Artificial Intelligence (AI) has the potential to revolutionize medicine, particularly in the field of cardiology. There are significant diagnostics and treatments variabilities in the field of cardiovascular medicine that affects racial and ethnic racially and ethnically diverse populations as well as female patients across all age groups. The efforts put forth towards the development of AI and precision medicine within the cardiovascular practice do not fully account for existing variations in cardiovascular care delivery. AI models and precision medicine tools that were created with uncomprehensive data primarily drawn from White populations risk embedding historical differences into clinical decision-support systems. This paper outlines the integrative approach taken to review the current variabilities that persist within younger adults (<65 years) and older adults (≥ 65 years) who have cardiovascular disease. Additionally, genetic factors, limited access to care, health literacy, lack of insurance coverage and adherence are examined, as these are frequently cited as major contributors to health care adverse outcomes but remain under-researched and unresolved even with the expansion of Medicaid. For instance, Black patients experience higher prevalence of heart failure (HF) and hypertension, especially transthyretin amyloid cardiomyopathy HF, with Black women being disproportionately affected due to higher structural, environmental and clinical factors. Also, racially and ethnically diverse children with CVDs have higher odds of mortality than their White counterparts. The integration of AI in cardiovascular medicine must first be preceded by an active effort to restructure systems and reduce variable outcomes. Future research must prioritize diverse genomic datasets and equitable comprehensive representation in clinical trials. These initiatives are better served if they are driven by institutions that historically serve racially and ethnically diverse populations and communities to better enhance inclusion and fairness in electronic medical record keeping. Accordingly, cardiovascular medical practices and technology can progress forward with AI and precision medicine models that are both equitable and accurate.

With reports of its emergence as far back as the early 1900s, human immunodeficiency virus (HIV) has become one of the deadliest and most difficult viruses to treat in the era of modern medicine. Although not always effective, HIV treatment has evolved and improved substantially over the past few decades. Despite the major advancements in the efficacy of HIV therapy, there are mounting concerns about the physiological, cardiovascular, and neurological sequelae of current treatments. The objective of this review is to (Blattner et al., Cancer Res., 1985, 45(9 Suppl), 4598s–601s) highlight the different forms of antiretroviral therapy, how they work, and any effects that they may have on the cardiovascular health of patients living with HIV, and to (Mann et al., J Infect Dis, 1992, 165(2), 245–50) explore the new, more common therapeutic combinations currently available and their effects on cardiovascular and neurological health. We executed a computer-based literature search using databases such as PubMed to look for relevant, original articles that were published after 1998 to current year. Articles that had relevance, in any capacity, to the field of HIV therapy and its intersection with cardiovascular and neurological health were included. Amongst currently used classes of HIV therapies, protease inhibitors (PIs) and combined anti-retroviral therapy (cART) were found to have an overall negative effect on the cardiovascular system related to increased cardiac apoptosis, reduced repair mechanisms, block hyperplasia/hypertrophy, decreased ATP production in the heart tissue, increased total cholesterol, low-density lipoproteins, triglycerides, and gross endothelial dysfunction. The review of Integrase Strand Transfer Inhibitors (INSTI), Nucleoside Reverse Transcriptase Inhibitors (NRTI), and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) revealed mixed results, in which both positive and negative effects on cardiovascular health were observed. In parallel, studies suggest that autonomic dysfunction caused by these drugs is a frequent and significant occurrence that needs to be closely monitored in all HIV + patients. While still a relatively nascent field, more research on the cardiovascular and neurological implications of HIV therapy is crucial to accurately evaluate patient risk.

