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At least 1,027 records · Page 57Linked to original sources
PubMed2001

Metabolic and structural abnormalities in dogs with early left ventricular dysfunction induced by incessant tachycardia.

OBJECTIVE: To assess morphologic and metabolic abnormalities in dogs with early left ventricular dysfunction (ELVD) induced by rapid right ventricular pacing (RRVP). ANIMALS: 7 Beagles. PROCEDURE: Plasma carnitine concentrations were measured before and after development of ELVD induced by RRVP. At the same times, transvenous endomyocardial biopsy was performed, and specimens were submitted for determination of myocardial carnitine concentrations and histologic, morphometric, and ultrastructural examination. RESULTS: In 4 dogs in which baseline plasma total carnitine concentration was normal, RRVP induced a decrease in myocardial total and free carnitine concentrations and an increase in myocardial esterified carnitine concentration. In 3 dogs in which baseline plasma total carnitine concentration was low, plasma and myocardial carnitine concentrations were unchanged after pacing. Structural changes associated with pacing included perinuclear vacuolization in 3 dogs. Morphometric analyses indicated there was a decrease in myofiber cross-sectional diameter and area following pacing. Electron microscopy revealed changes in myofibrils and mitochondria following pacing. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that moderate to severe alterations in myocyte cytoarchitecture are present in dogs with ELVD induced by RRVP and that in dogs with normal plasma carnitine concentrations, myocardial carnitine deficiency may be a biochemical marker of ELVD. Results also indicated that transvenous endomyocardial biopsy can be used to evaluate biochemical and structural myocardial changes in dogs with cardiac disease.

Animals↗
PubMed2005

Metabolic syndrome increases endogenous carbon monoxide production to promote hypertension and endothelial dysfunction in obese Zucker rats.

Vascular heme oxygenase (HO) metabolizes heme to form carbon monoxide (CO). Increased heme-derived CO inhibits nitric oxide synthase and can contribute to hypertension via endothelial dysfunction in Dahl salt-sensitive rats. Obese Zucker rats (ZR) are models of metabolic syndrome. This study tests the hypothesis that endogenous CO formation is increased and contributes to hypertension and endothelial dysfunction in obese ZR. Awake obese ZR showed increased respiratory CO excretion, which was lowered by HO inhibitor administration [zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) 25 micromol.kg(-1).24 h(-1) ip]. In awake obese ZR, chronically instrumented with femoral arterial catheters, blood pressure was elevated but was decreased by the HO inhibitor ZnDPBG. Body weight, blood glucose, glycated hemoglobin, plasma insulin, total and LDL cholesterol, oxidized LDL, and triglyceride levels were elevated in obese ZR, and, except for LDL cholesterol, were unchanged by HO inhibition. Total HO-1 protein levels were not different between lean and obese ZR aortas. In vitro experiments used isolated skeletal muscle arterioles with constant pressure and no flow, or constant midpoint, but altered endpoint pressures to establish graded levels of luminal flow. In obese ZR arterioles, responses to ACh and flow were attenuated. Acute in vitro pretreatment with an HO inhibitor, chromium mesoporphyrin, enhanced ACh and flow-induced dilation and abolished the differences between groups. Furthermore, exogenous CO prevented the restoration of flow-induced dilation by the HO inhibitor in obese ZR arterioles. These results suggest that HO-derived CO production is increased and promotes hypertension and arteriolar endothelial dysfunction in obese ZR with metabolic syndrome independent of affecting metabolic parameters.

Animals↗
PubMed1996

Proximal tubule dysfunction in cystine-loaded tubules: effect of phosphate and metabolic substrates.

Intracellular cystine loading by use of cystine dimethyl ester (CDME) results in a generalized inhibition in proximal tubule transport due, in part, to a decrease in intracellular ATP. The present study examined the importance of phosphate and metabolic substrates in the proximal tubule dysfunction produced by cystine loading. Proximal tubule intracellular phosphorus was 1.8 +/- 0.1 in control tubules and 1.1 +/- 0.1 nmol/mg protein in proximal tubules incubated in vitro with CDME P < 0.001). Infusion of sodium phosphate in rabbits and subsequent incubation of proximal tubules with a high-phosphate medium attenuated the decrease in proximal tubule respiration and prevented the decrease in intracellular ATP with cystine loading. Tricarboxylic acid cycle intermediates have been shown to preserve oxidative metabolism in phosphate-depleted proximal tubules. In proximal tubules incubated with either 1 mM valerate or butyrate, there was a 42 and 34% reduction (both P < 0.05) in the rate of oxygen consumption with cystine loading. However, tubules incubated with 1 mM succinate or citrate had only a 13 and 14% P = NS) reduction in the rate of oxygen consumption, respectively. These data are consistent with a limitation of intracellular phosphate in the pathogenesis of the proximal tubule dysfunction with cystine loading.

