scholarly journals Tumor-Induced Cardiac Dysfunction: A Potential Role of ROS

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1299
Author(s):  
Priyanka Karekar ◽  
Haley N. Jensen ◽  
Kathryn L. G. Russart ◽  
Devasena Ponnalagu ◽  
Sarah Seeley ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cardiac Function ◽  
Cancer Patients ◽  
Cardiac Dysfunction ◽  
Heart Function ◽  
Heart Diseases ◽  
The Body ◽  
Cardiac Defects ◽  
Mortality And Morbidity ◽  
Irregular Cell

Cancer and heart diseases are the two leading causes of mortality and morbidity worldwide. Many cancer patients undergo heart-related complications resulting in high incidences of mortality. It is generally hypothesized that cardiac dysfunction in cancer patients occurs due to cardiotoxicity induced by therapeutic agents, used to treat cancers and/or cancer-induced cachexia. However, it is not known if localized tumors or unregulated cell growth systemically affect heart function before treatment, and/or prior to the onset of cachexia, hence, making the heart vulnerable to structural or functional abnormalities in later stages of the disease. We incorporated complementary mouse and Drosophila models to establish if tumor induction indeed causes cardiac defects even before intervention with chemotherapy or onset of cachexia. We focused on one of the key pathways involved in irregular cell growth, the Hippo–Yorkie (Yki), pathway. We used overexpression of the transcriptional co-activator of the Yki signaling pathway to induce cellular overgrowth, and show that Yki overexpression in the eye tissue of Drosophila results in compromised cardiac function. We rescue these cardiac phenotypes using antioxidant treatment, with which we conclude that the Yki induced tumorigenesis causes a systemic increase in ROS affecting cardiac function. Our results show that systemic cardiac dysfunction occurs due to abnormal cellular overgrowth or cancer elsewhere in the body; identification of specific cardiac defects associated with oncogenic pathways can facilitate the possible early diagnosis of cardiac dysfunction.

Prediction of Poststorage Cardiac Function From Cardioplegic Effluent in an Ex Vivo Porcine Heart Model

2019 ◽  
Vol 2 (4) ◽  
Author(s):  
Benjamin Kappler ◽  
Sjoerd van Tuijl ◽  
Teus J. van Laar ◽  
Dara R. Pabittei ◽  
Marc P. Buijsrogge ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Ex Vivo ◽  
Heart Function ◽  
Laboratory Animals ◽  
Organ Protection ◽  
Isolated Hearts ◽  
Cardiac Functions ◽  
Proactive Measures

Abstract The use of slaughterhouse-based hearts has advantages over hearts obtained from laboratory animals for preclinical testing. However, slaughterhouse hearts have greater variability in cardiac function; this has resulted in a dispute over their actual reproducibility. This study explores the feasibility of examining the cardioplegic effluent during hypothermic cardiac arrest for the presence of biomarkers to predict poststorage heart function of slaughterhouse hearts. This may enable proactive measures to optimize preservation strategies and improve the initial cardiac performance of slaughterhouse heart experiments. Slaughterhouse pig hearts (n = 9; 420 ± 30 g) were arrested and flushed with an additional liter cardioplegia after 1 h. Effluent samples were examined for ammonia, lactate, troponin, and inorganic phosphate. After 2 h, hearts were hemoreperfused in the ex vivo heart platform PhysioHeart™ to restore physiological cardiac functions and to identify correlations between biomarkers and cardiac output. There was a negative correlation between cardiac output of revived hearts and levels of ammonia (r = −0.865; p = 0.002) and lactate (r = −0.763; p = 0.01). No correlation was found between cardiac output and levels of phosphate (r = −0.553; p = 0.12) and troponin (r = −0.367; p = 0.331). The analysis approach to assess cardioplegic biomarkers was feasible and enabled the estimation of the effectiveness of organ protection and cardiac function before reperfusion. Ammonia is a predictor for cardiac dysfunction. Effluent analysis prior to heart revival can uncover poststorage cardiac dysfunction in isolated hearts and may prevent failed experiments while improving reproducibility and standardization.

