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11. |
Lysoplasmenylethanolamine Accumulation in Ischemic/Reperfused Isolated Fatt Acid‐Perfused Hearts |
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Circulation Research,
Volume 70,
Issue 6,
1992,
Page 1161-1168
Norman Davies,
Richard Schulz,
Peter Olley,
Kenneth Strynadka,
Donna Panas,
Gary Lopaschuk,
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摘要:
Lysophospholipid accumulation has been implicated in the pathogenesis of irreversible injury during myocardial ischemia and reperfusion. Plasmalogens (phospholipids with a vinyl-ether bond in the sn-1 position) account for more than 50% of total myocardial sarcolemmal and sarcoplasmic reticulum phospholipids. Accumulation of plasmalogen choline and ethanolamine lysophospholipids (lysoplasme-nylcholine and lysoplasmenylethanolamine) or the effects of exogenous fatty acids on lysoplasmalogen accumulation during ischemia and reperfusion have not been examined. Isolated working rat hearts perfused with buffer containing either 11 mM glucose or 11 mM glucose plus 1.2 mM palmitate were subjected to aerobic, ischemic, or ischemia/reperfusion protocols. Levels of lysoplasmenylcholine and lysoplasmenylethanolamine were quantified using a two-stage high-performance liquid chromatographic technique. In hearts perfused with glucose alone, no significant differences in levels of lysoplasmenylcholine or lysoplasmenylethanolamine were seen during ischemia or reperfusion. In fatty acid-perfused hearts, however, significant accumulation of lysoplasmenylethanolamine occurred during reperfusion but not during ischemia (723±112, 734±83, and 1,394±193 nmol/g dry wt for aerobic, ischemic, and ischemic/reperfused hearts, respectively;p<0.05 for ischemic/reperfused hearts versus aerobic or ischemic hearts). Lysoplasmenylcholine levels after ischemia and reperfusion did not differ significantly from aerobic values, regardless of whether fatty acids were present or absent from the perfusate. Aerobic and ischemic/reperfused rabbit hearts, in the presence of fatty acid, showed a similar profile in their lysoplasmalogen content. We conclude that differential lysoplasmenylethanolamine accumulation occurs during myocardial reperfusion when exogenous fatty acid concentrations are high. This may reflect the selective action of fatty acid intermediates on the metabolism of lysoplasmenylethanolamines. The role of lysoplasmalogens in producing the depressed mechanical recovery of fatty acid-perfused hearts after ischemia/reperfusion remains to be determined.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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12. |
Right Ventricular Preload Recruitable Stroke Work, End‐Systolic Pressure‐Volume, and dP/dtmax‐End‐Diastolic Volume Relations Compared as Indexes of Right Ventricular Contractile Performance in Conscious Dogs |
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Circulation Research,
Volume 70,
Issue 6,
1992,
Page 1169-1179
Mohanraj Karunanithi,
Jerzy Michniewicz,
Susan Copeland,
Michael Feneley,
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摘要:
Three indexes developed originally to assess left ventricular contractile performance were applied instead to the right ventricle (RV) in 11 conscious dogs: the relation between stroke work and end-diastolic volume (EDV), termed the preload recruitable stroke work (PRSW) relation; the end-systolic pressure-volume (ESPV) relation; and the maximum dP/dt (dP/dtmax)-EDV relation. The reproducibility, inotropic sensitivity, chronotropic sensitivity, and afterload sensitivity of these RV relations were compared. RV volume was determined with an ellipsoidal shell subtraction model from orthogonal dimensions measured by sonomicrometry. RV transmural pressure was measured with micromanometers. After autonomic blockade, preload was varied by repeated, transient vena caval occlusions before and during partial occlusion of the main pulmonary artery, after release of the pulmonary arterial occlusion, after calcium infusion, and over a range of heart rates induced by atrial pacing. The slope and volume-axis intercept of the PRSW relation were more reproducible (SD/mean, 7.8±33%and 6.2±4.1%, respectively) than the slope and volume-axis intercept of the ESPV relation (10.1±6.7% and 23.0±313%, bothp<0.05) or the slope and volume-axis intercept of the dP/dtmax-EDV relation (43.4±70.4% and 153.8±184.6%, bothp<0.05). The slope of the PRSW relation increased 32±17% (p<0.05) after calcium infusion, but the volume-axis intercept did not change significantly. In contrast, the slopes of the ESPV and dP/dtmax-EDV relations did not change significantly after calcium infusion, but the volume-axis intercepts decreased significantly (bothp<0.05). Despite a 71±26% increase in mean RV ejection pressure during partial occlusion of the main pulmonary artery, the slopes and volume-axis intercepts of both the PRSW and dP/dtmax-EDV relations did not change significantly, but the slope of the ESPV relation increased 45±22% (p<0.05) without significant change in the volume-axis intercept. None of the relations demonstrated significant chronotropic sensitivity. The PRSW relation is the preferred index of RV contractile performance because 1) it is the most reproducible, 2) its slope alone sensitively detects changes in contractile state, and 3) unlike the ESPV relation, it is relatively insensitive to afterload.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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13. |
