Phosphorylated compounds and function in isolated hearts: a 31P-NMR study

1991 ◽  
Vol 260 (1) ◽  
pp. H110-H117
Author(s):  
J. Aussedat ◽  
A. Ray ◽  
S. Lortet ◽  
H. Reutenauer ◽  
S. Grably ◽  
...  
Keyword(s):  
Work Load ◽  
Creatine Phosphate ◽  
Myocardial Cell ◽  
Left Ventricular ◽  
Mitochondrial Activity ◽  
Isolated Hearts ◽  
Nmr Study ◽  
Phosphorylated Compounds ◽  
Developed Pressure ◽  
And Function

The potential role of phosphorylated compounds in the control of myocardial cell respiration was investigated by means of 31P-nuclear magnetic resonance (NMR) spectroscopy. Isolated isovolumic rat hearts, perfused with a 9 mM glucose, 2 mM pyruvate medium at a constant beating rate (6 Hz) and temperature (37 degrees C), were subjected to changes in work load by varying the calcium concentration ([Ca2+]) in the perfusion fluid from 0.5 to 1.0, 1.5, or 2.0 mM. Each change in left ventricular developed pressure (LVDP) induced by the [Ca2+] change was accompanied by alterations in the inorganic phosphate-to-creatine phosphate ratio ([Pi]/[PCr]), with the ATP level remaining constant. The relationship between [Pi]/[PCr] and LVDP followed a Michaelis-Menten pattern with an apparent Michaelis constant (Km) of 0.09 and a maximal LVDP of 91 mmHg. This Km corresponded to intracellular concentrations of 1.2 mM for Pi and 13.0 mM for PCr. The calculated [ADP] and phosphorylation potential corresponding to these values were 44 microM and 151,000 M-1, respectively. All these values are close to those estimated under in situ physiological conditions. These results support the assumption that in the rat heart, as in skeletal muscle, mitochondrial activity could be controlled by changes in phosphorylated compound concentrations under normoxic conditions.

Abstract P138: Long-term Effects Of Severe Caloric Restriction To The Heart Function

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Aline M De Souza ◽  
Jonathas Almeida ◽  
Nataliia Shults ◽  
Hong Ji ◽  
Kathryn Sandberg
Keyword(s):  
Cardiovascular Disease ◽  
Caloric Restriction ◽  
Heart Function ◽  
Left Ventricular ◽  
Structure And Function ◽  
Long Term Effects ◽  
Isolated Hearts ◽  
Ad Libitum ◽  
And Function

Severe caloric restriction (sCR) increases the risk for acute cardiovascular disease. Less understood are the long-term effects on cardiovascular disease risk after the sCR period has ended. We investigated the effects of sCR on heart structure and function months after refeeding (sCR-Refed). Female Fischer rats (3-months-old) were maintained on (CT) ad libitum or a 60% caloric restricted diet for 2 weeks. Thereafter, all rats received ad libitum chow for 3 months and they were analyzed by precision ultrasound to assess their heart function. After imaging, the animals were sacrificed and the hearts were subjected to ischemia-reperfusion (I/R) using a Langendorff preparation. After 2 weeks of sCR, rats lost 15% of their initial body weight (BW) [% (100*(Final-Initial/Initial)): CT, 1.5±0.8 vs sCR, -15.4±1.1; p<0.001;n=8]. After 3 months of refeeding, there was no detectable difference in BW between CT and sFR-Refed groups. Isolated hearts from the sCR-Refed rats exhibited worse myocardial pathology after I/R compared to CT rats. The parallel orientation of myofibers and striations normally present in cardiomyocytes was lost in sCR-Refed rats. Further analysis revealed uneven blood-filling of the microcirculatory vessels and prominent interstitial edema of the myocardium. Hearts from sCR-Refed rats had more atrophied cardiomyocytes than CT [Atrophied/Total (%): CT, 0.2±0.1 vs sCR-Refed, 50.6±1.1; p<0.001; n=5]. The number of arrhythmic events during a 30 min ischemic interval in isolated hearts doubled after 2 weeks on the sCR diet ( data not shown ) and remained doubled 3 months later [Arrhythmias (% of time): CT, 34±8 vs sCR-Refed, 68±9; p=0.02; n=8]. Ultrasound imaging showed no difference in stroke volume, coronary perfusion pressure and left ventricular mass. However, the thickness of the left ventricular posterior wall was significantly reduced in sCR-Refed rats [(mm): CT, 2.55 ±0.03 vs sCR-Refed, 2.10±0.04; p=0.002; n=4]. These findings indicate heart structure and function remained damaged months after the sCR period ended and BW was restored. These studies have adverse cardiovascular risk implications for who are subjected either voluntarily (crash diets) or involuntarily (very low food security) to periods of inadequate caloric intake.

