Overexpression of Na+/Ca2+ exchanger gene attenuates postinfarction myocardial dysfunction

2002 ◽  
Vol 283 (6) ◽  
pp. H2466-H2471 ◽  
Author(s):  
Jiang-Yong Min ◽  
Matthew F. Sullivan ◽  
Xinhua Yan ◽  
Xin Feng ◽  
Victor Chu ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Function ◽  
Myocardial Function ◽  
Contractile Response ◽  
Myocardial Dysfunction ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Papillary Muscles ◽  
Wild Type ◽  
Adrenergic Stimulation

We monitored myocardial function in postinfarcted wild-type (WT) and transgenic (TG) mouse hearts with overexpression of the cardiac Na+/Ca2+ exchanger. Five weeks after infarction, cardiac function was better maintained in TG than WT mice [left ventricular (LV) systolic pressure: WT, 41 ± 2; TG, 58 ± 3 mmHg; P < 0.05; maximum rising rate of LV pressure (+dP/d t max): WT, 3,750 ± 346; TG, 5,075 ± 334 mmHg/s; P < 0.05]. The isometric contractile response to β-adrenergic stimulation was greater in papillary muscles from TG than WT mice (WT, 13.2 ± 0.9; TG, 16.3 ± 1.0 mN/mm2 at 10−4 M isoproterenol). The sarcoplasmic reticulum (SR) Ca2+content investigated by rapid cooling contractures in papillary muscles was greater in TG than WT mouse hearts. We conclude that myocardial function is better preserved in TG mice 5 wk after infarction, which results from enhanced SR Ca2+ content via overexpression of the Na+/Ca2+ exchanger.

scholarly journals Enhanced gene expression of Na+/Ca2+exchanger attenuates ischemic and hypoxic contractile dysfunction

2000 ◽  
Vol 279 (6) ◽  
pp. H2846-H2854 ◽  
Author(s):  
Thomas G. Hampton ◽  
Ju-Feng Wang ◽  
Joseph DeAngelis ◽  
Ivo Amende ◽  
Kenneth D. Philipson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Function ◽  
Intracellular Calcium ◽  
Systolic Pressure ◽  
Contractile Dysfunction ◽  
Compensatory Mechanism ◽  
Wild Type ◽  
Generating Capacity ◽  
And Function

Enhanced gene expression of the Na+/Ca2+exchanger in failing hearts may be a compensatory mechanism to promote influx and efflux of Ca2+, despite impairment of the sarcoplasmic reticulum (SR). To explore this, we monitored intracellular calcium (Cai 2+) and cardiac function in mouse hearts engineered to overexpress the Na+/Ca2+ exchanger and subjected to ischemia and hypoxia, conditions known to impair SR Cai 2+transport and contractility. Although baseline Cai 2+and function were similar between transgenic and wild-type hearts, significant differences were observed during ischemia and hypoxia. During early ischemia, Cai 2+ was preserved in transgenic hearts but significantly altered in wild-type hearts. Transgenic hearts maintained 40% of pressure-generating capacity during early ischemia, whereas wild-type hearts maintained only 25% ( P < 0.01). During hypoxia, neither peak nor diastolic Cai 2+ decreased in transgenic hearts. In contrast, both peak and diastolic Cai 2+ decreased significantly in wild-type hearts. The decline of Cai 2+ was abbreviated in hypoxic transgenic hearts but prolonged in wild-type hearts. Peak systolic pressure decreased by nearly 10% in hypoxic transgenic hearts and >25% in wild-type hearts ( P < 0.001). These data demonstrate that enhanced gene expression of the Na+/Ca2+ exchanger preserves Cai 2+ homeostasis during ischemia and hypoxia, thereby preserving cardiac function in the acutely failing heart.

scholarly journals Endotoxin impairs cardiac hemodynamics by affecting loading conditions but not by reducing cardiac inotropism

2010 ◽  
Vol 299 (2) ◽  
pp. H492-H501 ◽  
Author(s):  
Li Jianhui ◽  
Nathalie Rosenblatt-Velin ◽  
Noureddine Loukili ◽  
Pal Pacher ◽  
François Feihl ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Myocardial Dysfunction ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Laboratory Animals ◽  
Lv Function ◽  
Stroke Work ◽  
Loading Conditions ◽  
Arterial Elastance ◽  
End Diastolic Volume

