Protective effects of amiodarone pretreatment on mitochondrial function and high energy phosphates in ischaemic rat heart

1987 ◽  
Vol 19 (6) ◽  
pp. 603-614 ◽  
Author(s):  
P NOKIN ◽  
L JUNGBLUTH ◽  
J MOUTON
Keyword(s):  
Mitochondrial Function ◽  
Rat Heart ◽  
High Energy ◽  
High Energy Phosphates ◽  
Protective Effects

Influence of intracellular acidosis on contractile function in the working rat heart

1987 ◽  
Vol 253 (6) ◽  
pp. H1499-H1505 ◽  
Author(s):  
F. M. Jeffrey ◽  
C. R. Malloy ◽  
G. K. Radda
Keyword(s):  
Stroke Volume ◽  
Intracellular Ph ◽  
Rat Heart ◽  
Contractile Function ◽  
High Energy ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Intracellular Acidosis ◽  
Tension Development ◽  
O2 Delivery

The decrease in myocardial contractility during ischemia, hypoxia, and extracellular acidosis has been attributed to intracellular acidosis. Previous studies of the relationship between pH and contractile state have utilized respiratory or metabolic acidosis to alter intracellular pH. We developed a model in the working perfused rat heart to study the effects of intracellular acidosis with normal external pH and optimal O2 delivery. Intracellular pH and high-energy phosphates were monitored by 31P nuclear magnetic resonance spectroscopy. Hearts were perfused to a steady state with a medium containing 10 mM NH4Cl (extracellular pH, 7.4). The subsequent washout of NH3 from the cytosol generated a slight acidosis (from intracellular pH 7.0 to 6.8) which was associated with little change in the determinants of O2 consumption (rate-pressure product) and O2 delivery (coronary flow). Acidosis induced a substantial decrease in aortic flow and stroke volume which was associated with little change in peak systolic pressure. Results were qualitatively similar at different external [Ca2+] (1.75, 2.5, 3.15 mM) and preload (12 or 21 cmH2O) but were most prominent at the lowest external [Ca2+] and left atrial pressure. In contrast to this model of isolated intracellular acidosis, hearts subject to a respiratory (extracellular plus intracellular) acidosis showed a marked reduction in pressure development. It was concluded that 1) for the same intracellular acidosis the influence on tension development was more pronounced with a combined extra- and intracellular acidosis than with an isolated intracellular acidosis, and 2) stroke volume at constant preload was impaired by intracellular acidosis even though changes in developed pressure were minimal. These observations suggest that isolated intracellular acidosis has adverse effects on diastolic compliance and/or relaxation.

scholarly journals Impaired Cerebral Mitochondrial Oxidative Phosphorylation Function in a Rat Model of Ventricular Fibrillation and Cardiopulmonary Resuscitation

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Jun Jiang ◽  
Xiangshao Fang ◽  
Yue Fu ◽  
Wen Xu ◽  
Longyuan Jiang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Ventricular Fibrillation ◽  
Cardiopulmonary Resuscitation ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Rat Model ◽  
Mitochondrial Function ◽  
High Energy ◽  
Mitochondrial Morphology ◽  
High Energy Phosphates

Postcardiac arrest brain injury significantly contributes to mortality and morbidity in patients suffering from cardiac arrest (CA). Evidence that shows that mitochondrial dysfunction appears to be a key factor in tissue damage after ischemia/reperfusion is accumulating. However, limited data are available regarding the cerebral mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR) and its relationship to the alterations of high-energy phosphate. Here, we sought to identify alterations of mitochondrial morphology and oxidative phosphorylation function as well as high-energy phosphates during CA and CPR in a rat model of ventricular fibrillation (VF). We found that impairment of mitochondrial respiration and partial depletion of adenosine triphosphate (ATP) and phosphocreatine (PCr) developed in the cerebral cortex and hippocampus following a prolonged cardiac arrest. Optimal CPR might ameliorate the deranged phosphorus metabolism and preserve mitochondrial function. No obvious ultrastructural abnormalities of mitochondria have been found during CA. We conclude that CA causes cerebral mitochondrial dysfunction along with decay of high-energy phosphates, which would be mitigated with CPR. This study may broaden our understanding of the pathogenic processes underlying global cerebral ischemic injury and provide a potential therapeutic strategy that aimed at preserving cerebral mitochondrial function during CA.

Propranolol effects on myocardial ultrastructure and high energy phosphates in anesthetized dogs subjected to ischemia and reperfusion

1979 ◽  
Vol 57 (9) ◽  
pp. 979-986 ◽  
Author(s):  
A. Ziegelhoffer ◽  
P. K. Das ◽  
G. P. Sharma ◽  
P. K. Singal ◽  
N. S. Dhalla
Keyword(s):  
Structural Damage ◽  
Structural Changes ◽  
Structural Integrity ◽  
Creatine Phosphate ◽  
High Energy ◽  
Ischemia And Reperfusion ◽  
High Energy Phosphates ◽  
Protective Effects ◽  
Myocardial Ultrastructure ◽  
Anesthetized Dogs

The effects of propranolol (1–5 mg/kg) on the ultrastructure and high energy phosphate content of dog myocardium were investigated after 2 h of ischemia and 2 h of reperfusion. Two adjoining major ventricular branches of the left circumflex coronary artery were occluded to produce ischemia. Propranolol was administered intravenously just before occlusion of the coronary arteries in all the experiments. Two hours of ischemia caused structural changes and significantly reduced creatine phosphate (CrP) and ATP contents, and increased AMP levels. Propranolol (5 mg/kg) had no effect on these ischemic changes.Propranolol was found to protect the myocardium from structural damage usually observed after 2 h of reperfusion. The size and number of amorphous electron-dense mitochondrial granules, which are considered to contain calcium, observed after reperfusion, were reduced in propranolol-treated animals. Stores of ATP and total nucleotides (ATP + ADP + AMP), and the ATP:AMP ratio were significantly higher in propranolol (5 mg/kg) treated dogs in comparison with the untreated controls after 2 h of reperfusion. There was, however, no difference between the CrP levels of propranolol-treated and untreated preparations. The study shows that propranolol is effective in reducing the reperfusion-dependent changes in ischemic myocardium. Reduction in the intracellular calcium overload as well as maintenance of the structural integrity of the cell, particularly that of mitochondria, may be involved in these protective effects of propranolol.

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)

Sign in / Sign up

Export Citation Format

Share Document