Safety of trastuzumab in women with HER2+ breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12522-e12522
Author(s):  
Somaira Nowsheen ◽  
Khaled Aziz ◽  
Jae Yoon Park ◽  
Hector R. Villarraga ◽  
Joerg Herrmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cardiac Function ◽  
Cancer Patients ◽  
Cardiac Dysfunction ◽  
Physical Symptoms ◽  
Left Ventricular ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer ◽  
History Of ◽  
Normal Lvef

e12522 Background: Trastuzumab is widely used in management of HER2+ breast cancer patients. A known adverse effect of trastuzumab use is cardiac dysfunction, which can often be reversed with cessation of therapy. Our objectives were to 1) assess if trastuzumab can be safely administered to breast cancer patients with reduced cardiac function and 2) identify patient characteristics that predict susceptibility to trastuzumab-induced cardiac dysfunction. Methods: A retrospective analysis was performed on female patients seen at Mayo Clinic for HER2+ breast cancer and treated with trastuzumab for localized or metastatic disease between January 1, 2000 and August 31, 2015. Eligibility criteria included documentation of and results from at least one echocardiogram prior to and at least one after trastuzumab initiation. Left ventricular (LV) ejection fraction (EF) of 53% or more was considered normal. Any LVEF reduction of 10% or more was considered significant. Among patients with normal EF, age strata of < 45, 45-60, and > 60 at time of trastuzumab initiation were used to assess risk factors for clinically diagnosed cardiac dysfunction (defined as EF < 53 or abnormal strain and physical symptoms of heart failure (HF)). Results: We identified 335 women (mean age 53.3, with 25.3% age < 45, 44.5% age 45-60, and 30.1% age > 60) who had normal LVEF (median EF 64, range: 53-75) and 23 women (mean age 53.4, with 30.4% age < 45, 43.5% age 45-60, and 26.1% age > 60) who had low LVEF at baseline (median EF 52, range: 25-52). Approximately a third (34.3%) of women with normal LVEF prior to initiation of therapy had at least one subsequent echocardiogram showing a drop of 10% or a low LVEF ( < 53). Approximately a quarter (26%) of women with low LVEF at baseline had a 10% drop in LVEF. HF incidence increased with age. Predictive factors for trastuzumab-induced cardiac dysfunction were obesity and history of coronary artery disease (CAD) across all age strata, and chest irradiation (IR) for those aged 45-60 only. Conclusions: Our results suggest that trastuzumab can be administered in women with reduced cardiac function at no greater risk than in those with preserved cardiac function. Some women with no obesity, history of CAD, or history of chest IR may not need echocardiograms during trastuzumab therapy.

scholarly journals The adult heart requires baseline expression of the transcription factor Hand2 to withstand right ventricular pressure overload

2021 ◽  
Author(s):  
Raquel F Videira ◽  
Anne-Marie C Koop ◽  
Lara Ottaviani ◽  
Ella M Poels ◽  
Jordy M M Kocken ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cardiac Function ◽  
Right Ventricular ◽  
Cardiac Dysfunction ◽  
Molecular Mechanisms ◽  
Pressure Overload ◽  
Mortality And Morbidity ◽  
Adult Heart ◽  
Expression Levels ◽  
Impaired Cardiac Function