Overnutrition is a poor dietary habit that has been correlated with increased health risks, especially in the developed world. This leads to an imbalance between energy storage and energy breakdown. Many biochemical processes involving hormones are involved in conveying the excess of energy into pathologic states, mainly atherosclerosis, hypertension, cardiovascular diseases, and diabetes. Diverse modalities of regular exercise have been shown to be beneficial, to varying extents, in overcoming the overnutrition comorbidities. Cellular exercises and hormesis are triggered by dietary protocols that could underlie the cellular mechanisms involved in modulating the deleterious effects of overnutrition through activation of specific cellular signal pathways. Of interest are the oxidative stress signaling, nuclear factor erythroid-2, insulin-like growth factor-1, AMP-activated protein kinase as well as sirtuins and nuclear factor-κB. Therefore, the value of intermittent fasting diets as well as different diet regimens inducing hormesis are evaluated in terms of their beneficial effects on health and longevity. In parallel, important effects of diets on the immune system are explored as essential components that can undermine the overall health outcome. Additionally, the subtle but relevant relation between diet and sleep is investigated for its impact on the cardiovascular system and quality of life. The aim of this review is to focus on how calorie restriction triggers multiple molecular pathways that ultimately lead to hormetic effects resulting in cell longevity and resistance to cardiovascular disease, stroke, and cancer.

COVID-19 patients with pre-existing cardiovascular conditions are at greater risk of severe illness due to the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus. This review evaluates the highest risk factors for these patients, not limited to pre-existing hypertension, cardiac arrhythmias, hypercoagulation, ischemic heart disease, and a history of underlying heart conditions. SARS-CoV-2 may also precipitate de novo cardiac complications. The interplay between existing cardiac conditions and de novo cardiac complications is the focus of this review. In particular, SARS-CoV-2 patients present with hypercoagulation conditions, cardiac arrhythmias, as significant complications. Also, cardiac arrhythmias are another well-known cardiovascular-related complication seen in COVID-19 infections and merit discussion in this review. Amid the pandemic, myocardial infarction (MI) has been reported to a high degree in SARS-CoV-2 patients. Currently, the specific causative mechanism of the increased incidence of MI is unclear. However, studies suggest several links to high angiotensin-converting enzyme 2 (ACE2) expression in myocardial and endothelial cells, systemic hyper-inflammation, an imbalance between myocardial oxygen supply and demand, and loss of ACE2-mediated cardio-protection. Furthermore, hypertension and SARS-CoV-2 infection patients' prognosis has shown mixed results across current studies. For this reason, an in-depth analysis of the interactions between SARS-CoV2 and the ACE2 cardio-protective mechanism is warranted. Similarly, ACE2 receptors are also expressed in the cerebral cortex tissue, both in neurons and glia. Therefore, it seems very possible for both cardiovascular and cerebrovascular systems to be damaged leading to further dysregulation and increased risk of mortality risk. This review aims to discuss the current literature related to potential complications of COVID-19 infection with hypertension and the vasculature, including the cervical one. Finally, age is a significant prognostic indicator among COVID-19 patients. For a mean age group of 70 years, the main presenting symptoms include fever, shortness of breath, and a persistent cough. Elderly patients with cardiovascular comorbidities, particularly hypertension and diabetes, represent a significant group of critical cases with increased case fatality rates. With the current understanding of COVID-19, it is essential to explore the mechanisms by which SARS-CoV-2 operates to improve clinical outcomes for patients suffering from underlying cardiovascular diseases and reduce the risk of such conditions de novo.

The Research Centers in Minority Institutions (RCMI) Program was congressionally mandated in 1985 to build research capacity at institutions that currently and historically recruit, train, and award doctorate degrees in the health professions and health-related sciences, primarily to individuals from underrepresented and minority populations. RCMI grantees share similar infrastructure needs and institutional goals. Of particular importance is the professional development of multidisciplinary teams of academic and community scholars (the "workforce") and the harnessing of the heterogeneity of thought (the "thinkforce") to reduce health disparities. The purpose of this report is to summarize the presentations and discussion at the RCMI Investigator Development Core (IDC) Workshop, held in conjunction with the RCMI Program National Conference in Bethesda, Maryland, in December 2019. The RCMI IDC Directors provided information about their professional development activities and Pilot Projects Programs and discussed barriers identified by new and early-stage investigators that limit effective career development, as well as potential solutions to overcome such obstacles. This report also proposes potential alignments of professional development activities, targeted goals and common metrics to track productivity and success.

