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PubMed2000

Relationship between hepatic mitochondrial functions in vivo and in vitro in rats with carbon tetrachloride-induced liver cirrhosis.

BACKGROUND/AIMS: The metabolic capacity of liver mitochondria is impaired in rats with carbon tetrachloride (CCl4)-induced cirrhosis. These studies were performed to find out whether benzoate and/or palmitate are suitable substrates for assessing hepatic mitochondrial function in vivo. METHODS: In vivo metabolism of benzoate and 1-14C-palmitate was assessed by monitoring urinary excretion of hippurate and exhalation of 14CO2, respectively, in cirrhotic and control rats (n=8 for each group). Isolation of liver mitochondria, and in vitro benzoate and palmitate metabolism were performed by methods published previously. The hepatic content of mitochondria was assessed by stereological analysis of the volume of hepatocytes and by biochemical determination, using the activity of citrate synthase. RESULTS: Renal excretion of hippurate following i.p. administration of benzoate was reduced in cirrhotic rats (64+/-15 vs. 85+/-14% of administered dose over 24 h), and showed a linear correlation with hippurate formation by isolated mitochondria. The activities of benzoyl-CoA synthase and benzoyl-CoA:glycine N-acyltransferase were reduced by approximately 60%, and the coenzyme A content by 50% in hepatic mitochondria from cirrhotic rats, explaining impaired hippurate formation. Peak exhalation of 14CO2 after i.p. administration of 1-14C-palmitate was reduced by 44% and the area under the 14CO2 exhalation-time curve by 34% in cirrhotic rats. Peak 14CO2 exhalation revealed a linear correlation with oxidative metabolism of palmitoylcarnitine in isolated mitochondria. Both in vivo benzoate and palmitate metabolism showed a linear correlation with the volume fraction of hepatocytes. The mitochondrial protein content was reduced in cirrhotic rats per g liver and per liver but equal to control rats per volume of hepatocytes. CONCLUSIONS: In vivo metabolism of both palmitate and benzoate reflects hepatic mitochondrial function in rats with CCl4-induced cirrhosis. Hepatic mitochondrial function is impaired in rats with CCl4-induced cirrhosis due to both reduced mitochondrial volume per liver and impaired metabolism of the remaining mitochondria. In contrast to rats with secondary biliary cirrhosis, rats with CCl4-induced cirrhosis showed no hepatic mitochondrial proliferation to counteract reduced mitochondrial function.

Animals↗

PubMed1986

Factors affecting the loss of mitochondrial function in autolyzing cardiac muscle.

Rates of loss of mitochondrial respiratory function were monitored during autolyses of canine myocardial samples pretreated so as to affect tissue pH and/or tissue ATP content prevailing during tissue autolysis. When autolyses occurred under conditions of differing tissue pH, but at nearly identical tissue ATP levels, the rate of loss of mitochondrial function was virtually unchanged suggesting that tissue acidosis in the absence of a concomitant tissue ATP differential had little or no effect upon the rate of progression of mitochondrial damage. In a second comparison, autolyses were carried out at constant tissue pH, but where tissue ATP content differed dramatically. Here, the rate of loss of mitochondrial function was increased markedly suggesting that tissue ATP depletion in the absence of a concomitant tissue pH differential had a major effect upon the rate of loss of mitochondrial function. Thus, of the two parameters studied, tissue ATP content alone was far more important than tissue pH alone in determining the rate of cell membrane damage during ischemia. Finally, autolyses were carried out where both tissue pH and ATP content differed. Here, an even more dramatic increase in the rate of progression of mitochondrial damage occurred suggesting the operation of synergism between tissue ATP depletion and acidosis in promoting cell injury in ischemic cardiac muscle.

Acidosis↗

PubMed1991

A redox reaction between MPP+ and MPDP+ to produce superoxide radicals does not impair mitochondrial function.

