scholarly journals Propofol-Induced Mitochondrial and Contractile Dysfunction of the Rat Ventricular Myocardium

2016 ◽  
pp. S601-S609 ◽  
Author(s):  
M. GRUNDMANOVÁ ◽  
D. JARKOVSKÁ ◽  
A. SÜß ◽  
Z. TŮMA ◽  
M. MARKOVÁ ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Complex I ◽  
Ventricular Myocardium ◽  
Myocardial Contraction ◽  
Complex Iii ◽  
Adult Rats ◽  
Arterial Blood ◽  
Cardiovascular Side Effects ◽  
Hypnotic Agent ◽  
The Right

Propofol is a short-acting hypnotic agent used in human medicine for sedation and general anesthesia. Its administration can be associated with serious cardiovascular side-effects that include decrease in arterial blood pressure and cardiac output. The aim of the present study was to evaluate propofol effects on mitochondrial respiration, myocardial contractility and electrophysiology in the same samples isolated from the heart ventricles of adult rats. Mitochondrial oxygen consumption was measured in permeabilized samples dissected from free walls of both ventricles using high-resolution respirometry. State LEAK was determined with malate and glutamate. Active respiration was induced by ADP (state PI) and further by succinate, a Complex II substrate (PI+II). Rotenone was injected to measure state PII. Antimycin A, a Complex III inhibitor was used to determine residual oxygen consumption (ROX). N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride and ascorbate were injected simultaneously for respirometric assay of cytochrome c oxidase activity (CIV). Isometric contractions and membrane potentials were determined on multicellular preparations isolated from right and left ventricles. Propofol concentrations used ranged from 0.005 to 0.5 mmol/l. All respiratory parameters were significantly higher in the left control ventricles compared to the right ones. Propofol significantly decreased Complex I activity at concentration 0.025 mmol/l and papillary muscle contraction force at 0.1 mmol/l. Propofol did not affect action potential duration at any concentration studied. Our study suggests that mechanisms contributing to the impaired myocardial contraction during propofol anesthesia might include also mitochondrial dysfunction manifested by compromised activity of the respiratory Complex I.

scholarly journals Impact of diabetes-associated lipoproteins on oxygen consumption and mitochondrial enzymes in porcine aortic endothelial cells.

2010 ◽  
Vol 57 (4) ◽  
Author(s):  
Xueping Xie ◽  
Subir Roy Chowdhury ◽  
Ganesh Sangle ◽  
Garry X Shen
Keyword(s):  
Endothelial Cells ◽  
Oxygen Consumption ◽  
Membrane Potential ◽  
Cytochrome C ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Complex Iii ◽  
Mitochondrial Enzymes ◽  
Key Enzymes ◽  
Cytochrome C Reductase

Impairments in mitochondrial function have been proposed to play an important role in the pathogenesis of diabetes. Atherosclerotic coronary artery disease (CAD) is the leading cause of mortality in diabetic patients. Mitochondrial dysfunction and increased production of reactive oxygen species (ROS) are associated with diabetes and CAD. Elevated levels of glycated low density lipoproteins (glyLDL) and oxidized LDL (oxLDL) were detected in patients with diabetes. Our previous studies demonstrated that oxLDL and glyLDL increased the generation of ROS and altered the activities of antioxidant enzymes in vascular endothelial cells (EC). The present study examined the effects of glyLDL and oxLDL on mitochondrial respiration, membrane potential and the activities and proteins of key enzymes in mitochondrial electron transport chain (mETC) in cultured porcine aortic EC (PAEC). The results demonstrated that glyLDL or oxLDL significantly reduced oxygen consumption in Complex I, II/III and IV of mETC in PAEC compared to LDL or vehicle control using oxygraphy. Incubation with glyLDL or oxLDL significantly reduced mitochondrial membrane potential, the activities of mitochondrial ETC enzymes - NADH dehydrogenase (Complex I), succinate cytochrome c reductase (Complex II + III), ubiquinol cytochrome c reductase (Complex III), and cytochrome c oxidase (Complex IV) in PAEC compared to LDL or control. Treatment with oxLDL or glyLDL reduced the abundance of subunits of Complex I, ND1 and ND6 in PAEC. However, the effects of oxLDL on mitochondrial activity and proteins were not significantly different from glyLDL. The findings suggest that the glyLDL or oxLDL impairs mitochondrial respiration, as a result from the reduction of the abundance of several key enzymes in mitochondria of vascular EC, which potentially may lead to oxidative stress in vascular EC, and the development of diabetic vascular complications.

