scholarly journals Neuronostatin inhibits cardiac contractile function via a protein kinase A- and JNK-dependent mechanism in murine hearts

2009 ◽  
Vol 297 (3) ◽  
pp. R682-R689 ◽  
Author(s):  
Yinan Hua ◽  
Heng Ma ◽  
Willis K. Samson ◽  
Jun Ren
Keyword(s):  
Contractile Function ◽  
Peptide Hormone ◽  
Left Ventricular ◽  
Maximal Velocity ◽  
Cardiac Contractile Function ◽  
Mechanical Responses ◽  
Cardiac Contractile ◽  
Short Term Exposure ◽  
The Impact ◽  
Dependent Mechanism

Neuronostatin, a newly identified peptide hormone sharing the same precursor with somatostatin, exerts multiple pharmacological effects in gastrointestinal tract, hypothalamus, and cerebellum. However, the cardiovascular effect of neuronostatin is unknown. The aim of this study was to elucidate the impact of neuronostatin on cardiac contractile function in murine hearts and isolated cardiomyocytes. Short-term exposure of neuronostatin depressed left ventricular developed pressure (LVDP), maximal velocity of pressure development (±dP/d t), and heart rate in Langendorff heart preparation. Consistently, neuronostatin inhibited peak shortening (PS) and maximal velocity of shortening/relengthening (±dL/d t) without affecting time-to-PS (TPS) and time-to-90% relengthening (TR90) in cardiomyocytes. The neuronostatin-elicited cardiomyocyte mechanical responses were mimicked by somatostatin, the other posttranslational product of preprosomatostatin. Furthermore, the neuronostatin-induced cardiomyocyte mechanical effects were ablated by the PKA inhibitor H89 (1 μM) and the Jun N-terminal kinase (JNK) inhibitor SP600125 (20 μM). The PKC inhibitor chelerythrine (1 μM) failed to alter neuronostatin-induced cardiomyocyte mechanical responses. To the contrary, chelerythrine, but not H89, abrogated somatostatin-induced cardiomyocyte contractile responses. Our results also showed enhanced c-fos and c-jun expression in response to neuronostatin exposure (0.5 to 2 h). Taken together, our data suggest that neuronostatin is a peptide hormone with overt cardiac depressant action. The neuronostatin-elicited cardiac contractile response appears to be mediated, at least in part, through a PKA- and/or JNK-dependent mechanism.

Lipid peroxidation contributes to cardiac deficits after ischemia and reperfusion of the small bowel

1993 ◽  
Vol 264 (5) ◽  
pp. H1686-H1692 ◽  
Author(s):  
J. W. Horton ◽  
D. J. White
Keyword(s):  
Lipid Peroxidation ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Cardiac Contractile Function ◽  
Langendorff Preparation ◽  
Cardiac Contractile ◽  
Intestinal Ischemia Reperfusion

Our previous studies showed that intestinal ischemia-reperfusion (IR) impairs cardiac contractile function. The present study examined the contribution of oxygen free radicals and lipid peroxidation of cardiac cell membrane to cardiac dysfunction after intestinal IR in a rat model of superior mesenteric artery (SMA) occlusion (atraumatic clip for 20 min) and collateral arcade ligation. Controls were sham operated (group 1, n = 25). In group 2, 30 rats with SMA occlusion were killed 3-4 h after reperfusion without treatment. Aminosteroid (U-74389F), a pharmacological agent known to inhibit lipid peroxidation of membranes, was given 1 min before occlusion of the SMA (group 3, n = 19). All rats were killed 3-4 h after reperfusion of the ischemic intestine, and the hearts were harvested for in vitro assessment of cardiac function (Langendorff preparation). Cardiac contractile depression occurred in the untreated group as indicated by a fall in left ventricular pressure (from 76 +/- 3 to 64 +/- 3 mmHg, P = 0.01), maximum +dP/dt (from 1,830 +/- 60 to 1,577 +/- 64 mmHg/s, P = 0.05), and maximum -dP/dt (from 1,260 +/- 50 to 950 +/- 60 mmHg/s, P = 0.005). Lipid peroxidation of cardiac membranes occurred after untreated IR as indicated by the rise in cardiac malondialdehyde levels (MDA) (from 0.203 +/- 0.046 to 0.501 +/- 0.044 nM/mg protein, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Feeding the fibrillating heart: Dichloroacetate improves cardiac contractile dysfunction following VF