Abstract 33: Prostaglandin E2 Reduces Cardiac Contractility via EP3 Receptor

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Xiaosong Gu ◽  
Jiang Xu ◽  
Xiao-Ping Yang ◽  
Edward Peterson ◽  
Pamela Harding
Keyword(s):  
Prostaglandin E2 ◽  
Cardiac Contractility ◽  
Peak Height ◽  
Left Ventricular ◽  
Reduced Ejection Fraction ◽  
Langendorff Preparation ◽  
Cell Contractility ◽  
Isolated Hearts ◽  
Developed Pressure ◽  
Ep3 Receptor

Prostaglandin E2 (PGE2) EP receptors EP3 and EP4 are present in the heart and signal via decreased and increased cAMP production, respectively. Previously we reported that cardiomyocyte-specific EP4 KO mice develop a phenotype of dilated cardiomyopathy with reduced ejection fraction. We thus hypothesized that PGE2 decreases contractility via EP3. To test this hypothesis, the effects of PGE2 and the EP1/EP3 agonist sulprostone (sulp) were examined in the mouse langendorff preparation and in adult mouse cardiomyocytes (AVM) using the IonOptix cell contractility system. Isolated hearts of 18-20 wk old male C57Bl/6 mice were mounted and equilibrated for 10 min, then perfused with PGE2 (10 -6 mol/l) or sulp (10 -6 mol/l) for 30 min. Values at the end of equilibration were set to 100%. Compared to vehicle, PGE2 decreased +dp/dt (77.8±3% vs 96.7±3%, p<0.01) and left ventricular developed pressure, LVDP (77.2±2% vs 96.8±3%, p<0.001). Sulp decreased +dp/dt (75.9±2% vs 96.7±3%, p<0.001), -dp/dt (72.2±1% vs 85.7±1%, p<0.01) and LVDP (70.9±1% vs 96.8±3%, p<0.001). The effects of both PGE2 and sulp were reversed by the EP3 antagonist, L789,106 (10 -6 mol/l). Myocyte contractility was evaluated on the IonOptix system with pacing at 1Hz. Treatment with PGE2 (10 -9 M) for 10 min reduced contractility as measured by peak height (3.69 ± 0.48% for vehicle vs 2.00 ± 0.22% for PGE2, p < 0.05 ), departure velocity (-171.9 ± 22.9 um/sec for vehicle vs -106.3± 12.5 um/sec for PGE2, p < 0.05) and return velocity (87.7 ± 16.3 um/sec for vehicle vs 36.7 ± 6.6 um/sec for PGE2, p < 0.05) with similar effects noted for sulp. Sulp reduced change in peak height (4.79 ± 1.15% for vehicle vs 1.81 ± 0.37% for sulp, p < 0.05), departure velocity (-169.1 ± 35.8 um/sec for vehicle vs -59.4 ± 10.3 um/sec for sulp, p < 0.05) and return velocity (86.5 ± 23.8 um/sec for vehicle vs 16.9 ± 14.7 um/sec for sulp, p < 0.05). We then examined the acute effects of PGE2 and sulp on expression of phosphorylated phospholamban (PLN) and SERCA using Western blot. Treatment of AVM for 15min with either PGE2 or sulp decreased expression of phosphorylated PLN corrected to total PLN, by 67% and 43%. SERCA2a expression was unaffected. In conclusion, PGE2 and sulp reduce contractility via the EP3 receptor through effects on PLN.

