SEARCH · PubMed Health

Results for “Mitochondrial function”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources

PubMed1991

Effect of various mixtures of diethylether, halothane, nitrous oxide and oxygen on low molecular weight iron content and mitochondrial function of the rat myocardium.

Anaesthetic drugs can induce reversible as well as irreversible changes in cell membranes and intracellular proteins as well as lipid peroxidation in the liver. Low molecular weight iron species (LMWI) can by their catalytic activity contribute to the generation of free radicals (hydroxyl radicals). Free radicals are a recognisable cause of intracellular damage. Impaired mitochondrial function is also a sign of intracellular damage, which is usually irreversible. Thus, an agent may be cytotoxic when it causes a significant increase in intracellular LMWI. Whether the LMWI arise from ferritin or is released from iron containing proteins, the same reaction occurs. As long as LMWI can undergo redox cycling, hydroxyl radicals can be formed. We investigated the effect of various mixtures of diethylether, halothane, nitrous oxide and oxygen on the intracellular LMWI content and mitochondrial function of the rat myocardium. Hearts isolated from rats anaesthetised with diethylether showed an increase in the cytosolic LMWI compared to the control group. No increase in mitochondrial LMWI was demonstrated. Subsequent perfusion of the isolated hearts showed a further increase in the LMWI. On perfusion the mitochondrial LMWI increased in comparison with controls. Mitochondrial function was significantly impaired as measured by the QO2 (state 3), ADP/O ratio and oxidative phosphorylation rate (OPR). Exposure of rats to 50% nitrous oxide for 15 minutes increased the myocardial LMWI, but had no effect on mitochondrial function. Exposure to room air for 30 minutes before isolating the hearts, still showed a significant increase in LMWI with no detectable change in mitochondrial function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Effect of ovarian hormones upon liver mitochondrial function in diabetic rats.

In the present study it is shown that streptozotocin (SZ)-induced chronic diabetes of female albino rats produced significant alterations in liver mitochondrial function after 30-35 days of diabetes. The disturbances were as follows: (1) a significant fall of the mean values of the respiratory control ratio and of state 3 of respiration using three substrates, 3-hydroxybutyrate, malate-glutamate and succinate, and (2) a significant increase of the mean damping factor of the oscillatory osmotic variations (with valinomycin as K+ ionophore and succinate as substrate). The same mitochondrial function parameters were analyzed for comparison in control non-diabetic rats (group N) and in the following groups of female rats with chronic diabetes: intact (group I), oophorectomized (6 days after the injection of SZ) (group O), and oophorectomized with restitution therapy of 17 beta-estradiol (from the operation until the day before killing) (group O + Eol). The O group showed significantly higher values of the respiratory control ratio and of state 3 of respiration and significantly lower damping factors than group I. The restitution treatment in the O + Eol group restored the mitochondrial functions assayed to values similar to those of group I. These data provide strong evidence that estrogens exert a negative effect at the molecular level upon impaired liver mitochondrial functions in SZ-induced diabetes.

Animals↗

PubMed1989

Influence of hypoxia on mitochondrial function and energy status in CCl4-induced cirrhotic rat liver.

The influence of hypoxia on hepatic mitochondrial function and energy status was studied in normal and carbon tetrachloride (CCl4)-induced cirrhotic rats. Under hypoxemia of 50 mm Hg-PaO2, hepatic energy status was suppressed both in normal and cirrhotic rats. After the reversal of hypoxia, it was completely restored in normal rats concomitant with a rapid elevation of hepatic mitochondrial redox state (overshoot phenomenon) and increase in the mitochondrial oxidative phosphorylative activity. By contrast, in cirrhotic rats, such an enhancement of mitochondrial function was not observed. It was clarified that cirrhotic liver mitochondrial function was not observed. It was clarified that cirrhotic liver mitochondria have little capacity to respond to the hypoxic stress. A lower resistance to hypoxic episode in cirrhotics might be attributable to the absence of mitochondrial enhancement which is a compensatory mechanism for the deranged energy metabolism of the liver.

Animals↗

PubMed2001

Cardioprotection by ischemic preconditioning preserves mitochondrial function and functional coupling between adenine nucleotide translocase and creatine kinase.