2015 ◽  
Vol 309 (9) ◽  
pp. H1543-H1553 ◽  
Author(s):  
Mohammed Ali Azam ◽  
Cory S. Wagg ◽  
Stéphane Massé ◽  
Talha Farid ◽  
Patrick F. H. Lai ◽  
...  
Keyword(s):  
Glucose Oxidation ◽  
Contractile Function ◽  
Lactate Production ◽  
Left Ventricular ◽  
Global Ischemia ◽  
Contractile Dysfunction ◽  
Anaerobic Glycolysis ◽  
Cardiac Contractile Function ◽  
Cardiac Contractile ◽  
Cardiac Contractile Dysfunction

Ventricular fibrillation (VF) is an important cause of sudden cardiac arrest following myocardial infarction. Following resuscitation from VF, decreased cardiac contractile function is a common problem. During and following myocardial ischemia, decreased glucose oxidation, increased anaerobic glycolysis for cardiac energy production are harmful and energetically expensive. The objective of the present study is to determine the effects of dichloroacetate (DCA), a glucose oxidation stimulator, on cardiac contractile dysfunction following ischemia-induced VF. Male Sprague-Dawley rat hearts were Langendorff perfused in Tyrode's buffer. Once stabilized, hearts were subjected to 15 min of global ischemia and 5 min of aerobic reperfusion in the presence or absence of DCA. At the 6th min of reperfusion, VF was induced electrically, and terminated. Left ventricular (LV) pressure was measured using a balloon. Pretreatment with DCA significantly improved post-VF left ventricular developed pressure (LVDP) and dp/d tmax. In DCA-pretreated hearts, post-VF lactate production and pyruvate dehydrogenase (PDH) phosphorylation were significantly reduced, indicative of stimulated glucose oxidation, and inhibited anaerobic glycolysis by activation of PDH. Epicardial NADH fluorescence was increased during global ischemia above preischemic levels, but decreased below preischemia levels following VF, with no differences between nontreated controls and DCA-pretreated hearts, whereas DCA pretreatment increased NADH production in nonischemic hearts. With exogenous fatty acids (FA) added to the perfusion solution, DCA pretreatment also resulted in improvements in post-VF LVDP and dp/d tmax, indicating that the presence of exogenous FA did not affect the beneficial actions of DCA. In conclusion, enhancement of PDH activation by DCA mitigates cardiac contractile dysfunction following ischemia-induced VF.

scholarly journals Mechanisms underlying hypothermia-induced cardiac contractile dysfunction

2010 ◽  
Vol 298 (3) ◽  
pp. H890-H897 ◽  
Author(s):  
Young-Soo Han ◽  
Torkjel Tveita ◽  
Y. S. Prakash ◽  
Gary C. Sieck
Keyword(s):  
Papillary Muscle ◽  
Myocardial Contractility ◽  
Troponin I ◽  
Contractile Function ◽  
Left Ventricular ◽  
Cardiac Contractile Function ◽  
Profound Hypothermia ◽  
Twitch Force ◽  
Cardiac Contractile ◽  
Cardiac Contractile Dysfunction

Rewarming patients after profound hypothermia may result in acute heart failure and high mortality (50–80%). However, the underlying pathophysiological mechanisms are largely unknown. We characterized cardiac contractile function in the temperature range of 15–30°C by measuring the intracellular Ca2+ concentration ([Ca2+]i) and twitch force in intact left ventricular rat papillary muscles. Muscle preparations were loaded with fura-2 AM and electrically stimulated during cooling at 15°C for 1.5 h before being rewarmed to the baseline temperature of 30°C. After hypothermia/rewarming, peak twitch force decreased by 30–40%, but [Ca2+]i was not significantly altered. In addition, we assessed the maximal Ca2+-activated force (Fmax) and Ca2+ sensitivity of force in skinned papillary muscle fibers. Fmax was decreased by ∼30%, whereas the pCa required for 50% of Fmax was reduced by ∼0.14. In rewarmed papillary muscle, both total cardiac troponin I (cTnI) phosphorylation and PKA-mediated cTnI phosphorylation at Ser23/24 were significantly increased compared with controls. We conclude that after hypothermia/rewarming, myocardial contractility is significantly reduced, as evidenced by reduced twitch force and Fmax. The reduced myocardial contractility is attributed to decreased Ca2+ sensitivity of force rather than [Ca2+]i itself, resulting from increased cTnI phosphorylation.

