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[Experimental and clinical studies of transvenous electrophrenic respiration (author's transl)].

The transvenous electrophrenic respiration (EPR) is one of the effective and relatively simple method for artificial respiration. Twenty seven mongrel dogs were subjected to the experiment which were subdevided into 4 groups. Stimulation is 44 times in group 1, 22 times in group 2 and 3. Ventilation is carried out by Harverd Respirator in group 4. The normal arterial pressure, the normal minute ventilatory volume and the normal arterial blood gases were unchanged for a 5 hour period of experiment in group 2. However, the frequent stimulation such as 44 times/min. in group 1 yielded the hypotension, the decreased ventilatory volume and brought the congestion of the portal venous area and rendered the subjects to death. The systemic pressure remained in slightly lowered levels in group 2, 3 and 4 at the end of a 24 hour of experiment. The ventilatory volume decreased one third of initial values in group 2 and 3 at the end of a 24 hour of experiment. The pulmonary arterial pressure decreased in group 3 significantly, whereas it increased in positive pressure respiration in group 4. Intermittent clinical application of EPR was performed in three patients. The arterial pressure, minute ventilatory volume, arterial gases and central venous pressure were maintained normal. The following conclusions were obtained: 1) EPR is more physiologic than positive pressure respiration in ventilatory and circulatory aspects. 2) Undesiable conditions of stimulation cause complications such as neural fatigue, portal hypertension, etc. 3) Intermittent clinical application of EPR has been quite successful in supporting the ventilation of the patients.

Adult↗

[Regulation of respiration in assisted ventilation].

Based on knowledge of the control of external respiration, the physiological reactions are discussed which should be evoked proprioceptively and chemoreceptively by an assisting respirator's disturbances of spontaneous breathing movements. The following possible states are discriminated: 1. "no adaption": the respiratory motor system does not remain passive during the machine's stroke; 2. "passive adaption": the respiratory motor system remains passive during the respirator's stroke; to changes of the blood gas-status, only the breathing frequency responds, but in just the same manner as during spontaneous ventilation; 3. "active adaption": the ventilatory motor apparatus remains passive during the respirator's operation; changes of the blood gases are responded to by the breathing frequency only, but in a manner different to spontaneous breathing and which compensates for the invariability of the fixed stroke-volume. - Related to these 3 states, consequences concerning the efficiency of chemical respiratory control can be derived which should reveal themselves during experimental manipulation of the blood gas partial pressures. Accordingly, the CO2-response curves of minute ventilation, breathing frequency and tidal-volume generated in 9 healthy, awake and cooperative subjects during spontaneous breathing and assisted (stroke-volume controlled) respiration with gas mixtures of 0, 3 and 6% CO2 were investigated and compared. (In each subject assisted ventilation with 2 or 3 different stroke-volumes was performed. The smallest stroke-volume equalled the medium tidal-volume of spontaneous ventilation. Every stroke-volume produced its particular CO2-response curve). Hence it follows that with assisted ventilation, using a stroke-volume larger than the spontaneous tidal-volume, the subjects maintain a state between "passive" and "active adaption".(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Dioxide↗

Selective paralysis of voluntary but not limbically influenced automatic respiration.

We describe a patient in whom a discrete infarction of the ventral basis pontis caused a complete loss of voluntary respiration, while automatic respiration remained intact. Respiratory excursions, quantified title volumes, and ventilatory response to carbon dioxide were normal, but the patient could not volitionally modify any respiratory parameters. Emotional stimuli producing laughter, crying, or anxiety appropriately modulated automatic respiration. This case established that pathways subserving limbic modulation of automatic respiration descend in the pontine tegmentum and/or lateral portion of the basis pontis spared by this lesion. Furthermore, descending limbic influences on automatic respiration are anatomically and functionally independent of the voluntary respiratory system.

Adult↗

Maxillary sinus mucosal blood flow during nasal vs tracheal respiration.