The effects of basic fibroblast growth factor in an animal model of acute mechanically induced right ventricular hypertrophy

2012 ◽  
Vol 22 (4) ◽  
pp. 436-442
Author(s):  
Vladimiro L. Vida ◽  
Arben Dedja ◽  
Elisabetta Faggin ◽  
Simone Speggiorin ◽  
Massimo A. Padalino ◽  
...  
Keyword(s):  
Growth Factor ◽  
Right Ventricular ◽  
Continuous Infusion ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Ventricular Myocardium ◽  
Fibroblast Growth ◽  
Adult Rats ◽  
The Right ◽  
Basic Fibroblastic Growth Factor

AbstractObjectiveTo evaluate the effect of a continuous infusion of basic fibroblast growth factor on the adaptive potential of the right ventricular myocardium after 30 days of mechanically induced overload in rats.Materials and methodsWe banded the pulmonary trunk, so as to increase the systolic workload of the right ventricle, in six Lewis/HanHsd rats at the age of 11 weeks, using six adult rats as controls. The six adult rats were also banded and received an additional continuous infusion of basic fibroblastic growth factor, using six rats with a continuous infusion of basic fibroblastic growth factor only as controls. We analysed the functional adaptation and structural changes of the right ventricular myocardium, blood vessels, and interstitial tissue 30 days after the increased afterload.ResultsThe pulmonary artery banding induced an increase in the right ventricular free wall thickness of banded rats when compared with controls, which was mainly justified by an increase in cardiomyocyte area and in the percentage of extracellular fibrosis. The infusion of basic fibroblastic growth factor promotes a more extensive capillary network in banded rats (p < 0.001), which modulates the compensatory response of the right ventricle, promoting the hypertrophy of contractile elements and limiting the areas in which fibrosis develops (p < 0.001).ConclusionsThe subcutaneous infusion with osmotic pumps was a valid and reproducible method of delivering basic fibroblast growth factor to heart tissue. This infusion contributed to better preserve the right ventricular capillary network, hampering the development of interstitial fibrosis.

Age is a risk factor for maladaptive changes in rats exposed to increased pressure loading of the right ventricular myocardium

2007 ◽  
Vol 17 (2) ◽  
pp. 202-211 ◽  
Author(s):  
Vladimiro L. Vida ◽  
Annalisa Angelini ◽  
Simonetta Ausoni ◽  
Alessandra Bilardi ◽  
Carlo Ori ◽  
...  
Keyword(s):  
Risk Factor ◽  
Right Ventricle ◽  
Right Ventricular ◽  
Age Groups ◽  
Ventricular Myocardium ◽  
P Value ◽  
Interstitial Tissue ◽  
Adult Rats ◽  
Functional Changes ◽  
The Right

Objective: To study the adaptive potential of the right ventricular myocardium after 30 days of mechanical-induced overload in rats from two different age groups. Materials and methods: We banded the pulmonary trunk, so as to increase the systolic work load of the right ventricle, in 19 adult Sprague-Dawley rats at the age of 10 weeks, and 16 weanlings when they were 3 weeks-old, using 10 adults and 10 weanlings as controls. We analysed the functional adaptation and structural changes of the right ventricular myocardium, blood vessels and interstitial tissue after 30 days of increased afterload. Results: The increased workload induced an increase of the right ventricular weight and free wall thickness in animals from both age groups when compared to controls. These changes were mostly related to cardiomyocytic hypertrophy, as confirmed by the expression of myocardial hypertrophic markers, without any apparent increase of their number, a “reactive” fibrosis especially evident in the adult rats, with p-value less than 0.0001, and a more extensive neocapillary network in the weanlings compared to the adults aubsequent to banding, the p-value being less than 0.0001. Conclusion: In response to right ventricular afterload, weanlings showed a higher adaptive capillary growth, which hampered the development of fibrosis as seen in the adult rats. Age seems to be a risk factor for adverse structural-functional changes of right ventricle subjected to increased workload.

scholarly journals Potent inhibition of tumour cell proliferation and immunoregulatory function by mitochondria-targeted atovaquone

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Gang Cheng ◽  
Micael Hardy ◽  
Paytsar Topchyan ◽  
Ryan Zander ◽  
Peter Volberding ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Cancer Cells ◽  
Complex I ◽  
Complex Iii ◽  
Antiproliferative Effect ◽  
Mitochondrial Complex ◽  
Mitochondrial Target ◽  
Potent Inhibition ◽  
Alkyl Side Chains ◽  
First Time

