Amelioration of ischemic calcium overload correlates with high-energy phosphates in senescent myocardium

1997 ◽  
Vol 273 (1) ◽  
pp. H418-H425 ◽  
Author(s):  
T. Tsukube ◽  
J. D. McCully ◽  
K. R. Metz ◽  
C. U. Cook ◽  
S. Levitsky
Keyword(s):  
Functional Recovery ◽  
Cytosolic Calcium ◽  
High Energy ◽  
Left Ventricular ◽  
Global Ischemia ◽  
Nucleoside Triphosphate ◽  
Mrna Levels ◽  
High Energy Phosphates ◽  
Surgically Induced ◽  
Free Magnesium

Previously, we have shown that potassium and magnesium (K-Mg, 20 mM each) cardioplegia ameliorated cytosolic calcium ([Ca2+]i) accumulation and was associated with enhanced functional recovery after surgically induced global ischemia in the aged heart. K-Mg cardioplegia was also shown to enhance cytosolic cytochrome oxidase I activity and mRNA levels, suggesting that enhanced functional recovery may involve the preservation of high-energy phosphates. To investigate this hypothesis, 31P nuclear magnetic resonance was used to measure serial alterations in phosphocreatine (PCr), inorganic phosphate, nucleoside triphosphate (NTP), intracellular free magnesium (Mgf), and intracellular pH (pHi) in Langendorff-perfused, aged (135 wk) rabbit hearts during preischemia, global ischemia (30 min), and reperfusion (30 min). K-Mg cardioplegia retarded PCr depletion (P <0.05) and significantly enhanced NTP preservation (P < 0.05) during ischemia and reperfusion. K-Mg cardioplegia also attenuated the increase in Mgf during ischemia (P < 0.05). These results were correlated with amelioration of [Ca2+]i accumulation during ischemia and preservation of left ventricular function after reperfusion and suggest that optimal functional recovery from surgically induced ischemia is provided by K-Mg cardioplegia in the aged myocardium.

Blood flow and high-energy phosphates in microregions of left ventricular subendocardium

1981 ◽  
Vol 240 (5) ◽  
pp. H804-H810 ◽  
Author(s):  
H. D. Kleinert ◽  
H. R. Weiss
Keyword(s):  
Blood Flow ◽  
Linear Relationship ◽  
Tissue Perfusion ◽  
High Energy ◽  
Left Ventricular ◽  
Significant Loss ◽  
Tissue Blood Flow ◽  
High Energy Phosphates ◽  
Tissue Samples ◽  
Heterogeneous Distribution

Blood flow and high-energy phosphate (HEP) content were determined simultaneously in multiple microregions of left ventricular subendocardium in 29 normal anesthetized open-chest rabbits by use of a new micromethod to determine whether a direct linear relationship existed between these parameters. Tissue samples weighed 1-2 mg. ATP and creatine phosphate (CP) content were quantitated in quick-frozen hearts by fluorometry at sites where tissue perfusion was measured by H2 clearance by use of bare-tipped platinum electrodes. A series of validation studies were conducted to ensure that 1) no significant damage to the tissue surrounding the electrode occurred during the period of experimentation and 2) no significant loss of biochemical constituents had occurred due to labile processes during freezing or storage of the tissue. Blood flow, ATP, and CP values averaged 79.1 +/- 24.1 (SD) ml.min-1.100 g-1, 4.9 +/- 1.3 mumol/g tissue, and 8.0 +/- 3.0 mumol/g tissue, respectively, and are similar to those reported in studies using larger tissue samples. Correlation between the heterogeneous distribution of tissue perfusion and HEP revealed no direct linear relationship between these parameters in the normal unstressed rabbit subendocardium.