Adenosine Triphosphate↗
PubMed1994

Hepatic microcirculatory perfusion failure is a determinant of liver dysfunction in warm ischemia-reperfusion.

Hepatic ischemia-reperfusion (I/R) is characterized by circulatory and metabolic derangements, liver dysfunction, and tissue damage. However, little is known about the causative role of I/R-induced microcirculatory disturbance on the manifestation of postischemic reperfusion injury. Therefore, the intention of the study was to assess changes of hepatic microvascular perfusion (intravital fluorescence microscopy) as related to hepatic morphology (light/electron microscopy), hepatocellular integrity (serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities), and excretory function (bile flow). Sprague-Dawley rats were subjected to 20 minutes (group B, n = 9) and 60 minutes (group C, n = 9) of left hepatic lobar ischemia followed by 60 minutes of reperfusion. Sham-operated animals without ischemia served as controls (group A, n = 10). Lobar ischemia for 20 minutes followed by reperfusion resulted in a significant reduction of sinusoidal perfusion rate (93.9 +/- 1.4%; P < 0.05) and a decrease in erythrocyte flux (90.0 +/- 5.6%) when compared with controls (99.4 +/- 0.2 and 97.9 +/- 2.7%). This was accompanied by a significant increase of serum AST and ALT activities (P < 0.05) and a reduction of bile flow (P < 0.05). Prolongation of lobar ischemia (group C, 60 minutes) aggravated postischemic reperfusion injury (sinusoidal perfusion rate: 87.4 +/- 2.9%; erythrocyte flux: 62.1 +/- 8.4%) and was paralleled by severed hepatocellular damage. Electron microscopy of postischemic tissue demonstrated alteration of nonparenchymal cells (swelling of sinusoidal lining cells and widening of Disse's space) and substantial parenchymal cell damage (swelling of mitochondria, disarrangement of rough endoplasmatic reticulum, vacuolization, complete cytoplasmic degeneration). Initial postischemic increase in serum AST and ALT activities and reduction of bile flow directly correlated with the extent of microcirculatory failure (P < 0.01), ie, impairment of sinusoidal perfusion and decrease of erythrocyte flux, indicating the decisive role of microvascular perfusion failure for the manifestation of hepatic tissue damage and liver dysfunction.

Alanine Transaminase↗
PubMedDate not supplied

Plasma and erythrocyte magnesium concentrations in thyroid disease: relation to thyroid function and the duration of illness.

To clarify magnesium metabolism in thyroid dysfunction, plasma and erythrocyte magnesium concentrations (P-Mg, E-Mg) were determined in patients with untreated thyroid diseases and their relations to thyroid hormone levels and the duration of illness were examined. P-Mg was significantly lower in hyperthyroid patients than in euthyroid or hypothyroid individuals. E-Mg was significantly higher in hypothyroid patients than in hyperthyroid or euthyroid individuals. In the entire series of 84 subjects, both P-Mg and E-Mg showed significant negative correlations with thyroid hormone levels, but the correlations were greater in P-Mg than E-Mg. In hyperthyroid patients, both P-Mg and E-Mg were negatively correlated with the duration of illness, but this correlation was greater in E-Mg than P-Mg. Also, both P-Mg and E-Mg were significantly higher in patients with destructive thyroiditis with a short duration (0.5 months) such as subacute or painless thyroiditis than in patients with Graves' disease (4.9 months). These results suggest that magnesium metabolism in thyroid dysfunction is affected not only by thyroid hormone levels but also by the duration of illness.

Acute Disease↗
PubMedDate not supplied

[Hemodynamic and metabolic changes at various levels of cerebral dysfunction during severe traumatic coma (author's transl)].

Cerebral blood flow (DSC) and oxygen consumption were measured in a series of patients in the acute phase of severe brain injury, and the results analyzed as a function of the level of cerebral dysfunction determined clinically. The most frequent modifications were increased cerebral blood flow and reduced oxygen consumption, whatever the degree of dysfunction. Hemodynamic data has no prognostic value whereas oxygen consumption results are more valid. Increased cerebral blood flow is noted constantly in patients at a level of mesencephalic dysfunction. Reduced O2 consumption associated with increased blood flow is the result of a disturbance in the blood flow-metabolism ratio and could be due to cerebral vasodilatation. This great increase in cerebral vasodilatation observed in cerebral dysfunction syndromes is in favour of the existence of a central neurogenic system in the brain stem regulating cerebral blood circulation.

