Antihypoxic effects of some quinones associated with restoration of the electron transport function of the respiratory chain of the isolated rat heart

1990 ◽  
Vol 110 (1) ◽  
pp. 922-925 ◽  
Author(s):  
A. A. Korneev ◽  
O. A. Popova ◽  
S. V. Zamula ◽  
L. D. Luk'yanova
Author(s):  
Alexandra Petrus ◽  
Oana Duicu ◽  
Adrian Sturza ◽  
Lavinia Noveanu ◽  
István Baczkó ◽  
...  

Background Mitochondrial dysfunction plays a major role in the pathogenesis of ischemia/reperfusion injury and cardiac arrhythmias. Mitochondrial ATP-sensitive potassium channel (mitoKATP) openers such as diazoxide and pinacidil have been reported to elicit cardioprotective effects via mild uncoupling and/or respiratory chain inhibition. The aim of the present study was to characterize the effects of two novel mitoKATP modulators (KL-1488 and KL 1495) on the respiratory rates and calcium retention capacity of isolated rat heart mitochondria. Methods Mitochondrial respiratory function was assessed by high-resolution respirometry (Oxygraph-2k Oroboros Ltd.) at 370C according to the Substrate-Uncoupler-Inhibitor Titration (SUIT) protocol, as follows: complex I (CI) and complex II (CII) dependent respiration was stimulated by glutamate + malate and rotenone + succinate, respectively (State 2) and subsequent ADP (State 3, OXPHOS state) addition; cytochrome c addition evaluated the intactness of the outer mitochondrial membrane; ATP synthase was inhibited by oligomycin (State 4); uncoupled respiration was obtained by FCCP titration; respiration was inhibited with antimycin A. Calcium retention capacity (CRC) was determined by spectrofluorimetry and calculated as the amount of calcium taken by mitochondria before opening of the mitochondrial permeability transition pore (mPTP) in the presence of the pharmacological agents. Results For both C I and C II-supported respiration, 150 µM of KL 1495 (but not of KL 1488) significantly increased respiratory rates in State 2 and 4, and decreased State 3 respiration, respectively. No inhibition of mPTP opening was observed in the presence of either compound. Conclusion The mitochondrial uncoupling and respiratory chain inhibition induced by KL 1495 could play a role in cardioprotection during the postischemic reperfusion. The research was funded by the POSDRU grant no. 159/1.5/S/136893 titled “Parteneriat strategic pentru creșterea calității cercetării științifice din universitățile medicale prin acordarea de burse doctorale și postdoctorale – DocMed.Net_2.0” (A.P.).


Author(s):  
Tetyana V Shimanskaya ◽  
Yulia V. Goshovska ◽  
Olena M. Semenykhina ◽  
Vadim F. Sagach

Circulation ◽  
1997 ◽  
Vol 95 (8) ◽  
pp. 2122-2129 ◽  
Author(s):  
Salvatore Pepe ◽  
Rui-Ping Xiao ◽  
Charlene Hohl ◽  
Ruth Altschuld ◽  
Edward G. Lakatta

Circulation ◽  
1997 ◽  
Vol 96 (9) ◽  
pp. 3148-3156 ◽  
Author(s):  
A. K. Snabaitis ◽  
M. J. Shattock ◽  
D. J. Chambers

2003 ◽  
Vol 285 (1) ◽  
pp. H316-H324 ◽  
Author(s):  
Richard Southworth ◽  
Pamela B. Garlick

The clinical hallmarks of hibernating myocardium include hypocontractility while retaining an inotropic reserve (using dobutamine echocardiography), having normal or increased [18F]fluoro-2-deoxyglucose-6-phosphate (18FDG6P) accumulation associated with decreased coronary flow [flow-metabolism mismatch by positron emission tomography (PET)], and recovering completely postrevascularization. In this study, we investigated an isolated rat heart model of hibernation using experimental equivalents of these clinical techniques. Rat hearts ( n = 5 hearts/group) were perfused with Krebs-Henseleit buffer for 40 min at 100% flow and 3 h at 10% flow and reperfused at 100% flow for 30 min (paced at 300 beats/min throughout). Left ventricular developed pressure fell to 30 ± 8% during 10% flow and recovered to 90 ± 7% after reperfusion. In an additional group, this recovery of function was found to be preserved over 2 h of reperfusion. Electron microscopic examination of hearts fixed at the end of the hibernation period demonstrated a lack of ischemic injury and an accumulation of glycogen granules, a phenomenon observed clinically. In a further group, hearts were challenged with dobutamine during the low-flow period. Hearts demonstrated an inotropic reserve at the expense of increased lactate leakage, with no appreciable creatine kinase release. PET studies used the same basic protocol in both dual- and globally perfused hearts (with 250MBq18FDG in Krebs buffer ± 0.4 mmol/l oleate). PET data showed flow-metabolism “mismatch;” whether regional or global,18FDG6P accumulation in ischemic tissue was the same as (glucose only) or significantly higher than (glucose + oleate) control tissue (0.023 ± 0.002 vs. 0.011 ± 0.002 normalized counts · s-1· g-1· min-1, P < 0.05) despite receiving 10% of the flow. This isolated rat heart model of acute hibernation exhibits many of the same characteristics demonstrated clinically in hibernating myocardium.


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