Rat brain mitochondria were incubated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its two metabolites (1-methyl-4-phenyl-2,3-dihydropyridium (MPDP+) and 1-methyl-4-phenylpyridinium (MPP+), and O2 uptake was assessed. MPP+ (500 and 1000 microM) inhibited state 3 and state 4 respiration with a reduction in the respiratory control ratio (RCR). In the presence of MPTP or MPDP+ (100-1000 microM) no inhibition of mitochondrial function occurred. Incubation with MPP+ (100-1000 microM) in combination with equimolar concentrations of MPDP+ or MPTP (100-1000 microM) did not increase the inhibition of mitochondrial function produced by MPP+ alone. Inhibition of mitochondrial function produced by MPP+ (500 microM) was not reduced by incorporation of superoxide dismutase (SOD) (50-1000 units/mL). However, the RCR in the presence of 500 microM MPP+ and 1000 units/mL SOD was not different from control values. SOD did not prevent the inhibition of state 3 and state 4 respiration produced by the combination of MPP+ and MPDP+. The results suggest that a redox reaction between MPP+ and MPDP+ to generate superoxide radicals does not contribute to the impairment of mitochondrial function produced by MPTP administration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2002

Mitochondrial function in response to cardiac ischemia-reperfusion after oral treatment with quercetin.

Polyphenolic compounds present in red wines, such as the flavonol quercetin, are thought capable of cardioprotection through mechanisms not yet clearly defined. It has been established that mitochondria play a critical role in myocardial recovery from ischemia-reperfusion (I-R) damage, and in vitro experiments indicate that quercetin can exert a variety of direct effects on mitochondrial function. The effects of quercetin at concentrations typically found in 1-2 glasses of red wine on cardiac I-R and mitochondrial function in vivo are not known. Quercetin was administered to rats (0.033 mg/kg per day by gavage for 4 d). Isolated Langendorff perfused hearts were subjected to I-R, and cardiac functional parameters determined both before and after I-R. Mitochondria were isolated from post-I-R hearts and their function assessed. Compared to an untreated control group, quercetin treatment significantly decreased the impairment of cardiac function following I-R. This protective effect was associated with improved mitochondrial function after I-R. These results indicate that oral low dose quercetin is cardioprotective, possibly via a mechanism involving protection of mitochondrial function during I-R.

Administration, Oral↗

PubMed1985

Lactic acidosis and recovery of mitochondrial function following forebrain ischemia in the rat.

The effect of different degrees of lactic acidosis on the recovery of brain mitochondrial function, measured as respiratory activity in isolated mitochondria or cortical concentrations of labile phosphates and carbohydrate substrates, was studied during 30 min of recirculation following 15 min of near-complete forebrain ischemia in rats. During ischemia, there was a marked decrease in mitochondrial State 3 respiration in vitro and a depletion of energy stores (i.e., phosphocreatine, ATP, glucose, and glycogen) in vivo that was similar in the high- and low-lactate ischemia groups. However, lactate concentrations differed markedly (20 and 10 mumol g-1, respectively). During recirculation, there was a near-complete recovery of both respiratory activity in vitro and adenylate energy charge (EC) in vivo regardless of the differences in lactic acidosis during ischemia. Respiratory activity and EC were well correlated. The changes in Ca2+ homeostasis during ischemia, an increase in tissue and a decrease in mitochondrial Ca2+ content, were reversed rapidly after ischemia in both high- and low-lactate ischemia animals and did not hinder an early recovery of mitochondrial function. It is concluded that lactic acidosis, with lactate levels reaching 20 mumol g-1 during 15-min ischemia, does not adversely affect early postischemic recovery of mitochondrial function.

Acidosis↗

PubMed1994

Nifedipine does not alter the increased cystolic free magnesium during inhibition of mitochondrial function in isolated cardiac myocytes.

1. The objectives of this investigation were to determine the effect of inhibition of mitochondrial function on intracellular free Mg concentration, [Mg2+]i, in the heart and to determine whether the calcium channel antagonist nifedipine would alter the response. 2. Cardiac myocytes were prepared as primary cultures from 7-day-old chick embryonic hearts. [Mg2+]i was determined in single ventricular cells with mag-fura-2. 3. Inhibition of mitochondrial function with carbonyl cyanide m-chlorophenylhydrozone (CCCP, 3 microM, plus amobarbital, 3 mM, produced a cessation of cardiac contractile frequency that was reversible. This was associated with an increase in [Mg2+]i from 0.48 to 0.98 mM which returned to near basal levels with removal of the drugs. [Ca2+]i oscillations with cell contraction were diminished in the presence of CCCP plus amobarbital and returned to normal following their removal. 4. In contrast, CCCP plus iodoacetate led to increased [Mg2+]i beyond 2 mM which was associated with elevated [Ca2+]i and cell death. 5. Nifedipine did not alter the cardiac contractile response to CCCP plus amobarbital. The increment in [Mg2+]i produced by CCCP plus amobarbital was not altered by nifedipine. These data suggest that [Mg2+]i is regulated by mitochondrial metabolism and nifedipine does not alter the increase in [Mg2+]i produced by inhibition of mitochondrial function suggesting increments in [Mg2+]i were from internal sources. Nifedipine may not interfere with the potentially beneficial actions of increased [Mg2+]i.

