Cardioprotective effects of exercise training on myofilament calcium activation in ovariectomized rats

The risks associated with hormone replacement therapy, especially cardiac diseases in postmenopausal women, have prompted extensive studies for other preventive or therapeutic alternatives. We investigated the cardioprotective effects of exercise training on the changes in cardiac myofilament Ca2+ activation in 10-wk-old ovariectomized rats. The exercise groups were subjected to a 9-wk running program on a motor-driven treadmill 1 wk after surgery. The relationship between pCa (-log molar free Ca2+ concentration) and myofibrillar MgATPase activity of exercise-sham myofibrils or exercise-ovariectomized myofibrils was the same and could not be distinguished from that of sedentary-sham control hearts. In contrast, a significant suppression in maximum MgATPase activity and a leftward shift of pCa50 (half-maximally activating pCa) in the pCa-ATPase activity relationship were detected in sedentary-ovariectomized rats. Exercise training also prevented the shift in myosin heavy chain (MHC) isoforms toward β-MHC in ovariectomized hearts. The upregulation of β1-adrenergic receptors in the left ventricular membranes of ovariectomized rat hearts, as measured by receptor binding and immunoblot analyses, was no longer observed in exercise-ovariectomized hearts. Immunoblot analyses of heat shock protein (HSP) 72, an inducible form of HSP70, demonstrated a significant downregulation in ovariectomized hearts. Exercise training in ovariectomized rats completely reversed the expression of HSP72 to the same level as sham controls. Our results clearly indicate the cardioprotective effects of exercise training on changes in cardiac myofilament Ca2+ activation in ovariectomized rats. Alterations in expression of β1-adrenergic receptors and HSP72 may, in part, play a mechanistic role in the cardioprotective effects.

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Hypersensitivity of myofilament response to Ca2+ in association with maladaptation of estrogen-deficient heart under diabetes complication

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00365.2006 ◽

2007 ◽

Vol 292 (2) ◽

pp. R844-R851 ◽

Cited By ~ 13

Author(s):

Ariyaporn Thawornkaiwong ◽

Jantarima Pantharanontaga ◽

Jonggonnee Wattanapermpool

Keyword(s):

Atpase Activity ◽

Ovariectomized Rats ◽

Myofibrillar Atpase ◽

Diabetes Complication ◽

Myofibrillar Atpase Activity ◽

Rat Hearts ◽

Cardiac Myofilament ◽

Myofilament Activation ◽

Cardioprotective Effects ◽

Kinetics Of

The amelioration of cardioprotective effect of estrogen in diabetes suggests potential interactive action of estrogen and insulin on myofilament activation. We compared Ca2+-dependent Mg2+-ATPase activity of isolated myofibrillar preparations from hearts of sham and 10-wk ovariectomized rats with or without simultaneous 8 wk-induction of diabetes and from diabetic-ovariectomized rats with estrogen and/or insulin supplementation. Similar magnitude of suppressed maximum myofibrillar ATPase activity was demonstrated in ovariectomized, diabetic, and diabetic-ovariectomized rat hearts. Such suppressed activity and the relative suppression in α-myosin heavy chain level in ovariectomy combined with diabetes could be completely restored by estrogen and insulin supplementation. Conversely, the myofilament Ca2+ hypersensitivity detected only in the ovariectomized but not diabetic group was also observed in diabetic-ovariectomized rats, which was restored upon estrogen supplementation. Binding kinetics of β1-adrenergic receptors and immunoblots of β1-adrenoceptors as well as heat shock 72 (HSP72) were analyzed to determine the association of changes in receptors and HSP72 to that of the myofilament response to Ca2+. The amount of β1-adrenoceptors significantly increased concomitant with Ca2+ hypersensitivity of the myofilament, without differences in the receptor binding affinity among the groups. In contrast, changes in HSP72 paralleled that of maximum myofibrillar ATPase activity. These results indicate that hypersensitivity of cardiac myofilament to Ca2+ is specifically induced in ovariectomized rats even under diabetes complication and that alterations in the expression of β1-adrenoceptors may, in part, play a mechanistic role underlying the cardioprotective effects of estrogen that act together with Ca2+ hypersensitivity of the myofilament in determining the gender difference in cardiac activation.

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Calcineurin Is Activated in Rat Hearts With Physiological Left Ventricular Hypertrophy Induced by Voluntary Exercise Training

Circulation ◽

10.1161/01.cir.101.18.2134 ◽

2000 ◽

Vol 101 (18) ◽

pp. 2134-2137 ◽

Cited By ~ 42

Author(s):

Yoko Eto ◽

Katsunori Yonekura ◽

Makoto Sonoda ◽

Naoto Arai ◽

Masataka Sata ◽

...