Adenosine antagonism decreases metabolic but not functional recovery from ischemia

1991 ◽  
Vol 260 (1) ◽  
pp. H193-H200 ◽  
Author(s):  
D. A. Angello ◽  
J. P. Headrick ◽  
N. M. Coddington ◽  
R. M. Berne
Keyword(s):  
Functional Recovery ◽  
Left Ventricular ◽  
Low Flow ◽  
Ischemia And Reperfusion ◽  
Constant Flow ◽  
Hemodynamic Parameters ◽  
Isolated Hearts ◽  
Rat Hearts ◽  
Adenosine Antagonism ◽  
Developed Pressure

The effect of adenosine receptor antagonism on function and metabolism was examined in isolated hearts during low flow ischemia and reperfusion. Isovolumic rat hearts perfused at constant flow were subjected to 30 min of ischemia followed by 30 min of reperfusion. Infusion of vehicle or 10 microM 8-phenyltheophylline (8-PT) was initiated 10 min before ischemia and maintained throughout reperfusion. 8-PT infusion had no significant effects on hemodynamic parameters or metabolism preischemia. During ischemia, left ventricular developed pressure declined to approximately 15% of preischemic values in control and 8-PT hearts, and ATP and PCr decreased to approximately 73 and 60% of preischemic values. Inorganic phosphate (Pi) increased to 353 = 41 and 424 +/- 53% of preischemic values in control and 8-PT hearts, respectively. After reperfusion, function recovered to greater than 95% of preischemic levels in control and 8-PT hearts. Unlike control hearts, recovery of metabolites was significantly different during reperfusion in 8-PT hearts (P less than 0.05); ATP, phosphocreatine, and Pi recovered to 82 +/- 8, 71 +/- 8, and 281 +/- 27% of preischemic values, respectively. Venous purine washout was significantly greater (P less than 0.05) during reperfusion in 8-PT hearts (327 +/- 113 nmol) than in control hearts (127 +/- 28 nmol). Blockade of adenosine receptors appears to adversely affect metabolic but not functional recovery in the ischemic-reperfused myocardium.

Protection of the reperfused heart by L-propionylcarnitine

1991 ◽  
Vol 71 (4) ◽  
pp. 1518-1522 ◽  
Author(s):  
J. A. Leipala ◽  
R. Bhatnagar ◽  
E. Pineda ◽  
S. Najibi ◽  
K. Massoumi ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Membrane Integrity ◽  
Creatine Phosphate ◽  
Left Ventricular ◽  
Optimal Time ◽  
Dependent Manner ◽  
Cell Membrane Integrity ◽  
Developed Pressure

The effects of L-propionylcarnitine on mechanical function, creatine phosphate and ATP content, and lactate dehydrogenase leakage were studied in isolated perfused rat hearts exposed to global no-flow ischemia for 30 min followed by reperfusion for 20 min. Five and 10 mM L-propionylcarnitine resulted in a 100% recovery of left ventricular-developed pressure, whereas the recovery was only 40% in the hearts perfused without this agent. Ischemia-reperfusion caused a 85% loss of creatine phosphate and a 77% loss of ATP, which was prevented by 10 mM L-propionylcarnitine. Five millimolar L-propionylcarnitine protected the heart from the loss of creatine phosphate but not from the loss of ATP. Ten millimolar L-propionylcarnitine failed to improve the postischemic left ventricular-developed pressure, when it was added to the perfusate only after ischemia. L-propionylcarnitine alleviated the decrease of coronary flow in the reperfused hearts. Lactate dehydrogenase leakage was aggravated in the beginning of the reperfusion period by 10 mM L-propionylcarnitine. This adverse effect was, however, transient. L-Propionylcarnitine provides protection for the postischemic reperfused heart in a dose-dependent manner. The optimal time for administration is before the ischemic insult. High doses of this compound may perturb cell membrane integrity. Moreover, the present data point to an intracellular, metabolic, and perhaps anaplerotic mechanism of action of L-propionylcarnitine in cardiac ischemia-reperfusion injury.