Adenosine Triphosphate↗

PubMed1976

Evaluation of Mannich bases and related compounds as inhibitors of mitochondrial function in yeast and inhibition of blood platelet aggregation, blood clotting, and in vitro metabolism of 5-dimethylamino-1-phenyl-1-penten-3-one hydrochloride.

Dimethylamino-1-phenyl-1-penten-3-one hydrochloride (Ia) and 32 analogs were tested for inhibition of respiratory-dependent growth in Saccharomyces cerevisiae. Thirteen of the 33 compounds tested appeared to affect mitochondrial function, since the inhibition of respiratory-dependent growth was statistically greater than the inhibition of growth on fermentable energy sources. Inhibition of mitochondrial function in yeast and growth inhibition of an in vitro culture of human epidermoid carcinoma (KB) were positively correlated since 83% of the compounds tested either had mitochondrial-inhibiting properties and significant activity in the KB test or were inactive in both tests. Similarly, 78% of compounds tested showed murine toxicity and mitochondrial inhibition or had no effect on murine toxicity and yeast mitochondrial function. Injection of Ia into rats resulted in the appearance of blood in the urine and feces. Compound Ia inhibited adenosine diphosphate and collagen-induced aggregation of rat platelets but had no effect on blood clotting. TLC, following incubation of Ia with a rat liver extract, showed that the structure of Ia was not enzymatically modified and indicated activity per se on platelet aggregation and mitochondrial function.

Adenosine Diphosphate↗

PubMed2002

The effects of cryopreservation on sperm morphology, motility and mitochondrial function.

BACKGROUND: The effects of cryoinjury were determined simultaneously on the mitochondrial function, motility, morphology and viability of ejaculated human sperm. METHOD: Rhodamine 123 (R123) uptake (% of sperm) and stain intensity were used to determine sperm mitochondrial activity before and after cryopreservation from the semen of 50 men attending for infertility investigation. Morphology was assessed using Tygerberg's strict criteria and viability was assessed by eosin Y. Sperm motility was measured using computer-assisted semen analysis (CASA). RESULTS: Freeze-thawing caused a 37% (P = 0.001) reduction in normal morphological forms of sperm. All CASA sperm motility parameters except amplitude of lateral head displacement were similarly reduced. R123 uptake and intensity within sperm mitochondria decreased by 36 and 47% respectively (both P = 0.001). In addition, there was a similar significant decrease (31%, P = 0.001) in the viability of the sperm. CONCLUSIONS: Sperm morphology, motility, mitochondrial activities and viability are equally susceptible to cryopreservation-induced damage. R123 intensity is a novel and robust indicator of mitochondrial function before and after such trauma.

Cell Survival↗

PubMed2004

Method for in situ detection of the mitochondrial function in neurons.

Conventional studies of neuronal mitochondria have been limited to the use of purified preparations of isolated mitochondria, neural cell homogenates, living neurons, or brain slices. However, each technique has several drawbacks. Here, we demonstrate that the neuronal cell's membrane can be effectively permeabilized by saponin-treatment and that these permeabilized neurons can be used for qualitative and quantitative assessments of oxygen consumption in combination with registration of mitochondrial membrane potential and free [Ca2+] in the matrix. Under these conditions, the mitochondrial function can be studied without removing the mitochondria from their natural milieu thus avoiding the damage of the associated cytoskeleton and outer membrane. At the same time, the method allows the estimation of the mitochondrial function independently of other processes in the cell, and the easy manipulation of the milieu surrounding the mitochondria. Thus, the presented method offers the opportunity to study the neuronal mitochondrial function in situ and can also be applied to examine the mitochondrial function by other commonly used methods.

Animals↗

PubMed1982

Preservation of ischemic rat liver mitochondrial functions and liver viability with CoQ10.