M. N. Laclau, S. Boudina, J. B. Thambo, L. Tariosse, G. Gouverneur, S. Bonoron-Adèle, V. A. Saks, K. D. Garlid and P. Dos Santos. Cardioprotection by Ischemic Preconditioning Preserves Mitochondrial Function and Functional Coupling Between Adenine Nucleotide Translocase and Creatine Kinase. Journal of Molecular and Cellular Cardiology (2001) 33, 947-956. This study investigates the effect of ischemic preconditioning on mitochondrial function, including functional coupling between the adenine nucleotide translocase and mitochondrial creatine kinase, which is among the first reactions to be altered in ischemia. Three groups of Langendorff-perfused rat hearts were studied: a control group, a group subjected to 30 min ischemia followed by 15 min reperfusion, and a group subjected to ischemic preconditioning prior to 30 min ischemia and 15 min reperfusion. Ischemic preconditioning significantly delayed the onset and amplitude of contracture during ischemia, decreased enzymatic release, and improved the recovery of heart contractile function after reperfusion. Mitochondrial function was assessed in permeabilized skinned fibers. The protective effect of preconditioning was associated with preservation of mitochondrial function, as evidenced by maintenance of the high K(1/2)for ADP in regulation of mitochondrial respiration and V(max)of respiration, the near absence of respiratory stimulation by exogenous cytochrome c, and preservation of functional coupling between mitochondrial creatine kinase and adenine nucleotide translocase. These data suggest that ischemic preconditioning preserves the structure-function of the intermembrane space, perhaps by opening the mitochondrial ATP-sensitive K(+)channel. The consequence is preservation of energy transfer processes from mitochondria to ATP-utilizing sites in the cytosol. Both of these factors may contribute to cardioprotection and better functional recovery of preconditioned hearts.

Adenosine Diphosphate↗

PubMed1982

Exercise-induced alterations of hepatic mitochondrial function.

In order to examine the effect of a single bout of exercise on hepatic mitochondrial function, starved untrained male rats swam at 34-35 degrees C with a tail weight (5% of body wt.) for 100 min. The rates of ADP-stimulated and uncoupled respiration were higher in the mitochondria isolated from the exercised rats regardless of the substrate utilized. Succinate-linked Ca2+ uptake was 48% greater in the exercised group; however, Ca2+ efflux was markedly depressed. The inhibition of Ca2+ uptake by Mg2+ was higher in the control group, so that the difference in Ca2+ uptake between the two groups was greater in the presence of Mg2+ than in its absence. The response of phosphorylating respiration and Ca2+ fluxes to exogenous phosphate and the pH of the assay medium differed in the exercise group. These observations with the exercised group were not related to non-specific stress. The exercise-induced mitochondrial-functional alterations are reminiscent of those obtained from mitochondria isolated from glucagon- or catecholamine-treated sedentary rats. Thus, adrenergic stimulation as well as other factors may be operating during exercise, leading to an alteration of mitochondrial function in vitro.

Animals↗

PubMed1997

Mitochondrial function is not decreased in stunned papillary muscle at 20 degrees C.

It is unclear to what extent mitochondrial function in vivo is changed after brief anoxia. Heat measurements allow evaluation of mitochondrial function within intact cardiac muscle. Heat production was determined using fast metal-film thermopiles, during contraction and post-contractile recovery in control and stunned superfused rabbit papillary muscles at 20 degrees C. Heat rate was measured for a train of ten twitches (0.2 Hz) before anoxia and after 40 min anoxia followed by 2 h of normoxic recovery. During anoxia muscles were stimulated at 0.2 Hz (group A) or at 1.0 Hz (group B). A normoxic control group C was stimulated at 0.2 Hz. After 2 h recovery, tension was 77 +/- 5% (S.E.M.), 72 +/- 7% and 94 +/- 3% of initial values, for group A, B and C respectively, indicating stunning by anoxia. The economy of contraction or the ratio of recovery heat to initial heat did not change significantly in groups A and B when compared with control, indicating that stunning with this protocol is not associated with mitochondrial uncoupling. Post-contractile recovery heat initially decayed exponentially with time constant 24.9 +/- 2.2 s for all groups and with 22.7 +/- 1.1, 22.0 +/- 0.8 and 41.7 +/- 4.4 s at the end for group A, B and C respectively. The cause of the remarkable slowing of the recovery rate over time in controls is unknown, but is mimicked by blocking fatty acid utilization. No slowing of metabolic recovery is observed in the stunned papillary muscles. We conclude that stunning is not associated with a decrease in mitochondrial function or oxidative capacity in cardiac muscle.

Analysis of Variance↗

PubMed2005

Angiotensin II blockade improves mitochondrial function in spontaneously hypertensive rats.