Brain↗
PubMed2003

Peroxisome proliferator-activated receptor alpha (PPARalpha) agonist treatment reverses PPARalpha dysfunction and abnormalities in hepatic lipid metabolism in ethanol-fed mice.

Proper function of the peroxisome proliferator-activated receptor alpha (PPARalpha) is essential for the regulation of hepatic fatty acid metabolism. Fatty acid levels are increased in liver during the metabolism of ethanol and should activate PPARalpha. However, recent in vitro data showed that ethanol metabolism inhibited the function of PPARalpha. We now report that ethanol feeding impairs fatty acid catabolism in the liver in part via blocking PPARalpha-mediated responses in C57BL/6J mice. Ethanol feeding decreased PPARalpha/retinoid X receptor alpha binding in electrophoretic mobility shift assay of liver nuclear extracts. mRNAs for PPAR-regulated genes were reduced (long chain and medium chain acyl-CoA dehydrogenases) or failed to be induced (acyl-CoA oxidase, liver carnitine palmitoyl-CoA transferase, very long chain acyl-CoA synthetase, very long chain acyl-CoA dehydrogenase) in livers of the ethanol-fed animals, and ethanol feeding did not increase the rate of fatty acid beta-oxidation. Wy14,643, a PPARalpha agonist, restored the DNA binding activity of PPARalpha/retinoid X receptor alpha, induced mRNA levels of PPARalpha target genes, stimulated the rate of fatty acid beta-oxidation, and prevented fatty liver in ethanol-fed animals. Impairment of PPARalpha function during ethanol consumption contributes to the development of alcoholic fatty liver, which can be overcome by Wy14,643.

Animals↗
PubMed2006

Is reversal of endothelial dysfunction by tea related to flavonoid metabolism?

Dietary flavonoids can improve endothelial function, but the response varies between individuals. Wide variability is also seen in flavonoid O-methylation, a major pathway of flavonoid metabolism. The O-methylation of flavonoids could alter activity, and thus influence any effect on endothelial function. The objective of the current analysis was to investigate whether variability in the endothelial function response to ingestion of tea, a rich source of flavonoids, is related to the degree of O-methylation of flavonoids. This relationship was investigated in two studies in which endothelium-dependent flow-mediated dilatation (FMD) of the brachial artery was assessed and urinary 4-O-methylgallic acid (4OMGA) excretion was used as a marker of the O-methylation of tea-derived flavonoids. In the first study, amongst participants consuming five cups of tea per day for 4 weeks, the degree of increase in 4OMGA excretion was inversely associated with the change in FMD responses (r -078, P=0.008). In the second study, there was a significant difference in the FMD responses to acute ingestion of three cups of tea between individuals with a low ( median) 4OMGA response (1.94 (sem 0.79) % and -0.25 (sem 0.53) %, respectively; P=0.03). That is, any improvement in FMD following ingestion of tea may be enhanced in individuals who O-methylate less of the absorbed flavonoids. The present results are consistent with the suggestion that differences in flavonoid metabolism may influence their effect on endothelial function. Thus, differences in flavonoid metabolism could be related to the level of benefit of dietary flavonoids on the risk of CVD.

Brachial Artery↗
PubMed2003

Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase.

OBJECTIVE: Plasma levels of an endogenous nitric oxide (NO) synthase inhibitor, asymmetric dimethylarginine (ADMA), are elevated in chronic renal failure, hypertension, and chronic heart failure. In patients with renal failure, plasma ADMA levels are an independent correlate of left ventricular ejection fraction. However, the cardiovascular effects of a systemic increase in ADMA in humans are not known. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled study in 12 healthy male volunteers, we compared the effects of intravenous low-dose ADMA and placebo on heart rate, blood pressure, cardiac output, and systemic vascular resistance at rest and during exercise. We also tested the hypothesis that ADMA is metabolized in humans in vivo by dimethylarginine dimethylaminohydrolase (DDAH) enzymes. Low-dose ADMA reduced heart rate by 9.2+/-1.4% from 58.9+/-2.0 bpm (P<0.001) and cardiac output by 14.8+/-1.2% from 4.4+/-0.3 L/min (P<0.001). ADMA also increased mean blood pressure by 6.0+/-1.2% from 88.6+/-3.4 mm Hg (P<0.005) and SVR by 23.7+/-2.1% from 1639.0+/-91.6 dyne. s. cm-5 (P<0.001). Handgrip exercise increased cardiac output in control subjects by 96.8+/-23.3%, but in subjects given ADMA, cardiac output increased by only 35.3+/-10.6% (P<0.05). DDAHs metabolize ADMA to citrulline and dimethylamine. Urinary dimethylamine to creatinine ratios significantly increased from 1.26+/-0.32 to 2.73+/-0.59 after ADMA injection (P<0.01). We estimate that humans generate approximately 300 micromol of ADMA per day, of which approximately 250 micromol is metabolized by DDAHs. CONCLUSIONS: This study defines the cardiovascular effects of a systemic increase in ADMA in humans. These are similar to changes seen in diseases associated with ADMA accumulation. Finally, our data also indicate that ADMA is metabolized by DDAHs extensively in humans in vivo.

