Cardiac Workload Research Articles

Abstract 4131100: Effect of metabolic surgery on cardiovascular outcomes in people with obesity and pre-existing cardiovascular disease: A systematic review and meta-analysis

Background: Previous literature shows that metabolic surgery effectively decreases the risk of cardiovascular disease (CVD) events in patients with obesity. The use of metabolic surgery has, however, been limited in people with obesity and pre-existing CVD due to concerns of poor post-operative cardiovascular outcomes. This study aims to determine the effectiveness and safety of metabolic surgery in patients with pre-existing CVD. Methods: A search of electronic databases, PubMed, Cochrane Central and SCOPUS was conducted from their inception till May 2024. The study was conducted adhering to the PRISMA guidelines. Outcomes of interest were risk of all-cause mortality, major adverse cardiovascular events (MACE), risk of myocardial infarction (MI), and cerebrovascular events in patients with and without prior CVD undergoing bariatric surgery. Data was pooled as generic inverse variance using a random effects model, and presented as hazard ratios (HR) with their 95% confidence intervals (CI). Results: We included four studies in our analysis (n = 5,244). Our pooled analysis shows that metabolic surgery leads to significant reduction in risk of all-cause mortality (HR = 0.51, 95% CI: [0.42, 0.61]; p<0.01). We also observed a significant risk reduction of 43% in MACE with metabolic surgery (HR = 0.57, 95% CI: [0.5, 0.64]; p<0.01). Metabolic surgery was not associated with a significant reduction in the risk of MI (HR = 0.53, 95% CI: [0.24, 1.18]; p = 0.12, I 2 = 83%). Similarly, a non-significant decrease in risk of cerebrovascular events was observed with metabolic surgery (HR = 0.89, 95% CI: [0.65, 1.22]; p = 0.48) Conclusion: Metabolic surgery is associated with decreased risk of all-cause mortality and MACE in patients with obesity and established CVD. These results are thought to be mediated through reduction in risk factors such as obesity, but also by reducing inflammatory mediators and having other beneficial effects on cardiac structure and left ventricular workload.

Importance of environmental signals for cardiac morphological development in Atlantic salmon.

The hearts of salmonids display remarkable plasticity, adapting to various environmental factors that influence cardiac function and demand. For instance, in response to cold temperature, the salmonid heart undergoes growth and remodeling to counterbalance the reduced contractile function associated with dropping temperatures. Alongside heart size, the distinct pyramidal shape of the wild salmonid heart is essential for optimal cardiac performance, yet the environmental drivers behind this optimal cardiac morphology remain to be fully understood. Intriguingly, farmed salmonids often have rounded, asymmetrical ventricles and misaligned bulbi from an early age. These deformities are noteworthy given that farmed salmon are often not exposed to natural cues, such as a gradual temperature increase and changing day lengths, during critical developmental stages. In this study, we investigated whether natural environmental conditions during early life stages are pivotal for proper cardiac morphology. Atlantic salmon were raised under simulated natural conditions (low temperature with a natural photoperiod; SimNat) and compared with those reared under simulated farming conditions (SimFarm). Our findings reveal that the ventricle shape and bulbus alignment in SimNat fish closely resemble those of wild salmon, while functional analyses indicate significant differences between SimNat and SimFarm hearts, suggesting diastolic dysfunction and higher cardiac workload in SimFarm hearts. These findings highlight the profound influence of environmental factors such as water temperature and photoperiod on the structural development of the salmonid heart, underscoring the importance of early environmental conditions for cardiac health.

Impact of peripheral venoarterial extracorporeal membrane oxygenation support for heart failure on systemic hemodynamics and aortic blood flow

Peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an advanced temporary life support system for patients with refractory cardiogenic shock or severe cardiopulmonary failure. However, the reperfusion of oxygenated blood into the arterial system via a peripheral artery will induce substantial hemodynamic changes that might contribute to the development of complications. In this study, we developed two types of computational models to quantify the hemodynamic changes induced by the peripheral VA-ECMO support for systolic heart failure (HF) of various severities. One was a lumped-parameter model used for exploring the optimal workload of extracorporeal membrane oxygenation (ECMO) for a specific severity of HF, whereas the other one was a geometrical multiscale model capable of simulating the detailed flow field in the aorta while accounting for the hemodynamic coupling of VA-ECMO with the cardiovascular system. Numerical results revealed that the retrograde transmission of ECMO-supplied blood flow toward the heart not only considerably inhibited cardiac output but also induced marked flow disturbance and regionally high or oscillatory wall shear stress (WSS) in the aorta that may increase the risk of thrombosis and vascular dysfunction. The major characteristics of flow disturbance and spatial distribution of abnormal WSS were codetermined by the cardiac function and workload of ECMO while less influenced by the morphology of aorta. These findings emphasized the importance of tuning the workload of ECMO based on patient-specific cardiac function to balance the amount of blood oxygenation support by ECMO against the risk of complications associated with hemodynamic abnormalities.