Angiotensin II can induce oxidant stress by stimulating vascular superoxide production. Hypertension promotes mitochondrial function decline in brain, liver and heart. The aim of this study was to investigate whether a) hypertension is associated to kidney mitochondrial dysfunction, and b) angiotensin II blockade can reverse potential mitochondrial changes in hypertension. Four-month-old male spontaneously hypertensive rats (SHR) received drinking water containing candesartan (7.5 mg/kg/day, SHR+Cand), or no additions (SHR) for 4-months. Eight-month-old Wistar-Kyoto rats (WKY), that received water with no additions, were used as control. Systolic blood pressure, proteinuria, cortical glomerular area, and glomerular and tubulointerstitial alpha-smooth muscle actin labeling, were significantly higher, and creatinine clearance was significantly lower, in SHR relative to WKY and SHR+Cand. In SHR, kidney mitochondria membrane potential, and nitric oxide synthase and cytochrome oxidase activities were significantly lower than in WKY and SHR+Cand. In SHR, mitochondrial hydrogen peroxide production was significantly higher than in WKY and SHR+Cand. The results suggest that, in hypertension, increased mitochondrial oxidant production may mediate kidney mitochondria dysfunction. Candesartan preserved mitochondrial function, probably favoring the maintenance of adequate cellular and tissue function in the kidney. The known renal protective effects of candesartan in hypertension may be related to the improvement of mitochondrial function. This may be an additional or alternative explanation for some of the beneficial effects of AT1 receptor antagonists.

Actins↗

PubMed1985

Effect of dextran sulfate on the survival time and mitochondrial function of Adriamycin (doxorubicin)-treated mice.

The effect of dextran sulfate on the survival time and mitochondrial function of adriamycin (ADM)-treated mice was studied. ADM-induced toxicity in mice was reduced by treatment with dextran sulfate (60, 100, 300, and 600 mg/kg, sc). The optimum dextran sulfate dose for protection against ADM-induced toxicity in mice was about 200 mg/kg/day (sc) and 100 mg/kg/day (po). Groups treated with dextran sulfate (300 mg/kg) had significantly improved mitochondrial function as measured by oxygen uptake of state 3 (p less than 0.01), dinitrophenol-altered respiration (p less than 0.01), and respiratory control index level (p less than 0.01). From these observations, it was concluded that ADM-induced toxicity due to reduced mitochondrial function can be ameliorated by the membrane stabilizing effect of dextran sulfate.

Administration, Oral↗

PubMed2006

Alterations in mitochondrial function, hydrogen peroxide release and oxidative damage in mouse hind-limb skeletal muscle during aging.

Mitochondrial function, hydrogen peroxide generation and oxidative damage were measured in hind-limb skeletal muscle from young (6-8 month) and old (27-29 month) wildtype and heterozygous Mn-superoxide dismutase (MnSOD) knockout mice (Sod2(+/-)). The reduction in MnSOD activity in the Sod2(+/-) mice makes these mice a good model to examine the implications of life-long elevated endogenous mitochondrial oxidative stress on mitochondrial function. ATP production was reduced approximately 30% with age in skeletal muscle mitochondria isolated from wildtype mice, and reduced 40-45% in mitochondria from both young and old Sod2(+/-) mice compared to the young wildtype mice. Release of hydrogen peroxide from skeletal muscle mitochondria increased 40-50% with age in both wildtype and Sod2(+/-) but was not higher in mitochondria from Sod2(+/-) mice. Activities of electron transport Complexes I and V were decreased 25-30% in both young and old Sod2(+/-) mice compared to wildtype mice, and were 25-30% lower in mitochondria from old wildtype and old Sod2(+/-) mice. DNA oxidative damage (oxo8dG levels) increased more than 45% with age and over 130% in the young Sod2(+/-) mice compared to the wildtype mice. These data show that mitochondrial oxidative stress in mouse skeletal muscle is increased with age, leading to alterations in mitochondrial function. In addition, increased oxidative stress generated by reduced activity of MnSOD does not exacerbate these alterations during aging.

Aging↗

PubMed1992

Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation.