Activation of multiple pathways is associated with cardiac hypertrophy and heart failure. We previously published that CXCR4 negatively regulates β-adrenergic receptor (β-AR) signaling and ultimately limits β-adrenergic diastolic (Ca2+) accumulation in cardiac myocytes. In isolated adult rat cardiac myocytes; CXCL12 treatment prevented isoproterenol-induced hypertrophy and interrupted the calcineurin/NFAT pathway. Moreover; cardiac specific CXCR4 knockout mice show significant hypertrophy and develop cardiac dysfunction in response to chronic catecholamine exposure in an isoproterenol-induced (ISO) heart failure model. We set this study to determine the structural and functional consequences of CXCR4 myocardial knockout in the absence of exogenous stress. Cardiac phenotype and function were examined using (1) gated cardiac magnetic resonance imaging (MRI); (2) terminal cardiac catheterization with in vivo hemodynamics; (3) histological analysis of left ventricular (LV) cardiomyocyte dimension; fibrosis; and; (4) transition electron microscopy at 2-; 6- and 12-months of age to determine the regulatory role of CXCR4 in cardiomyopathy. Cardiomyocyte specific-CXCR4 knockout (CXCR4 cKO) mice demonstrate a progressive cardiac dysfunction leading to cardiac failure by 12-months of age. Histological assessments of CXCR4 cKO at 6-months of age revealed significant tissue fibrosis in knockout mice versus wild-type. The expression of atrial naturietic factor (ANF); a marker of cardiac hypertrophy; was also increased with a subsequent increase in gross heart weights. Furthermore, there were derangements in both the number and the size of the mitochondria within CXCR4 cKO hearts. Moreover, CXCR4 cKO mice were more sensitive to catocholamines, their response to β-AR agonist challenge via acute isoproterenol (ISO) infusion demonstrated a greater increase in ejection fraction, dp/dtmax, and contractility index. Interestingly, prior to ISO infusion, there were significant differences in baseline hemodynamics between the CXCR4 cKO compared to littermate controls. However, upon administering ISO, the CXCR4 cKO responded in a robust manner overcoming the baseline hemodynamic deficits reaching WT values supporting our previous data that CXCR4 negatively regulates β-AR signaling. This further supports that, in the absence of the physiologic negative modulation, there is an overactivation of down-stream pathways, which contribute to the development and progression of contractile dysfunction. Our results demonstrated that CXCR4 plays a non-developmental role in regulating cardiac function and that CXCR4 cKO mice develop a progressive cardiomyopathy leading to clinical heart failure.

Background Little data are available about radiation exposure during cardiac electrical device implantation, and no dose reference levels have been published. This multicenter, prospective, observational study assesses patient and staff radiation exposure during cardiac device implantations, and aims at defining dose reference levels. Methods Patient demographic, procedural, and radiation data were obtained for 657 procedures from nine institutions. Physician and staff exposure were measured using real-time dosimeters worn beneath and above lead apron. Statistical analysis included fluoroscopy time (FT), dose-area product (DAP), and DAP adjusted for FT and body mass index. Results Pacemakers and cardioverter defibrillators were implanted in 481 and 176 patients, respectively. Of these, 152 were treated with cardiac resynchronization therapy (CRT). Median FTs were 837s (interquartile range [IQR]: 480-1323), 117s (IQR: 69-209), and 101s (IQR: 58-162), and median DAPs were 1410 (IQR: 807-2601), 150 (IQR: 72-338), and 129 (IQR: 72-332) cGy.cm(2) for biventricular, dual chamber, and ventricular device implantation, respectively. Dose reference levels correspond to the third quartile values. During CRT, higher exposure was observed with four X-ray systems than with the two newer and customizable ones (adjusted DAP of 0.90 [IQR: 0.26-1.01] and 0.29 [IQR: 0.23-0.39], respectively; P < .001). Conclusion Based on real-life measurements, this multicenter registry provides dose reference levels and may help centers assess radiation exposure. Although biventricular device implantation was responsible for the highest radiation exposure, FT was meaningfully shortened compared to previously reported values. For a same FT, the use of new generators and custom settings has significantly reduced DAP.