Haemodynamics of hyperthyroidism: increased cardiac work and findings related to vasodilatation.

Hyperthyroidism increases cardiovascular morbidity and mortality, but the underlying mechanisms are not fully understood. In this study we compared non-invasive haemodynamics between 20 hyperthyroid patients and 60 euthyroid subjects. The measurements were performed median 6 days after the initiation of antithyroid medication when the patients were still hyperthyroid. Three controls matched for age, sex, body mass index, and smoking status were selected for each patient. Recordings were performed during rest and passive head-up tilt using whole-body impedance cardiography, radial pulse wave analysis, and finger blood pressure measurements. Systolic and diastolic blood pressures in the aorta and radial artery were similar in hyperthyroid and euthyroid subjects, while finger blood pressure was 16/12 mmHg lower in hyperthyroidism (p<0.001). Pulse wave velocity and aortic pulse pressure were similar, but radial pulse pressure was ~5 mmHg higher in hyperthyroidism (p=0.040) due to augmented amplification (p=0.045). Systemic vascular resistance was reduced (-18%), whereas heart rate (+19 beats/min), cardiac index (+28%), and left cardiac work (+31%) were increased in hyperthyroidism (p<0.001). Subendocardial viability ratio, reflecting the balance between coronary perfusion and pressure load, was reduced by 19% in hyperthyroidism (p<0.001). Compared with euthyroid subjects, hyperthyroid patients presented with reductions in systolic and diastolic finger blood pressures (p<0.001), and higher increase in heart rate (p=0.014) during upright posture. Hyperthyroid patients exhibited hyperdynamic circulation, reduced vascular resistance, reduced peripheral but not central blood pressure, and higher pulse pressure amplification. Furthermore, left cardiac workload was increased in parallel with unfavourable changes in coronary perfusion conditions.

Evaluating the Efficacy and Safety of Antihypertensive Drugs in the Treatment of Congenital Heart Disease in Paediatric Patients: A Comprehensive Study

CHD is the most common of all congenital anomalies causing mortality among children, characterized by structural abnormalities present at birth that vary in severity and complexity. Increased cardiac workload due to CHD may stipulate a growth delay in the affected children. The complexity of treatment is further compounded by medication errors, and hence, rigorous strategies of evaluation and management become necessary. This study was conducted to determine antihypertensive drug consumption patterns and to evaluate their therapeutic efficacy among 92 patients with CHD to meet the evaluation criteria, including appropriateness of treatment for the condition of the patient, adherence to indications, accuracy of dosage, and drug use practice. Females constituted the highest proportion of patients at 53.26 percent, infants were the most common age group at 43.48 percent, and Atrial seal defect accounted for 22.5 percent of the CHD patients. The antihypertensive drugs predominantly prescribed are Furosemide, used by 44.9% of the subjects, followed by Captopril, used by 30.3%, and Spironolactone, used by 10.1%. Therapy was evaluated for its effectiveness; appropriateness, both for the patient's indications and drug usage, was found to be very high, at 98.9% and 97.8%, respectively, whereas adherence to prescribed dosage was relatively lower at 62.7%. This study points toward further challenges in the management of antihypertensive treatment among children with CHD. It needs combined efforts by a pediatric cardiologist, pharmacist, nurse, and caregiver for total care to reduce the risk from treatment. Continuous monitoring and alterations in the plan of treatment, coupled with education, could be significant in optimizing medication adherence to improve long-term health outcomes in CHD children. The research done in this field, at large, improves pediatric cardiology practice to reduce morbidity and mortality rates associated with congenital heart disease around the world.

Cardiovascular effects of long-duration space flight.