Structural mitochondrial damage accompanies the cytotoxic effects of several drugs including tumor necrosis factor (TNF). Using various inhibitors of mitochondrial electron transport we have investigated the mechanism of TNF-mediated cytotoxicity in L929 and WEHI 164 clone 13 mouse fibrosarcoma cells. Inhibitors with different sites of action modulated TNF cytotoxicity, however, with contrasting effects on final cell viability. Inhibition of mitochondrial electron transport at complex III (cytochrome c reductase) by antimycin A resulted in a marked potentiation of TNF-mediated injury. In contrast, when the electron flow to ubiquinone was blocked, either at complex I (NADH-ubiquinone oxidoreductase) with amytal or at complex II (succinate-ubiquinone reductase) with thenoyltrifluoroacetone, cells were markedly protected against TNF cytotoxicity. Neither uncouplers nor inhibitors of oxidative phosphorylation nor complex IV (cytochrome c oxidase) inhibitors significantly interfered with TNF-mediated effects, ruling out the involvement of energy-coupled phenomena. In addition, the toxic effects of TNF were counteracted by the addition of antioxidants and iron chelators. Furthermore, we analyzed the direct effect of TNF on mitochondrial morphology and functions. Treatment of L929 cells with TNF led to an early degeneration of the mitochondrial ultrastructure without any pronounced damage of other cellular organelles. Analysis of the mitochondrial electron flow revealed that TNF treatment led to a rapid inhibition of the mitochondria to oxidize succinate and NADH-linked substrates. The inhibition of electron transport was dose-dependent and became readily detectable 60 min after the start of TNF treatment, thus preceding the onset of cell death by at least 3-6 h. In contrast, only minor effects were observed on complex IV activity. The different effects observed with the mitochondrial respiratory chain inhibitors provide suggestive evidence that mitochondrial production of oxygen radicals mainly generated at the ubisemiquinone site is a causal mechanism of TNF cytotoxicity. This conclusion is further supported by the protective effect of antioxidants as well as the selective pattern of damage of mitochondrial chain components and characteristic alterations of the mitochondrial ultrastructure.

Amobarbital↗

PubMed2006

Disruption of mitochondrial function in interpopulation hybrids of Tigriopus californicus.

Electron transport system (ETS) function in mitochondria is essential for the aerobic production of energy. Because ETS function requires extensive interactions between mitochondrial and nuclear gene products, coadaptation between mitochondrial and nuclear genomes may evolve within populations. Hybridization between allopatric populations may then expose functional incompatibilities between genomes that have not coevolved. The intertidal copepod Tigriopus californicus has high levels of nucleotide divergence among populations at mitochondrial loci and suffers F2 hybrid breakdown in interpopulation hybrids. We hypothesize that hybridization results in incompatibilities among subunits in ETS enzyme complexes and that these incompatibilities result in diminished mitochondrial function and fitness. To test this hypothesis, we measured fitness, mitochondrial function, and ETS enzyme activity in inbred recombinant hybrid lines of Tigriopus californicus. We found that (1) both fitness and mitochondrial function are reduced in hybrid lines, (2) only those ETS enzymes with both nuclear and mitochondrial subunits show a loss of activity in hybrid lines, and (3) positive relationships exist between ETS enzyme activity and mitochondrial function and between mitochondrial function and fitness. We also present evidence that hybrid lines harboring mitochondrial DNA (mtDNA) and mitochondrial RNA polymerase (mtRPOL) from the same parental source population have higher fitness than those with mtDNA and mtRPOL from different populations, suggesting that mitochondrial gene regulation may play a role in disruption of mitochondrial performance and fitness of hybrids. These results suggest that disruption of coadaptation between nuclear and mitochondrial genes contributes to the phenomenon of hybrid breakdown.

Adaptation, Biological↗

PubMed1989

Assessment of mitochondrial function in vivo with a breath test utilizing alpha-ketoisocaproic acid.

A breath test to assess hepatic mitochondrial function in vivo was evaluated in rats. Following the i.p. administration of [1-14C]-alpha-ketoisocaproic acid, 14CO2 exhalation reached a peak within 10 to 20 min and then declined exponentially, with a half-life of 14.3 min. Control animals exhaled 38.6% of the administered radioactivity within 1 hr. In functionally anhepatic animals, 14CO2 in breath amounted to 23% of that in control animals, indicating that alpha-ketoisocaproic acid decarboxylation reflects mainly hepatic mitochondrial function in vivo. Ethanol (3 gm per kg) significantly decreased alpha-ketoisocaproic acid decarboxylation (21.8% of the dose appearing in breath in 1 hr), probably due to the ethanol-induced shift in the NAD+:NADH ratio. In contrast, an uncoupler of mitochondrial respiration, sodium salicylate (375 mg per kg), increased the decarboxylation of alpha-ketoisocaproic acid (56.3% of the dose recovered as 14CO2 in 1 hr). Mitochondrial damage induced by 4-pentenoic acid decreased the decarboxylation of alpha-ketoisocaproic acid but did not affect the microsomal metabolism of antipyrine. The present data indicate that the alpha-ketoisocaproic acid breath test provides a noninvasive estimate of hepatic mitochondrial function in vivo which, when applied to man, might yield clinically useful information.

