Effect of the Na+/H+ exchange inhibitor eniporide on cardiac performance and myocardial high energy phosphates in pigs subjected to cardioplegic arrest

2004 ◽  
Vol 77 (2) ◽  
pp. 658-663 ◽  
Author(s):  
Oliver Klass ◽  
Uwe M Fischer ◽  
Elisabeth Perez ◽  
Jerry Easo ◽  
Marfalda Bosse ◽  
...  
Keyword(s):  
High Energy ◽  
Cardiac Performance ◽  
High Energy Phosphates ◽  
Cardioplegic Arrest ◽  
Exchange Inhibitor

Pyruvate-fortified cardioplegia suppresses oxidative stress and enhances phosphorylation potential of arrested myocardium

2005 ◽  
Vol 289 (3) ◽  
pp. H1123-H1130 ◽  
Author(s):  
E. Marty Knott ◽  
Myoung-Gwi Ryou ◽  
Jie Sun ◽  
Abraham Heymann ◽  
Arti B. Sharma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Redox State ◽  
Energy State ◽  
High Energy ◽  
High Energy Phosphates ◽  
Cardioplegic Arrest ◽  
Phosphorylation Potential ◽  
Lactate And Pyruvate ◽  
Postischemic Myocardium

Cardioplegic arrest for bypass surgery imposes global ischemia on the myocardium, which generates oxyradicals and depletes myocardial high-energy phosphates. The glycolytic metabolite pyruvate, but not its reduced congener lactate, increases phosphorylation potential and detoxifies oxyradicals in ischemic and postischemic myocardium. This study tested the hypothesis that pyruvate mitigates oxidative stress and preserves the energy state in cardioplegically arrested myocardium. In situ swine hearts were arrested for 60 min with a 4:1 mixture of blood and crystalloid cardioplegia solution containing 188 mM glucose alone (control) or with additional 23.8 mM lactate or 23.8 mM pyruvate and then reperfused for 3 min with cardioplegia-free blood. Glutathione (GSH), glutathione disulfide (GSSG), and energy metabolites [phosphocreatine (PCr), creatine (Cr), Pi] were measured in myocardium, which was snap frozen at 45 min arrest and 3 min reperfusion to determine antioxidant GSH redox state (GSH/GSSG) and PCr phosphorylation potential {[PCr]/([Cr][Pi])}. Coronary sinus 8-isoprostane indexed oxidative stress. Pyruvate cardioplegia lowered 8-isoprostane release ∼40% during arrest versus control and lactate cardioplegia. Lactate and pyruvate cardioplegia dampened ( P < 0.05 vs. control) the surge of 8-isoprostane release following reperfusion. Pyruvate doubled GSH/GSSG versus lactate cardioplegia during arrest, but GSH/GSSG fell in all three groups after reperfusion. Myocardial [PCr]/([Cr][Pi]) was maintained in all three groups during arrest. Pyruvate cardioplegia doubled [PCr]/([Cr][Pi]) versus control and lactate cardioplegia after reperfusion. Pyruvate cardioplegia mitigates oxidative stress during cardioplegic arrest and enhances myocardial energy state on reperfusion.

scholarly journals HOE-642 (cariporide) alters pHi and diastolic function after ischemia during reperfusion in pig hearts in situ

2001 ◽  
Vol 280 (2) ◽  
pp. H830-H834 ◽  
Author(s):  
Michael A. Portman ◽  
Anthony L. Panos ◽  
Yun Xiao ◽  
David L. Anderson ◽  
Xue-Han Ning
Keyword(s):  
Diastolic Function ◽  
High Energy ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Exchange Inhibitor ◽  
Diastolic Stiffness ◽  
Ischemic And Reperfusion Injury ◽  
Intracellular Alkalinization

The specific Na+/H+ exchange inhibitor HOE-642 prevents ischemic and reperfusion injury in the myocardium. Although this inhibitor alters H+ ion flux during reperfusion in vitro, this action has not been confirmed during complex conditions in situ. Myocardial intracellular pH (pHi) and high-energy phosphates were monitored using 31P magnetic resonance spectroscopy in open-chest pigs supported by cardiopulmonary bypass during 10 min of ischemia and reperfusion. Intravenous HOE-642 (2 mg/kg; n = 8) administered before ischemia prevented the increases in diastolic stiffness noted in control pigs ( n = 8), although it did not alter the postischemic peak-elastance or pressure-rate product measured using a distensible balloon within the left ventricle. HOE-642 induced no change in pHi during ischemia but caused significant delays in intracellular realkalinization during reperfusion. HOE-642 did not alter phosphocreatine depletion and repletion but did improve ATP preservation. Na+/H+ exchange inhibition through HOE-642 delays intracellular alkalinization in the myocardium in situ during reperfusion in association with improved diastolic function and high-energy phosphate preservation.