scholarly journals Impaired cardiac contractile function in ventricular myocytes from leptin-deficient ob/ob obese mice

2006 ◽  
Vol 188 (1) ◽  
pp. 25-36 ◽  
Author(s):  
F Dong ◽  
X Zhang ◽  
X Yang ◽  
L B Esberg ◽  
H Yang ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Ventricular Myocytes ◽  
Contractile Function ◽  
Contractile Dysfunction ◽  
Maximal Velocity ◽  
Obese Mice ◽  
Cardiac Contractile Function ◽  
Cardiac Contractile ◽  
Leptin Deficiency ◽  
Intracellular Ca

The level of the obese gene product leptin is often positively correlated with body weight, supporting the notion that hyperleptinemia contributes to obesity-associated cardiac dysfunction. However, a link between leptin levels and cardiac function has not been elucidated. This study was designed to examine the role of leptin deficiency (resulting from a point mutation of the leptin gene) in cardiomyocyte contractile function. Mechanical properties and intracellular Ca2 + transients were evaluated in ventricular myocytes from lean control and leptin-deficient ob/ob obese mice at 12 weeks of age. Cardiac ultrastructure was evaluated using transmission electron microscopy. ob/ob mice were overtly obese, hyperinsulinemic, hypertriglycemic, hypoleptinemic and euglycemic. Ultrastructural examination revealed swelling and disorganization of cristae in mitochondria from ob/ob mouse ventricular tissues. Cardiomyocytes from ob/ob mice displayed reduced expression of the leptin receptor Ob-R, larger cross-sectional area, decreased peak shortening and maximal velocity of shortening/relengthening, and prolonged relengthening but not shortening duration compared with lean counterparts. Consistent with mechanical characteristics, myocytes from ob/ob mice displayed reduced intracellular Ca2 + release upon electrical stimulus associated with a slowed intracellular Ca2 + decay rate. Interestingly, the contractile aberrations seen in ob/ob myocytes were significantly improved by in vitro leptin incubation. Contractile dysfunction was not seen in age- and gender-matched high fat-induced obese mice. These results suggested that leptin deficiency contributes to cardiac contractile dysfunction characterized by both systolic and diastolic dysfunction, impaired intracellular Ca2 + hemostasis and ultrastructural derangement in ventricular myocytes.

scholarly journals The impact of myocardial compressibility on organ-level simulations of the normal and infarcted heart

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hao Liu ◽  
João S. Soares ◽  
John Walmsley ◽  
David S. Li ◽  
Samarth Raut ◽  
...  
Keyword(s):  
Contractile Function ◽  
Patient Specific ◽  
Cardiac Contractile Function ◽  
Systolic Volume ◽  
Tissue Volume ◽  
Therapeutic Modalities ◽  
Cardiac Contractile ◽  
Infarcted Heart ◽  
Improved Accuracy ◽  
The Impact

AbstractMyocardial infarction (MI) rapidly impairs cardiac contractile function and instigates maladaptive remodeling leading to heart failure. Patient-specific models are a maturing technology for developing and determining therapeutic modalities for MI that require accurate descriptions of myocardial mechanics. While substantial tissue volume reductions of 15–20% during systole have been reported, myocardium is commonly modeled as incompressible. We developed a myocardial model to simulate experimentally-observed systolic volume reductions in an ovine model of MI. Sheep-specific simulations of the cardiac cycle were performed using both incompressible and compressible tissue material models, and with synchronous or measurement-guided contraction. The compressible tissue model with measurement-guided contraction gave best agreement with experimentally measured reductions in tissue volume at peak systole, ventricular kinematics, and wall thickness changes. The incompressible model predicted myofiber peak contractile stresses approximately double the compressible model (182.8 kPa, 107.4 kPa respectively). Compensatory changes in remaining normal myocardium with MI present required less increase of contractile stress in the compressible model than the incompressible model (32.1%, 53.5%, respectively). The compressible model therefore provided more accurate representation of ventricular kinematics and potentially more realistic computed active contraction levels in the simulated infarcted heart. Our findings suggest that myocardial compressibility should be incorporated into future cardiac models for improved accuracy.