Animals↗

PubMed2003

Preserved response of mitochondrial function to short-term endurance training in skeletal muscle of heart transplant recipients.

OBJECTIVES: We sought to determine whether intrinsic mitochondrial function and regulation were altered in heart transplant recipients (HTRs) and to investigate the response of mitochondrial function to six-week endurance training in these patients. BACKGROUND: Despite the normalization of central oxygen transport during exercise, HTRs are still characterized by limited exercise capacity, which is thought to result from skeletal muscle metabolic abnormalities. METHODS: Twenty HTRS agreed to have vastus lateralis biopsies and exercise testing: before and after training for 12 of them and before and after the same control period for eight subjects unwilling to train. Mitochondrial respiration was evaluated on saponin-permeabilized muscle fibers in the absence or presence (maximum respiration rate [V(max)]) of saturating adenosine diphosphate. RESULTS: Mitochondrial function was preserved at the level of sedentary subjects in untrained HTRs, although they showed 28 +/- 5% functional aerobic impairment (FAI). After training, V(max), citrate synthase, cytochrome c oxidase, and mitochondrial creatine kinase (CK) activities were significantly increased by 48%, 40%, 67%, and 53%, respectively (p < 0.05), whereas FAI decreased to 12 +/- 5% (p < 0.01). The control of mitochondrial respiration by creatine and mitochondrial CK was also improved (p < 0.01), suggesting that phosphocreatine synthesis and transfer by the mitochondrial CK become coupled to oxidative phosphorylation, as shown in trained, healthy subjects. CONCLUSIONS: In HTRs, the mitochondrial properties of skeletal muscle were preserved and responded well to training, reaching values of physically active, healthy subjects. This suggests that, in HTRs, immunosuppressive drugs do not alter the intrinsic muscle oxidative capacities and that the patients' physical handicap results from nonmitochondrial mechanisms.

Cell Respiration↗

PubMed2000

Practical problems in detecting abnormal mitochondrial function and genomes.

Mitochondrial respiratory chain dysfunction causes a wide range of primary diseases in adults and children, with highly variable organ involvement. Diagnosis involves weighing evidence from a number of sources, including the clinical presentation, metabolic measurements in vivo, imaging studies, analysis of respiratory chain function or enzyme activities in vitro, studies of mitochondrial morphology after biopsy, and mitochondrial (mt) DNA mutation analysis. Irrespective of the category of the information, it can be difficult to determine whether abnormal results are due to primary defects of the respiratory chain or to practical problems that complicate the diagnostic methodology. This review describes six sources of such problems: genetic complexity, tissue and temporal variation, methodological limitations, secondary effects, logistical issues, and questions of interpretation. When these issues are all addressed, a reliable categorization of the diagnosis as definite, probable, or possible respiratory chain defect becomes possible.

DNA Mutational Analysis↗

PubMed2004

Mitochondrial function is required for hydrogen peroxide-induced growth factor receptor transactivation and downstream signaling.

The transactivation of growth factor receptors is an early event in H(2)O(2)-induced signaling, although proximal targets in this process remain unclear. We found that inhibition of flavin- or heme-containing proteins eliminated H(2)O(2)-induced transactivation of the epidermal growth factor receptor and stimulation of its downstream targets, JNK and Akt. Inhibition of mitochondrial function with rotenone, antimycin A, KCN, carbonylcyanide-m-chlorophenylhydrazone, or oligomycin reproduced this effect, as did generation of mitochondrial DNA-deficient (pseudo-rho(0)) cells. Mitochondrial function had no role in JNK activation in response to UV irradiation or tumor necrosis factor-alpha. The impact of mitochondrial function on H(2)O(2)-induced growth factor transactivation was ubiquitous and applied to both the vascular endothelial growth factor (VEGF)-2 receptor and the platelet-derived growth factor-beta receptor in endothelium and fibroblasts, respectively. In contrast, ligand-induced growth factor activation was unrelated to mitochondrial function. Growth factor receptor transactivation and its downstream signaling in response to H(2)O(2) appeared to involve redox-sensitive mitochondrial events as they were abrogated by a mitochondrial-targeted antioxidants but not their nontargeted counterparts. Functionally, we found that mitochondrial-targeted antioxidants inhibited H(2)O(2)-induced apoptosis and cell death but had no effect with UV irradiation. These data establish a novel role for the mitochondrion as a proximal target specific to H(2)O(2)-induced signaling and growth factor transactivation.