Early studies exploring the physiological effects of space travel have indicated the body's capacity for reversible adaptation. However, the impact of long-duration spaceflight, exceeding 6 months, presents more intricate challenges. Extended exposure to microgravity and radiation profoundly affects the CV system. Notable phenomena include fluid shifts toward the head and modified arterial pressure. These changes disrupt blood pressure regulation and elevate cardiac output. Additionally, the loss of venous compression leads to a reduction in central venous pressure. The displacement of fluid from the vascular system to the interstitium, driven by baroreceptor stimulation, results in a 10%-15% decline in plasma volume. Intriguingly, despite potential increases in cardiac workload, cardiac muscle atrophy and perplexing variations in hematocrit levels have been observed. The mechanism underlying atrophy appears to involve a shift in protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated mechanisms. Instances of arrhythmias have been recurrently documented, although generally nonlethal, in both Russian and American space missions. Long-duration spaceflight has been associated with the prolongation of the QT interval, particularly in extended missions. Exposure of the heart to the proton and heavy ion radiation pervasive in deep space contributes to coronary artery degeneration, augmented aortic stiffness, and carotid intima thickening through collagen-mediated processes. Moreover, it accelerates the onset of atherosclerosis and triggers proinflammatory responses. Upon reentry, astronauts frequently experience orthostatic intolerance and altered sympathetic responses, which bear potential hazards in scenarios requiring rapid mobilization or evacuation. Consequently, careful monitoring of these cardiac risks is imperative for forthcoming missions. While early studies illuminate the adaptability of the body to space travel's challenges, the intricacies of long-duration missions and their effects on the CV system necessitate continued investigation and vigilance to ensure astronaut health and mission success.

Increased Diastolic Energy Loss Associated with Cardiac Events in Adults with Pulmonary Atresia Suffering from Intact Ventricular Septum.

To assess right heart diastolic energy loss (EL) as a cardiac workload and evaluate its association with major cardiac events (MACE) in adult patients with pulmonary atresia with an intact ventricular septum (PAIVS). We retrospectively enrolled and compared 30 consecutive adult patients (18 with PAIVS and 12 with pulmonary stenosis [PS] as controls) who underwent right ventricular (RV) outflow tract reconstruction and 4D flow MRI. EL, conventional parameters on MRI, and the severity of tricuspid regurgitation (TR) on echocardiography were assessed. We also evaluated the association between MACE including arrhythmias, heart failure, surgical intervention, and imaging parameters in adults with PAIVS. Patients with PAIVS were younger, had a higher diastolic EL/cardiac output (CO) ratio, and had a more significant TR than those with PS (controls). However, RV volume, ejection fraction (EF), and pulmonary regurgitation (PR) severity did not differ between the two groups. Higher RV end-diastolic pressure (EDP) and lower cardiac index (CI) correlated with the diastolic EL/CO in patients with PAIVS. Univariate logistic analysis demonstrated that older age and a higher diastolic EL/CO ratio were important factors for MACE in adults with PAIVS (P = 0.048, 0.049). A higher diastolic EL/CO ratio was associated with a higher RV EDP and lower CI. A high diastolic EL/CO ratio is also associated with MACE in adults with PAIVS. Even in adults with normal RV volume and EF, the right heart EL was elevated, suggesting an excessive right-sided cardiac workload that integrated both afterload and preload beyond the RV size in adult patients with PAIVS.

Transcriptomic analysis reveals PC4's participation in thermotolerance of scallop Argopecten irradians irradians by regulating myocardial bioelectric activity

Rising ocean temperatures due to global warming pose a significant threat to the bay scallop aquaculture industry. Understanding the mechanisms of thermotolerance in bay scallops is crucial for developing thermotolerant breeds. Our prior research identified Arg0230340.1, part of the positive cofactor 4 (PC4) family, as a key gene associated with the thermotolerance index Arrhenius break temperature (ABT) in bay scallops. Further validation through RNA interference (RNAi) reinforced PC4's role in thermotolerance, offering a solid basis for investigating thermal response mechanisms in these scallops. In this study, we performed a comparative transcriptomic analysis on the temperature-sensitive hearts of bay scallops after siRNA-mediated RNAi targeting Arg0230340.1, to delve into the detailed molecular mechanism of PC4's participation in thermotolerance regulation. The analysis revealed that silencing Arg0230340.1 significantly reduced the expression of mitochondrial tRNA and rRNA, potentially affecting mitochondrial function and the heart's blood supply capacity. Conversely, the up-regulation of genes involved in energy metabolism, RNA polymerase II (RNAPII)-mediated basal transcription, and aminoacyl-tRNA synthesis pathways points to an intrinsic protective response, providing energy and substrates for damage repair and maintenance of essential functions under stress. GO and KEGG enrichment analyses indicated that the up-regulated genes were primarily associated with energy metabolism and spliceosome pathways, likely contributing to myocardial remodeling post-Arg0230340.1 knockdown. Down-regulated genes were enriched in ion channel pathways, particularly those for Na+, K+, and Ca2+ channels, whose dysfunction could disrupt normal myocardial bioelectric activity. The impaired cardiac performance resulting from RNAi targeting Arg0230340.1 reduced the cardiac workload in scallop hearts, thus affecting myocardial oxygen consumption and thermotolerance. We propose a hypothetical mechanism where PC4 down-regulation impairs cardiac bioelectric activity, leading to decreased thermotolerance in bay scallops, providing theoretical guidance for breeding thermotolerant scallop varieties and developing strategies for sustainable aquaculture in the face of long-term environmental changes.