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

1999 ◽  
Vol 91 (5) ◽  
pp. 1349-1349 ◽  
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.

scholarly journals The Effects of Potassium Cyanide on the Functional Recovery of Isolated Rat Hearts after Ischemia and Reperfusion: The Role of Oxidative Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Anica M. Petkovic ◽  
Vladimir Lj. Jakovljevic ◽  
Jovana V. Bradic ◽  
Jovana N. Jeremic ◽  
Nevena S. Jeremic ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Functional Recovery ◽  
Heart Function ◽  
Potassium Cyanide ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Global Ischemia ◽  
Albino Rats ◽  
Rat Hearts ◽  
Isolated Rat

This investigation is aimed at examining the effects of pharmacological PostC with potassium cyanide (KCN) on functional recovery, gene expression, cytochrome c expression, and redox status of isolated rat hearts. Rats were divided into the control and KCN groups. The hearts of male Wistar albino rats were retrogradely perfused according to the Langendorff technique at a constant perfusion pressure of 70 cmH2O. After stabilisation, control hearts were subjected to global ischemia (5 minutes), followed by reperfusion (5 minutes), while experimental hearts underwent global ischemia (5 minutes) followed by 5 minutes of reperfusion with 10 μmol/L KCN. The following parameters of heart function were measured: maximum and minimum rates of pressure development, systolic and diastolic left ventricular pressure, heart rate, and coronary flow. Levels of superoxide anion radical, hydrogen peroxide, nitrites, and index of lipid peroxidation (measured as thiobarbituric acid-reactive substances) were measured in coronary venous effluent, and activity of catalase was determined in heart tissue. Expression of Bax, Bcl-2, SOD-1, SOD-2, and cytochrome c was studied as well. It was shown that expression of Bax, Bcl-2, and SOD-2 genes did not significantly differ between groups, while expression of SOD-1 gene and cytochrome c was lower in the KCN group. Our results demonstrated that KCN improved the recovery of myocardial contractility and systolic and diastolic function, enhanced catalase activity, and diminished generation of prooxidants. However, all possible mechanisms and potential adverse effects of KCN should be further examined in the future.

Diabetes decreases creatine kinase enzyme activity and mRNA level in the rat heart

1989 ◽  
Vol 257 (4) ◽  
pp. E573-E577 ◽  
Author(s):  
B. K. Popovich ◽  
K. R. Boheler ◽  
W. H. Dillmann
Keyword(s):  
Creatine Kinase ◽  
Enzyme Activity ◽  
Northern Blot Analysis ◽  
Mrna Level ◽  
Cdna Probe ◽  
High Energy ◽  
Diabetic Rats ◽  
Mrna Levels ◽  
High Energy Phosphates ◽  
Contractile Performance

Several of the adenosinetriphosphatase enzymes that are responsible for cardiac muscle contraction rely on high-energy phosphates supplied by the creatine kinase (CK) system. Experimental diabetes mellitus has been shown to cause a decrease in the maximal contractile performance of the heart. We postulated that the decrease in contractile performance may be explained in part by a decrease in CK enzyme activity. To evaluate this possibility, we determined the level of CK activity and isoenzyme distribution in ventricular homogenates from normal, diabetic, and insulin-treated diabetic rats. We found that total CK activity was decreased by 35% in diabetic hearts and that a 66% reduction in the cardiac-specific MB isoenzyme occurs. Using a cDNA probe for CK-muscle (M) RNA in Northern blot analysis, we determined that a 61.1% decrease in CK-M mRNA occurs in diabetes. Chronic insulin therapy for 1 mo restores CK-M mRNA levels and enzyme activity. In conclusion, diabetes-induced CK enzyme decreases are mediated in part by a lower level of CK-M mRNA that codes for the major CK-M subunit protein. Decreased performance of the CK system may contribute to diabetic cardiomyopathy.