Animals↗

PubMed2006

[Evaluation of sperm mitochondrial function using Rh123/PI dual fluorescent staining].

OBJECTIVE: To investigate the feasibility and clinical significance of detecting sperm mitochondrial function by using Rh123/PI dual fluorescent staining and flow cytometry analysis, and to explore the relationship between the results of Rh123/PI dual fluorescent staining and seminal parameters. METHODS: Sixty-three semen samples were classified as normal (n=31) and abnormal (n=32) according to the World Health Organization guidelines. Rh123/PI dual fluorescent staining was then carried out to evaluate sperm mitochondrial function by flow cytometry analysis. RESULTS: Significant differences in Rh123+ PI-, Rh123- /PI+ and Rh123- /PI- were detected between the normal and abnormal semen samples (P < 0.05). There was a significant positive correlation between the Rh123+ PI- sperm and sperm motility and a significant inverse correlation between Rh123+ PI- and immotile sperm. But the Rh123- PI+ sperm showed a contrary relationship with Rh123+ PI-. A significant inverse correlation was also observed between the Rhl23- /PI- sperm and sperm concentration in the abnormal group. CONCLUSION: Rh123/PI dual fluorescent staining and flow cytometry analysis can readily and quickly detect sperm mitochondrial function and be used to evaluate semen quality.

Adult↗

PubMed1985

Protection of canine cardiac mitochondrial function by verapamil-cardioplegia during ischemic arrest.

Hemodynamic and mitochondrial function recover following 60 minutes of ischemic arrest and reperfusion in hearts pretreated with verapamil. The present study was carried out to determine whether verapamil prevents the onset of mitochondrial oxidative impairment after 60 minutes of ischemic arrest without reperfusion. Two preparations of mitochondria isolated following Polytron homogenization and subsequent treatment of the myofibrillar pellet with Nagarse were examined for phosphorylating respiration. The Polytron mitochondria were more sensitive to ischemic arrest than were the Nagarse mitochondria with either glutamate-malate (57% vs. 22% inhibition), succinate (+ rotenone) (41% vs. 14% inhibition), or palmitoylcarnitine (57% vs. 27% inhibition) as respiratory substrates. Verapamil pretreatment significantly increased oxidation of all substrates by the subsequently isolated Polytron mitochondria, but only succinate-supported respiration returned to control levels. In contrast, the small amount of respiratory inhibition exhibited by the Nagarse mitochondria after ischemic arrest was insensitive to verapamil pretreatment. We conclude that the Polytron preparation of mitochondria is more susceptible to ischemia than the Nagarse mitochondria, and this susceptibility correlates with a striking sensitivity to verapamil protection. In general, oxidation of NADH-linked substrates, including palmitoylcarnitine, is more affected by ischemic arrest than succinate, and only oxidation of the latter substrate is totally protected by verapamil. The beneficial action of verapamil on mitochondrial function occurs prior to reperfusion. The data suggest that alterations in calcium homeostasis occur during the ischemic period, as well as in the subsequent reperfusion period.

Animals↗

PubMed1983

Effect of hypoxia and reoxygenation on mitochondrial function in neonatal myocardium.

The effect of hypoxia and reoxygenation on mitochondrial function was studied in the newborn and adult rabbit hearts. In control muscle, mitochondrial state 3 respiration (state 3 QO2), respiratory control index (RCI), energy-dependent calcium uptake, ATP content, and adenine nucleotide translocase in the newborn were significantly greater than in the adult. After 60 min hypoxia, both the newborn and adult showed significant decrease in 1) tissue glycogen, adenine nucleotides, and creatine phosphates and 2) mitochondrial adenine nucleotides, adenine nucleotide translocase, and glutamate-supported state 3 respiration. In the adult, reoxygenation following 60 min hypoxia was not associated with significant recovery in any of the variables described above, and there was significant decrease in the rate of calcium uptake. In the newborn, the values of all variables returned to control except for tissue glycogen and adenine nucleotide translocase. The data suggest that the effect of hypoxia on mitochondrial function in the newborn is less than in the adult. This occurs because of 1) the lower energy demand in the newborn, 2) higher tissue glycogen and higher rates of glycolysis in the newborn, 3) increased degradation and/or efflux of ATP and ADP in the adult, and 4) possibly a difference in the sarcolemmal resistance to hypoxia in the two age groups.

Adenine Nucleotides↗