Abstract Aims Research on the pathophysiology of right ventricular (RV) failure has, in spite of the associated high mortality and morbidity, lagged behind compared to the left ventricle (LV). Previous work from our lab revealed that the embryonic basic helix-loop-helix transcription factor heart and neural crest derivatives expressed-2 (Hand2) is re-expressed in the adult heart and activates a ‘foetal gene programme’ contributing to pathological cardiac remodelling under conditions of LV pressure overload. As such, ablation of cardiac expression of Hand2 conferred protection to cardiac stress and abrogated the maladaptive effects that were observed upon increased expression levels. In this study, we aimed to understand the contribution of Hand2 to RV remodelling in response to pressure overload induced by pulmonary artery banding (PAB). Methods and results In this study, Hand2F/F and MCM- Hand2F/F mice were treated with tamoxifen (control and knockout, respectively) and subjected to six weeks of RV pressure overload induced by PAB. Echocardiographic- and MRI-derived haemodynamic parameters as well as molecular remodelling were assessed for all experimental groups and compared to sham-operated controls. Six weeks after PAB, levels of Hand2 expression increased in the control-banded animals but, as expected, remained absent in the knockout hearts. Despite the dramatic differences in Hand2 expression, pressure overload resulted in impaired cardiac function independently of the genotype. In fact, Hand2 depletion seems to sensitize the RV to pressure overload as these mice develop more hypertrophy and more severe cardiac dysfunction. Higher expression levels of HAND2 were also observed in RV samples of human hearts from patients with pulmonary hypertension. In turn, the LV of RV pressure-overloaded hearts was also dramatically affected as reflected by changes in shape, decreased LV mass, and impaired cardiac function. RNA-sequencing revealed a distinct set of genes that are dysregulated in the pressure-overloaded RV, compared to the previously described pressure-overloaded LV. Conclusion Cardiac-specific depletion of Hand2 is associated with severe cardiac dysfunction in conditions of RV pressure overload. While inhibiting Hand2 expression can prevent cardiac dysfunction in conditions of LV pressure overload, the same does not hold true for conditions of RV pressu re overload. This study highlights the need to better understand the molecular mechanisms driving pathological remodelling of the RV in contrast to the LV, in order to better diagnose and treat patients with RV or LV failure.

Abstract 50: Therapeutic Silencing of miRNA-652 Restores Cardiac Function and Attenuates Pathological Remodeling in a Mouse Model of Pressure Overload

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Bianca C Bernardo ◽  
Sally S Nguyen ◽  
Catherine E Winbanks ◽  
Xiao-Ming Gao ◽  
Esther J Boey ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mouse Model ◽  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Heart Function ◽  
Pressure Overload ◽  
Post Treatment ◽  
Locked Nucleic Acid ◽  
Luciferase Assay ◽  
Sham Operation

Introduction: Targeting microRNAs differentially regulated in settings of stress and protection could represent a new approach for the treatment of heart failure. miR-652 expression increased in hearts of a cardiac stress mouse model and was downregulated in a model of cardiac protection. Aim: To assess the therapeutic potential of silencing miR-652 in a mouse model with established pathological hypertrophy and cardiac dysfunction due to pressure overload. Methods: Mice were subjected to a sham operation (n=10) or transverse aortic constriction (TAC, n=14) for 4 weeks to induce hypertrophy and cardiac dysfunction. Mice were subcutaneously administered a locked nucleic acid (LNA)-antimiR-652 or LNA-control. Cardiac function was assessed by echocardiography before and 8 weeks post treatment, followed by molecular and histological analyses. Results: Expression of miR-652 increased in hearts subjected to pressure overload compared to sham operated mice (2.9 fold, n=3-5, P<0.05), but was silenced in hearts of mice administered LNA-antimiR-652 (95% decrease, n=3-7, P<0.05). In mice subjected to pressure overload, inhibition of miR-652 improved cardiac function (29±1% at 4 weeks post TAC compared to 35±1% post treatment, n=7, P<0.001) and attenuated cardiac hypertrophy. Functional and morphologic improvements in hearts of treated mice were associated with reduced cardiac fibrosis, apoptosis, cardiomyocyte size; decreased B-type natriuretic peptide gene expression; and preserved angiogenesis (all P<0.05, n=4-7/group). Mechanistically, we identified Jagged1, a Notch1 ligand, as a direct target of miR-652 by luciferase assay. Jagged1 and Notch1 mRNA were upregulated in hearts of TAC treated mice (1.2-1.7 fold, n=7, P<0.05). Importantly, chronic knockdown of miR-652 was not associated with any notable toxicity in other tissues. Conclusion: Therapeutic silencing of miR-652 protects the heart against pathological cardiac remodeling and improves heart function via mechanisms that are associated with preserved angiogenesis, decreased fibrosis and upregulation of a miR-652 target, Jagged1. These studies provide the first evidence that targeted inhibition of miR-652 could represent an attractive approach for the treatment of heart failure.