OBJECTIVE: To determine the effect of changes from nasal to tracheal respiration on maxillary sinus mucosal blood flow in rabbits with unobstructed sinus ostia. DESIGN: Animals underwent tracheotomy with a T tube and then a small window of intact maxillary sinus mucosa was exposed. Mucosal blood flow was recorded during normal nasal respiration using laser-Doppler velocimetry. At hourly intervals, respiration was changed from the nasal to the tracheal route and then back again. SUBJECTS: Ten anesthetized rabbits were used: 5 underwent single and 4 underwent multiple shifts in the respiratory route, while 1 was monitored continuously during long-term nasal breathing only. RESULTS: A significant decrease in maxillary sinus blood flow occurred on switching from nasal to tracheal respiration and a significant increase in blood flow occurred on return to nasal respiration. Where multiple switches were made, blood flow changes diminished in magnitude, but significant decreases (nasal to tracheal) or increases (tracheal to nasal) were evident in all cases. CONCLUSIONS: It is proposed that the maxillary sinus may act in an accessory capacity to the nose for humidification of inspired air via secretions liberated from the sinus ostium. Furthermore, we suggest that nasal airflow is involved with the reflex regulation of sinus blood flow, probably via stimulation of sensory receptors in the nasal cavity. Reduced maxillary sinus mucosal blood flow may thus contribute to supra-systemic levels of antral carbon dioxide. Since elevated carbon dioxide levels have been shown to reduce maxillary sinus mucociliary activity in vitro, nasal airflow compromise may contribute to the initiation of a cascade of pathophysiological events leading to acute sinusitis.

Animals↗

An electrocardiograph-respiration gating device for MR studies.

A versatile gating device for magnetic resonance (MR) spectroscopy and imaging is presented. The device uses electrocardiograph (ECG) and respiration signals as input, applies appropriate signal conditioning, and generates control signals for ECG, respiration, or combined gating studies. In the combined ECG and respiration mode, in conjunction with a proper MR pulse program, one can acquire MR data gated by the ECG signal within a selected window of the respiration cycle, while maintaining a steady level of magnetization saturation during the remainder of the respiration cycle, by gating the radio-frequency excitation with the ECG while inhibiting data acquisition.

Animals↗

Contributions of syringeal muscles to respiration and vocalization in the zebra finch.

Acute and chronic electromyographic (EMG) recordings from individual syringeal muscles were used to study syringeal participation in respiration and vocalization. In anesthetized birds, all syringeal muscles recorded were active to some degree during the expiratory phase of respiration, following activity in the abdominal musculature and preceding the emergence of breath from the nostril. In awake birds, the ventralis (V) muscle fired a strong, consistent burst, but the dorsalis (D) was variable both in strength and timing. Denervation of V is sufficient to produce the wheezing respiration originally seen in birds with complete bilateral section of the tracheosyringeal nerve. Complete syringeal denervation also removed almost all the acoustic features that distinguish individual song syllables, but had a minor effect on the temporal structure of song. When activity in V and D was recorded in awake, vocalizing birds, D was active before and during sound production, and V showed a small burst before sound onset and a vigorous burst timed to the termination of sound. During song, V was consistently active at sound offset, but also participated during sound for narrow bandwidth syllables. For some syllables (simple harmonic stacks), neither muscle was active. These data suggest that V contributes to syllable termination during vocalization and may silence the syrinx during normal respiration. D contributes to the acoustic structure of most syllables, and V may contribute to a special subset of syllables. In summary, the syringeal muscles show different activity patterns during respiration and vocalization and can be independently activated during vocalization, depending on the syllable produced.

Animals↗

Oxygen conformance of cellular respiration. A perspective of mitochondrial physiology.

Oxygen pressure declines from normoxic air-level to the microenvironment of mitochondria where cytochrome c oxidase (COX) reduces oxygen to water at oxygen levels as low as 0.3 kPa (2 Torr; 3 microM; 1.5 % air saturation). Intracellular hypoxia is defined as (1) local oxygen pressure below normoxic reference states, or (2) limitation of mitochondrial respiration by oxygen levels below kinetic saturation, resulting in oxyconformance. High-resolution respirometry provides the methodology to measure mitochondrial and cellular oxygen kinetics in the relevant low oxygen range < 1 kPa (7.5 mmHg; 9-10 microM; 5% air saturation). Respiration of isolated heart mitochondria follows hyperbolic oxygen kinetics with half-saturating oxygen pressure, p50, of 0.04 kPa (0.3 Torr; 0.4 microM) in ADP-stimulated state 3. Thus mitochondrial respiration proceeds at 90% of its hyperbolic maximum at the p50 of myoglobin, suggesting the possibility of a small but significant oxygen limitation even under normoxia in active muscle. Any impairment of oxygen delivery, therefore, induces oxyconformance. In addition, a shift of mitochondrial oxygen kinetics to the right, particularly by competitive inhibition of COX by NO, causes a further depression of respiration and a compensatory increase of local oxygen pressure. Above 1 kPa, mitochondrial oxygen uptake increases above hyperbolic saturation, which is probably due to oxygen radical production rather than the kinetics of COX. In cultured cells, the pronounced oxygen uptake above mitochondrial saturation at air-level oxygen pressure cannot be inhibited by rotenone and antimycin A, amounting to > 20 % of routine respiration in fibroblasts. Biochemical models of oxyconformance of COX are evaluated relative to patterns of intracellular oxygen distribution in the tissue and enzyme turnover in vivo, considering the kinetic effects of COX excess capacity on flux through the mitochondrial electron transport chain.