Alcohol abuse can affect more than the heart and the liver. Many observers often do not appreciate the complex and differing aspects of alcohol's effects in pathophysiologies that have been reported in multiple organs. Chronic alcohol abuse is known to be associated with pathophysiological changes that often result in life-threatening clinical outcomes, e.g., breast and colon cancer, pancreatic disease, cirrhosis of the liver, diabetes, osteoporosis, arthritis, kidney disease, immune system dysfunction, hypertension, coronary artery disease, cardiomyopathy, and can be as far-reaching as to cause central nervous system disorders. In this review article, we will discuss the various organs impacted by alcohol abuse. The lack of clear guidelines on the amount and frequency of alcohol intake, complicated by personal demographics, make extrapolations to real-life practices at best difficult for public health policy-makers.

Alcohol is one of the most commonly abused substances in the United States. Chronic consumption of ethanol has been responsible for numerous chronic diseases and conditions globally. The underlying mechanism of liver injury has been studied in depth, however, far fewer studies have examined other organs especially the heart and the central nervous system (CNS). The authors conducted a narrative review on the relationship of alcohol with heart disease and dementia. With that in mind, a complex relationship between inflammation and cardiovascular disease and dementia has been long proposed but inflammatory biomarkers have gained more attention lately. In this review we examine some of the consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver. The article reviews the potential role of inflammatory markers such as TNF-α in predicting dementia and/or cardiovascular disease. It was found that TNF-α could promote and accelerate local inflammation and damage through autocrine/paracrine mechanisms. Unraveling the mechanisms linking chronic alcohol consumption with proinflammatory cytokine production and subsequent inflammatory signaling pathways activation in the heart and CNS, is essential to improve our understanding of the disease and hopefully facilitate the development of new remedies.

Despite the efforts of the National Institutes of Health (NIH) to encourage racial diversity in science and increase training and funding opportunities in minority groups, there continues to be disparity in NIH RO1 type grant funding. Although traditional African American medical schools are relatively low on ranking of medical schools receiving NIH support in the U.S., these discrepancies hide a more serious problem, i.e., how so few African American investigators have individual NIH support. This serious issue is concealed by the total NIH and government support to these schools, derived from large NIH grants targeted to improve the infrastructure of minority institutions, even including training grants, which contribute the major fraction to their totals for NIH funding. The more important statistics, which drill down to the key area of disparity, which needs to be rectified, are those that show the reduced percentage of NIH research grants awarded to minority Principal Investigators, e.g., RO1 grants. We examined data from 6 minority medical schools, where their mean ± SE ranking for total NIH support for all medical schools in the U.S. was 227 ± 25, and compared these data with those from 6 non‐minority institutions with the same level of total NIH support, i.e., with an average ranking of 230 ± 2 of all medical schools in the U.S., similar to the ranking level of the minority institutions. Although the average total NIH funding was similar in the two groups ($14,622,989 for the minority schools vs. $11,779,546 for the non‐minority schools), the minority institutions received 85 ± 4% of their NIH funding from institutional grants designed to address gaps in infrastructure. In the minority medical schools only 15 ± 4% of the total NIH support went to RO1 type funding in the minority institutions, whereas 65 ± 11% of the total NIH support went to RO1 type funding at non‐minority institutions. Therefore, although NIH initiatives have been helpful in bridging the gap of funding for minority institutions, it has not corrected the problem of the reduced number NIH RO1 grants awarded to minority investigators. A potential novel solution to correct this discrepancy is to mentor the mentors simultaneously with mentoring the minority candidates, by a faculty mentor with a strong history of NIH RO1 funding. This is important because a large number of minority scientists reside at minority institutions, where the faculty have relatively few RO1s and are members of NIH study sections, which provide needed mentoring in writing and the review of NIH grants to the junior minority investigators. Therefore, it is our concept that there should be support for a novel program that provides for joint mentoring of minority doctoral and post‐doctoral candidates from their local mentor at the minority institution and well‐funded mentors from another institution. In this manner, both the student and the mentor from the minority institution, working together with senior well‐funded faculty at the non‐minority institution, will all benefit.