Abstract 519: Talin is Required for Normal Adult Heart Function

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Yoshitake Cho ◽  
Ruixia Li ◽  
Ana M Manso ◽  
Robert S Ross
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Cardiac Development ◽  
Heart Function ◽  
Left Ventricular ◽  
Mass Spectrometry Analysis ◽  
Adult Heart ◽  
Spectrometry Analysis ◽  
Functional Changes

Talin (Tln) is a component of muscle costameres that links integrins to other components of the cellular cytoskeleton and plays an important role in maintaining the cellular integrity of cardiac myocytes (CM). There are two talin genes, Tln1 and Tln2, expressed in the heart. Tln1 is ubiquitously expressed, and Tln2 is dominantly expressed in CM. In our previous study, we show that the global deletion of Tln2 in mice (T2KO) caused no structural or functional changes in the heart, presumably because CM Tln1 became up-regulated. However, we found that mice lacking both CM Tln1 and Tln2 exhibit cardiac dysfunction by 4 weeks (w) of age with 100% mortality by 6 months (m), showing Tln plays an essential role in cardiac development and in maintaining cardiac function. In this study, we produced a tamoxifen (Tamo)-inducible mouse model in which Tln1 could be explicitly reduced in the adult CM (T1icKO), and then generate T1icKO:T2KO (T1/2dKO), so that the function of Tln could be assessed in the postnatal heart. T2KO and Tln1/2dKO mice were injected with Tamo at 8w. Echocardiograms were performed to evaluate cardiac function up to 8w post-Tamo injection. While T2KO mice showed normal cardiac function, T1/2dKO exhibited a gradual decrease in function post-Tamo injection. At 8w post-Tamo injection, T1/2dKO mice showed cardiac hypertrophy, fibrosis, and heart failure. To understand the mechanism by which deletion CM talin leads to cardiac dysfunction, left ventricular tissue protein lysates from T2KO and T1/2dKO mice at 4w post-Tamo when cardiac function (echo) and structure were preserved in dKO. The protein lysates were subjected to quantitative mass spectrometry analysis. We found there are 1,100 proteins differentially expressed in T2KO and T1/2dKO hearts. Pathway analysis was performed, and the results showed that proteins involved in vesicle transport, protein folding, and innate immunity are most up-regulated in the T1/2dKO heart. Taken together, our results show that Tln is required for maintaining proper cardiac function in the adult heart. The deletion of Tln in CM results in the up-regulation of multiple intracellular pathways, and we are currently studying the role of each pathway in the pathogenesis of heart failure induced by CM Tln deletion.

scholarly journals Identification of RyR2-PBmice and the effects of transposon insertional mutagenesis of the RyR2 gene on cardiac function in mice

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6942
Author(s):  
Qianqian Wang ◽  
Chao Wang ◽  
Bo Wang ◽  
Qirui Shen ◽  
Leilei Qiu ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Insertional Mutagenesis ◽  
Cardiac Tissue ◽  
Fluorescent Protein ◽  
Heart Function ◽  
Heart Diseases ◽  
Mrna Level ◽  
Significant Difference ◽  
Cardiac Function Tests ◽  
And Function

Ryanodine receptor 2 (RyR2) plays an important role in maintaining the normal heart function, and mutantions can lead to arrhythmia, heart failure and other heart diseases. In this study, we successfully identified a piggyBac translocated RyR2 gene heterozygous mouse model (RyR2-PBmice) by tracking red fluorescent protein (RFP) and genotyping PCR. Cardiac function tests showed that there was no significant difference between the RyR2-PBmice and corresponding wild-type mice (WTmice), regardless of whether they were in the basal state or injected with epinephrine and caffeine. However, the sarcoplasmic reticulum Ca2+ content was significantly reduced in the cardiomyocytes of RyR2-PBmice as assessed by measuring caffeine-induced [Ca2+]i transients; the cardiac muscle tissue of RyR2-PBmice displayed significant mitochondrial swelling and focal dissolution of mitochondrial cristae, and the tissue ATP content in the RyR2-PBmice heart was significantly reduced. To further analyze the molecular mechanism behind these changes, we tested the expression levels of related proteins using RT-PCR and Western blot analyses. The mRNA level of RyR2 in RyR2-PBmice cardiac tissue decreased significantly compared with the WTmice, and the protein expression associated with the respiratory chain was also downregulated. These results suggested that the piggyBac transposon inserted into the RyR2 gene substantively affected the structure and function of mitochondria in the mouse cardiomyocytes, leading to disorders of energy metabolism.