Animals↗

Transient phase locking patterns among respiration, heart rate and blood pressure during cardiorespiratory synchronisation in humans.

The interactions between respiration, heart rate and blood pressure variability (HRV, BPV), are considered to be of paramount importance for the study of the functional organisation of the autonomic nervous system (ANS). The aim of the reported study is to detect and classify the intermittent phase locking (PL) phenomena between respiration, HRV and BPV during cardiorespiratory synchronisation experiments, by using the following time-domain techniques: Poincaré maps, recurrence plots, time-space separation plots and frequency tracking locus. The experimental protocol consists of three stages, with normal subjects in paced breathing at 15, 12 and 8 breaths min-1. Transient phenomena of coordination between respiration and the major rhythms of HRV and BPV (low and high frequency, LF and HF) have been detected and classified: no interaction between LF and HF rhythms at 15 breaths min-1; short time intervals of stable 1:2 frequency and phase synchronisation during the 12 breaths min-1 stage; 1:1 PL during the 8 breaths min-1 stage. 1:1 and 1:2 PL phenomena occurred when the respiration frequency was quite close to the LF frequency or when it was about twice the LF frequency, respectively. The complex organisation of the ANS seems to provoke transient rather than permanent PL phenomena between the co-ordinating components of respiration and cardiovascular variability series.

Adult↗

Respiratory sinus arrhythmia during anaesthesia: assessment of respiration related beat-to-beat heart rate variability analysis methods.

Beat-to-beat heart rate variability analysis is a powerful tool for the diagnosis of neuropathy. Respiration-related heart rate variability (respiratory sinus arrhythmia, RSA) reflects the function of parasympathetic nervous system during spontaneous ventilation while awake. RSA is also claimed to monitor the depth of anaesthesia. Power spectrum analysis or various averaging techniques of the heart rate variability are usually applied. The current literature, however, does not usually interpret the ground rules and limitations of the method used, and this may sometimes lead to erroneous conclusions on the data. The aim of our study was to compare and analyse critically the performance of different methods of evaluating RSA during anaesthesia and positive pressure ventilation. Power spectrum analysis, the root mean square of the successive RR-interval difference (RMSSD), and two respiration related methods, RSA index and average phase RSA, were included in the comparison. To test these methods, 11 patients were anaesthetised with isoflurane and their lungs were ventilated mechanically with a frequency of 6 cycles min-1. Each patient received a bolus dose of atropine (20 micrograms kg-1) during the trial. Electrocardiogram, electroencephalogram and tracheal pressure signal from respirator were recorded and analyses were performed off-line. We demonstrated that general indices, such as RMSSD, may be strongly affected by heart rate level and other non-respiration related variations in heart rate. We also showed that the effect of unwanted fluctuations on RSA can be reduced with respiration dependent beat-to-beat methods. Furthermore we confirmed that in addition to the amplitude, also the pattern of respiratory sinus arrhythmia is of interest: the pattern is reversed in phase compared to spontaneous breathing while awake, as we have shown earlier. To analyse RSA during anaesthesia, we recommend the use of an average phase RSA method based on beat-to-beat variability that shows both the amplitude and pattern of RSA. Finally, no measure of RSA should be used without a presentation of the actual beat-to-beat heart rate curve.

Adjuvants, Anesthesia↗

Variation in the ratio of respirable particulates over inhalable particulates by type of dust workplace.