Cardioprotection in chronically hypoxic rabbits persists on exposure to normoxia: role of NOS and KATP channels

2005 ◽  
Vol 288 (1) ◽  
pp. H62-H68 ◽  
Author(s):  
Colleen M. Fitzpatrick ◽  
Yang Shi ◽  
William C. Hutchins ◽  
Jidong Su ◽  
Garrett J. Gross ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Chronic Hypoxia ◽  
Katp Channels ◽  
Left Ventricular ◽  
Adaptation To Hypoxia ◽  
Isolated Hearts ◽  
Percent Recovery ◽  
Subsequent Exposure ◽  
Developed Pressure ◽  
Oxide Synthase

Hypoxia from birth increases resistance to myocardial ischemia in infant rabbits. We hypothesized that increased cardioprotection in hearts chronically hypoxic from birth persists following development in a normoxic environment and involves increased activation of nitric oxide synthase (NOS) and ATP-dependent K (KATP) channels. Resistance to myocardial ischemia was determined in rabbits raised from birth to 10 days of age in a normoxic (FiO2 = 0.21) or hypoxic (FiO2 = 0.12) environment and subsequently exposed to normoxia for up to 60 days of age. Isolated hearts ( n = 8/group) were subjected to 30 min of global ischemia followed by 35 min of reperfusion. At 10 days of age, resistance to myocardial ischemia (percent recovery postischemic recovery left ventricular developed pressure) was higher in chronically hypoxic hearts (68 ± 4%) than normoxic controls (43 ± 4%). At 10 days of age, NG-nitro-l-arginine methyl ester (200 μM) and glibenclamide (3 μM) abolished the cardioprotective effects of chronic hypoxia (45 ± 4% and 46 ± 5%, respectively) but had no effect on normoxic hearts. At 30 days of age resistance to ischemia in normoxic hearts declined (36 ± 5%). However, in hearts subjected to chronic hypoxia from birth to 10 days and then exposed to normoxia until 30 days of age, resistance to ischemia persisted (63 ± 4%). l-NAME or glibenclamide abolished cardioprotection in previously hypoxic hearts (37 ± 4% and 39 ± 5%, respectively) but had no effect on normoxic hearts. Increased cardioprotection was lost by 60 days. We conclude that cardioprotection conferred by adaptation to hypoxia from birth persists on subsequent exposure to normoxia and is associated with enhanced NOS activity and activation of KATP channels.

scholarly journals l-Arginine attenuates cardiovascular impairment in DOCA-salt hypertensive rats

2005 ◽  
Vol 289 (4) ◽  
pp. H1408-H1416 ◽  
Author(s):  
Andrew Fenning ◽  
Glenn Harrison ◽  
Roselyn Rose’meyer ◽  
Andrew Hoey ◽  
Lindsay Brown
Keyword(s):  
Blood Vessels ◽  
Chronic Administration ◽  
Normal Function ◽  
Left Ventricular ◽  
Internal Diameter ◽  
Hypertensive Rats ◽  
Functional Changes ◽  
Isolated Hearts ◽  
Ventricular Wall Thickness ◽  
And Function

Nitric oxide (NO) is essential for normal function of the cardiovascular system. This study has determined whether chronic administration of l-arginine, the biological precursor of NO, attenuates the development of structural and functional changes in hearts and blood vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Uninephrectomized rats treated with DOCA (25 mg every 4th day sc) and 1% NaCl in the drinking water for 4 wk were treated with l-arginine (5% in food, 3.4 ± 0.3 g·kg body wt−1·day−1). Changes in cardiovascular structure and function were determined by echocardiography, microelectrode studies, histology, and studies in isolated hearts and thoracic aortic rings. DOCA-salt hypertensive rats developed hypertension, left ventricular hypertrophy with increased left ventricular wall thickness and decreased ventricular internal diameter, increased inflammatory cell infiltration, increased ventricular interstitial and perivascular collagen deposition, increased passive diastolic stiffness, prolonged action potential duration, increased oxidative stress, and inability to increase purine efflux in response to an increased workload. l-Arginine markedly attenuated or prevented these changes and also normalized the reduced efficacy of norepinephrine and acetylcholine in isolated thoracic aortic rings of DOCA-salt hypertensive rats. This study suggests that a functional NO deficit in blood vessels and heart due to decreased NO synthase activity or increased release of reactive oxygen species such as superoxide may be a key change initiating many aspects of the cardiovascular impairment observed in DOCA-salt hypertensive rats. These changes can be prevented or attenuated by administration of l-arginine.