Abstract The FDA-approved prophylactic antimalarial drug atovaquone (ATO) recently was repurposed as an antitumor drug. Studies show that ATO exerts a profound antiproliferative effect in several cancer cells, including breast, ovarian, and glioma. Analogous to the mechanism of action proposed in parasites, ATO inhibits mitochondrial complex III and cell respiration. To enhance the chemotherapeutic efficacy and oxidative phosphorylation inhibition, we developed a mitochondria-targeted triphenylphosphonium-conjugated ATO with varying alkyl side chains (Mito4-ATO, Mito10-ATO, Mito12-ATO, and Mito16-ATO). Results show, for the first time, that triphenylphosphonium-conjugated ATO potently enhanced the antiproliferative effect of ATO in cancer cells and, depending upon the alkyl chain length, the molecular target of inhibition changes from mitochondrial complex III to complex I. Mito4-ATO and Mito10-ATO inhibit both pyruvate/malate-dependent complex I and duroquinol-dependent complex III-induced oxygen consumption whereas Mito12-ATO and Mito16-ATO inhibit only complex I-induced oxygen consumption. Mitochondrial target shifting may have immunoregulatory implications.

scholarly journals Effect of increasing concentrations of serotonin and adrenaline on contractility myocardium of the right ventricle of the heart of adult rats

2021 ◽  
Vol 103 (3) ◽  
pp. 26-30
Author(s):  
Meruyert Akhmetova ◽  
◽  
Razina Ramazanovna Nigmatullina ◽  
Farida Anvarovna Mindubaуeva ◽  
Gulmira Tykezhanova ◽  
...  
Keyword(s):  
Right Ventricle ◽  
Adrenergic Receptors ◽  
Negative Inotropic Effect ◽  
Ventricular Myocardium ◽  
The Body ◽  
Inotropic Response ◽  
Adult Rats ◽  
The Right

In recent years progress has been evident in studies of the importance of serotonin in the physiological and pathological processes of the body and its mechanisms. The role of the serotonin system in the development of diseases such as atherosclerosis, arterial hypertension, and ischemic heart disease is largely discussed. In the myocardium of mammals and humans two types of serotonin receptors (5-HT2 and 5-HT4) have been identified. The activity of the heart is also controlled by the action of catecholamines on the adrenergic receptors of cardiomyocytes. In the implementation of the contraction of cardiomyocytes in the hearts of humans and animals there is also activation of adrenergic receptors, such as β1, β4 and α1A. Serotonin and adrenaline are regulators and modulators of physiological processes in organism, which, under pathological conditions, turn into factors contributing to the development of the disease. In studies on myocardial contractility in vitro in adult rats we found that with an increase in each concentration of serotonin, depending on the dose, a positive inotropic response to the right ventricular myocardium was observed. The effect of serotonin at the last dose on the force of contraction of the right ventricle compared with the first dose increased by 48.3 %. However, with an increase in the dose of epinephrine, the positive inotropic response weakened. At the maximum concentration of 10.0 mM epinephrine, a negative inotropic effect of 10.4 % was observed compared to the previous concentration. Thus, despite the fact that the distribution and functional role of serotonergic receptors in the heart repeats the role of adrenergic receptors, the inotropic response of cardiomyocytes to serotonin and adrenaline is different.

scholarly journals Caspase-mediated loss of mitochondrial function and generation of reactive oxygen species during apoptosis

2003 ◽  
Vol 160 (1) ◽  
pp. 65-75 ◽  
Author(s):  
Jean-Ehrland Ricci ◽  
Roberta A. Gottlieb ◽  
Douglas R. Green
Keyword(s):  
Reactive Oxygen Species ◽  
Oxygen Consumption ◽  
Electron Transport ◽  
Cytochrome C ◽  
Mitochondrial Function ◽  
Complex I ◽  
Caspase 3 ◽  
Reactive Oxygen ◽  
Complex Iii ◽  
Oxygen Species

During apoptosis, the permeabilization of the mitochondrial outer membrane allows the release of cytochrome c, which induces caspase activation to orchestrate the death of the cell. Mitochondria rapidly lose their transmembrane potential (ΔΨm) and generate reactive oxygen species (ROS), both of which are likely to contribute to the dismantling of the cell. Here we show that both the rapid loss of ΔΨm and the generation of ROS are due to the effects of activated caspases on mitochondrial electron transport complexes I and II. Caspase-3 disrupts oxygen consumption induced by complex I and II substrates but not that induced by electron transfer to complex IV. Similarly, ΔΨm generated in the presence of complex I or II substrates is disrupted by caspase-3, and ROS are produced. Complex III activity measured by cytochrome c reduction remains intact after caspase-3 treatment. In apoptotic cells, electron transport and oxygen consumption that depends on complex I or II was disrupted in a caspase-dependent manner. Our results indicate that after cytochrome c release the activation of caspases feeds back on the permeabilized mitochondria to damage mitochondrial function (loss of ΔΨm) and generate ROS through effects of caspases on complex I and II in the electron transport chain.