Relation Between Glycolysis and Calcium Homeostasis in Postischemic Myocardium |
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Circulation Research,
Volume 70,
Issue 6,
1992,
Page 1180-1190
Richmond Jeremy,
Yukihiro Koretsune,
Eduardo Marban,
Lewis Becker,
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摘要:
This study examined the hypothesis that glycolysis is required for functional recovery of the myocardium during reperfusion by facilitating restoration of calcium homeostasis. [Ca2+]iwas measured in isolated perfused rabbit hearts by using the Ca2+indicator 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (5F-BAPTA) and19F nuclear magnetic resonance spectroscopy. In nonischemic control hearts, inhibition of glycolysis with iodoacetate did not alter [Ca2+]i. In hearts subjected to 20 minutes of global zero-flow ischemia, [Ca2+]iincreased from 260±80 nM before ischemia to 556±44 nM after 15 minutes of ischemia (p<0.05). After reperfusion with 5 mM pyruvate as a carbon substrate, [Ca2+]iincreased further in hearts with intact glycolysis to 851±134 nM (p<0.05 versus ischemia) during the first 10 minutes of reperfusion, before returning to preischemic levels. In contrast, inhibition of glycolysis during the reperfusion period resulted in persistent severe calcium overload ([Ca2+]i, 1,380±260 nM after 15 minutes of reperfusion,p<0.02 versus intact glycolysis group). Furthermore, despite the presence of pyruvate and oxygen, inhibition of glycolysis during early reperfusion resulted in greater impairment of functional recovery (rate/pressure product, 3,722±738 mm Hg/min) than did reperfusion with pyruvate and intact glycolysis (rate/pressure product, 9,851±590 mm Hg/min,p<0.01). Inhibition of glycolysis during early reperfusion was also associated with a marked increase in left ventricular end-diastolic pressure during reperfusion (41±5 mm Hg) compared with hearts with intact glycolysis (16±2 mm Hg,p<0.01). The detrimental effects of glycolytic inhibition during early reperfusion were, however, prevented by initial reperfusion with a low calcium solution ([Ca]o, 0.63 mM for 30 minutes, then 2.50 mM for 30 minutes). In these hearts, the rate/pressure product after 60 minutes of reperfusion was 12,492±1,561 mm Hg/min (p<0.01 versus initial reflow with [Ca]oof 2.50 mM). These findings indicate that the functional impairment observed in postischemic myocardium is related to cellular Ca2+overload. Glycolysis appears to play an important role in restoration of Ca2+homeostasis and recovery of function of postischemic myocardium.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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14. |
Oxidized Low Density Lipoproteins Induce mRNA Expression and Release of Endothelin From Human and Porcine Endothelium |
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Circulation Research,
Volume 70,
Issue 6,
1992,
Page 1191-1197
Chantal Boulanger,
Felix Tanner,
Marie-Luce Béa,
Alfred Hahn,
Annick Werner,
Thomas Lüscher,
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摘要:
Experiments were designed to examine the effect of oxidized low density lipoproteins (Ox-LDLs) on the expression and the release of endothelin from cultured endothelial cells and intact blood vessels. Ox-LDLs (30–300 μg/ml), but not native low density lipoproteins (200 μg/ml), stimulated the expression of preproendothelin mRNA in porcine and human endothelial cells, leading to a time- and concentration-dependent release of the peptide into the culture medium. The Ox-LDL-stimulated release of endothelin was mimicked by acetylated low density lipoprotein and abolished by downregulation of protein kinase C by phorbol ester. In the intact porcine aorta, Ox-LDLs, but not native low density lipoproteins, also increased the release of peptide in an endothelium- and concentration-dependent manner. The maximal effect was observed at a concentration of 100 μg/ml. Incubation of the intact porcine aorta with the scavenger receptor antagonist dextran sulfate decreased the formation of endothelin evoked by Ox-LDLs. The Ox-LDL-stimulated production of the peptide was further augmented in the presence of thrombin (4 units/ml) and was unaffected by nitric oxide-generating compound 3-morpholinosydnonimine (10−5M). These results suggest that Ox-LDL may be an endogenous mediator of the augmented release of endothelin observed in hyperlipidemia and atherosclerosis. The increased production of the peptide could contribute to vasospastic events and may promote vascular smooth muscle proliferation and progression of atherosclerotic vascular disease.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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15. |