OBJECTIVE: The aim of the present study was to clarify the quantitative relationship between respirable particulates and inhalable particulates in various dust workplaces. METHODS: Both respirable particulate and inhalable particulate concentrations were measured in 1644 dust workplaces by means of elutriation, and the ratio of respirable particulate mass over that of inhalable particulate (R/I ratio) was calculated for each workplace. RESULTS: Statistical analyses showed that the R/I ratio varied substantially, depending on the type of dust work. The ratio was highest in welding workplaces (mean +/- SD: 53 +/- 19%) and lowest in foundries (23 +/- 16%); the former value suggests that respirable particulate exposure may be underestimated in substantial parts of welding work when only the occupational exposure limit for inhalable particulates is taken for compliance testing. CONCLUSIONS: Simple compliance with the limit for inhalable particulates is not sufficient, and the limit for respirable particulates should also be simultaneously cleared.

Dust↗

Keeling plots for hummingbirds: a method to estimate carbon isotope ratios of respired CO(2) in small vertebrates.

The carbon isotope composition of an animal's breath reveals the composition of the nutrients that it catabolizes for energy. Here we describe the use of Keeling plots, a method widely applied in ecosystem ecology, to measure the delta(13)C of respired CO(2) of small vertebrates. We measured the delta(13)C of Rufous Hummingbirds ( Selasphorus rufus) in the laboratory and of Mourning ( Zenaida macroura) and White-winged ( Z. asiatica) Doves in the field. In the laboratory, when hummingbirds were fed a sucrose based C3 diet, the delta(13)C of respired CO(2) was not significantly different from that of their diet (delta(13)C(C3 diet)). The delta(13)C of respired CO(2) for C3 fasted birds was slightly, albeit significantly, depleted in delta(13)C relative to delta(13)C(C3 diet). Six hours after birds were shifted to a sucrose based C4 diet, the isotopic composition of their breath revealed that birds were catabolizing a mixture of nutrients derived from both the C3 and the C4 diet. In the field, the delta(13)C of respired CO(2) from Mourning and White-winged Doves reflected that of their diets: the CAM saguaro cactus ( Carnegeia gigantea) and C3 seeds, respectively. Keeling plots are an easy, effective and inexpensive method to measure delta(13)C of respired CO(2) in the lab and the field.

Animal Nutritional Physiological Phenomena↗

Endogenous benzodiazepine system and regulation of respiration in the cat.

Benzodiazepines, a class of drugs widely used as anxiolytics, can induce a depression of respiration. This study was designed to determine if endogenous benzodiazepine ligands could act in a similar fashion and exert a tonic inhibitory influence on respiration. Administration of a benzodiazepine antagonist should then facilitate respiration. This might be especially visible in hypoxia, the condition characterized by both central respiratory depression and potentially enhanced benzodiazepine expression. We addressed this issue by comparing the effects on the phrenic neurogram of the specific benzodiazepine antagonist flumazenil (200 micrograms i.v. boluses) in the contrasting conditions of hypoxia and hyperoxia in anesthetized, both spontaneously breathing and paralyzed ventilated cats. Contrary to our hypothesis, flumazenil showed a modest but definite inhibitory effect on respiration. Flumazenil also lengthened the duration of the Hering-Breuer inspiratory inhibition. The respiratory depression was neither related to chemical drive nor to the GABA receptor complex, for it was sustained after antagonism of GABA with picrotoxin and bicuculline. We conclude that the endogenous benzodiazepine system is unlikely to play an inhibitory role in the regulation of respiration. The physiologic role of this system remains to be established.

Animals↗

Motility pattern and lung respiration of embryonic chicks under the influence of L-thyroxine and thiourea.

Pressure changes in the air cell and at the egg shell have been used to monitor respiratory and somatic movements of embryonic chicks. During the prehatching period a phase of reduced activity is observed. Pulmonary respiration is initiated during this phase. Exogenous L-thyroxine exerts an accelerating effect on the hatching process and on the onset of the phase of reduced motility and of lung respiration. In thiourea-treated embryos the opposite effects on the hatching process and on the motility and respiration pattern are registered. When, however, the egg shell above the air cell was sealed with glue, times of hatching and of the beginning of lung respiration were similar to those of controls, although pipping the egg shell occurred earlier than normal. It is suggested that the effects of L-thyroxine and thiourea on the hatching process are caused by a premature or delayed onset, respectively, of pulmonary respiration.