Acute myocardial dysfunction is a typical manifestation of septic shock. Experimentally, the administration of endotoxin [lipopolysacharride (LPS)] to laboratory animals is frequently used to study such dysfunction. However, a majority of studies used load-dependent indexes of cardiac function [including ejection fraction (EF) and maximal systolic pressure increment (dP/d tmax)], which do not directly explore cardiac inotropism. Therefore, we evaluated the direct effects of LPS on myocardial contractility, using left ventricular (LV) pressure-volume catheters in mice. Male BALB/c mice received an intraperitoneal injection of E. coli LPS (1, 5, 10, or 20 mg/kg). After 2, 6, or 20 h, cardiac function was analyzed in anesthetized, mechanically ventilated mice. All doses of LPS induced a significant drop in LV stroke volume and a trend toward reduced cardiac output after 6 h. Concomitantly, there was a significant decrease of LV preload (LV end-diastolic volume), with no apparent change in LV afterload (evaluated by effective arterial elastance and systemic vascular resistance). Load-dependent indexes of LV function were markedly reduced at 6 h, including EF, stroke work, and dP/d tmax. In contrast, there was no reduction of load-independent indexes of LV contractility, including end-systolic elastance (ejection phase measure of contractility) and the ratio dP/d tmax/end-diastolic volume (isovolumic phase measure of contractility), the latter showing instead a significant increase after 6 h. All changes were transient, returning to baseline values after 20 h. Therefore, the alterations of cardiac function induced by LPS are entirely due to altered loading conditions, but not to reduced contractility, which may instead be slightly increased.

Anti-Apoptotic Effect of Magnolol in Myocardial Ischemia and Reperfusion Injury Requires Extracellular Signal-Regulated Kinase1/2 Pathways in Rat In Vivo

2008 ◽  
Vol 233 (10) ◽  
pp. 1280-1288 ◽  
Author(s):  
Yong Chun Jin ◽  
Kil Jung Kim ◽  
Young Min Kim ◽  
Yu Mi Ha ◽  
Hye Jung Kim ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Infarct Size ◽  
Function Analysis ◽  
Heart Function ◽  
Myocardial Dysfunction ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Ischemia And Reperfusion ◽  
Myocardial Ischemia And Reperfusion

Magnolol, an active component extracted from Magnolia officinalis, has been reported to have protective effect on ischemia and reperfusion (I/R)-induced injury in experimental animals. The aim of the present investigation was to further evaluate the mechanism(s) by which magnolol reduces I/R-induced myocardial injury in rats in vivo. Under anesthesia, left anterior descending (LAD) coronary artery was occluded for 30 min followed by reperfusion for 24 h (for infarct size and cardiac function analysis). In some experiments, reperfusion was limited to 1 h or 6 h for analysis of biochemical and molecular events. Magnolol and DMSO solution (vehicle) were injected intra-peritoneally 1 h prior to I/R insult. The infarct size was measured by TTC technique and heart function was monitored by Millar Catheter. Apoptosis related events such as p-ERK, p-Bad, Bcl-xl and cytochrome c expression were evaluated by Western blot analysis and myocardial caspase-3 activity was also measured. Magnolol (10 mg/kg) reduced infarct size by 50% ( P < 0.01 versus vehicle), and also improved I/R-induced myocardial dysfunction. Left ventricular systolic pressure and positive and negative maximal values of the first derivative of left ventricular pressure (dP/dt) were significantly improved in magnolol-treated rats. Magnolol increased the expression of phosphor ERK and Bad which resulted in inhibition of myocardial apoptosis as evidenced by TUNEL analysis and DNA laddering experiments. Application of PD 98059, a selective MEK1/2 inhibitor, strongly antagonized the effect of magnolol. Taken together, we concluded that magnolol inhibits apoptosis through enhancing the activation of ERK1/2 and modulation of the Bcl-xl proteins which brings about reduction of infarct size and improvement of cardiac function in I/R-induced injury.