Oxygen Transport by the Circulatory System of the Green Iguana (Iguana Iguana) at Different Body Temperatures

1966 ◽  
Vol 44 (1) ◽  
pp. 77-92
Author(s):  
VANCE A. TUCKER
Keyword(s):  
Heart Rate ◽  
Oxygen Consumption ◽  
Stroke Volume ◽  
Venous Blood ◽  
Circulatory System ◽  
Body Temperatures ◽  
Iguana Iguana ◽  
Arterial Blood ◽  
Percentage Saturation ◽  
The Right

1. Oxygen consumption, stroke volume, heart rate and the difference in oxygen contents of arterial and venous blood (AV difference) were measured in the resting iguana at body temperatures of 20, 30 and 38° C. Oxygen consumption increased by a factor of 4.4 as temperature changed from 20 to 38° C. This increase was accomplished by a decrease in stroke volume by a factor of 0.5, and increases in heart rate and AV difference by factors of 4.1 and 2.2, respectively. 2. During activity increases in oxygen consumption at a given temperature were accompanied by increases in heart rate and AV difference, but stroke volume did not change consistently. 3. The percentage saturation of arterial blood with oxygen in the iguana may differ in the right and left systemic arches. In some lizards, both arches carried equally saturated blood, but in others the left arch carried blood containing less oxygen than the right arch. 4. An hypothesis is presented concerning the function of the double systemic arches and incompletely divided ventricles of lizards. These structures may be a device for permitting increased cardiac output associated with thermoregulation to bypass the lungs while maintaining a supply of well-oxygenated blood to the head. 5. Data on oxygen capacity, percentage saturation of blood with oxygen, haematocrit and pH of iguana blood are included in this study.

scholarly journals DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yvanna Pantner ◽  
Rohini Polavarapu ◽  
Lih-Shen Chin ◽  
Lian Li ◽  
Yuuki Shimizu ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Complex I ◽  
Ischemia Reperfusion ◽  
Active Form ◽  
Atp Synthesis ◽  
Complex Iii ◽  
Ischemic Heart ◽  
Atp Production ◽  
Myocardial Ischemia Reperfusion ◽  
Complex Activities

AbstractDJ-1 is a ubiquitously expressed protein that protects cells from stress through its conversion into an active protease. Recent work found that the active form of DJ-1 was induced in the ischemic heart as an endogenous mechanism to attenuate glycative stress—the non-enzymatic glycosylation of proteins. However, specific proteins protected from glycative stress by DJ-1 are not known. Given that mitochondrial electron transport proteins have a propensity for being targets of glycative stress, we investigated if DJ-1 regulates the glycation of Complex I and Complex III after myocardial ischemia–reperfusion (I/R) injury. Initial studies found that DJ-1 localized to the mitochondria and increased its interaction with Complex I and Complex III 3 days after the onset of myocardial I/R injury. Next, we investigated the role DJ-1 plays in modulating glycative stress in the mitochondria. Analysis revealed that compared to wild-type control mice, mitochondria from DJ-1 deficient (DJ-1 KO) hearts showed increased levels of glycative stress following I/R. Additionally, Complex I and Complex III glycation were found to be at higher levels in DJ-1 KO hearts. This corresponded with reduced complex activities, as well as reduced mitochondrial oxygen consumption ant ATP synthesis in the presence of pyruvate and malate. To further determine if DJ-1 influenced the glycation of the complexes, an adenoviral approach was used to over-express the active form of DJ-1(AAV9-DJ1ΔC). Under I/R conditions, the glycation of Complex I and Complex III were attenuated in hearts treated with AAV9-DJ1ΔC. This was accompanied by improvements in complex activities, oxygen consumption, and ATP production. Together, this data suggests that cardiac DJ-1 maintains Complex I and Complex III efficiency and mitochondrial function during the recovery from I/R injury. In elucidating a specific mechanism for DJ-1’s role in the post-ischemic heart, these data break new ground for potential therapeutic strategies using DJ-1 as a target.

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