Cardiac surgery during wartime in Israel

BackgroundThe war that began on October 7th, 2023, has impacted all major tertiary medical centers in Israel. In the largest cardiac surgery department in Israel there has been a surprising increase in the number of open-heart procedures, despite having approximately 50% of surgeons recruited to military service. The purpose of this study is to characterize this increase in the number of operations performed during wartime and assess whether the national crisis has affected patient outcomes.MethodsThe study was based on a prospectively collected registry of 275 patients who underwent cardiac surgery or extracorporeal membrane oxygenation (ECMO) during the first two months of war, October 7th 2023 – December 7th 2023, as well as patients that underwent cardiac surgery during the same period of time in 2022 (October 7th, 2022 – December 7th, 2022).Results120 patients (43.6%) were operated on in 2022, and 155 (56.4%) during wartime in 2023. This signifies a 33.0% increase in open-heart procedures (109 in 2022 vs. 145 in 2023, p-value 0.26). There were no significant differences in the baseline characteristics of patients when comparing the 2022 patients to those in 2023. No significant differences between the two groups were found with regards to intraoperative characteristics or the type of surgery. However, compared to 2022, there was a 233% increase in the number of transplantations in the 2023 cohort (p-value 0.24). Patient outcomes during wartime were similar to those of 2022, including postoperative complications, length of stay, and mortality.ConclusionsPatients who underwent cardiac surgery during wartime presented with comparable outcomes when compared to those of last year despite the increase in cardiac surgery workload. There was an increase in the number of transplants this year, attributed to the unfortunate increase in organ donors.

Ventricular unloading causes prolongation of the QT interval and induces ventricular arrhythmias in rat hearts.

Ventricular unloading during prolonged bed rest, mechanical circulatory support or microgravity has repeatedly been linked to potentially life-threatening arrhythmias. It is unresolved, whether this arrhythmic phenotype is caused by the reduction in cardiac workload or rather by underlying diseases or external stimuli. We hypothesized that the reduction in cardiac workload alone is sufficient to impair ventricular repolarization and to induce arrhythmias in hearts. Rat hearts were unloaded using the heterotopic heart transplantation. The ECG of unloaded and of control hearts were telemetrically recorded over 56 days resulting in >5 × 106 cardiac cycles in each heart. Long-term electrical remodeling was analyzed using a novel semi-automatic arrhythmia detection algorithm. 56 days of unloading reduced left ventricular weight by approximately 50%. While unloading did not affect average HRs, it markedly prolonged the QT interval by approximately 66% and induced a median tenfold increase in the incidence of ventricular arrhythmias in comparison to control hearts. The current study provides direct evidence that the previously reported hypertrophic phenotype of repolarization during cardiac unloading translates into an impaired ventricular repolarization and ventricular arrhythmias in vivo. This supports the concept that the reduction in cardiac workload is a causal driver of the development of arrhythmias during ventricular unloading.