Animals↗

Somatostatin inhibition of fictive respiration is modulated by pH.

We studied the respiratory effects of the tetradecapeptide somatostatin (SST) upon fictive respiration using the in vitro brain stem spinal cord preparation from new-born mouse. We found that SST inhibits respiration, an effect that was potentiated when the chemical drive to respiration was increased. SST inhibited fictive respiration decreasing both the frequency and amplitude in a dose-dependent way. SST inhibition was not antagonized by cyclosomatostatin (cyclo [7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)]), a putative SST antagonist, which in contrast behaved as a partial agonist. When the chemical drive to respiration was increased, by lowering the pH of the brain stem superfusion medium from 7.4 to 7.3, the inhibitory effect of SST on respiratory frequency was potentiated. These results suggest an interaction between SST and respiratory central chemoreception in new-born mouse.

Animals↗

Control of skeletal muscle mitochondria respiration by adenine nucleotides: differential effect of ADP and ATP according to muscle contractile type in pigs.

Skeletal muscle exhibits considerable variation in mitochondrial content among fiber types, but it is less clear whether mitochondria from different fiber types also present specific functional and regulatory properties. The present experiment was undertaken on ten 170-day-old pigs to compare functional properties and control of respiration by adenine nucleotides in mitochondria isolated from predominantly slow-twitch (Rhomboideus (RM)) and fast-twitch (Longissimus (LM)) muscles. Mitochondrial ATP synthesis, respiratory control ratio (RCR) and ADP-stimulated respiration with either complex I or II substrates were significantly higher (25-30%, P<0.05) in RM than in LM mitochondria, whereas no difference was observed for basal respiration. Based on mitochondrial enzyme activities (cytochrome c oxidase [COX], F0F1-ATPase, mitochondrial creatine kinase [mi-CK]), the higher ADP-stimulated respiration rate of RM mitochondria appeared mainly related to a higher maximal oxidative capacity, without any difference in the maximal phosphorylation potential. Mitochondrial K(m) for ADP was similar in RM (4.4+/-0.9 microM) and LM (5.9+/-1.2 microM) muscles (P>0.05) but the inhibitory effect of ATP was more marked in LM (P<0.01). These findings demonstrate that the regulation of mitochondrial respiration by ATP differs according to muscle contractile type and that absolute muscle oxidative capacity not only relies on mitochondrial density but also on mitochondrial functioning per se.

Adenosine Diphosphate↗

Inhibition of mitochondrial respiration and oxygen uptake in isolated rat renal tubular fragments by atractyloside.

Atractyloside (ATR) is widely used as a specific inhibitor of mitochondrial adenine nucleotide translocase and it is also a potent nephrotoxin that selectively injures the proximal tubule in vivo. This regioselectivity has been attributed to the prominence of mitochondria in the proximal tubule cells, but there have been no investigations to confirm this. In order to better understand the molecular basis of ATR-induced renal injury, oxidative phosphorylation was studied in freshly isolated rat proximal tubular and glomeruli fragments, and in isolated rat renal cortical mitochondria. In isolated renal mitochondrial, ATR significantly inhibited state 3 respiration in a dose-dependent manner, with the maximum inhibition achieved at the highest ATR concentration. Low doses of ATR (53 microM) inhibited respiration by 50%, an effect which was reversed by 2.5 mumol ADP. 2,4-Dinitrophenol (5 mM), which stimulated respiration in control mitochondria, failed to do this in the presence of ATR. Basal oxygen consumption was significantly inhibited by ATR (> 50 microM) in proximal tubule previously incubated for 1 h at 37 degrees C. The concentration-dependent inhibition of oxygen uptake by the proximal tubule was maintained in the presence of 1 mM ouabain or 0.25 mg/ml nystatin. Glomeruli have active mitochondrial respiration (about half that of the proximal tubules), but were not affected by ATR at concentrations up to 500 microM. These data demonstrates that both purified renal mitochondria and freshly isolated fragments of the proximal tubule exposed to ATR in vitro exhibit similar alteration in respiratory parameters that demonstrate inhibition of state 3 mitochondrial respiration, but there was no significant effect on glomeruli cells. Thus, the inhibition of oxidative phosphorylation may be an early event in ATR-induced nephrotoxicity, where the prominence of mitochondria in the proximal tubule explain, in part, the localised injury. The resistance of the glomeruli suggest that preferential transport of ATR may also contribute to the sensitivity of the proximal tubule.