Energy-linked functional alterations in experimental cardiomyopathies

1991 ◽  
Vol 261 (4) ◽  
pp. L39-L44 ◽  
Author(s):  
V. I. Kapelko ◽  
V. I. Veksler ◽  
M. I. Popovich ◽  
R. Ventura-Clapier
Keyword(s):  
Diastolic Pressure ◽  
Contractile Function ◽  
High Energy ◽  
Left Ventricular ◽  
High Energy Phosphates ◽  
Phosphate Content ◽  
High Energy Phosphate ◽  
Cardiac Contractile Function ◽  
Myocardial Stiffness ◽  
Cardiac Contractile

Changes in high-energy phosphate content and cardiac contractile function of isolated rat hearts as well as changes in Ca2+ sensitivity and mitochondrial respiration of myocardial skinned fibers were assessed in hereditary cardiomyopathies and in cardiomyopathies induced by chronic treatment with adriamycin or norepinephrine, by autoimmunization, by diabetes, or by creatine deficiency. The sum of ATP and phosphocreatine contents as well as cardiac output at standard load conditions was substantially lower in almost all groups. The common features of cardiac pump failure were mild bradycardia, elevated left ventricular (LV) diastolic pressure, and stiffness that limited cardiac contractile adaptation to volume or resistance loads. The LV diastolic stiffness at maximal functional load was inversely correlated with high-energy phosphate content. Increased myofibrillar sensitivity to Ca2+ and defective function of mitochondrial creatine kinase were found in skinned myocardial fibers. These results suggested that both increased myofibrillar Ca2+ sensitivity and energy deficiency within myofibrils may contribute to increased myocardial stiffness. Increased stiffness limits LV filling but facilitates pressure development, which partly compensates for decreased contractility of cardiomyopathic hearts. cardiac contractile function; high-energy phosphates; isolated heart; myocardial stiffness

Energy-linked functional alterations in experimental cardiomyopathies

1991 ◽  
Vol 261 (4) ◽  
pp. 39-44 ◽  
Author(s):  
V. I. Kapelko ◽  
V. I. Veksler ◽  
M. I. Popovich ◽  
R. Ventura-Clapier
Keyword(s):  
Diastolic Pressure ◽  
Contractile Function ◽  
High Energy ◽  
Left Ventricular ◽  
High Energy Phosphates ◽  
Phosphate Content ◽  
High Energy Phosphate ◽  
Cardiac Contractile Function ◽  
Myocardial Stiffness ◽  
Cardiac Contractile

Changes in high-energy phosphate content and cardiac contractile function of isolated rat hearts as well as changes in Ca2+ sensitivity and mitochondrial respiration of myocardial skinned fibers were assessed in hereditary cardiomyopathies and in cardiomyopathies induced by chronic treatment with adriamycin or norepinephrine, by autoimmunization, by diabetes, or by creatine deficiency. The sum of ATP and phosphocreatine contents as well as cardiac output at standard load conditions was substantially lower in almost all groups. The common features of cardiac pump failure were mild bradycardia, elevated left ventricular (LV) diastolic pressure, and stiffness that limited cardiac contractile adaptation to volume or resistance loads. The LV diastolic stiffness at maximal functional load was inversely correlated with high-energy phosphate content. Increased myofibrillar sensitivity to Ca2+ and defective function of mitochondrial creatine kinase were found in skinned myocardial fibers. These results suggested that both increased myofibrillar Ca2+ sensitivity and energy deficiency within myofibrils may contribute to increased myocardial stiffness. Increased stiffness limits LV filling but facilitates pressure development, which partly compensates for decreased contractility of cardiomyopathic hearts. cardiac contractile function; high-energy phosphates; isolated heart; myocardial stiffness

Chronic exercise alters contractility and morphology of isolated rat cardiac myocytes