Effect of Consumption of Caffeinated Energy Drinks on the Myocardium of the Adult Male Albino Rat (A Histological and Morphometric Study)

Abstract Background Energy drinks are non-alcoholic beverages containing mainly caffeine. Chronic consumption of energy drinks may be associated with increased blood pressure, and cardiac work load, as well as, increased heart rate. Energy drinks consumption has been related to myocardial infarction in healthy young adult. Aim of the Work The aim of the present work was to study the harmful effect of energy drinks histologically and morphometrically, on the myocardium of the adult male albino rats. Material and Methods 20 Adult male albino rats aging 4-6 moths were divided randomly into two groups; Group I (Control group) which consisted of 10 male albino rats with free access to food (rat chew) and water and Group II (Experimental group): 10 male albino rats which received 3.75 ml/kg body weight red bull through oral gavage daily for 4 weeks with free access to food (rat chew) and water. At the end of experiment, rats werescarificed, and cardiac muscle was extracted and processed into paraffin blocks for light microscopic examination. Morphometric study and statistical analysis were done. Results The present work demonstrated that Red Bull induced several histopathological changes of the cardiac muscle. The results showed the cardiac muscle of rats with irregularities in the arrangement of fibers and wide spaces in between. Some cardiomyocytes showed areas of pale stained sarcoplasm, partial loss of the cross striations and ill-defined intercalated discs. Localized areas of hyaline degeneration and areas of tissue disruption were also noticed with less frequently localized coalesced cytoplasmic vacuoles. The nuclei of the cardiomyocytes appeared small, darkly stained, and pyknotic. Others were flattened and deeply stained. Congested, and thick walled blood vessels were also observed, with mononuclear cellular infiltrations. In Masson’s Trichrome sections, relative increase in collagen deposition between the cardiac muscle fibers was observed which was associated with focal fibrous degeneration. Examination of the semithin sections showed partial disruption of the cardiomyocytes. The nuclei of the cardiomyocytes were small, darkly stained with perinuclear degeneration. Some nuclei were eccentric, or with an irregular outline, and peripheral chromatin condensation. The characteristic finding was the presence of longitudinal wavy cardiac muscle fibers with relatively wide spaces in between and localized areas of partially lost cross striations and intercalated discs. Dilated, thick walled blood vessels was noticed between the bundles of cardiac muscle. Mononuclear inflammatory cellular infiltrations were also detected. Conclusion The present study demonstrated the degenerative and cardiotoxic effects of Red Bull as an example of energy drinks on the histological structure of the cardiac muscle.

Overexpression of macrophage migration inhibitory factor protects against pressure overload-induced cardiac hypertrophy through regulating the miR-29b-3p/HBP1 axis.

Cardiac hypertrophy is an adaptive response to stressors such as high cardiac workload, which might lead to abnormal cardiac function and heart failure. Previous studies have indicated that macrophage migration inhibitory factor (MIF) might play a protective role in cardiac hypertrophy. Here, we aimed to illustrate the mechanism of MIF in protecting against pressure overload-induced cardiac hypertrophy. Transverse aortic constriction (TAC) mouse model was established and we found that overexpression of MIF protected against pressure overload-induced cardiac hypotrophy in TAC treated mice, as evidenced by significantly decreased the heart weight. In addition, transthoracic echocardiography showed that overexpression of MIF restored ejection fraction in TAC-treated mice. While TAC treatment resulted in a much larger cardiomyocyte size in mice, MIF overexpression notably decreased the cardiomyocyte size. Next, we demonstrated that MIF overexpression promoted the expression of miR-29b-3p which further downregulated the expression of its downstream target HMG box protein 1 (HBP1). Overexpression of HBP1 reversed the effect of MIF in alleviating Ang-II induced oxidative stress in cardiomyocytes. In conclusion, our findings suggest that MIF could attenuate pressure overload-induced cardiac hypertrophy through regulating the miR-29b-3p/HBP1 axis.

Cardiac workload study in patients with hypertrophic cardiomyopathy

The relevance of studying the heart load is determined by the need to assess its reserves at different degrees of heart failure for further selection of treatment tactics. The aim of the work is to evaluate the influence of pressure and cardiac output changes on the left and right ventricular workload in patients with hypertrophic obstructive cardiomyopathy. The haemodynamic data of 69 patients divided into two subgroups according to the value of cardiac index greater and less than the mean value were considered. It was found that the change in the left ventricular power of the heart of patients with hypertrophic obstructive cardiomyopathy is determined by the change in both cardiac index and blood pressure. In better-off patients with high cardiac index, the effect of blood pressure is higher and cardiac output is lower. In severe patients with a low cardiac index, the influence of blood pressure is reduced and cardiac index is increased. The formation of right ventricular power, both in patients with high cardiac index and low, is not affected by changes in cardiac output. Changes in the right ventricular power index are determined by variations in pulmonary artery pressure to a greater extent in well patients and to a lesser extent in severe patients. Since there are 23.1% variations in cardiac index and 60% variations in pulmonary arterial pressure, it is assumed that there is a regulatory mechanism that changes cardiac output opposite to pulmonary artery pressure fluctuations. Comparison of left and right ventricular power indices with the data given in the literature showed that both for all examined patients with hypertrophic obstructive cardiomyopathy and divided into groups, the average values of left and right ventricular power indices correspond to the range of power fluctuations in healthy people at rest. The range of left ventricular power index variation by 3.5 times, and right ventricular power index variation by 10 times in patients with hypertrophic obstructive cardiomyopathy is determined by multifunctional relationships of cardiovascular system function indices (pressures and cardiac output), which determines the necessity of personalised therapy selection, taking into account the mechanisms of their formation. The results obtained during the study of the effect of changes in pressure and cardiac index on the power developed by the left and right parts of the heart must be taken into account when choosing therapy in patients with hypertrophic obstructive cardiomyopathy. Practical significance. The results will be used in the choice of treatment in order to optimize the load on the heart in patients with hypertrophic obstructive cardiomyopathy.