Approaches to Improving Cardiac Structure and Function During and After an Acute Myocardial Infarction

2015 ◽  
Vol 21 (4) ◽  
pp. 363-367 ◽  
Author(s):  
Robert A. Kloner ◽  
Wangde Dai ◽  
Sharon L. Hale ◽  
Jianru Shi
Keyword(s):  
Myocardial Infarction ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Myocardial Infarct ◽  
Myocardial Cell ◽  
Left Ventricular ◽  
Structure And Function ◽  
Myocardial Infarct Size ◽  
Cardiac Structure And Function ◽  
And Function

While progress has been made in improving survival following myocardial infarction, this injury remains a major source of mortality and morbidity despite modern reperfusion therapy. While one approach has been to develop therapies to reduce lethal myocardial cell reperfusion injury, this concept has not translated to the clinics, and several recent negative clinical trials raise the question of whether reperfusion injury is important in humans undergoing reperfusion for acute ST segment elevation myocardial infarction. Therapy aimed at reducing myocardial cell death while the myocytes are still ischemic is more likely to further reduce myocardial infarct size. Developing new therapies to further reduce left ventricular remodeling after the acute event is another approach to preserving structure and function of the heart after infarction. Such therapy may include chronic administration of pharmacologic agents and/or therapies developed from the field of regenerative cardiology, including cellular or non-cellular materials such as extracellular matrix. The optimal therapy will be to administer agents that both reduce myocardial infarct size in the acute phase of infarction as well as reduce adverse left ventricular remodeling during the chronic or healing phase of myocardial infarction. Such a dual approach will help optimize the preservation of both cardiac structure and function.

Catecholamines and preconditioning: studies of contraction and function in isolated rat hearts

1999 ◽  
Vol 277 (1) ◽  
pp. H136-H143 ◽  
Author(s):  
David J. Hearse ◽  
Fiona J. Sutherland
Keyword(s):  
Ischemic Preconditioning ◽  
Untreated Control ◽  
Vehicle Control ◽  
Left Ventricular ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Developed Pressure ◽  
And Function ◽  
Postischemic Recovery ◽  
Isolated Perfused Rat Hearts

The aims of this study were to determine whether 1) like ischemic preconditioning, transient exposure to norepinephrine before ischemia exacerbates contracture during ischemia and 2) protection afforded by norepinephrine is stereospecific (receptor mediated). Isolated perfused rat hearts were randomized into five groups ( n = 6/group): 1) ischemic preconditioning (3 min of ischemia + 3 min of reperfusion + 5 min of ischemia + 5 min of reperfusion), 2) untreated control, 3) vehicle control (ascorbic acid), 4) substitution of preconditioning ischemia by perfusion with d-norepinephrine, and 5) substitution of preconditioning ischemia by perfusion with l-norepinephrine. This was followed by 40 min of zero-flow ischemia and 50 min of reperfusion. Ischemic preconditioning and l-norepinephrine exacerbated contracture (time to 50% contracture = 9.2 ± 1.1 and 9.0 ± 1.1 vs. 13.3 ± 0.3, 12.4 ± 0.5, and 13.2 ± 0.4 min for untreated control, vehicle control, and d-norepinephrine, respectively, P < 0.05). Postischemic left ventricular developed pressure was poor in untreated control (23.0 ± 2.2%), vehicle control (26.9 ± 2.3%), and d-norepinephrine (19.8 ± 2.8%) groups but good in preconditioned (52.4 ± 5.1%) and l-norepinephrine (52.5 ± 1.1%) groups ( P < 0.05). Thus norepinephrine preconditioning, like ischemic preconditioning, causes a paradoxical exacerbation of contracture coupled with enhanced postischemic recovery; both effects are stereospecific.