Gene delivery to the cardiovascular system as a therapeutic strategy has exploded recently, especially in the setting of inherited cardiomyopathies.1–3 In the last few years, a novel non-viral vector system based on modified mRNA (modRNA) has emerged. In this issue of Molecular Therapy, Sultana et al.4 report on the optimization of cardiac delivery of modRNA both in vitro and in vivo. Several recent reports, including Sultana et al.,4 make it clear that modRNAs have become an exciting platform for cardiac gene therapy.

Alcohol has always been present in human life, and currently it is estimated that 50% of women of childbearing age consume alcohol. It has become increasingly clear over the last years that alcohol exposure during fetal development can have detrimental effects on various organ systems, and these effects are exerted by alcohol through multiple means, including effects on free radical formation, cellular apoptosis, as well as gene expression. Fetal alcohol exposure can lead to a spectrum of short term as well as long-term problems, with Fetal Alcohol Syndrome being on the more severe end of that spectrum. This syndrome is morbid, yet preventable, and is characterized by midfacial hypoplasia, thin upper lip, widely spaced small eyes, long smooth philtrum and inner epicanthal folds. Other findings include growth restriction as well as various neurodevelopmental abnormalities. This article is the first comprehensive review combining the molecular as well as the gross physiological and anatomical effects of alcohol exposure during pregnancy on various organ systems in the body. Our knowledge of these various mechanisms is crucial for our understanding of how alcohol exposure during fetal development can lead to its detrimental effects.

Gene delivery to the cardiovascular system as a therapeutic strategy has exploded recently, especially in the setting of inherited cardiomyopathies.1–3 In the last few years, a novel non-viral vector system based on modified mRNA (modRNA) has emerged. In this issue of Molecular Therapy, Sultana et al.4 report on the optimization of cardiac delivery of modRNA both in vitro and in vivo. Several recent reports, including Sultana et al.,4 make it clear that modRNAs have become an exciting platform for cardiac gene therapy.

Despite the efforts of the National Institutes of Health (NIH) to encourage racial diversity in science and increase training and funding opportunities to minority institutions, there continues to be disparity in NIH R01 grant funding ([ 1 ][1]–[ 3 ][2]). As one example, only five investigators at

Historically Black Colleges and Universities (HBCUs) have a long history of student engagement and institutional commitment to developing STEMM degrees. To become even better at fostering a diverse STEMM field, HBCUs must assess their strengths, weaknesses and challenges as well as opportunities in order to remain competitive in the 21st century. This chapter explores factors related to improving STEMM student academic preparation, retention and engagement. The authors provide recommendations to enhance experiential learning and offer educational pathways that lead to long-term retention and engagement of minority students. Furthermore, in the face of the need to advance and diversify the scientific workforce, we examine whether and how specific institutional contexts shape student interactions with faculty and institutional cultures. Historically black colleges and universities have played an important role in diversifying the Science Technology, Engineering, Mathematics, and Medicine (STEMM) workforce. In this paper we offer practical suggestions to clarify and strengthen their roles in student recruitment, retention, engagement, and advancement in STEMM. Preparatory summer institutes give minority students access to curriculum, tutoring, research opportunities, psycho-social support while encouraging the development of peer and faculty relationships. Such institutes nurture a successful socialization of minority students into STEMM disciplines. Dual admissions between two year and four year degree granting institutions will likely enhance student retention. Institutional agents and mentors play a major role by providing experiential learning opportunities that capture and retain students' interests. A combination of experiential learning, dual articulation, and the creation of strong and engaged institutional agents as well as mentors will likely facilitate student retention and successful integration into a larger STEMM network.