Keyword(s):

Exercise Training ◽

Left Ventricular Hypertrophy ◽

Ventricular Hypertrophy ◽

Left Ventricular ◽

Voluntary Exercise ◽

Rat Hearts

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Cardioprotective Effects of Propofol and Sevoflurane in Ischemic and Reperfused Rat Hearts

Anesthesiology ◽

10.1097/00000542-199911000-00027 ◽

1999 ◽

Vol 91 (5) ◽

pp. 1349-1349 ◽

Cited By ~ 55

Author(s):

Sanjiv Mathur ◽

Parviz Farhangkhgoee ◽

Morris Karmazyn

Keyword(s):

High Energy ◽

Left Ventricular ◽

High Energy Phosphates ◽

Constant Flow Rate ◽

Rat Hearts ◽

Reperfusion Period ◽

Coronary Syndromes ◽

Cardioprotective Effects ◽

Developed Pressure

Background Sodium ion-hydrogen ion (Na(+)-H(+)) exchange inhibitors are effective cardioprotective agents. The N(+)-H(+) exchange inhibitor HOE 642 (cariporide) has undergone clinical trials in acute coronary syndromes, including bypass surgery. Propofol and sevoflurane are also cardioprotective via unknown mechanisms. The authors investigated the interaction between propofol and HOE 642 in the ischemic reperfused rat heart and studied the role of adenosine triphosphate-sensitive potassium (K(ATP)) channels in the myocardial protection associated with propofol and sevoflurane. Methods Isolated rat hearts were perfused by the Langendorff method at a constant flow rate, and left ventricular function and coronary pressures were assessed using standard methods. Energy metabolites were also determined. To assess the role of K(ATP) channels, hearts were pretreated with the K(ATP) blocker glyburide (10 microM). Hearts were then exposed to either control buffer or buffer containing HOE 642 (5 microM), propofol (35 microM), sevoflurane (2.15 vol%), the K(ATP) opener pinacidil (1 microM), or the combination of propofol and HOE 642. Each heart was then subjected to 1 h of global ischemia followed by 1 h of reperfusion. Results Hearts treated with propofol, sevoflurane, pinacidil, or HOE 642 showed significantly higher recovery of left ventricular developed pressure and reduced end-diastolic pressures compared with controls. The combination of propofol and HOE 642 provided superior protection toward the end of the reperfusion period. Propofol, sevoflurane, and HOE 642 also attenuated the onset and magnitude of ischemic contracture and preserved high-energy phosphates (HEPs) compared with controls. Glyburide attenuated the cardioprotective effects of sevoflurane and abolished the protection observed with pinacidil. In contrast, glyburide had no effect on the cardioprotection associated with propofol treatment. Conclusion HOE 642, propofol, and sevoflurane provide cardioprotection via different mechanisms. These distinct mechanisms may allow for the additive and superior protection observed with the combination of these anesthetics and HOE 642.

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Cardioprotective effects of novel tetrahydroisoquinoline analogs of nitrobenzylmercaptopurine riboside in an isolated perfused rat heart model of acute myocardial infarction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01191.2005 ◽

2007 ◽

Vol 292 (6) ◽

pp. H2921-H2926 ◽

Cited By ~ 4

Author(s):

Z. Zhu ◽

P. A. Hofmann ◽

J. K. Buolamwini

Keyword(s):

Infarct Size ◽

Diastolic Pressure ◽

Left Ventricular ◽

Nucleoside Transport ◽

Total Risk ◽

Risk Area ◽

Perfused Heart ◽

Rat Hearts ◽

Cardioprotective Effects ◽

Developed Pressure

We have investigated the cardioprotective effects of novel tetrahydroisoquinoline nitrobenzylmercaptopurine riboside (NBMPR) analog nucleoside transport (NT) inhibitors, compounds 2 and 4, in isolated perfused rat hearts. Langendorff-perfused heart preparations were subjected to 10 min of treatment with compound 2, compound 4, or vehicle (control) followed by 30 min of global ischemia and 120 min of reperfusion. For determination of infarct size, reperfusion time was 180 min. At 1 μM, compounds 2 and 4 provided excellent cardioprotection, with left ventricular developed pressure (LVDP) recovery and end-diastolic pressure (EDP) increase of 82.9 ± 4.0% ( P < 0.001) and 14.1 ± 2.0 mmHg ( P < 0.03) for compound 2-treated hearts and 79.2 ± 5.9% ( P < 0.002) and 7.5 ± 2.7 mmHg ( P < 0.01) for compound 4-treated hearts compared with 41.6 ± 5.2% and 42.5 ± 6.5 mmHg for control hearts. LVDP recovery and EDP increase were 64.1 ± 4.2% and 29.1 ± 2.5 mmHg for hearts treated with 1 μM NBMPR. Compound 4 was the best cardioprotective agent, affording significant cardioprotection, even at 0.1 μM, with LVDP recovery and EDP increase of 76.0 ± 4.9% ( P < 0.003) and 14.1 ± 1.0 mmHg ( P < 0.03). At 1 μM, compound 4 and NBMPR reduced infarct size, with infarct area-to-total risk area ratios of 29.13 ± 3.17 ( P < 0.001) for compound 4 and 37.5 ± 3.42 ( P < 0.01) for NBMPR vs. 51.08 ± 5.06% for control hearts. Infarct size was more effectively reduced by compound 4 than by NBMPR ( P < 0.02). These new tetrahydroisoquinoline NBMPR analogs are not only potent cardioprotective agents but are, also, more effective than NBMPR in this model.