Breathing nitric oxide plus hydrogen gas reduces ischemia-reperfusion injury and nitrotyrosine production in murine heart

2013 ◽  
Vol 305 (4) ◽  
pp. H542-H550 ◽  
Author(s):  
Toshihiro Shinbo ◽  
Kenichi Kokubo ◽  
Yuri Sato ◽  
Shintaro Hagiri ◽  
Ryuji Hataishi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiac Function ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Neutrophil Infiltration ◽  
Left Ventricular ◽  
Hydrogen Gas ◽  
Coronary Artery Ligation

Inhaled nitric oxide (NO) has been reported to decrease the infarct size in cardiac ischemia-reperfusion (I/R) injury. However, reactive nitrogen species (RNS) produced by NO cause myocardial dysfunction and injury. Because H2 is reported to eliminate peroxynitrite, it was expected to reduce the adverse effects of NO. In mice, left anterior descending coronary artery ligation for 60 min followed by reperfusion was performed with inhaled NO [80 parts per million (ppm)], H2 (2%), or NO + H2, starting 5 min before reperfusion for 35 min. After 24 h, left ventricular function, infarct size, and area at risk (AAR) were assessed. Oxidative stress associated with reactive oxygen species (ROS) was evaluated by staining for 8-hydroxy-2′-deoxyguanosine and 4-hydroxy-2-nonenal, that associated with RNS by staining for nitrotyrosine, and neutrophil infiltration by staining for granulocyte receptor-1. The infarct size/AAR decreased with breathing NO or H2 alone. NO inhalation plus H2 reduced the infarct size/AAR, with significant interaction between the two, reducing ROS and neutrophil infiltration, and improved the cardiac function to normal levels. Although nitrotyrosine staining was prominent after NO inhalation alone, it was eliminated after breathing a mixture of H2 with NO. Preconditioning with NO significantly reduced the infarct size/AAR, but not preconditioning with H2. In conclusion, breathing NO + H2 during I/R reduced the infarct size and maintained cardiac function, and reduced the generation of myocardial nitrotyrosine associated with NO inhalation. Administration of NO + H2 gases for inhalation may be useful for planned coronary interventions or for the treatment of I/R injury.

Relation between contractile function and regulatory cardiac proteins in hypertrophied hearts

1996 ◽  
Vol 270 (6) ◽  
pp. H2021-H2028 ◽  
Author(s):  
B. Stein ◽  
S. Bartel ◽  
U. Kirchhefer ◽  
S. Kokott ◽  
E. G. Krause ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Troponin I ◽  
Contractile Function ◽  
Papillary Muscles ◽  
Camp Accumulation ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
C Protein ◽  
Camp Formation ◽  
Phosphate Incorporation

The aim of this study was to examine the mechanism(s) underlying the reduced isoproterenol-induced positive inotropic and lusitropic effects in hypertrophied hearts. Chronic beta-adrenergic stimulation (2.4 mg isoproterenol.kg-1. day-1 for 4 days) induced cardiac hypertrophy by 33 +/- 2% in rats. A parallel downregulation of phospholamban (PLB) and sarcoplasmic reticulum Ca2(+)-ATPase (SERCA2) protein expression by 49 and 40%, respectively, was observed, whereas troponin I (TNI) and C protein remained unchanged. In papillary muscles from chronically beta-adrenergically stimulated rats, the isoproterenol-induced positive inotropic and lusitropic effects, as well as adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, were attenuated compared with those in control animals. Acute exposure to isoproterenol induced phosphate incorporation into PLB, TNI, and C protein of 48 +/- 4.6, 55 +/- 5.0, and 27 +/- 4.9 pmol/mg homogenate protein, respectively, in control animals. In the hypertrophied hearts, phosphate incorporation into PLB was reduced by 76%, whereas phosphate incorporation into TNI or C protein remained unchanged. In conclusion, chronic beta-adrenergic stimulation reduced the isoproterenol-stimulated positive inotropic and lusitropic effects in papillary muscles, which were accompanied by 1) diminished cAMP formation, 2) attenuation of cAMP-mediated PLB phosphorylation, and 3) downregulation of PLB and SERCA2 protein.

Improvement by isosorbide dinitrate of exercise-induced regional myocardial dysfunction

1980 ◽  
Vol 239 (3) ◽  
pp. H399-H405
Author(s):  
T. Kumada ◽  
K. P. Gallagher ◽  
M. Miller ◽  
M. McKown ◽  
F. White ◽  
...  
Keyword(s):  
Isosorbide Dinitrate ◽  
Myocardial Function ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Segment Length ◽  
Wall Thickening ◽  
Regional Myocardial Function ◽  
Exercise Induced ◽  
Coronary Obstruction ◽  
Control Exercise