The present study was undertaken to determine whether CoQ10 administration to rats can protect hepatic mitochondrial functions, improve energy metabolism during hepatic ischemia and subsequent reperfusion, and prolong the viability of the organ. Although ischemia of the liver for 90 minutes did not permit survival of the animals, CoQ10 administration (6 mg/kg of body weight) increased the survival rate to 60%. The period of ischemia was accompanied by decreases in hepatic adenosine triphosphate (ATP) level and respiratory control index without significant increases in mitochondrial calcium content and lipid peroxide formation. The subsequent restoration of blood flow resulted in a low recovery of ATP level, recovery of respiratory control and ADP:O ratio to levels significantly lower than normal, and on the contrary, marked increases in mitochondrial calcium and lipid peroxide levels. However, in CoQ10-treated animals mitochondrial functions were all completely reversible, and resynthesis of ATP was accelerated even after 90 minutes of ischemia. The pretreatment also completely suppressed the elevation of mitochondrial calcium and lipid peroxide levels. These results suggest that preservation with CoQ10 of cellular damages caused by hepatic ischemia is probably due to protection of cellular and subcellular membranes from lipid peroxidation, so that mitochondrial functions are restored and cellular calcium homeostasis is maintained.

Adenosine Triphosphate↗

PubMedDate not supplied

Improvement of mitochondrial function evaluated by ketoisocaproic acid breath test in patients with HCV infection undergoing albumin dialysis.

BACKGROUND AND AIM: Oxidative injury occurs as a direct result of hepatitis C virus (HCV) core protein expression both in vitro and in vivo, and may be due to a direct effect on mitochondria. The ketoisocaproic acid (KICA) breath test is a simple, reliable, and noninvasive test to evaluate hepatic mitochondrial function. Albumin dialysis (MARS) is an effective bridge treatment for patients with acute failure superimposed on chronic liver disease. The aim of our study was to evaluate the improvement of mitochondrial function measured by KICA in patients undergoing MARS for acute-on-chronic HCV liver failure. MATERIALS AND METHODS: Five patients with HCV chronic infection undergoing MARS treatment for acute decompensation were enrolled. Before and after each MARS treatment, patients underwent blood testing for the main hematochemical parameters as well as for mitochondrial function by the KICA breath test and the arterial ketone bodies ratio (AKBR). RESULTS: MARS treatment effectively decreased the serum level of total bilirubin, bile acids, urea, and ammonium. Moreover, MARS treatment produced an increase in AKBR and in the cumulative percentage of (13)CO(2) recovered in exhaled air 2 hours after KICA ingestion. CONCLUSION: Liver mitochondrial function appears to be beneficially affected by MARS treatment.

Adult↗

PubMed1991

The role of altered mitochondrial function in citrinin-induced toxicity to rat renal proximal tubule suspensions.

Citrinin (CTN), a mycotoxin produced by several species of Penicillium and Aspergillus, causes renal proximal tubule (RPT) cell injury and death by an unknown mechanism of action. Using suspensions of rat RPT, the cellular events preceding CTN-induced cytotoxicity were investigated. Tubule viability decreased in a concentration- and time-dependent manner after CTN exposure, with cell death beginning 1, 2, and 4 hr after exposure to 500, 125-250, and 63 microM, respectively. Basal oxygen consumption (QO2) of RPT increased from 41 to 53 nmol O2.mg protein-1.min-1 30 min after exposure to 250 microM CTN and returned to control values 1 hr after exposure. A similar concentration- and time-dependent transitory rise in basal QO2 occurred at all concentrations of CTN tested (63-500 microM). Nystatin-stimulated QO2, an indirect measure of mitochondrial state 3 respiration in RPT, decreased 11% at 0.5 and 1 hr after exposure to 500 and 250 microM CTN, respectively, but was not affected after exposure to 63 and 125 microM CTN. Adenosine triphosphate content declined 22% to 48% in RPT at 0.5 and 1.5 hr after exposure to 500 and 125-250 microM CTN, respectively. Although lipid peroxidation occurred concurrently with RPT cell death, iron-mediated oxidative stress was not a causative factor in the development of toxicity since pretreatment with 1 mM deferoxamine prevented iron-mediated lipid peroxidation but did not protect RPT from CTN-induced cell death. Further studies using RPT and isolated renal cortical mitochondria (RCM) showed that CTN had multiple effects on mitochondrial function. Direct probing of mitochondrial function within RPT showed that a 1-hr exposure to 250 microM CTN increased spontaneous respiration 55% in RPT respiring on the site I respiratory substrates glutamate/malate while state 3 respiration decreased 34%. CTN also decreased succinate supported respiration but had no effect on cytochrome c-cytochrome oxidase. With isolated RCM, a 3-min exposure to 125 and 250 microM CTN increased state 4 respiration in the absence of a phosphate acceptor 27 and 67%, respectively, while 250 microM CTN decreased state 3 respiration 23%. Respiration in the presence of a known uncoupler was reduced after CTN exposure (63-250 microM) in a concentration-dependent manner. These results indicate that CTN has multiple effects on mitochondrial function in RPT and isolated RCM which may contribute to the development of cell death in rat RPT.