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A119. Cardioprotective effects of exercise training on the altered SR Ca2+-uptake function in ovariectomized rats

Journal of Molecular and Cellular Cardiology ◽

10.1016/j.yjmcc.2006.03.414 ◽

2006 ◽

Vol 40 (6) ◽

pp. 910-911

Author(s):

Jitanan Laosiripisan ◽

Jonggonnee Wattanapermpool

Keyword(s):

Exercise Training ◽

Ovariectomized Rats ◽

Cardioprotective Effects

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Differential effects of ovariectomy on calcium activation of cardiac and soleus myofilaments

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.277.2.h467 ◽

1999 ◽

Vol 277 (2) ◽

pp. H467-H473 ◽

Cited By ~ 29

Author(s):

Jonggonnee Wattanapermpool ◽

Peter J. Reiser

Keyword(s):

Thin Filament ◽

Troponin I ◽

Left Ventricular ◽

Hormone Deficiency ◽

Ovariectomized Rats ◽

Maximal Tension ◽

Cardiac Myofilament ◽

Myofilament Activation ◽

Thin Filament Proteins ◽

Ventricular Trabeculae

The hypothesis that ovarian sex hormone deficiency affects cardiac myofilament activation was tested. Chemically skinned ventricular trabeculae and single soleus muscle fibers were prepared from 10- and 14-wk ovariectomized and control rats. Tension-pCa (−log [Ca2+]) relations of left ventricular trabeculae and soleus fibers were compared to test whether thin filament proteins are potential sites of modulated activation. Trabeculae from ovariectomized rats exhibited a significant increase in Ca2+ sensitivity with no change in maximal tension-generating ability. In contrast, soleus fibers demonstrated no shift in Ca2+ sensitivity but generated significantly less maximal tension. No changes in thin filament protein isoform expression or loss of thin filament proteins were apparent in the trabeculae or soleus fibers from ovariectomized rats. Although not directly tested, our results are consistent with a possible modulation of regulatory proteins (e.g., cardiac troponin I) to account for the observed change in myofilament responsiveness of hearts from ovariectomized rats. Other possible mechanisms for the altered myocardial Ca2+ sensitivity after ovariectomy are discussed.

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Abstract P300: A Novel Highly Selective Adenosine A 1 Receptor Agonist (VCP28) Reduces Ischemia/Reperfusion Injury at Concentrations that Do Not Affect Heart Rate

Circulation Research ◽

10.1161/res.109.suppl_1.ap300 ◽

2011 ◽

Vol 109 (suppl_1) ◽

Author(s):

Paul J White ◽

Vijay Urmaliya ◽

Colin W Pouton ◽

Shane Devine ◽

Peter Scammells

Keyword(s):

