase of TyG, the levels of left ventricular mass index (LVMI), left ventricular mass (LVM), left ventricular end diastolic diameter (LVDd), posterior wall thickness (PWT), and interventricular septum thickness (IVST) were also increased in T2DM individuals. Multivariate linear regression analysis showed that TyG was an independent determinant of LVEF, PWT, IVST, and ejection time (ET) after adjusting for confounding factors. In addition, individuals with visceral obesity had higher TyG and TyG can be used as a predictor of T2DM with an AUC of 0.903 (95% CI:0.879–0.927).ConclusionsThe increase of TyG index is closely related to cardiac hemodynamics of T2DM patients, which is expected to be a simple and practical biological index to predict the changes of cardiac function in patients with T2DM.

The value of transthoracic echocardiography in the detection of extra-cardiac lesions

ObjectiveTransthoracic echocardiography (TTE) is generally recognized as the top choice for detecting myocardial and cardiac cavity lesions. Sonographers mostly focus on myocardium, cardiac cavity and cardiac hemodynamics, whereas the abnormal extra-cardiac lesions are easily remain unrecognized. The aim of this study was to investigate the ultrasonic image features in abnormal extra-cardiac lesions and the value of TTE in the detection of extra-cardiac lesions.Methods49 cases of abnormal extra-cardiac lesion detected by TTE from January 2014 to December 2019 were collected, which were confirmed by surgical pathology. The two-dimensional ultrasonic characteristics and the relationships with the cardiac and great vessels were summarized on the basis of multi-view by TTE. All patients were also examined by computed tomography (CT).ResultsIn 49 patients with abnormal extra-cardiac lesions, 37 malignant cases and 12 benign cases were included. There were 41 cases (41/49, 86.67%) of mediastinal lesions and 8 cases (8/49, 16.33%) of lung lesions. The maximum diameter ranged from 3.2 cm to 13.66 cm, and the median diameter was about 7.4 cm, among which 29 cases (29/49, 59.18%) were larger than 5 cm. 4 cases (4/49, 8.16%) of cystic anechoic lesions were pericardial cyst. 2 cases (2/49, 4.08%) of cystic-solid echogenic lesions were teratoma. The remaining 43 cases (43/49, 87.76%) presented as solid hypoechoic or heterogeneous masses. 6 cases compressed the heart and 21 cases encroached on the heart and vessels. Diagnosis coincidence rates of TTE and CT were respectively 77.55% and 93.88%, with a statistical difference (p = 0.012).ConclusionAlthough the diagnostic coincidence rate of TTE is slightly lower than that of CT, TTE has certain diagnostic value for extra-cardiac lesions.

Study of the Risk Factors for Coronary Artery Disease and their Correlation with Thyroid Hormone Profile amongst Women with ST Segment Elevation in Acute Myocardial Infarction

Background: Thyroid hormone has a major role in the cardiovascular function and cardiac hemodynamics as well as to maintain the cardiovascular homeostasis. The present study was planned to assess risk factors for coronary artery disease and their correlation with thyroid hormone profile amongst women with ST segment elevation in acute myocardial infraction. Material and Methods: A total number of 78 females having ST elevation myocardial infarction diagnosed through detailed clinical history and ECG evaluations were included after they satisfy the eligibility criteria. Patients were subsequently evaluated for presence of risk factors of ischemic heart disease such age, marital status, parity, and menopause, use of oral contraceptives, family history, obesity, diabetes mellitus, hypertension, hypercholesterolemia and hypertriglyceridemia. Their thyroid hormone profiles (T3, T4, TSH) were done and were correlated with risk factors for ischemic heart disease. Results: A total 78 patient included in the study most of the study population belongs to the age group of 40 to 50 years (43.6 %). Hypertension was the most common clinical features amongst study population (59%) followed by Diabetes (50%). Most of the study population had Normal Thyroid status (57.69%) followed by Hypothyroidism (25.64%) and Hyperthyroidism (16.67%) and SERUM TSH is the most sensitive test for evaluation. Diabetes Mellitus was statistically significant risk factor (p value&lt;0.05) in patients with STEMI with different levels of thyroid. Conclusion: Patients with coronary artery disease especially in the presence of other risk factors should be screened for thyroid dysfunction specially diabetes. We recommend tests for thyroid disorders in acute coronary syndrome can give predictor for risk of morbidity and mortality in those subjects.