Animals↗

PubMed2005

Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men.

OBJECTIVE: The goal of this study was to examine the relationship between serum testosterone levels and insulin sensitivity and mitochondrial function in men. RESEARCH DESIGN AND METHODS: A total of 60 men (mean age 60.5 +/- 1.2 years) had a detailed hormonal and metabolic evaluation. Insulin sensitivity was measured using a hyperinsulinemic-euglycemic clamp. Mitochondrial function was assessed by measuring maximal aerobic capacity (V(O2max)) and expression of oxidative phosphorylation genes in skeletal muscle. RESULTS: A total of 45% of subjects had normal glucose tolerance, 20% had impaired glucose tolerance, and 35% had type 2 diabetes. Testosterone levels were positively correlated with insulin sensitivity (r = 0.4, P < 0.005). Subjects with hypogonadal testosterone levels (n = 10) had a BMI >25 kg/m(2) and a threefold higher prevalence of the metabolic syndrome than their eugonadal counterparts (n = 50); this relationship held true after adjusting for age and sex hormone-binding globulin but not BMI. Testosterone levels also correlated with V(O2max) (r = 0.43, P < 0.05) and oxidative phosphorylation gene expression (r = 0.57, P < 0.0001). CONCLUSIONS: These data indicate that low serum testosterone levels are associated with an adverse metabolic profile and suggest a novel unifying mechanism for the previously independent observations that low testosterone levels and impaired mitochondrial function promote insulin resistance in men.

Adult↗

PubMed1993

[Effect of Na-L-glutamate on mitochondrial function of ATP synthesis after prolonged preservation in rat heart].

We studied the effect of Na-L-glutamate (Glu) on mitochondrial functions of ATP synthesis after prolonged hypothermic preservation of rat hearts. We divided isolated rat hearts into the following three groups: group A, hearts without immersion as control; group B, hearts immersed in Euro-Collins solution (E-C) without Glu for 24 h at 4 degrees C; group C, hearts immersed in E-C with 10mM Glu for 24 h at 4 degrees C. Number of each group used was 6. Mitochondrial functions of ATP production were determined by measuring respiratory control index (RCI). P/O ratio and state III respiration rate. The ability of ATP production (oxidative phosphorylation rate, OPR) was calculated. RCI and P/O ratio of groups B and C were significantly lower than those of group A. RCI and P/O ratio of group C were significantly higher than that of group B. S3 rates of groups B and C were significantly lower than those of group A. S4 rate of group B was significantly higher than those of groups A and C. OPRs of groups B and C were significantly lower than that of group A. OPR of group C was significantly higher than that of group B. We concluded that Na-L-glutamate effectively protected mitochondrial functions to synthesize ATP during prolonged hypothermic preservation.

Adenosine Triphosphate↗

PubMed1984

ATP-MgCl2 produces sustained improvement in hepatic mitochondrial function and blood flow after hepatic ischemia.