Heart Rate ◽

Receptor Agonist ◽

Left Ventricular ◽

Adenosine A1 Receptor ◽

Rat Hearts ◽

Adenosine A1 ◽

Si Model ◽

A1 Receptor ◽

Cardioprotective Effects ◽

Isolated Rat

Whilst adenosine A1 receptor agonists have repeatedly been shown to protect the ischaemic myocardium, the clinical use of these agents is limited by strong cardiodepressant effects. The cardioprotective effects of a novel adenosine A1 receptor agonist N6-(2,2,5,5-tetramethylpyrrolidin-1-yloxyl-3-ylmethyl) adenosine (VCP28) were compared with the selective adenosine A1receptor agonist N6-cyclopentyladenosine (CPA) in a H9c2(2–1) cardiac cell line-simulated ischemia (SI) model (12 hours) and a global ischemia (30 minutes) and reperfusion (60 minutes) model in isolated rat heart model. H9c2(2–1) cells were treated with CPA and VCP28 at the start of ischemia for entire ischemic duration, whereas isolated rat hearts were treated at the onset of reperfusion for 15 minutes. In a H9c2(2–1) cell SI model, CPA and VCP28 (100 nM) significantly (P , 0.05, n = 5–6) reduced the proportion of nonviable cells (30.88% 6 2.49% and 16.17% 6 3.77% of SI group, respectively) and lactate dehydrogenase efflux. In isolated rat hearts, CPA and VCP28 significantly (n = 6–8, P , 0.05) improved postischemic contractility (dP/dtmax, 81.69% 6 10.96%, 91.07% 6 19.87% of baseline, respectively), left ventricular developed pressure, and end diastolic pressure and reduced infarct size. The adenosine A1 receptor antagonist DPCPX abolished the cardioprotective effects of CPA and VCP28 in both models. At the concentrations used in the ischaemia models, VCP28 had no effect on heart rate, unlike CPA. In conclusion, the adenosine A1 receptor agonist VCP28 has cardioprotective equal effects to the prototype A1 agonist CPA at concentrations that have no effect on heart rate.

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Exercise training prevents the changes in cardiac myofilament activity and β-adrenergic receptor density in ovariectomized rats

Journal of Molecular and Cellular Cardiology ◽

10.1016/s0022-2828(01)90065-3 ◽

2001 ◽

Vol 33 (6) ◽

pp. A17

Author(s):

Tepmanas Bupha-Intr ◽

Jonggonnee Wattanapermpool

Keyword(s):

Exercise Training ◽

Adrenergic Receptor ◽

Ovariectomized Rats ◽

Receptor Density ◽

Cardiac Myofilament

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Glutamine Is Cardioprotective in Patients with Ischemic Heart Disease following Cardiopulmonary Bypass

The Heart Surgery Forum ◽

10.1532/hsf98.20111074 ◽

2011 ◽

Vol 14 (6) ◽

pp. 384 ◽

Cited By ~ 17

Author(s):

Vladimir V. Lomivorotov ◽

Sergey M. Efremov ◽

Vladimir A. Shmirev ◽

Dmitry N. Ponomarev ◽

Vladimir N. Lomivorotov ◽

...

Keyword(s):

Heart Disease ◽

Placebo Group ◽

Cardiopulmonary Bypass ◽

Ischemic Heart Disease ◽

Troponin I ◽

Left Ventricular ◽

Ischemic Heart ◽

Left Ventricular Ejection ◽

Study Group ◽

Cardioprotective Effects

Background: The aim of the present study was to investigate the cardioprotective effects of the perioperative use of N(2)-L-alanyl-L-glutamine (GLN) in patients with ischemic heart disease (IHD) who undergo their operations under cardiopulmonary bypass (CPB).Methods: This double-blind, placebo-controlled, randomized study included 50 patients who underwent cardiac surgery with CPB. Exclusion criteria were a left ventricular ejection fraction <50%, diabetes mellitus, <3 months since the onset of myocardial infarction, and emergency surgery. Patients in the study group (n = 25) received 0.4 g/kg GLN (Dipeptiven, 20% solution) per day. Patients in the control group (n = 25) were administered a placebo (0.9% NaCl). The primary end point was the dynamics of troponin I at the following stages: (1) prior to anesthesia, (2) 30 minutes after CPB, (3) 6 hours after CPB, (4) 24 hours after surgery, and (5) 48 hours after surgery. Secondary end points included measurements of hemodynamics with a Swan-Ganz catheter.Results: On the first postoperative day after the surgery, the median troponin I level was significantly lower in the study group than in the placebo group: 1.280 ng/mL (interquartile range [IQR], 0.840-2.230 ng/mL) versus 2.410 ng/mL (IQR, 1.060-6.600 ng/mL) (P = .035). At 4 hours after cardiopulmonary bypass (CPB), the median cardiac index was higher in the patients in the study group: 2.58 L/min per m2 (IQR, 2.34-2.91 L/min per m2) versus 2.03 L/min per m2 (IQR, 1.76-2.32 L/min per m2) (P = .002). The median stroke index also was higher in the patients who received GLN: 32.8 mL/m2 (IQR, 27.8-36.0 mL/m2) versus 26.1 mL/m2 (IQR, 22.6-31.8 mL/m2) (P = .023). The median systemic vascular resistance index was significantly lower in the study group than in the placebo group: 1942 dyn�s/cm5 per m2 (IQR, 1828-2209 dyn�s/cm5 per m2) versus 2456 dyn�s/cm5 per m2 (IQR, 2400-3265 dyn�s/cm5 per m2) (P = .001).Conclusion: Perioperative administration of GLN during the first 24 hours has cardioprotective effects in IHD patients following CPB. This technique enhances the troponin concentration at 24 hours after surgery and is associated with improved myocardial function.

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