Time course of myocardial sodium accumulation after burn trauma: a 31P- and 23Na-NMR study

2001 ◽  
Vol 91 (6) ◽  
pp. 2695-2702 ◽  
Author(s):  
Patricia J. Sikes ◽  
Piyu Zhao ◽  
David L. Maass ◽  
Jureta W. Horton
Keyword(s):  
Nmr Spectroscopy ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Intracellular Ph ◽  
Total Body Surface Area ◽  
High Energy ◽  
Left Ventricular ◽  
High Energy Phosphates ◽  
Ventricular Performance ◽  
Burn Trauma

In this study,23Na- and 31P- nuclear magnetic resonance (NMR) spectra were examined in perfused rat hearts harvested 1, 2, 4, and 24 h after 40% total body surface area burn trauma and lactated Ringer resuscitation, 4 ml · kg−1 · %−1 burn.23Na-NMR spectroscopy monitored myocardial intracellular Na+ using the paramagnetic shift reagent thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylenephosphonic acid). Left ventricular function, cardiac high-energy phosphates (ATP/PCr), and myocyte intracellular pH were studied by using31P NMR spectroscopy to examine the hypothesis that burn-mediated acidification of cardiomyocytes contributes to subsequent Na+ accumulation by this cell population. Intracellular Na+ accumulation was confirmed by sodium-binding benzofuran isophthalate loading and fluorescence spectroscopy in cardiomyocytes isolated 1, 2, 4, 8, 12, 18, and 24 h postburn. This myocyte Na+ accumulation as early as 2 h postburn occurred despite no changes in cardiac ATP/PCr and intracellular pH. Left ventricular function progressively decreased after burn trauma. Cardiomyocyte Na+ accumulation paralleled cardiac contractile dysfunction, suggesting that myocardial Na+overload contributes, in part, to the progressive postburn decrease in ventricular performance.

scholarly journals Reduced in vivo high-energy phosphates precede Adriamycin-induced cardiac dysfunction

2010 ◽  
Vol 299 (2) ◽  
pp. H332-H337 ◽  
Author(s):  
M. Y. Maslov ◽  
V. P. Chacko ◽  
G. A. Hirsch ◽  
A. Akki ◽  
M. K. Leppo ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Ejection Fraction ◽  
High Energy ◽  
Left Ventricular ◽  
Peak Filling Rate ◽  
High Energy Phosphates ◽  
Cardiac Energetics ◽  
Filling Rate ◽  
Lv Dysfunction

Adriamycin (ADR) is an established, life-saving antineoplastic agent, the use of which is often limited by cardiotoxicity. ADR-induced cardiomyopathy is often accompanied by depressed myocardial high-energy phosphate (HEP) metabolism. Impaired HEP metabolism has been suggested as a potential mechanism of ADR cardiomyopathy, in which case the bioenergetic decline should precede left ventricular (LV) dysfunction. We tested the hypothesis that murine cardiac energetics decrease before LV dysfunction following ADR (5 mg/kg ip, weekly, 5 injections) in the mouse. As a result, the mean myocardial phosphocreatine-to-ATP ratio (PCr/ATP) by spatially localized 31P magnetic resonance spectroscopy decreased at 6 wk after first ADR injection (1.79 ± 0.18 vs. 1.39 ± 0.30, means ± SD, control vs. ADR, respectively, P < 0.05) when indices of systolic and diastolic function by magnetic resonance imaging were unchanged from control values. At 8 wk, lower PCr/ATP was accompanied by a reduction in ejection fraction (67.3 ± 3.9 vs. 55.9 ± 4.2%, control vs. ADR, respectively, P < 0.002) and peak filling rate (0.56 ± 0.12 vs. 0.30 ± 0.13 μl/ms, control vs. ADR, respectively, P < 0.01). PCr/ATP correlated with peak filling rate and ejection fraction, suggesting a relationship between cardiac energetics and both LV systolic and diastolic dysfunction. In conclusion, myocardial in vivo HEP metabolism is impaired following ADR administration, occurring before systolic or diastolic abnormalities and in proportion to the extent of eventual contractile abnormalities. These observations are consistent with the hypothesis that impaired HEP metabolism contributes to ADR-induced myocardial dysfunction.