Abstract 323: MicroRNA208a Silencing Attenuates Doxorubicin Induced Cardiac Toxicity and Dysfunction

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Hasahya Tony ◽  
Qiutang Zeng ◽  
Kunwu Yu
Keyword(s):  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Cardiac Toxicity ◽  
Heart Function ◽  
Control Groups ◽  
Improve Heart Function ◽  
Myocyte Apoptosis ◽  
And Control ◽  
Subsequent Improvement ◽  
Fractional Shortening

Aims: Salvaging GATA4 expression mitigates doxorubicin-induced myocyte apoptosis and cardiac dysfunction. We investigated if therapeutic silencing of miR-208a, a heart specific microRNA known to target GATA4, could attenuate doxorubicin-induced myocyte apoptosis and improve heart function. Methods: Eight weeks old female Balb/C mice were randomly assigned to Sham, antagomir and Control groups. Antagomir group mice were pre-treated with 50nmols of miR-208a antagomir 4 days prior to giving doxorubicin. At day 0, control and antagomir group got 20mg/kg of doxorubicin while sham mice received phosphate buffered solution. Echocardiography was done at day 7, after which animals were sacrificed, and hearts assessed for apoptosis and expression of miR-208a, GATA4 and Bcl-2 by quantitative PCR. Results: Doxorubicin significantly upregulated miR-208a P=0.008 , downregulated GATA4 P=0.025 , and increased myocyte apoptosis P=0.001. Therapeutic silencing of miR-208a mitigated the doxorubicin-induced increase in miR-208a, P= 0.003 and salvaged GATA4 expression, with noted increase in Bcl-2 levels compared to controls, P=0.033. Doxorubicin significantly increased cardiomyocyte apoptosis P= 0.001, and this effect was attenuated by pretreatment with miR-208a antagomir, P=0.002 (Figure 1A and B). Doxorubicin also caused significant cardiac dysfunction, P=0.005, while antagomir treatment attenuated doxorubicin-induced cardiac dysfunction as assessed by fractional shortening P=0.011 (Figure 1Cand D) Conclusion: Therapeutic silencing of miR-208a salvages GATA4 and attenuates doxorubicin-induced myocyte apoptosis with subsequent improvement in cardiac function.

Theoretical Modeling on Monitoring Left Ventricle Deformation Using Conformal Piezoelectric Sensors

2019 ◽  
Vol 87 (1) ◽  
Author(s):  
Yangyang Zhang ◽  
Chaofeng Lü ◽  
Bingwei Lu ◽  
Xue Feng ◽  
Ji Wang
Keyword(s):  
Real Time ◽  
Output Voltage ◽  
Piezoelectric Materials ◽  
Heart Function ◽  
Heart Diseases ◽  
Left Ventricular ◽  
Deformation Monitoring ◽  
Volume Data ◽  
Mortality And Morbidity ◽  
Lv Volume

Abstract Left ventricular (LV) volume is a crucial indicator for the assessment of the heart function. However, the current clinical practice cannot be used to monitor the LV volume continuously or warn patients with high risk in time before heart attack occurs in everyday life, resulting in high mortality and morbidity. Here, we theoretically validate the potentiality of a conformal real-time LV deformation-monitoring sensor using piezoelectric materials. The electromechanical relationship between the deformation of the hearts and output voltage signals of the sensors is demonstrated first. End-to-end displacements and deformations of piezoelectric films under cyclic load are derived from the output voltage signals and then compared with experimental values. Then, the real-time LV volumes of a pig and a cow are derived and compared by employing the experimental output voltage signals of the flexible sensor mounted on the LV surface. Finally, by employing the LV volume data of healthy people and patients with various heart diseases in the literature, the theoretical output voltage signals of flexile sensors when mounted on LV surface are calculated and compared. These predicted output voltage signals show significant differences for people with different kinds of cardiac diseases. The results in this study demonstrate that the conformal piezoelectric sensor is fully potential to continuously monitor the cardiac deformation and correspondingly provide timely warning for cardiologists and patients with heart diseases.

