Myocardial and coronary sinus purines as indicators of pig heart energy metabolism during reperfusion after extracorporeal circulation

Safranow, Krzysztof; Rzeuski, Ryszard; Listewnik, Mariusz; Jakubowska, Katarzyna; Rać, Monika; Olszewska, Maria; Chlubek, Dariusz

doi:10.1111/j.1365-201x.2005.01454.x

Cited by 5 publications

(4 citation statements)

References 31 publications

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“…Within the total NAD and NADP pool, NADP makes up ϳ6% of the total pool (24). The majority of NADH measured is thought to originate from the mitochondria (4,14).…”

Section: Discussionmentioning

confidence: 99%

O₂delivery and redox state are determinants of compartment-specific reactive O₂species in myocardial reperfusion

Stoner¹,

Clanton²,

Aune³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Stoner JD, Clanton TL, Aune SE, Angelos MG. O2 delivery and redox state are determinants of compartment-specific reactive O2 species in myocardial reperfusion. Am J Physiol Heart Circ Physiol 292: H109 -H116, 2007. First published October 6, 2006; doi:10.1152/ajpheart.00925.2006.-Reperfusion of the ischemic myocardium leads to a burst of reactive O2 species (ROS), which is a primary determinant of postischemic myocardial dysfunction. We tested the hypothesis that early O2 delivery and the cellular redox state modulate the initial myocardial ROS production at reperfusion. Isolated buffer-perfused rat hearts were loaded with the fluorophores dihydrofluorescein or Amplex red to detect intracellular and extracellular ROS formation using surface fluorometry at the left ventricular wall. Hearts were made globally ischemic for 20 min and then reperfused with either 95% or 20% O2-saturated perfusate. The same protocol was repeated in hearts loaded with dihydrofluorescein and perfused with either 20 or 5 mM glucose-buffered solution to determine relative changes in NADH and FAD. Myocardial O2 delivery during the first 5 min of reperfusion was 84.7 Ϯ 4.2 ml O2/min with 20% O2-saturated buffer and 354.4 Ϯ 22.8 ml O2/min with 95% O2 (n ϭ 8/group, P Ͻ 0.001). The fluorescein signal (intracellular ROS) was significantly increased in hearts reperfused with 95% O2 compared with 20% O2. However, the resorufin signal (extracellular ROS) was significantly increased with 20% O2 compared with 95% O2 during reperfusion. Perfusion of hearts with 20 mM glucose reduced the ⅐ NADH during ischemia (P Ͻ 0.001) and the ⅐ ROS at reperfusion (P Ͻ 0.001) compared with 5.5 mM-perfused glucose hearts. In conclusion, initial O2 delivery to the ischemic myocardium modulates a compartment-specific ROS response at reperfusion such that high O2 delivery promotes intracellular ROS and low O2 delivery promotes extracellular ROS. The redox state that develops during ischemia appears to be an important precursor for reperfusion ROS production. ischemia; reoxygenation; oxygen radicals REINTRODUCTION OF O 2 to the globally ischemic heart triggers a cascade of reperfusion events, including an initial burst of reactive O 2 species (ROS). Studies of the isolated heart suggest that ROS production peaks within the first few minutes of reperfusion (37). Although ROS at low levels appear to have signaling capabilities that are cardioprotective, particularly during ischemia (13), it is thought that the much larger ROS burst at the onset of reperfusion impairs recovery of ventricular function (8). Cell injury from ROS may be wide ranging and include direct injury to membrane lipids, oxidative modification of protein and deoxyribonucleic acid, and cellular signaling for mitochondrial apoptotic transition (32). Known sources for ROS during reperfusion include endothelial xanthine oxidase (30), NAD(P)H oxidase (12), and the mitochondrial electron transport chain (complexes 1 and 3) (6), although other sources are also possible.The role of ROS, including the ROS burst...

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“…Within the total NAD and NADP pool, NADP makes up ϳ6% of the total pool (24). The majority of NADH measured is thought to originate from the mitochondria (4,14).…”

Section: Discussionmentioning

confidence: 99%

O₂delivery and redox state are determinants of compartment-specific reactive O₂species in myocardial reperfusion

Stoner¹,

Clanton²,

Aune³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…With regard to the purine metabolism in cardiac pathological process, findings demonstrate overwhelmingly that purine release is directly related to the rate of energy consumption in the heart, and is significantly connected to a wide range of cardiovascular activity, including dilating the coronary artery, reducing reperfusion injury, inhibiting cardiomyocyte apoptosis, and so on. Furthermore, this metabolic pathway is involved in the oxidative stress injury of cardiomyocytes caused by the release of reactive oxygen species ( Hisatome et al, 1990 ; Zucchi et al, 1990 ; Safranow et al, 2005 ; Sansbury et al, 2014 ). The sphingolipids are also known to play a pivotal role in signal transduction; growth and differentiation; immune response, proliferation, and apoptosis; inflammatory response; and other important signal molecules.…”

Section: Discussionmentioning

confidence: 99%

Potential cardiotoxicity induced by Euodiae Fructus: In vivo and in vitro experiments and untargeted metabolomics research

Zhang

Lü²,

Ren³

et al. 2022

Front. Pharmacol.