Animals↗

Effects of tramadol and meperidine on respiration, plasma catecholamine concentrations, and hemodynamics.

STUDY OBJECTIVE: To evaluate the effects of high analgesic doses of tramadol and meperidine on respiration, plasma catecholamine concentrations, and hemodynamic parameters. STUDY DESIGN: Randomized, double-blind, cross-over, controlled volunteer study. SETTING: Laboratory at a university hospital. SUBJECTS: 8 healthy male volunteers. INTERVENTIONS: Tramadol was given as a 150 mg bolus plus a succeeding 3-hour steady infusion of 250 mg (83.3 mg/hr). Meperidine was given in a similar manner as a bolus dose of 112.5 mg plus 187.5 mg in a 3-hour steady infusion (62.5 mg/hr). Experimental pain was induced using a tourniquet. MEASUREMENTS AND MAIN RESULTS: Respiration was studied noninvasively with respiratory inductive plethysmography and pulse oximetry. Arterial line was used for measurement of hemodynamics and blood sampling. Tramadol did not have any clinically significant effects on respiration, breathing pattern, or hemodynamics, but an increase in plasma epinephrine levels was noted. Meperidine bolus decreased tidal volume (p < 0.05, difference from baseline) and pulse oxygen saturation (from 97% to 94%, p < 0.05), but during the succeeding infusion, the respiratory drive, measured as mean inspiratory flow, was enhanced (p < 0.05 difference from baseline), and the respiratory parameters returned to baseline level. No change in hemodynamics was noted, but a significant increase in plasma norepinephrine and epinephrine levels (from 0.9 to 1.6 nmol/L and from 0.3 to 0.8 nmol/L, respectively; p < 0.05) was observed after meperidine administration. Tramadol caused nausea more often than meperidine (p < 0.05, between treatments). CONCLUSIONS: Tramadol exhibited a minimal effect on respiration and breathing pattern in healthy volunteers. The respiratory effects of meperidine bolus were predictable with decreasing tidal volume and pulse oxygen saturation. In contrast, during meperidine infusion, adequate respiration was preserved despite the large amount of meperidine infused.

Adult↗

Protective effect of creatine against inhibition by methylglyoxal of mitochondrial respiration of cardiac cells.

Previous publications from our laboratory have shown that methylglyoxal inhibits mitochondrial respiration of malignant and cardiac cells, but it has no effect on mitochondrial respiration of other normal cells [Biswas, Ray, Misra, Dutta and Ray (1997) Biochem. J. 323, 343-348; Ray, Biswas and Ray (1997) Mol. Cell. Biochem. 171, 95-103]. However, this inhibitory effect of methylglyoxal is not significant in cardiac tissue slices. Moreover, post-mitochondrial supernatant (PMS) of cardiac cells could almost completely protect the mitochondrial respiration against the inhibitory effect of methylglyoxal. A systematic search indicated that creatine present in cardiac cells is responsible for this protective effect. Glutathione has also some protective effect. However, creatine phosphate, creatinine, urea, glutathione disulphide and beta-mercaptoethanol have no protective effect. The inhibitory and protective effects of methylglyoxal and creatine respectively on cardiac mitochondrial respiration were studied with various concentrations of both methylglyoxal and creatine. Interestingly, neither creatine nor glutathione have any protective effect on the inhibition by methylglyoxal on the mitochondrial respiration of Ehrlich ascites carcinoma cells. The creatine and glutathione contents of several PMS, which were tested for the possible protective effect, were measured. The activities of two important enzymes, namely glyoxalase I and creatine kinase, which act upon glutathione plus methylglyoxal and creatine respectively, were also measured in different PMS. Whether mitochondrial creatine kinase had any role in the protective effect of creatine had also been investigated using 1-fluoro-2,4-dinitrobenzene, an inhibitor of creatine kinase. The differential effect of creatine on mitochondria of cardiac and malignant cells has been discussed with reference to the therapeutic potential of methylglyoxal.

Animals↗