Measurement of cytosolic free calcium in perfused rat heart using TF-BAPTA

1994 ◽  
Vol 266 (5) ◽  
pp. C1323-C1329 ◽  
Author(s):  
E. Murphy ◽  
C. Steenbergen ◽  
L. A. Levy ◽  
S. Gabel ◽  
R. E. London
Keyword(s):  
Rat Heart ◽  
High Energy ◽  
Left Ventricular ◽  
Free Calcium ◽  
High Energy Phosphates ◽  
Perfused Rat Heart ◽  
Fast Exchange ◽  
Exchange Kinetics ◽  
Developed Pressure ◽  
Dissociation Constant Kd

The feasibility and usefulness of loading 1,2-bis(2-amino-5,6-difluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (TF-BAPTA), a new high-dissociation constant (KD) (65 microM) Ca2+ indicator, into perfused rat heart is demonstrated. TF-BAPTA-loaded perfused rat heart showed less than a 10% reduction in left ventricular developed pressure. In addition, loading perfused rat heart with TF-BAPTA had no effect on cell high-energy phosphates measured by 31P-nuclear magnetic resonance (NMR). Cytosolic free Ca2+ (Ca2+i) can be monitored in TF-BAPTA-loaded perfused rat heart using 19F-NMR. TF-BAPTA has a Ca(2+)-insensitive resonance (6F) and a Ca(2+)-sensitive fluorine (5F) that responds to changes in Ca2+ binding with fast exchange kinetics at magnetic fields < or = 8.5 T. Thus the shift difference between the 5F and 6F resonances is a measure of Ca2+i. Given the high KD and the slight differences in intra- vs. extracellular fluorine shifts, TF-BAPTA is not well suited for measuring basal Ca2+i, but it is useful for measuring increases in Ca2+i above this level. For studies in which intracellular pH changes are significant, e.g., during ischemia, pH-dependent corrections must be made to obtain an accurate Ca2+i value. Given its fast exchange kinetics, TF-BAPTA is also useful for measurement of free Ca2+ in different compartments or cells with different Ca2+i. We show that the rise in Ca2+i is not uniform during prolonged global ischemia (60 min); several different Ca2+i values are present. Thus TF-BAPTA is a useful new indicator for measuring elevations in Ca2+i or compartmentation of Ca2+i.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Mitochondrial ATPase and high-energy phosphates in failing hearts

2001 ◽  
Vol 281 (3) ◽  
pp. H1319-H1326 ◽  
Author(s):  
Jingbo Liu ◽  
Chunsheng Wang ◽  
Yo Murakami ◽  
Guangrong Gong ◽  
Yutaka Ishibashi ◽  
...  
Keyword(s):  
Protein Expression ◽  
High Energy ◽  
Left Ventricular ◽  
Initiation Factor ◽  
Resonance Spectroscopy ◽  
Coronary Artery Ligation ◽  
Mitochondrial Atpase ◽  
High Energy Phosphates ◽  
Α Subunit ◽  
Dopamine Infusion

This study examined high-energy phosphates (HEP) and mitochondrial ATPase protein expression in hearts in which myocardial infarction resulted in either compensated left ventricular remodeling (LVR) or congestive heart failure (CHF). The response of HEP (measured via 31P magnetic resonance spectroscopy) to a modest increase in the cardiac work state produced by dobutamine-dopamine infusion and pacing (if needed) was examined in 17 pigs after left circumflex coronary artery ligation (9 with LVR and 8 with CHF) and compared with 7 normal pigs. In hearts with LVR, the baseline phosphocreatine (PCr)-to-ATP ratio decreased, and calculated ADP increased; these changes were most severe in hearts with CHF. HEP levels did not change in normal or LVR hearts during dobutamine-dopamine infusion. However, in hearts with CHF, the PCr-to-ATP ratio decreased further, and free ADP increased. The mitochondrial protein levels of the F0F1-ATPase subunits were normal in hearts with compensated LVR. However, in failing hearts, the α-subunit decreased by 36%, the β-subunit decreased by 16%, the oligomycin sensitivity-conferring protein subunit decreased by 40%, and the initiation factor 1 subunit decreased by 41%. Thus in failing hearts, reductions in mitochondrial F0F1-ATPase protein expression are associated with increased myocardial free ADP.

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