1993 ◽  
Vol 264 (5) ◽  
pp. C1180-C1189 ◽  
Author(s):  
R. L. Moore ◽  
T. I. Musch ◽  
R. V. Yelamarty ◽  
R. C. Scaduto ◽  
A. M. Semanchick ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Contractile Function ◽  
Left Ventricular ◽  
Potential Contribution ◽  
Chronic Exercise ◽  
Cardiac Contractile Function ◽  
Cell Width ◽  
Cardiac Contractile ◽  
Rat Cardiac Myocytes ◽  
Ventricular Dimension

Chronic exercise training elicits positive adaptations in cardiac contractile function and ventricular dimension. The potential contribution of single myocyte morphological and functional adaptations to these global responses to training was determined in this study. Left ventricular cardiac myocytes were isolated from the hearts of sedentary control (Sed) or exercise-trained (TR) rats. Training elicited an approximately 5% increase in resting myocyte length (Sed, 121.0 +/- 2.0 vs. TR, 126.7 +/- 2.0 microns; P < 0.05), whereas resting sarcomere length and midpoint cell width were unaffected. These data suggest that longitudinal myocyte growth contributes to the training-induced increase in end-diastolic dimension. Single myocytes (28 degrees C) were stimulated at 0.067 and 0.2 Hz and shortening dynamics assessed at extracellular Ca2+ concentrations ([Ca2+]o) of 0.6, 1.1, and 2.0 mM. In both groups, maximal extent of myocyte shortening (ESmax) increased as [Ca2+]o increased and decreased as contraction frequency increased. TR myocytes were more strongly influenced by the effects of [Ca2+]o and frequency. At 0.067 Hz and 2.0 mM, ESmax was greater in TR than in Sed myocytes. The magnitude of this difference decreased as [Ca2+]o was reduced. At 0.2 Hz, ESmax was similar in Sed and TR myocytes at 2.0 mM [Ca2+]o. As [Ca2+]o was reduced, ESmax decreased more rapidly in TR than in Sed myocytes; at 0.6 mM, ESmax was greater in Sed than in TR myocytes. Our data indicate that chronic exercise influences cardiac contractile function at the single myocyte level. This study also provides evidence in support of the hypothesis that chronic exercise influences myocyte Ca2+ influx and efflux pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac contractile function following repetitive brief ischemia: effects of nucleoside transport inhibition

1994 ◽  
Vol 267 (1) ◽  
pp. H57-H65 ◽  
Author(s):  
K. A. Kirkeboen ◽  
A. Ilebekk ◽  
T. Tonnessen ◽  
E. Leistad ◽  
P. A. Naess ◽  
...  
Keyword(s):  
Contractile Function ◽  
Saline Group ◽  
Left Ventricular ◽  
Nucleoside Transport ◽  
Segment Length ◽  
Cardiac Contractile Function ◽  
Cardiac Contractile ◽  
Transport Inhibition ◽  
Group 2 ◽  
Nucleoside Transport Inhibitor

The effects of nucleoside transport inhibition on cardiac contractile function were examined in anesthetized pigs subjected to five 6-min left anterior descending coronary artery (LAD) occlusions, separated by 20-min reperfusion, and followed by 150-min reperfusion. In group 1 (n = 8), saline was infused. In group 2 (n = 9), endogenous myocardial accumulation of adenosine was increased by intracoronary infusion of the specific nucleoside transport inhibitor R-75 231. Left ventricular segment lengths were recorded by ultrasonic crystals in the inner one-third of the myocardium. Percent systolic segment length shortening (SS) (normalized to percent of preischemic value) was significantly better maintained in the R-75 231 group compared with the saline group after each occlusion. SS in the saline group reached a nadir of 30% (22-40) at 30-min reperfusion after the last occlusion compared with 66% (54–73) in the R-75 231 group. In the R-75 231 group, but not in the saline group, maximal postischemic decline in SS and decline at 20-min reperfusion were significantly reduced following the last occlusion. We conclude that R-75 231, which inhibits nucleoside transport, attenuates contractile dysfunction following repetitive brief ischemia and results in a preconditioning-like effect against stunning in the pig. On the basis of the well-documented biochemical effects of R-75 231, increased accumulation of endogenous adenosine most likely explains these findings.

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