Progestogens Do Not Affect Aortic Accumulation of Cholesterol in Ovariectomized Cholesterol‐Fed Rabbits |
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Circulation Research,
Volume 70,
Issue 6,
1992,
Page 1198-1202
Jens Haarbo,
Ole Svendsen,
Claus Christiansen,
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摘要:
Cardiovascular disease is a major killer in postmenopausal women in the industrialized societies. To investigate the effect of progestogen and 17 β-estradiol replacement therapy on atherogenesis, we studied 60 cholesterol-fed ovariectomized rabbits for 13 weeks. They were randomly assigned to four groups of 15 rabbits each and received oral treatment with norethisterone acetate, levonorgestrel, 17 β-estradiol, or placebo. The active treatment groups achieved serum hormone concentrations, which produced physiological effects on the uterus. No significant differences in serum total cholesterol or ultracentrifuged lipoproteins (very low density, intermediate density, low density, or high density lipoproteins) were found between the four groups during the experimental period. There were no significant differences between the progestogen and placebo groups in the aortic accumulation of cholesterol. The estradiol group had only accumulated about half the aortic cholesterol as compared with the placebo group and the progestogen groups (p<0.05). The antiatherogenic effect of 17 β-estradiol was estimated to be equal to a 40–50%, reduction in serum total cholesterol. These findings suggest that two commonly prescribed 19-nortestosterone-derived progestogens, which are considered to be “atherogenic,” do not affect atherogenesis in cholesterol-fed ovariectomized rabbits, whereas 17 β-estradiol produces a significant antiatherogenic effect that is independent of lipid metabolism in plasma, possibly the result of a direct action on the arterial wall.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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16. |
Adrenergic Blockade Blunts Adenosine Concentration and Coronary Vasodilation During Hypoxia |
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Circulation Research,
Volume 70,
Issue 6,
1992,
Page 1203-1216
Steven Herrmann,
Eric Feigl,
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摘要:
Myocardial hypoxia is thought to be an important stimulus for increasing interstitial adenosine concentration. The adenosine hypothesis of coronary control was investigated during steady-state hypoxia by making measurements of coronary venous and epicardial well adenosine concentrations in adrenergically intact dogs and in animals with α- and β-receptor blockade. In the adrenergically intact group, hypoxia sufficient to lower coronary venous oxygen tension to 8 mm Hg increased coronary blood flow 243% from normoxic values. Both coronary venous and epicardial well adenosine concentrations were increased throughout the hypoxic period. In the adrenergically blocked group, hypoxia to a similar level of coronary venous oxygen tension produced an increase in coronary blood flow of only 75%, which was significantly less than in the adrenergically intact group (p<0.01). Coronary venous adenosine was only transiently elevated, and epicardial well adenosine was unchanged from control levels. In a separate group of α- and β-receptor-blocked animals that received an infusion of l-homocysteine thiolactone during hypoxia, there was no difference in tissueS-adenosylhomocysteine levels compared with those of normoxic controls. It is concluded that much of the coronary vasodilation associated with systemic hypoxia is dependent on adrenergic activation and that adenosine may only play a role in sustained hypoxic vasodilation when adrenergic receptors are intact.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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17. |
Depression of Peak Force Without Altering Calcium Sensitivity by the Superoxide Anion in Chemically Skinned Cardiac Muscle of Rat |
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Circulation Research,
Volume 70,
Issue 6,
1992,
Page 1217-1224
N. MacFarlane,
D. Miller,
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摘要:
Among the mechanisms postulated to contribute to myocardial “stunning” is a depression of contractility by oxygen-derived free radicals. It has been suggested that these radicals might depress the calcium sensitivity of the contractile proteins. We have exposed the myofilaments (in chemically “skinned” rat cardiac muscle) to the superoxide anion and measured isometric force at controlled degrees of activation. Superoxide was generated by the xanthine/xanthine oxidase system: the effects to be described were shown to be specifically attributable to superoxide. Maximum calcium-activated force is reduced, or even completely abolished, in a dose-dependent fashion and without any alteration in calcium sensitivity. The myofilaments are highly sensitive to superoxide: significant force reduction has been shown to be caused by enzyme concentrations as low as 2 microunits/ml xanthine oxidase and with exposures of less than 1 minute to the generating system (at higher enzyme concentrations). Once force has been depressed, it cannot be recovered within the duration of the experiments described. When xanthine oxidase is applied during the calcium-induced contracture, tension falls steadily. However, a similar concentration is without immediate effect on the rigor contracture (evoked by applying ATP-free solutions). To account for the depression of maximum calcium-activated force, we conclude that some aspect of crossbridge behavior is particularly vulnerable to superoxide rather than that the radical has a nonspecific “proteolytic” effect. This action on the fundamental units of force production could contribute to myocardial stunning since the effects we report are consistent with many aspects of this phenomenon.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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18. |
Alteration of Contractile Function and Excitation‐Contraction Coupling in Dilated Cardiomyopathy |
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Circulation Research,
Volume 70,
Issue 6,
1992,
Page 1225-1232
Gerd Hasenfuss,
Louis Mulieri,
Bruce Leavitt,
Paul Allen,
Joe Haeberle,
Norman Alpert,
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摘要:
Myocardial failure in dilated cardiomyopathy may result from subcellular alterations in contractile protein function, excitation-contraction coupling processes, or recovery metabolism. We used isometric force and heat measurements to quantitatively investigate these subcellular systems in intact left ventricular muscle strips from nonfailing human hearts (n=14) and from hearts with end-stage failing dilated cardiomyopathy (n=13). In the failing myocardium, peak isometric twitch tension, maximum rate of tension rise, and maximum rate of relaxation were reduced by 46% (p=0.013), 51% (p=0.003), and 46% (p=0.018), respectively (37°C, 60 beats per minute). Tension-dependent heat, reflecting the number of crossbridge interactions during the isometric twitch, was reduced by 61% in the failing myocardium (p=0.006). In terms of the individual crossbridge cycle, the average crossbridge force-time integral was increased by 33% (p=0.04) in the failing myocardium. In the nonfailing myocardium, the crossbridge force-time integral was positively correlated with the patient's age (r=0.86,p<0.02), whereas there was no significant correlation with age in the failing group. The amount and rate of excitation—contraction coupling-related heat evolution (tension-independent heat) were reduced by 69% (p=0.024) and 71% (p=0.028), respectively, in the failing myocardium, reflecting a considerable decrease in the amount of calcium released and in the rate of calcium removal. The efficiency of the metabolic recovery process, as assessed by the ratio of initial heat to total activity-related heat, was similar in failing and nonfailing myocardium (0.54±0.03 versus 0.50±0.02,p=0.23). Thus, in failing dilated cardiomyopathy, contractile protein function is altered with an increased force-time integral of the individual crossbridge cycle. However, this alteration does not explain failure since the same changes are present in nonfailing myocardium from older patients. The findings suggest that reduced tension generation in failing dilated cardiomyopathy primarily results from disturbed excitation-contraction coupling processes with a reduced amount of calcium released and a reduced rate of calcium removal.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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19. |
Immunolocalization and Expression of Functional and Nonfunctional Cell‐to‐Cell Channels From Wild‐Type and Mutant Rat Heart Connexin43 cDNA |
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Circulation Research,
Volume 70,
Issue 6,
1992,
Page 1233-1243
Bernadette Dunham,
Shuguang Liu,
Steven Taffet,
Elizabeth Trabka-Janik,
Mario Delmar,
Raymond Petryshyn,
Shuang Zheng,
Raisa Perzova,
Mary Vallano,
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摘要:
The carboxyl terminal cytoplasmic domain of distinct gap junction proteins may play an important role in assembly of functional channels as well as differential responsiveness to pH, voltage, and intracellular second messengers. Oligonucleotide-directed site-specific mutagenesis in a pairedXenopus laevisoocyte expression system was used to examine the expression of mRNAs encoding wild-type and carboxyl terminal mutant connexin43 (Cx43) proteins. Oocytes were stripped, injected with mRNA or distilled water (dH2O), preincubated for 16–20 hours, and then paired for 5–10 hours; this process was followed by electrophysiological recording using the dual voltage-clamp technique. Initial experiments compared the relative junctional conductances (Gjs) in oocyte pairs expressing Cx43 (382 amino acid residues) and two truncated mutants lacking most or a portion of the cytoplasmic carboxyl terminal. The shortest mutant (M241) contained 240 amino acid residues and was devoid of all phosphorylatable serine residues in the cytoplasmic tail; its length approximated the length of liver connexin26. The longest mutant (M257) tested contained 256 amino acid residues, including two serine residues. Oocyte pairs expressing M241 yielded a Gj similar to that of oocytes injected with dH2O, whereas M257 yielded a Gj similar to that of oocytes injected with Cx43. Immunoprecipitation studies showed that Cx43, M257, and M241 proteins were readily detectable in oocytes injected with their respective mRNAs, indicating that the lack of Gj observed with the M241 mRNA was not due to reduced translation. Immunocytochemical studies revealed that wild-type and both truncated mutants were localized to the area of cell-to-cell contact between the paired oocytes, indicating that protein targeting to the membrane was not inhibited in oocytes injected with M241 mRNA. Oocyte pairs expressing mutants in which serine residues were replaced with nonphosphorylatable amino acids (serine codon No. 255 AGC was converted to GCC, alanine, designated as M255S→A, and serine codon No. 244 AGC was converted to GGC, glycine, designated as M244S→G) showed Gjs similar to M257, indicating that these serine residues and, by inference, their phosphorylation state are not critical for expression of functional channels. The importance of the length of the carboxyl terminus was assessed by comparing the Gjs in a series of mutants that were intermediate in length between M257 and M241. Gradual shortening of the carboxyl terminus produced a gradual reduction of Gj relative to M257. However, simple deletion of amino acid residues 241–257 from the wild-type Cx43 did not affect Gj relative to M257. These data suggest that a critical length, and not phosphorylation, of carboxyl terminus is required for detectable expression of Cx43 channels in theXenopusoocyte system.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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20. |
Passive Mechanical Stretch Releases Atrial Natriuretic Peptide From Rat Ventricular Myocardium |
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Circulation Research,
Volume 70,
Issue 6,
1992,
Page 1244-1253
Paivi Kinnunen,
Olli Vuolteenaho,
Paavo Uusimaa,
Heikki Ruskoaho,
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摘要:
Ventricular hypertrophy is characterized by augmentation of synthesis, storage, and release of atrial natriuretic peptide (ANP) from ventricular tissue, but the physiological stimulus for ANP release from ventricles is not known. We determined the effect of graded, passive myocardial stretch on ANP release in isolated, arrested, perfused heart preparations after removal of the atria in 13–20-month-old Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). By this age, ANP gene expression was increased in the hypertrophic ventricular cells of SHR, as reflected by elevated levels of immunoreactive ANP and ANP mRNA and the increased ANP secretion (SHR, 93±14 pg/ml,n=22; WKY rats, 22±2 pg/ml,n=20;p<0.001) from perfused ventricles after removal of the atria. The release of ANP from ventricles was examined at two levels of left ventricular pressure by increasing the volume of the intraventricular balloon for 10 minutes. Stretching of the ventricles produced a rapid but transient increase in ANP secretion. As left ventricular pressure rose from 0 to 14 and 26 mm Hg in WKY rats and from 0 to 13 and 27 mm Hg in SHR, increases in ANP release into the perfusate of 1.4±0.1-fold and 1.5±0.2-fold (p<0.05) in WKY rats and 1.1±0.1-fold and 1.6±0.2-fold (p<0.05) in SHR, respectively, were observed. There was a highly significant correlation between the left ventricular pressure level and the maximal concentration of ANP in the perfusate during stretching (p<0.001,r=0.59,n=42), as well as between the maximal ANP concentrations in perfusate during stretching and the ventricular weight/body weight ratios of the corresponding animals (r=0.38,p<0.05,n=42). High performance liquid chromatographic analysis revealed that the ventricles both before and during stretch primarily released the processed, active, 28-amino acid ANP-like peptide into the perfusate. These results indicate that stretching is a direct stimulus for ventricular ANP release and show that ANP is also a ventricular hormone.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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