Sonomicrometry was used in 10 conscious dogs to measure regional segment length and dynamic wall thickness by telemetry in a zone supplied by the left circumflex coronary artery after implantation of an ameroid constrictor. When coronary obstruction was nearly complete and collaterals had developed (24-42 days), control exercise and exercise runs after oral isosorbide dinitrate were carried out. During control runs, significant increases occurred in hemodynamic parameters, and percent shortening in normal segments increased (P < 0.01). During the repeat runs after isosorbide dinitrate, there were smaller increases in left ventricular systolic and end-diastolic pressures and significantly reduced end-diastolic dimensions. In addition, percent wall thickening and percent segment shortening in the ischemic zone did not deteriorate significantly during exercise. In this animal model, which appears to mimic chronic single-vessel coronary heart disease, isosorbide dinitrate can prevent exercise-induced deterioration of regional myocardial function.

Muscle metabolism and cardiac function of the myopathic hamster following training

1977 ◽  
Vol 43 (6) ◽  
pp. 936-941 ◽  
Author(s):  
W. L. Sembrowich ◽  
M. B. Knudson ◽  
P. D. Gollnick
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Function ◽  
Myocardial Function ◽  
Cardiac Contractility ◽  
Muscle Metabolism ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Treadmill Running ◽  
Succinate Dehydrogenase Activity ◽  
Positive Effect

The effect of 18 wk of treadmill running on skeletal muscle metabolism and myocardial function of normal and myopathic hamsters was examined. BIO 14.6 hamsters could tolerate an exercise intensity of about 18 m/min for 40 min, 5 days/wk. Further increases in speed or number of bouts per day resulted in a falloff in performance. Normal hamsters could tolerate higher speeds and longer exercise bouts. Exercise did not change the severity of lesions of either the heart or skeletal muscle of the myopathic hamsters. A training effect was evidenced by increased succinate dehydrogenase activity in the soleus muscle. Cardiac function was evaluated as contractility measured from left ventricular pressure curves and expressed as (dP/dt)/kP. The results suggested that cardiac contractility was not as severely depressed in the trained BIO 14.6 strain of hamsters as in nontrained controls. However, (dP/dt)/kP was lower in the trained myopathic animals than in normal hamsters. ATP, CP, and glycogen levels were lower in myopathic hamsters with the lowest values occurring in the trained group. These data demonstrate that the BIO 14.6 strain of hamster can tolerate exercise training and that such training may have a positive effect on cardiac function.

The Effect of Gypenosides on Cardiac Function and Expression of Cytoskeletal Genes of Myocardium in Diabetic Cardiomyopathy Rats

2009 ◽  
Vol 37 (06) ◽  
pp. 1059-1068 ◽  
Author(s):  
Min Ge ◽  
Shanfeng Ma ◽  
Liang Tao ◽  
Sudong Guan
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Diastolic Pressure ◽  
Pure Water ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Sprague Dawley ◽  
Gene Expressions ◽  
Ventricular Systolic Pressure

The relationship between changes of cardiac function and the gene expressions of two major myocardial skeleton proteins, titin and nebulin, and the effect of gypenosides on these gene expressions in diabetic cardiomyopathy rat were explored in the present study. Forty Sprague-Dawley rats were randomly divided into three groups: control group, diabetic cardiomyopathy group and gypenosides-treated diabetic cardiomyopathy group. The diabetic cardiomyopathy was induced in rats by injecting streptozotocin (STZ, 55 mg/kg) intraperitoneally. Seven weeks after the rats suffered from diabetes, the rats were treated with gypenosides 100 mg/kg per day orally for six weeks in gypenosides-treated group. In the meanwhile, the pure water was given to diabetic cardiomyopathy and the control groups. Subsequently, the cardiac functions, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), ± dP/dtmax and t–dP/dmaxt, as well as the mRNA content and proteins of titin and nebulin in myocardium were determined. The results indicated that (1) the diabetic cardiomyopathy rats had decreased LVSP and ± dP/dtmax, increased LVEDP, and prolonged t–dP/dtmax than normal rats; (2) LVSP and ± dP/dtmax in diabetic cardiomyopathy rats treated with gypenosides were significantly higher and LVEDP and t–dP/dtmax were significantly lower than those without giving gypenosides; (3) the mRNA contents and proteins of titin and nebulin in diabetic cardiomyopathy rats were remarkably lower than those in the control rats and gypenosides had no effect on mRNA and protein expression levels of titin and nebulin in diabetic cardiomyopathy rats. We conclude that (1) the cardiac function as well as the mRNA expressions of titin and nebulin decreased in diabetic cardiomyopathy rats; (2) gypenosides secure cardiac muscles and their function from diabetic impairment and these beneficial effects of gypenosides are not by changing the expressions of titin and nebulin.