Verapamil preserves adenine nucleotide pool in cardiomyopathic Syrian hamster

1986 ◽  
Vol 250 (1) ◽  
pp. H22-H28 ◽  
Author(s):  
J. Wikman-Coffelt ◽  
R. Sievers ◽  
W. W. Parmley ◽  
G. Jasmin
Keyword(s):  
Heart Failure ◽  
Syrian Hamster ◽  
Adenine Nucleotides ◽  
High Energy ◽  
Cardiac Performance ◽  
Calcium Entry ◽  
High Energy Phosphates ◽  
Calcium Entry Blocker ◽  
Entry Blocker ◽  
Adenine Nucleotide Pool

There is a decrease in total adenine nucleotides, cyclic AMP (cAMP), ATP/total ADP, and phosphocreatine (PCr)/creatine (Cr) both in situ and in the perfused heart in the heart failure stage of the cardiomyopathic Syrian hamster. There were decreases in developed pressure, dP/dt, and O2 consumption associated with the decrease in total adenine nucleotides and cAMP. Cardiomyopathic Syrian hamsters (180-240 days old) with congestive heart failure were given water with the calcium entry blocker, verapamil, as an additive 2 mo before death. In the cardiomyopathic group given verapamil the adenine nucleotides, cAMP, and high-energy phosphates were preserved and cardiac performance was not significantly different from that of the verapamil-treated healthy hamsters at the time of death. Pretreatment of cardiomyopathic animals with verapamil (6.6 mg verapamil/ml water consumed by drinking) resulted in significantly higher ATP/total ADP and PCr/Cr compared with nontreated cardiomyopathic hamsters. This is the first report demonstrating that a calcium entry blocker may improve cardiac performance and preserve total adenine nucleotides during the heart failure stage of the cardiomyopathic hamster.

Preservation of myocardial high energy phosphates during cardioplegic arrest with nifedipine

1988 ◽  
Vol 44 (3) ◽  
pp. 216-223 ◽  
Author(s):  
John H. Ip ◽  
James M. Levett ◽  
Mark H. Kadowaki ◽  
Robert B. Karp
Keyword(s):  
High Energy ◽  
High Energy Phosphates ◽  
Cardioplegic Arrest

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.

Manipulating the intracellular environment of hippocampal slices: pH and high-energy phosphates

1989 ◽  
Vol 28 (1-2) ◽  
pp. 83-91 ◽  
Author(s):  
Tim S. Whittingham ◽  
Eduardo Warman ◽  
Hussein Assaf ◽  
Thomas J. Sick ◽  
Joseph C. LaManna
Keyword(s):  
Hippocampal Slices ◽  
High Energy ◽  
High Energy Phosphates ◽  
Intracellular Environment

Reduced substrate oxidation in postischemic myocardium: 13C and 31P NMR analyses

1990 ◽  
Vol 258 (5) ◽  
pp. H1357-H1365 ◽  
Author(s):  
E. D. Lewandowski ◽  
D. L. Johnston
Keyword(s):  
Steady State ◽  
31P Nmr ◽  
Tca Cycle ◽  
High Energy ◽  
Substrate Oxidation ◽  
High Energy Phosphates ◽  
Atp Content ◽  
And Control ◽  
13C And 31P Nmr ◽  
Postischemic Myocardium