Chronic low alcohol exposure has been shown clinically to have beneficial cardiac effects; whereas chronic high alcohol consumption can lead to heart failure. We have previously shown that cardiac inotropy is closely related to the activation of the survival PI3K/Akt. This study aimed to determine the effects of chronic low and high alcohol on cardiac function as well as to determine if low alcohol can alleviate the development of volumeoverload-dependent (shunt) cardiac hypertrophy. Littermate adult rats were put on a 3-months isocaloric Lieber-Decarli liquid diet with either low alcohol (LA: 5mM) or high alcohol (HA: 100mM) levels. The rats were further divided into sham or shunted group. The measured final blood alcohol concentrations were 0.02% and 0.20% respectively. In vivo intra-ventricular catheterization (Scisense/iWorks) of the left ventricle (LV) showed that an improved LV contractility and ejection fraction of the LA group while the opposite occurred with the HA group. Since we currently do not have all experimental results, our partial results show that shunted rats developed eccentric cardiac hypertrophy as expected, which was exacerbated by high alcohol consumption, whereas low alcohol seems to alleviate the effect of volume-overload on the cardiac function to a certain extent. The results of the present study suggest that there is an association between alcohol intake and cardiac function; chronic low alcohol exposure seems to have beneficial cardiac effects; whereas chronic high alcohol consumption is associated with reduced cardiac contractile function and could lead to heart failure over the time.

Few data exist about radiation exposure during implantation of cardiac electrical device. No dose reference levels (DRLs) were reported. Purpose to define DRLs and to analyze factors related to an increased radiation dose delivered to patients and medical staff. Methods the Raypace study is a multicenter, prospective observational registry. Using a national database, patient demographic, procedural and radiation data were collected. Fluoroscopy time (FT) and dose-area product (DAP) were registered. Physician/staff exposure was measured using 2 real-time personal dosimeters, one worn under the lead apron and the other one worn outside the apron. Statistical analysis used log-transformation of DAP, FT and DAP/FT ratio. A total of 657 procedures from 9 institutions were reviewed. Pacemaker (PM) and cardioverter-defibrillator (ICD) implantation was performed in 481 and 176 patients, respectively. A cardiac resynchronization device was implanted in 153 patients. Fluoroscopy time was similar for PM and ICD implantations. Median fluoroscopy time was 836, 117 and 101 second and median DAP was 1410, 150 and 129 cGy.cm2 for biventricular, dual chamber and ventricular device implantation, respectively. LAO projection, in addition to AP projection, was used in 47% of the procedures. Five centers out of 9 used collimation. The median Hp (10) effective dose measured outside the lead apron was 4.6 µSv and 0.1 µSv under the lead apron. Regarding CRT implant procedures, four systems out of 6 were responsible for an increased exposure (p<0.001). DRLs were 2600, 338 and 332 cGy.cm2 for biventricular, dual chamber and ventricular device implantation, respectively. DAP reduction was improved with the use of latest generators but needed customized settings. Biventricular device implantation was responsible for the highest radiation exposure. However, radiation exposure during those procedures have decreased as compared to previously reported values.