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Background: Euodiae Fructus, a well-known herbal medicine, is widely used in Asia and has also gained in popularity in Western countries over the last decades. It has known side effects, which have been observed in clinical settings, but few studies have reported on its cardiotoxicity.Methods: In the present study, experiments using techniques of untargeted metabolomics clarify the hazardous effects of Euodiae Fructus on cardiac function and metabolism in rats in situations of overdosage and unsuitable syndrome differentiation. In vitro assays are conducted to observe the toxic effects of evodiamine and rutaecarpine, two main chemical constituents of Euodiae Fructus, in H9c2 and neonatal rat cardiomyocytes (NRCMs), with their signaling mechanisms analyzed accordingly.Results: The cardiac cytotoxicity of evodiamine and rutaecarpine in in vivo experiments is associated with remarkable alterations in lactate dehydrogenase, creatine kinase, and mitochondrial membrane potential; also with increased intensity of calcium fluorescence, decreased protein expression of the cGMP-PKG pathway in H9c2 cells, and frequency of spontaneous beat in NRCMs. Additionally, the results in rats with Yin deficiency receiving a high-dosage of Euodiae Fructus suggest obvious cardiac physiological dysfunction, abnormal electrocardiogram, pathological injuries, and decreased expression of PKG protein. At the level of endogenous metabolites, the cardiac side effects of overdose and irrational usage of Euodiae Fructus relate to 34 differential metabolites and 10 metabolic pathways involving among others, the purine metabolism, the glycerophospholipid metabolism, the glycerolipid metabolism, and the sphingolipid metabolism.Conclusion: These findings shed new light on the cardiotoxicity induced by Euodiae Fructus, which might be associated with overdose and unsuitable syndrome differentiation, that comes from modulating the cGMP-PKG pathway and disturbing the metabolic pathways of purine, lipid, and amino acid. Continuing research is needed to ensure pharmacovigilance for the safe administration of Chinese herbs in the future.

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“…Determinations of purines with highperformance liquid chromatography were carried out according to the validated method of SAFRANOW et al (2005), modified to account for material specificity. A small fragment was cut off from the foot at maximum contraction, with care to maintain consistency as to size and site of collection.…”

Section: Methodsmentioning

confidence: 99%

Guanine and Inosine Nucleotides, Nucleosides and Oxypurines in Snail Muscles as Potential Biomarkers of Fluoride Toxicity

Rać¹,

Safranow²,

Dołęgowska³

et al. 2007

folia biol (krakow)

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The aim of the present study was to determine the toxicity of fluorides on energy metabolism in muscles of the Helix aspersa maxima snail. Qualitative and quantitative analysis of purine compounds was performed in slices of foot from mature snails with high-performance liquid chromatography. Fluoride concentrations were measured using an ion-selective electrode and gas chromatography. The results show that exposure to fluoride pollution was accompanied by a statistically significant increase in fluoride concentrations in soft tissues. This effect was already noticeable with the smallest fluoride dose. Accumulation was greatest in the shell. There is a significant and positive correlation between fluoride concentrations in foot muscles and guanine and inosine nucleotides or uridine content. The content of low-energy guanylate, inosylate and oxypurine in foot muscles significantly increased with rising dose of fluoride. The difference as compared with controls was significant only for the highest dose of fluoride. Interestingly, uric acid, the final product of purine catabolism, dominated quantitatively in the foot muscles of snails. In conclusion, increased low-energy guanylate and inosylate as well as decreased xanthine concentrations in snail muscle can be indicators of the toxic influence of fluoride on the organism. The measuring of fluoride accumulation in the shell is the most suitable bioindicator of fluoride pollution in the environment.

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Myocardial and coronary sinus purines as indicators of pig heart energy metabolism during reperfusion after extracorporeal circulation

Cited by 5 publications

References 31 publications

O₂delivery and redox state are determinants of compartment-specific reactive O₂species in myocardial reperfusion

O₂delivery and redox state are determinants of compartment-specific reactive O₂species in myocardial reperfusion

Potential cardiotoxicity induced by Euodiae Fructus: In vivo and in vitro experiments and untargeted metabolomics research

Guanine and Inosine Nucleotides, Nucleosides and Oxypurines in Snail Muscles as Potential Biomarkers of Fluoride Toxicity

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Myocardial and coronary sinus purines as indicators of pig heart energy metabolism during reperfusion after extracorporeal circulation

Cited by 5 publications

References 31 publications

O2delivery and redox state are determinants of compartment-specific reactive O2species in myocardial reperfusion

O2delivery and redox state are determinants of compartment-specific reactive O2species in myocardial reperfusion

Potential cardiotoxicity induced by Euodiae Fructus: In vivo and in vitro experiments and untargeted metabolomics research

Guanine and Inosine Nucleotides, Nucleosides and Oxypurines in Snail Muscles as Potential Biomarkers of Fluoride Toxicity

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O₂delivery and redox state are determinants of compartment-specific reactive O₂species in myocardial reperfusion

O₂delivery and redox state are determinants of compartment-specific reactive O₂species in myocardial reperfusion