Effect of human urotensin-II infusion on hemodynamics and cardiac function

2003 ◽  
Vol 81 (2) ◽  
pp. 125-128 ◽  
Author(s):  
Ghada S Hassan ◽  
Fazila Chouiali ◽  
Takayuki Saito ◽  
Fu Hu ◽  
Stephen A Douglas ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Diastolic Pressure ◽  
Cardiac Contractility ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Urotensin Ii ◽  
Ventricular Systolic Pressure ◽  
Wide Range ◽  
Dose Dependent Decrease

Recent studies have shown that the vasoactive peptide urotensin-II (U-II) exerts a wide range of action on the cardiovascular system of various species. In the present study, we determined the in vivo effects of U-II on basal hemodynamics and cardiac function in the anesthetized intact rat. Intravenous bolus injection of human U-II resulted in a dose-dependent decrease in mean arterial pressure and left ventricular systolic pressure. Cardiac contractility represented by ±dP/dt was decreased after injection of U-II. However, there was no significant change in heart rate or diastolic pressure. The present study suggests that upregulation of myocardial U-II may contribute to impaired myocardial function in disease conditions such as congestive heart failure.Key words: urotensin-II, rat, infusion, heart.

scholarly journals Effect of dobutamine on intrinsic myocardial function and myocardial apoptosis in septic rats with myocardial dysfunction

2020 ◽  
Author(s):  
Xiang-Xu Tang ◽  
Ya-Qian Xu ◽  
Xiao-Meng Dai ◽  
Yun Xing ◽  
Duo-Meng Yang ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Myocardial Function ◽  
Myocardial Dysfunction ◽  
Cecal Ligation ◽  
Left Ventricular ◽  
Cardiomyocyte Apoptosis ◽  
Fatty Acid Binding ◽  
Myocardial Apoptosis ◽  
Tnf Α

Abstract Background Dobutamine (DOB) has been recommended as the first-line inotrope for septic patients with low cardiac output, but its long-term impact on intrinsic myocardial dysfunction during sepsis remains unclear. This study investigated the long-term effect of DOB on intrinsic myocardial function and cardiomyocyte apoptosis in sepsis. Methods Male Sprague-Dawley rats were randomly divided into sham and cecal ligation and puncture (CLP) groups. The intrinsic myocardial function and other organ functions were measured at different time points, the inflammatory response and serum biomarkers of myocardial injury were also determined. In separate experiments, the effect of DOB (5 or 10 µg/kg) treatment on survival, intrinsic myocardial function, serum and myocardial cytokines and myocardial apoptosis were measured in septic rats. Results The mortality rate of septic rats was 70% on day 10 after CLP. At 6 h after CLP, the left ventricular ± dP/dt were significantly depressed, serum tumor necrosis factor (TNF) –α level, cardiac TNF-α, intercellular adhesion molecule and vascular cell adhesion molecule-1 (VCAM-1) mRNA, and VCAM-1 protein levels were increased, but not serum cTnI, N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid-binding protein (H-FABP), creatinine and urea nitrogen concentrations as well as lung wet-dry weight ratios in CLP group compared with those in sham group. At 9 h after CLP, serum alanine aminotransferase and aspartate aminotransferase activities were higher in CLP rats than controls. At 6 h after CLP, treatment with DOB did not affect the left ventricular ± dP/dt, the levels of TNF-α, interleukin (IL) − 1β and IL-6 in the serum and myocardium as well as cardiomyocyte apoptosis at 20 h after CLP. However, administration of 10.0 µg/kg DOB at 6 h after CLP significantly increased serum IL-10 level and improved survival in septic rats. Conclusions The intrinsic myocardial depression occurs earlier than hepatic and renal dysfunction in severe sepsis and serum cTnI, NT-proBNP and H-FABP are not suitable as an early biomarker for this kind of cardiac dysfunction. For septic rats, DOB treatment in the presence of intrinsic myocardial dysfunction neither improves myocardial function nor attenuates myocardial inflammation and cardiomyocyte apoptosis at the later stage of sepsis.

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