Arterial properties change during hypertension (HTN) development. The time course of the changes can be used as a marker of vascular remodeling in the development of HTN. Study Aim: To determine whether pressure induced changes in vascular properties result in alterations in pressure-flow patterns that impact the load for ventricular function: input & characteristic impedance, A rterial C ompliance (AC)= SV/PP (stroke volume)/(pulse pressure), AC=Tau/peripheral resistance (PR), and PP were investigated. Methods: Pressure and flow relations were investigated in dogs during the development of renal-HTN over 4-weeks (Wks). The sensitivity of hemodynamic markers of vascular remodeling was evaluated by changes in AC= SV/PP, and by AC= Tau/PR and PP. Results: All BP components increased during the development of HTN. Changes in Input Impedance, increased through Wks 2 to 4. Increases in the steady component of the cardiac cycle were reflected by peripheral PR, and changes in the pulsatile component were reflected by changes in AC=SV/PP, and AC=Tau /RP; and changes in characteristic impedance. PP and PAP increased by Week 2, reflection of the cardiac and arterial workloads and vascular Tension RP that progressed through Wk 4 Conclusion: Reliable and accessible markers that indicate changes in arterial pressure, flow & volume, are: PP and AC (SV/PP), and AC (Tau /TPR). These variables detected increases in the heart-load and alterations in pressure-flow patterns that impair cardiovascular-function resulting in HTN-CVD; input and characteristic impedance, also provides remodeling information about the arterial system but are not readily available to clinicians.

Alcoholism: Clinical and Experimental ResearchVolume 39, Issue 5 p. 787-789 Commentary Convergence of Theories of Alcohol Administration Postanabolic Stimulation on mTOR Signaling: Lessons for Exercise Regimen Zebalda D. Bamji, Zebalda D. Bamji Division of Medical Genetics , Department of Pediatrics, Howard University, Washington, District of ColumbiaSearch for more papers by this authorGeorges E. Haddad, Corresponding Author Georges E. Haddad Department of Physiology and Biophysics , College of Medicine, Howard University, Washington, District of ColumbiaReprint requests: Georges E. Haddad, PhD, Professor, Department of Physiology and Biophysics, 520 W St., NW, Suite 2309, College of Medicine, Howard University, Washington, DC 20059; Tel.: 202-806-6305; Fax: 202-806-4479; E-mail: ghaddad@howard.eduSearch for more papers by this author Zebalda D. Bamji, Zebalda D. Bamji Division of Medical Genetics , Department of Pediatrics, Howard University, Washington, District of ColumbiaSearch for more papers by this authorGeorges E. Haddad, Corresponding Author Georges E. Haddad Department of Physiology and Biophysics , College of Medicine, Howard University, Washington, District of ColumbiaReprint requests: Georges E. Haddad, PhD, Professor, Department of Physiology and Biophysics, 520 W St., NW, Suite 2309, College of Medicine, Howard University, Washington, DC 20059; Tel.: 202-806-6305; Fax: 202-806-4479; E-mail: ghaddad@howard.eduSearch for more papers by this author First published: 06 April 2015 https://doi.org/10.1111/acer.12702Citations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume39, Issue5May 2015Pages 787-789 RelatedInformation

Chronic low alcohol exposure has been proven to have beneficial cardiac effects; whereas chronic high alcohol consumption could lead to heart failure. Oxidative stress is thought to be partly responsible for the alcoholic negative effects on the heart function. We have previously shown that cardiac inotropy is closely related to the activation of the survival PI3K/Akt. The objective of this study was to elucidate the signaling pathways conveying the beneficial versus the detrimental effects of chronic low and high alcohol on the heart function, respectively. Littermate adult rats were put on a 4‐months isocaloric Lieber‐Decarli liquid diet with either low alcohol (LA: 5mM) or high alcohol (HA: 100mM) levels. The measured final blood alcohol concentrations were 0.02% and 0.20% respectively. In vivo intra‐ventricular catheterization (Scisense/iWorks) of the left ventricle (LV) showed that an improved LV contractility and ejection fraction of the LA group while the opposite occurred with the HA group. in vitro cellular and sarcomeric inotropic measurements (Ionoptix) showed similar profile to the LV in vivo data. In addition, LA enhanced Ca2+ sequestration in the sarcoplasmic reticulum whereas HA reduced it with elevation of intracellular Ca2+ level. Our data show that improved cardiac function by LA is mediated by enhanced SERCA2 activity whereas the detrimental effects of HA are associated with reduced SERCA2a function. Funded by NIH/NIAAA 1 R15 AA019816‐01A1 and 2G12 RR003048 NIH/RCMI, DRI.