Recent studies have shown that infusion of ATP-MgCl2 following hepatic ischemia significantly improved mitochondrial function and hepatic blood flow 1 hr after treatment. To determine if the improvement in the above parameters by ATP-MgCl2 is short-lived or whether it persists for prolonged periods of time after treatment, hepatic ischemia in rats was produced for 90 min followed by reperfusion. The rats then received iv 0.5 ml of saline or ATP-MgCl2 (12.5 mumole each). Twenty-four hours after reflow, hepatic blood flow was measured by H2 polarography following which the animals were sacrificed and hepatic mitochondria isolated. The results indicated that 24 hr after reflow, mitochondrial state 3 respiration, respiratory control ratio, adenine nucleotide translocase activity, ATP synthetic activity, and hepatic blood flow were depressed by approximately 50% in animals which were treated with saline after hepatic ischemia. In addition, there was a fourfold increase in mitochondrial free fatty acid levels of such animals. Animals which were treated with ATP-MgCl2 following hepatic ischemia showed significantly improved mitochondrial function (used as an index of cellular recovery) and hepatic blood flow. These results in conjunction with previous results suggest that infused ATP-MgCl2 improves mitochondrial function and blood flow and that these effects persist even 24 hr after administration of ATP-MgCl2. Thus, infusion of ATP-MgCl2 following severe ischemia produces sustained improvement in cellular function.

Adenosine Triphosphate↗

PubMed1998

Permeabilized cell and skinned fiber techniques in studies of mitochondrial function in vivo.

In this chapter we describe in details the permeabilized cell and skinned fiber techniques and their applications for studies of mitochondrial function in vivo. The experience of more than 10 years of research in four countries is summarized. The use of saponin in very low concentration (50-100 microg/ml) for permeabilisation of the sarcolemma leaves all intracellular structures, including mitochondria, completely intact. The intactness of mitochondrial function in these skinned muscle fibers is demonstrated in this work by multiple methods, such as NADH and flavoprotein fluorescence studies, fluorescence imaging, confocal immunofluorescence microscopy and respiratory analysis. Permeabilized cell and skinned fiber techniques have several very significant advantages for studies of mitochondrial function, in comparison with the traditional methods of use of isolated mitochondria: (1) very small tissue samples are required; (2) all cellular population of mitochondria can be investigated; (3) most important, however, is that mitochondria are studied in their natural surrounding. The results of research by using this method show the existence of several new phenomenon--tissue dependence of the mechanism of regulation of mitochondrial respiration, and activation of respiration by selective proteolysis. These phenomena are explained by interaction of mitochondria with other cellular structures in vivo. The details of experimental studies with use of these techniques and problems of kinetic analysis of the results are discussed. Examples of large-scale clinical application of these methods are given.

Adenosine Diphosphate↗

PubMed1992

Mitochondrial function in neurodegeneration and ageing.

The mitochondrial respiratory chain and oxidative phosphorylation system are responsible for the production of ATP by aerobic metabolism. Defects of the respiratory chain are increasingly recognised as important causes of human disease, and neurodegenerative disorders in particular. This article will seek to review the clinical and biochemical effects of respiratory chain defects, and summarise what is known about the molecular mechanisms that underlie them. Increasing age is also associated with a decline in mitochondrial function. The biochemical correlates of this dysfunction and the possible molecular defects that may cause it will also be reviewed.

Aging↗

PubMed1989

Mitochondrial function after asphyxia in newborn lambs.

We examined mitochondrial oxidative function 5 minutes and 2 hours after a gradual asphyxial insult in newborn lambs. We subjected 16 ventilated newborn lambs to 75-90 minutes of hypoxia and hypercarbia that resulted in bradycardia and systemic hypotension over the final 15 minutes of the insult. At the end of asphyxia, the lambs were resuscitated and returned to control ventilator settings. Samples of brain were removed 5 minutes (n = 8) and 2 hours (n = 8) after asphyxia. Each group of eight lambs was subdivided into those less than 3 or greater than 3 days old to evaluate the effect of age on postasphyxia mitochondrial function. After classification into nonsynaptic and synaptic mitochondria, mitochondrial respiration (oxygen consumption) was measured using five different substrates. Data from asphyxiated lambs were compared with that from a control group of ventilated nonasphyxiated lambs (n = 8). In the lambs less than 3 days old, there was significant depression of mean +/- SEM nonsynaptic mitochondrial state 3 (adenosine diphosphate-dependent) respiration to 29.5 +/- 5.2% of control with four of the five substrates and of state 4 respiration to 33.7 +/- 0.9% of control with three of the five substrates 5 minutes after asphyxia. By 2 hours after asphyxia, mean +/- SEM nonsynaptic mitochondria state 3 respiration increased to 70.4 +/- 6.4% of control while state 4 respiration increased to 58.2 +/- 4.5% of control. In contrast, lambs greater than 3 days old exhibited no inhibition of nonsynaptic mitochondrial function after asphyxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