Cardiomyocyte Ketone Metabolism Regulates Myocardial Hyperemia

Myocardial perfusion is inextricably coupled to metabolism, with increases in physiologic cardiac demand promoting coronary vasodilation. Despite its wide acceptance, the hypothesis that cardiomyocyte metabolism autoregulates myocardial perfusion lacks mechanistic detail; however, clinical and preclinical studies suggest a signaling role for intermediary metabolites in the vasodilatory response. In particular, the ketone body precursor, β-hydroxybutyrate (3-OHB), enhances myocardial blood flow in humans, but the mechanism by which it does so remains unclear. Here, we determined the extent to which 3-OHB influences myocardial hyperemia in mice. Intravenous 3-OHB infusion (0.5 g/kg) in adult mice (12–24 wks) raised circulating 3-OHB levels (0.5 ± 0.1 to 5.1 ± 0.6 mM; p=0.005) and increased myocardial perfusion (18.6 ± 4.4 to 50.9 ± 10.4 mL/min/g; p=0.024), as measured by myocardial contrast echocardiography. Enhanced perfusion induced by 3-OHB occurred in the absence of changes in cardiac output or systolic performance. Next, to determine if 3-OHB directly dilates the coronary vasculature, we exposed pressurized (80 mmHg), small-diameter (100–260 μm) coronary arteries from mice (C57/Bl6J and 6N) to 3-OHB (0.1–5 mM) but found no significant changes in diameter. Based on these results, we tested whether cardiomyocyte metabolism of 3-OHB is required for the vasodilatory response. We deleted β-hydroxybutyrate dehydrogenase (BDH1) selectively in cardiomyocytes using Bdh1fl/fl mice crossed with tamoxifen-inducible Cre recombinase mice (csBDH1−/−). Although 3-OHB robustly enhanced myocardial perfusion (6.9 ± 1.4 to 21.3 ± 5.6 mL/min/g; p=0.031) at sustained cardiac workloads and peripheral vascular resistance in Cre-negative littermate (control) mice, csBDH1−/− mice completely lacked the 3-OHB-induced hyperemic response (8.0 ± 2.5 to 6.3 ± 2.8 mL/min/g; p&gt;0.999). Together, these data indicate that 3-OHB evokes workload-independent enhancement of myocardial perfusion through a mechanism that requires cardiomyocyte metabolism of 3-OHB. Our results support the general concept that acute changes in metabolic substrate availability may influence oxygen delivery to cardiomyocytes via a cardiomyocyte-vascular signaling nexus. R01HL163818, R01HL142710, R01HL163003, P30GM127607, P30GM127607-05S1, Jewish Heritage Fund for Excellence (JHFE), S10OD025178. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Numerical study of hemodynamic flow in the aortic vessel of Williams syndrome patient with congenital heart disease