13C and 31P nuclear magnetic resonance (NMR) spectra were used to assess substrate oxidation and high-energy phosphates in postischemic (PI) isolated rabbit hearts. Phosphocreatine (PCr) increased in nonischemic controls on switching from glucose perfusion to either 2.5 mM [3-13C]pyruvate (120%, n = 7) or [2-13C]acetate (114%, n = 8, P less than 0.05). ATP content, oxygen consumption (MVO2), and hemodynamics (dP/dt) were not affected by substrate availability in control or PI hearts. dP/dt was 40-60% lower in PI hearts during reperfusion after 10 min ischemia. Hearts reperfused with either pyruvate (n = 11) or acetate (n = 8) regained preischemic PCr levels within 45 s. Steady-state ATP levels were 55-70% of preischemia with pyruvate and 52-60% with acetate. Percent maximum [4-13C]glutamate signal showed reduced conversion of pyruvate to glutamate via the tricarboxylic acid (TCA) cycle at 4-min reperfusion (PI = 24 +/- 4%, means +/- SE; Control = 48 +/- 4%). The increase in 13C signal from the C-4 position of glutamate was similar to control hearts within 10.5 min. The increase in [4-13C]glutamate signal from acetate was not different between PI and control hearts. The ratio of [2-13C]Glu:[4-13C]Glu, reflecting TCA cycle activity, was reduced in PI hearts with acetate for at least 10 min (Control = 0.76 +/- 0.03; PI = 0.51 +/- 0.09) until steady state was reached. Despite rapid recovery of oxidative phosphorylation, contractility remained impaired and substrate oxidation was significantly slowed in postischemic hearts.

Responses of beta-adrenoceptor in rat soleus to phosphorus compound levels and/or unloading

1994 ◽  
Vol 266 (5) ◽  
pp. C1257-C1262 ◽  
Author(s):  
Y. Ohira ◽  
K. Saito ◽  
T. Wakatsuki ◽  
W. Yasui ◽  
T. Suetsugu ◽  
...  
Keyword(s):  
Contractile Activity ◽  
Creatine Supplementation ◽  
High Energy ◽  
Hindlimb Suspension ◽  
Phosphorus Compounds ◽  
High Energy Phosphates ◽  
High Energy Phosphate ◽  
Gravitational Unloading ◽  
Beta Adrenoceptor ◽  
Muscle Contractile

Responses of beta-adrenoceptor (beta-AR) in rat soleus to gravitational unloading and/or changes in the levels of phosphorus compounds by feeding either creatine or its analogue beta-guanidinopropionic acid (beta-GPA) were studied. A decrease in the density of beta-AR (about -35%) was induced by 10 days of hindlimb suspension, but the affinity of the receptor was unaffected. Suspension unloading tended to increase the levels of adenosine triphosphate and phosphocreatine and decrease inorganic phosphate. Even without unloading, the beta-AR density decreased after an oral creatine supplementation (about -20%), which also tended to elevate the high-energy phosphate levels in muscle. However, an elevation of beta-AR density was induced (about +36%) after chronic depletion of high-energy phosphates by feeding beta-GPA (about +125%). Data suggest that the density of beta-AR in muscle is elevated if the high-energy phosphate contents are chronically decreased and vice versa. However, it may not be directly related to the degree of muscle contractile activity.

Magnetic resonance spectroscopy of high-energy phosphates and lactate immediately after coronary artery bypass surgery

Perfusion ◽  
1998 ◽  
Vol 13 (5) ◽  
pp. 328-333 ◽  
Author(s):  
D NF Harris ◽  
J A Wilson ◽  
S D Taylor-Robinson ◽  
K M Taylor
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Cerebral Ischaemia ◽  
Artery Bypass ◽  
High Energy ◽  
Jugular Bulb ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Intracellular Acidosis ◽  
High Incidence

Hypothermic cardiopulmonary bypass (CPB) is associated with a high incidence of neuropsychological defects, marked cerebral swelling immediately after surgery and jugular bulb desaturation during rewarming. This suggests cerebral ischaemia may occur, but evidence is indirect. We studied four patients with 31P magnetic resonance spectroscopy (MRS) and four with 1H MRS before and immediately after coronary surgery. There was no visible lactate in 1H MR spectra. In 31P MR spectra, the ratio of phosphocreatine to adenosine triphosphate was maintained (before: 2.13 ± 0.86 vs after: 2.57 ± 1.31; mean ± 1 SD) and there was no intracellular acidosis (intracellular pH: 7.1 ± 0.04 vs 7.16 ± 0.08), while phosphocreatine/inorganic phosphate was increased immediately after the operation (2.92 ± 0.37 vs 6.39 ± 2.67, p = 0.03). This suggests rebound replacement of energy stores following recovery from temporary cerebral ischaemia during CPB: intra-operative studies would be needed to test this hypothesis further.

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