Adult↗
PubMed2003

Identification of subjects with insulin resistance and beta-cell dysfunction using alternative definitions of the metabolic syndrome.

Recently, the metabolic syndrome (MetS) has attracted much attention as a risk cluster for cardiovascular disease. Although it is believed that individuals with the MetS have insulin resistance (IR), there are few data using direct measures of IR such as glucose clamps or frequently sampled intravenous glucose tolerance tests (FSIGTTs). We examined associations of MetS with FSIGTT-derived measures of insulin sensitivity and secretion among nondiabetic subjects in the Insulin Resistance Atherosclerosis Study. Two sets of MetS criteria were evaluated: those from the 1999 World Health Organization (WHO) and the 2001 National Cholesterol Education Program (NCEP). Both WHO and NCEP MetS definitions were significantly associated with risk of being in the lowest quartile of directly measured insulin sensitivity (P < 0.0001 for all subjects as well as within ethnic subgroups). However, the associations with WHO-MetS were stronger for all subjects combined (WHO: odds ratio [OR] = 10.2; 95% CI 7.5-13.9; NCEP: OR = 4.6; 3.4-6.2) and in separate analyses of non-Hispanic whites, blacks, and Hispanics. WHO and NCEP MetS definitions were also significantly associated with risk of being in the lowest quartile of insulin sensitivity-adjusted acute insulin response (AIR) and disposition index (DI; all P < 0.01), although the associations were generally weaker than those for insulin sensitivity and there was no difference between the two definitions in all subjects combined (low AIR, WHO: OR = 1.7, 1.2-2.4; NCEP: OR = 1.7, 1.2-2.5). There were, however, a number of ethnic differences, including a stronger association of NCEP-MetS with low AIR among blacks. WHO-MetS was significantly more sensitive than NCEP-MetS in detecting low insulin sensitivity (65.4 vs. 45.6%, respectively; P < 0.0001), with no significant differences in specificity between the definitions (84.4 vs. 84.6%; P = 0.91), although WHO-MetS had a larger area under the receiver operating characteristic curve (75% vs. 65%; P < 0.0001). In conclusion, although both the WHO and NCEP MetS criteria identify nondiabetic individuals with low insulin sensitivity, the associations were notably stronger using the WHO definition. The definitions are generally less useful for identifying those with low AIR or DI, although NCEP-MetS seems to differentiate black subjects with insulin secretion defects.

Black People↗
PubMed1976

[Blood proteins, thiol group metabolism and testosterone content in prostatic dysfunction].

A study was made of the blood serum proteins, thiol groups, aldolase activity, testosterone content in rabbits under conditions of insufficiency of the prostate gland caused by its suturing. It was revealed that at the late postoperative periods there was an increase in the blood serum proteins of albumin fraction, and a reduction of the thiol group level (SH-free, masked and disulfide). Aldolase activity increased at the early periods and then sharply fell. The incretory function of the testes was disturbed.

Animals↗
PubMed1992

[Coenzyme Q10: contractile dysfunction of the myocardial cell and metabolic therapy].

Coenzyme Q10, a mitoquinone involved in mitochondrial energy synthesis and the removal of free radicals, may be lacking in a number of cardiac pathologies leading to reduced contractile activity. The administration of exogenous coenzyme Q10 may help to improve contractile activity. In order to assess this hypothesis 63 patients suffering from altered myocardial contractile function (29 dilated cardiopathies, 15 valvular cardiopathies, 19 ischemic cardiopathies) which presented a NYHA class above 2 were selected. The study was open and patients were subdivided into two groups, one of which received conventional therapy alone whereas the other also received exogenous coenzyme Q10. After 4 months of follow-up clinical (NYHA class, effort tolerance) and echocardiographical (ventricular diameter and contraction fraction %) parameters were evaluated. In those patients treated with coenzyme Q10 and suffering from dilated cardiomyopathy a significant reduction in the NYHA class and a marked improvement in echocardiographic parameters were observed at the end of this period. The variations observed in other groups of patients treated were less conspicuous and not always statistically significant. The results of this study confirm that the association of coenzyme Q10 and conventional therapy may lad to a marked improvement in contractile function and correlated clinical conditions.

Adult↗