scholarly journals Propylthiouracil-induced hypothyroidism is associated with increased tolerance of the isolated rat heart to ischaemia-reperfusion

2003 ◽  
Vol 178 (3) ◽  
pp. 427-435 ◽  
Author(s):  
C Pantos ◽  
V Malliopoulou ◽  
I Mourouzis ◽  
K Sfakianoudis ◽  
S Tzeis ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Isolated Hearts ◽  
Global Ischaemia ◽  
Basal Expression ◽  
Kinase C ◽  
Ischaemia Reperfusion ◽  
Protein Kinase C Epsilon ◽  
Developed Pressure ◽  
Jnk Activation

The present study investigated the response of the hypothyroid heart to ischaemia-reperfusion. Hypothyroidism was induced in Wistar rats by oral administration of propylthiouracil (0.05%) for 3 weeks (HYPO rats), while normal animals (NORM) served as controls. Isolated hearts from NORM and HYPO animals were perfused in Langendorff mode and subjected to zero-flow global ischaemia followed by reperfusion (I/R). Post-ischaemic recovery of left ventricular developed pressure was expressed as % of the initial value (LVDP%). Basal expression of protein kinase C epsilon (PKCepsilon) and PKCdelta and phosphorylation of p46 and p54 c-jun NH(2)-terminal kinases (JNKs) in response to I/R were assessed by Western blotting. LVDP% was found to be significantly higher in HYPO hearts than in NORM. At baseline, PKCepsilon expression was 1.4-fold more in HYPO than in NORM hearts, P<0.05, while PKCdelta was not changed. Furthermore, basal phospho-p54 and -p46 JNK levels were 2.2- and 2.6-fold more in HYPO than in NORM hearts, P<0.05. In response to I/R, in NORM hearts, phospho-p54 and -p46 JNK levels were 5.5- and 6.0-fold more as compared with the baseline values, P<0.05, while they were not significantly altered in HYPO hearts. HYPO hearts seem to display a phenotype of cardioprotection against ischaemia-reperfusion and this is associated with basal PKCepsilon overexpression and attenuated JNK activation after I/R.

Effects of anti-free radical agents on Na+, Ca2+, and function in reperfused rat hearts

1990 ◽  
Vol 259 (1) ◽  
pp. H137-H143 ◽  
Author(s):  
M. Tani
Keyword(s):  
Free Radicals ◽  
Free Radical ◽  
Contractile Function ◽  
Recovery Of Function ◽  
Left Ventricular ◽  
Free Radical Scavengers ◽  
Protective Effects ◽  
Rat Hearts ◽  
Developed Pressure ◽  
And Function

The purpose of the present study was to determine whether the combined administration of superoxide dismutase (SOD) and catalase (CAT) or efforts to maintain the glutathione redox pathways with sulfhydryl agents could improve Na+ imbalance, reduce Ca2+ overload, and enhance recovery of function and metabolites upon reperfusion in isolated ischemic rat hearts, presumably by scavenging oxygen free radicals. After a 30-min exposure to zero-flow ischemia, left ventricular developed pressure (LVDP) and heart rate recovered to 31 and 81% of the preischemic value, respectively, ATP fell by approximately 40%, and 45Ca2+ uptake rose from 0.8 to 10.4 mumol/g dry tissue. A combination of SOD and CAT at low concentrations (5 X 10(4) and 7.5 X 10(4) U/l, respectively) had a beneficial effect on recovery of LVDP (to 59%), reperfusion 45Ca2+ uptake (to 7.9 mumol/g dry tissue), and recovery of Na+ imbalance. When sulfhydryl donors, such as glutathione, cysteine, N-acetyl-L-cysteine, or dithiothreitol, were administered 20 min before induction of ischemia, no significant protective effects were observed. These results indicated that the extracellular free radical scavengers, SOD and CAT, could attenuate partially the ionic imbalance in ischemic-reperfused myocardium and result in improved recovery of contractile function. Attempts to enhance the intrinsic scavenging system were not successful, suggesting that this system may not play an important role in disposing of free radicals.

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