Congenital arterial stenosis such as supravalvar aortic stenosis (SVAS) are highly prevalent in Williams syndrome (WS) and other arteriopathies pose a substantial health risk. Conventional tools for severity assessment, including clinical findings and pressure gradient estimations, often fall short due to their susceptibility to transient physiological changes and disease stage influences. Moreover, in the pediatric population, the severity of these and other congenital heart defects (CHDs) often restricts the applicability of invasive techniques for obtaining crucial physiological data. Conversely, evaluating CHDs and their progression requires a comprehensive understanding of intracardiac blood flow. Current imaging modalities, such as blood speckle imaging (BSI) and four-dimensional magnetic resonance imaging (4D MRI) face limitations in resolving flow data, especially in cases of elevated flow velocities. To address these challenges, we devised a computational framework employing zero-dimensional (0D) lumped parameter models coupled with patient-specific reconstructed geometries pre- and post-surgical intervention to execute computational fluid dynamic (CFD) simulations. This framework facilitates the analysis and visualization of intricate blood flow patterns, offering insights into geometry and flow dynamics alterations impacting cardiac function. In this study, we aim to assess the efficacy of surgical intervention in correcting an extreme aortic defect in a patient with WS, leading to reductions in wall shear stress (WSS), maximum velocity magnitude, pressure drop, and ultimately a decrease in cardiac workload.

Abstract MP64: Cardiovascular Responses to Occupational Physical Activity Are Exaggerated by Work-Related Stress and Low Fitness

Introduction: Proposed mechanisms explaining the link between high occupational physical activity (OPA) and cardiovascular disease hypothesize that high work-related stress and low worker fitness may exacerbate cardiovascular responses to OPA. Hypothesis: Direct associations between OPA and acute cardiovascular responses will be stronger under high work-related stress and in workers with lower fitness. Methods: 19 male workers (age=46.6±7.9, 68.4% White) with high OPA jobs were observed for seven days. Steps, light (LPA), and moderate-to-vigorous physical activity (MVPA) during work were measured using a thigh-worn activPAL3 micro, hip-worn Actigraph GT3X-BT, and time-use diary. Heart rate (HR) was measured continuously with a Polar chest strap. 24-hour blood pressure (BP) was measured using an ambulatory BP monitor on one workday. Rate-pressure product (RPP), an indirect measure of cardiac workload, was calculated as systolic BP x HR. Daily work-related stress was measured with the Stress in General Scale (scores=-3-21 where higher scores indicate more stress). Worker fitness was estimated as VO 2 max (ml·kg -1 ·min -1 ) using a submaximal treadmill test. Effect modification by stress and fitness on the associations between OPA and RPP was examined using mixed effects models with interaction terms. Results: Work-related stress was directly associated with 24-hour RPP (β=94.10 mmHg*bpm/stress point, p=0.024) while worker fitness was not (β=-33.0 mmHg*bpm/VO 2 max, p=0.561). Direct association between RPP and occupational MVPA were stronger with higher work-related stress and lower fitness (Table 1, p-for-interaction&lt;0.05 for all). Lower intensity OPA (steps and LPA) were also associated with exacerbated RPP responses outside of work with higher work-related stress (Table 1, p-for-interaction&lt;0.001 for all). Conclusions: OPA performed under high stress or by workers with low fitness may exaggerate cardiovascular responses and contribute to OPA's paradoxical cardiovascular health associations.

Role of AMP deaminase in diabetic cardiomyopathy.

Diabetes mellitus is one of the major causes of ischemic and nonischemic heart failure. While hypertension and coronary artery disease are frequent comorbidities in patients with diabetes, cardiac contractile dysfunction and remodeling occur in diabetic patients even without comorbidities, which is referred to as diabetic cardiomyopathy. Investigations in recent decades have demonstrated that the production of reactive oxygen species (ROS), impaired handling of intracellular Ca2+, and alterations in energy metabolism are involved in the development of diabetic cardiomyopathy. AMP deaminase (AMPD) directly regulates adenine nucleotide metabolism and energy transfer by adenylate kinase and indirectly modulates xanthine oxidoreductase-mediated pathways and AMP-activated protein kinase-mediated signaling. Upregulation of AMPD in diabetic hearts was first reported more than 30years ago, and subsequent studies showed similar upregulation in the liver and skeletal muscle. Evidence for the roles of AMPD in diabetes-induced fatty liver, sarcopenia, and heart failure has been accumulating. A series of our recent studies showed that AMPD localizes in the mitochondria-associated endoplasmic reticulum membrane as well as the sarcoplasmic reticulum and cytosol and participates in the regulation of mitochondrial Ca2+ and suggested that upregulated AMPD contributes to contractile dysfunction in diabetic cardiomyopathy via increased generation of ROS, adenine nucleotide depletion, and impaired mitochondrial respiration. The detrimental effects of AMPD were manifested at times of increased cardiac workload by pressure loading. In this review, we briefly summarize the expression and functions of AMPD in the heart and discuss the roles of AMPD in diabetic cardiomyopathy, mainly focusing on contractile dysfunction caused by this disorder.