Stachytine Hydrochloride Improves Cardiac Function in Mice with ISO-Induced Heart Failure by Inhibiting the α-1,6-Fucosylation on N-Glycosylation of β1AR.

Background: Cardiovascular diseases have become a major public health problem that seriously threatens human health. The cumulative effects of various cardiovascular events will eventually develop into chronic heart insufficiency and even heart failure, and the β1 adrenergic receptor signal pathway plays an important role in this process. Stachytine hydrochloride is the main active ingredient of Yimucao, which is a traditional Chinese medicine used to treat gynecological diseases. Modern studies have found that stachytine hydrochloride has a good cardioprotective effect, but it is still unclear whether stachytine hydrochloride has an effect on the β1 adrenergic receptor signal pathway. The purpose of this study is to explore the effect of stachytine hydrochloride on the β1 adrenergic receptor signal pathway. Method: In this study, a continuous infusion of isoproterenol (40 mg/kg/day) was administered to mice and ventricular myocytes explored the potential mechanism of stachytine hydrochloride (12 mg/kg/day) on the β1 adrenergic receptor signal pathway in the heart. Evaluate changes in cardiac morphology and function by echocardiography, cardiac hemodynamics, and histological methods, and detect molecular changes by Western blot and immunofluorescence. Treat primary cultured adult mouse or neonatal rat ventricular myocytes with or without isoproterenol (0.1 μMol), PNGase F (10–2 units/ml), and stachytine hydrochloride (10 μMol) at different time points. Detect α-1,6-fucosylation on N-glycosylation, calcium transient, contraction, and relaxation function and related signals. Results: Stachytine hydrochloride reduces cardiac remodeling and modulates hemodynamic parameters during chronic β1 adrenergic receptor activation in vivo. The N-glycosylation of β1 adrenergic receptors decreased after continuous isoproterenol stimulation, while stachytine hydrochloride can increase the N-glycosylation of β1AR in the heart of mice with isoproterenol-induced heart failure. Decreased N-glycosylation of β1 adrenergic receptors will downregulate the cAMP/PKA signal pathway and inhibit myocardial excitation and contraction coupling. Stachytine hydrochloride significantly reduced isoproterenol-induced cardiac N-linked glycoproteins with α-1,6-fucosylation. Conclusion: Our results show that stachytine hydrochloride inhibits the synthesis of α-1,6-fucosylation on the N-terminal sugar chain by reducing α-1,6-fucosyltransferase (FUT8) and α-1,3-mannosyl-glycoprotein 4-β-N-acetylglucosaminyltransferase A (MGAT4a), upregulating the N-glycosylation level on β1 adrenergic receptors, and maintaining cAMP/PKA signal pathway activation.

Milrinone effects on cardiac mitochondria, hemodynamics, and death in catecholamine-infused rats.

BackgroundCatecholamine-storm is considered the major cause of enterovirus 71-associated cardiopulmonary death. To elucidate the effect of milrinone on cardiac mitochondria and death, a rat model of catecholamine-induced heart failure was investigated.MethodsYoung male Spray-Dawley rats received a continuous intravenous infusion of norepinephrine then followed by co-treatment with and without milrinone or esmolol. Vital signs were monitored and echocardiography was performed at indicated time points. At the end of experiments, hearts were extracted to study mitochondrial function, biogenesis, and DNA copy numbers.ResultsHypernorepinephrinemia induced persistent tachycardia, hypertension, and high mortality and significantly impaired the activities of the electron transport chain and suppressed mitochondrial DNA copy number, mitochondrial transcription factor A and peroxisome proliferator-activated receptor-gamma coactivator 1-α. Norepinephrine-induced hypertension could be significantly suppressed by milrinone and esmolol. Milrinone improved but esmolol deteriorated the survival rate. The left ventricle was significantly enlarged shortly after norepinephrine infusion but later gradually reduced in size by milrinone. The impairment and suppression of mitochondrial function could be significantly reversed by milrinone but not by esmolol.ConclusionsMilrinone may protect the heart via maintaining mitochondrial function from hypernorepinephrinemia. This study warrants the importance of milrinone and the preservation of mitochondrial function in the treatment of catecholamine-induced death.Impact Milrinone may protect the heart from hypernorepinephrinemia-induced death via maintaining myocardial mitochondrial activity, function, and copy number.Maintenance of cardiac mitochondrial function may be a potential therapeutic strategy in such catecholamine-induced heart failure.