Hypertriglyceridemia in experimental diabetes: relationship to cardiac dysfunction

1994 ◽  
Vol 72 (5) ◽  
pp. 447-455 ◽  
Author(s):  
Brian Rodrigues ◽  
Paul F. Grassby ◽  
Mary L. Battell ◽  
Stephanie Y. N. Lee ◽  
John H. McNeill
Keyword(s):  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Heart Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Plasma Triglyceride ◽  
Diabetic Rat ◽  
Diabetic Patients ◽  
Beneficial Effects ◽  
Rate Of Increase

The incidence of mortality from cardiovascular disease is higher in diabetic patients. The objective of the present investigation was to test die hypothesis that the diabetes-induced depression in cardiac function may be due to hypertriglyceridemia. Hyperlipidemia and a depressed left ventricular developed pressure and rate of increase and decrease of ventricular pressure (±dP/dt) were produced in isolated hearts from rats made diabetic with streptozotocin compared with hearts from control animals. This depressed cardiac performance was successfully prevented by hydralazine treatment (for 3 weeks), which also lowered plasma triglyceride levels and suggested that hyperlipidemia may be important in altering cardiac function in experimental diabetic rats. The beneficial effects of clofibrate, verapamil, prazosin, enalapril, and benazepril administration were then studied in diabetic rats. The treatments (with die exception of enalapril) significantly reduced plasma triglyceride levels but did not prevent die onset of heart dysfunction in chronically diabetic rats. These studies suggest that in the chronically diabetic rat, hypertriglyceridemia may not be as important as previously suggested, in the development of cardiac dysfunction. Since acute dichloroacetate perfusion improves cardiac function in 6 week (but not 24 week) diabetic rats, it appears more likely that improving myocardial glycose utilization is more critical than triglyceride lowering, in preventing cardiac dysfunction in die diabetic rat at this time point.Key words: diabetes, triglycerides, heart function, glucose oxidation.

Effects of free fatty acids and dichloroacetate on isolated working diabetic rat heart

1991 ◽  
Vol 261 (4) ◽  
pp. H1053-H1059 ◽  
Author(s):  
T. A. Nicholl ◽  
G. D. Lopaschuk ◽  
J. H. McNeill
Keyword(s):  
Fatty Acids ◽  
Heart Rate ◽  
Cardiac Function ◽  
Free Fatty Acids ◽  
Cardiac Dysfunction ◽  
Glucose Oxidation ◽  
Heart Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Diabetic Heart

It is well established that cardiac dysfunction independent of atherosclerosis develops in both humans and animals with diabetes mellitus. The etiology is complex, involving many different processes, one of which may be increased fatty acid utilization and/or a concomitant decrease in glucose utilization by the diabetic heart. We compared control and 6-wk streptozotocin (STZ)-induced diabetic isolated working rat hearts and were able to demonstrate cardiac dysfunction in the diabetic as assessed by depressed heart rate (HR), heart rate peak systolic pressure product (HR.PSP), left ventricular developed pressure (LVDP), and rate of pressure rise (+dP/dt). Paralleling depressed cardiac function in the diabetic were hyperglycemia, hyperlipidemia, and decreased body weight gain compared with age-matched controls. The addition of free fatty acids, in the form of 1.2 mM palmitate, to the isolated working heart perfusate had no effect on either control or diabetic heart function, with the exception of a depressive effect on +dP/dt of diabetic hearts. But diabetic hearts perfused with palmitate-containing perfusate plus the glucose oxidation stimulator dichloroacetate (DCA) showed a marked improvement in function. HR and HR.PSP in spontaneously beating hearts, as well as LVDP and +dP/dt in paced hearts were all restored to control heart values in diabetic hearts perfused in the presence of DCA. Creatine phosphate and ATP levels were similar under all perfusion conditions, thus eliminating energy stores as the limiting factor in heart function. Results indicate that DCA will acutely reverse diabetic cardiac function depression. Therefore glucose oxidation depression in the diabetic heart may be a significant factor contributing to cardiac dysfunction.

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