The effect of histidine-tryptophan-ketoglutarate cardioplegia alone or combined with preoperative infusion of levosimendan on vasoactive inotropic score in patients with poor cardiac function undergoing coronary artery bypass grafting

ABSTRACT Background: Patients with poor left ventricular function undergoing cardiac surgery frequently require inotropic drug support immediately after cardiopulmonary bypass. Levosimendan is an effective agent that acts via two complementary mechanisms. It enhances cardiac contractility and reduces cardiac workload. Aim: to assess the effect of histidine-tryptophan-ketoglutarate cardioplegia (HTK cardioplegia) alone or combined with preoperative infusion of levosimendan on the vasoactive inotropic score in patients with poor left ventricular function undergoing coronary artery bypass grafting. Material and method: this double-blinded randomized controlled trial was carried on 100 patients, divided into two groups; Levosimendan group (n = 49): patients received 0.1ug/kg/min levosimendan without loading, 12 hours preoperatively and continued for a total of 24 hours. Control group (n = 51): patients received a placebo 12 hours before surgery and continued for a total 24 hours. Both groups received HTK cardioplegia after cross-clamping of the aorta approximately 20 ml/kg into the ascending aorta over 6–8 minutes at a temperature of 4−10°C. Results: Levosimendan group was superior to control group with statistical significance regarding the need of intraaortic balloon pump (IABP), vasoactive inotropic score over the first 24 hours, troponin levels over the first 72 hours, ICU stays, hospital stay, and cumulative hospital costs. Although the incidence of postoperative low Cardiac output syndrome (LCOS), atrial fibrillation (AF), acute kidney injury (AKI), and overall mortality was lower in levosimendan group, but all were not statistically significant. Conclusion: Preoperative infusion of levosimendan combined with HTK cardioplegia in patients with poor cardiac function decreased vasoactive inotropic score and lowered the costs of hospital stay.

Subclinical myocardial dysfunction among fetal growth restriction neonates: a case-control study

Objectives To evaluate cardiac structural and functional changes in neonates with fetal growth restriction (FGR) compared to appropriate-for-gestational-age (AGA) neonates using conventional echocardiography, tissue Doppler imaging (TDI), and speckle tracking echocardiography. Method This case-control study included 85 FGR neonates and 75 non-FGR, weight adequate for gestational age neonates. Among these, 37 were symmetric FGR and 48 were asymmetric FGR. All the biophysical profiles of these newborns were assessed. An echocardiographic test was performed to evaluate cardiac dimension, Left ventricular ejection fraction (LV EF), Mitral valve Doppler flow velocities, myocardial performance index, tissue annular velocities, and LV global longitudinal strain (GLS). Results Although LVEF was found to be within the normal range, mean EF was reduced among neonates with FGR than non-FGR controls (EF: 66.14 ± 3.85% vs 69.46 ± 3.58%; p < 0.001, in FGR and non-FGR, respectively). Furthermore, LV E/E’ a measure of LV diastolic function was altered among both types of FGR neonates. Similarly, LV GLS was reduced among FGR neonates (LV GLS: −20.69 ± 2.7% vs −19.06 ± 2.9%; p < 0.001 in non-FGR and FGR, respectively). Conclusion FGR neonates exhibit significant alterations in cardiac geometry compared to AGA controls. FGR neonates also demonstrated a significant reduction in LV EF, FS, and LV global longitudinal strain, depicting failure to adapt to the increased cardiac workload after birth.

Characterization and Validation of Radiotracer Kinetics Using the Langendorff Isolated Perfused Heart.

The Langendorff isolated perfused heart is a physiologically relevant and controllable ex vivo model well suited to characterizing and validating novel radiotracers for a wide range of molecular imaging applications. It allows the monitoring of first pass tracer uptake kinetics either as a bolus injection or as a continuous infusion in beating myocardial tissue with a high degree of experimental control in terms of cardiac workload, perfusion, energy substrate delivery and composition, and drug co-administration. The radiotracer pharmacokinetic data that it provides is not contaminated by confounding factors such as off-target tracer metabolism, and as a non-imaging technique, time activity curves can be acquired with very high temporal resolution. In this chapter, we describe the basic principles and practice for setting up and using Langendorff isolated perfused hearts for the assessment of novel radiotracers and outline their potential for modeling pathophysiological conditions relevant to cardiovascular disease.