Maternal diabetes and fetal cardiac output.

The intrauterine environment is a key determinant for long-term health outcomes. Adverse fetal environments, such as maternal diabetes, obesity and placental insufficiency are strongly associated with long-term health risks in children. Little is known about differences in fetal cardiac output hemodynamics of diabetic mothers (DM) vs. non-diabetic mothers (NDM). Our study aims to investigate the left-sided, right-sided, and combined cardiac output (CCO) in fetuses of DM vs. NDM. Retrospective data were collected in fetuses of DM (N = 532) and NDM (103) at mean gestational age 24 weeks. Examination included 2D echo and pulse wave Doppler. Wilcoxon rank sum tests and Chi-square tests were used to test for distribution difference of maternal and fetal continuous and categorical measures respectively between DM and NDM. Intraclass correlation coefficients were calculated to assess intra-observer reliability of fetal cardiac measurements. DM mothers had higher mean weight (89.7±22.2 kg) than NDM (76.8±19.8 kg), p < 0.0001 and higher mean BMI (33.4±7.5) than NDM (28.3±5.8), p < 0.0001. C-section delivery occurred in 66% of DM vs. 35% of NDM fetuses. Fetuses of DM mothers had significantly larger semilunar valve diameter, higher left ventricular (LV) output, higher combined cardiac output and lower right ventricle /left ventricle ratio compared to NDM. The greater CCO (adjusted for fetal weight), left sided cardiac output in the fetuses of DM, compared to NDM, represent differences in cardiac adaptation to the diabetic environment.

Cardiac Catheterization and Hemodynamics in a Multicenter Cohort of Children with Pulmonary Hypertension.

Rationale: Hemodynamic assessments direct care among children with pulmonary hypertension, yet the use of cardiac catheterization is highly variable, which could impact patient care and research. Objectives: We analyzed hemodynamic findings from right heart catheterization (RHC) and left heart catheterization and acute vasodilator testing (AVT) and the safety of catheterization in children with World Symposium on Pulmonary Hypertension (WSPH) group 1 and 3 subtypes in a large multicenter North American cohort. Methods: Of 1,475 children enrolled in the Pediatric Pulmonary Hypertension Network Registry (2014-2020), there were 1,383 group 1 and 3 patients, of whom 671 (48.5%) underwent RHC at diagnosis and were included for analysis. Results: Compared with those without diagnostic RHC, these children were older, less likely to be an infant or preterm, more often female, treated with targeted pulmonary hypertension medications at diagnosis, and had advanced World Health Organization functional class. Catheterization was performed without a difference in complication rates between WSPH groups. Pulmonary capillary wedge pressure was well correlated with left ventricular end-diastolic pressure and left atrial pressures. Results of AVT using three different methods were comparable; positive AVT results were observed in 8.0-11.8% of subjects, did not differ between WSPH groups 1 and 3, and were not associated with freedom from the composite endpoint of lung transplantation or death during follow-up. Conclusions: In a large pediatric pulmonary hypertension cohort, diagnostic RHC with or without left heart catheterization in WSPH group 1 and 3 patients was performed safely at experienced pediatric pulmonary hypertension centers. Hemodynamic differences were noted between group 1 and 3 subjects. Higher mean pulmonary arterial pressure and mean pulmonary arterial pressure/mean systemic arterial pressure ratio were associated with a higher risk of death/transplantation. Findings suggest overall safety and potential value of RHC as a standard diagnostic approach to guide pulmonary hypertension management in children.