Abstract:
:During myocardial ischemia, electrical uncoupling and contracture herald irreversible damage. In the present study, we tested the hypothesis that an increase of intracellular Ca2+ is an important factor initiating these events. Therefore, we simultaneously determined tissue resistance, mechanical activity, pH(0), and intracellular Ca2+ (with the fluorescent indicator indo 1, Molecular Probes, Inc) in arterially perfused rabbit papillary muscles. Sustained ischemia was induced in three experimental groups: (1) control, (2) preparations preconditioned with two 5-minute periods of ischemia followed by reperfusion, and (3) preparations pretreated with 1 mmol/L iodoacetate to block anaerobic metabolism and minimize acidification during ischemia. In a fourth experimental group, intracellular Ca2+ was increased under nonischemic conditions by perfusing with 0.1 mmol/L ionomycin and 0.1 mumol/L gramicidin. Ca2+ transients and contractions rapidly disappeared after the induction of ischemia. In the control group, diastolic Ca2+ began to rise after 12.6 +/- 1.3 minutes of ischemia; uncoupling, after 14.5 +/- 1.2 minutes of ischemia; and contracture, after 12.6 +/- 1.5 minutes of ischemia (mean +/- SEM). Preconditioning significantly postponed Ca2+ rise, uncoupling, and contracture (21.5 +/- 4.0, 24.0 +/- 4.1, and 23.0 +/- 5.3 minutes of ischemia, respectively). Pretreatment with iodoacetate significantly advanced these events (1.9 +/- 0.7, 3.6 +/- 0.9, and 1.9 +/- 0.2 minutes of ischemia, respectively). In all groups, the onset of uncoupling always followed the start of Ca2+ rise, whereas the start of contracture was not different from the rise in Ca2+. Perfusion with ionomycin and gramicidin permitted estimation of a threshold [Ca2+] for electrical uncoupling of 685 +/- 85 nmol/L. In conclusion, the rise in intracellular Ca2+ is the main trigger for cellular uncoupling during ischemia. Contracture is closely associated with the increase of intracellular Ca2+ during ischemia.
journal_name
Circ Resjournal_title
Circulation researchauthors
Dekker LR,Fiolet JW,VanBavel E,Coronel R,Opthof T,Spaan JA,Janse MJdoi
10.1161/01.res.79.2.237subject
Has Abstractpub_date
1996-08-01 00:00:00pages
237-46issue
2eissn
0009-7330issn
1524-4571journal_volume
79pub_type
杂志文章abstract::Cyclic GMP (cGMP) kinase is intimately involved in the regulation of vascular smooth muscle tone. Its tissue concentration was determined in normotensive and hypertensive rats by use of monospecific anti-cGMP kinase antibodies. Hearts of spontaneously hypertensive rats and renovascular (Goldblatt II) hypertensive rats...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.5.1361
更新日期:1989-11-01 00:00:00
abstract::Mast cells in rat hearts were studied quantitatively during normal postnatal growth and in two types of cardiac hypertrophy. Normally, cardiac mast cell density in 11-12-day-old animals is very low, but increases markedly in the following 2-3 weeks to its highest values, with a subsequent decline toward adult values. ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.2.511
更新日期:1990-02-01 00:00:00
abstract::Inflammation is a condition that underscores many cardiovascular pathologies including endothelial dysfunction, but no link is yet established between the vascular pathology of the metabolic syndrome with a particular inflammatory cytokine. We hypothesized that impairments in coronary endothelial function in the obese...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000229685.37402.80
更新日期:2006-07-07 00:00:00
abstract::Although coronary artery spasm has been implicated as an important cause of myocardial ischemia in humans, an animal model of reversible segmental coronary constriction has not been described. To provoke coronary spasm in open-chest dogs, selected vasoconstricting agents adsorbed to viscous ion exchange gels were appl...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.52.4.423
更新日期:1983-04-01 00:00:00
abstract::Heart failure (HF) has been singled out as an epidemic and is a staggering clinical and public health problem, associated with significant mortality, morbidity, and healthcare expenditures, particularly among those aged ≥ 65 years. The case mix of HF is changing over time with a growing proportion of cases presenting ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.113.300268
更新日期:2013-08-30 00:00:00
abstract::The major goal of this study was to determine the interactions of VLDL surface and core lipids with the artery wall. We first demonstrated in vitro that surface lipid in VLDL could be traced using the phospholipid-like fluorescent probe 1,1'-dioctadecyl-3,3, 3',3'-tetramethyl-indocarbocyanine (DiI). The core of VLDL p...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.7.768
更新日期:2000-04-14 00:00:00
abstract::We have used an immunological approach to investigate the role of myosin light chain phosphorylation (MLC-Pi) in the control of contractility in smooth muscle. Our aim was to specifically inhibit myosin light chain kinase (MLCK) in the presence of physiologically activating levels of Ca2+ so that other putative Ca2(+)...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.2.457
更新日期:1991-02-01 00:00:00
abstract::Increased activity of matrix metalloproteinases (MMPs) has been implicated in numerous disease processes, including tumor growth and metastasis, arthritis, and periodontal disease. It is now becoming increasingly clear that extracellular matrix degradation by MMPs is also involved in the pathogenesis of cardiovascular...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/hh1501.094396
更新日期:2001-08-03 00:00:00
abstract::The SCN5A gene encodes the alpha subunit of the human heart sodium channel (hH1), which plays a critical role in cardiac excitability. Mutations of SCN5A underlie Brugada syndrome, an inherited disorder that leads to ventricular fibrillation and sudden death. This study describes changes in cellular localization and f...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1201.093270
更新日期:2001-06-22 00:00:00
abstract::Intussusceptive angiogenesis is a novel mode of blood vessel formation and remodeling, which occurs by internal division of the preexisting capillary plexus without sprouting. In this study, the process is demonstrated in developing chicken eye vasculature and in the chorioallantoic membrane by methylmethacrylate (Mer...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.3.286
更新日期:2000-02-18 00:00:00
abstract::Protein kinase A (PKA)-mediated enhancement of L-type calcium currents (I(Ca,L)) is essential for sympathetic regulation of the heartbeat and is the classic example of channel regulation by phosphorylation, and its loss is a common hallmark of heart failure. Mechanistic understanding of how distinct Ca(V) channel subu...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.171736
更新日期:2008-04-11 00:00:00
abstract::Endothelial cells, either in vivo or freshly isolated, respond when exposed to muscarinic agonists with an increase in cytosolic free calcium concentration ([Ca2+]i) and release of endothelium-derived relaxing factor (EDRF). When placed in culture, however, endothelial cells rapidly lose these responses, which may be ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.2.234
更新日期:1992-02-01 00:00:00
abstract::Increasing evidence suggests that endogenous NO inhibits sympathetic outflow in anesthetized animals. However, in a recent study from this laboratory, we were unable to find any evidence of increased renal sympathetic nerve activity (RSNA) in response to blockade of NO synthesis in conscious rabbits. Because angiotens...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.82.4.496
更新日期:1998-03-09 00:00:00
abstract::The relationship between cell swelling and plasma membrane disruption has been evaluated in thin myocardial slices incubated in oxygenated or anoxic Krebs-Ringer phosphate media. Electron microscopy and measurements of inulin-diffusible space were used to monitor plasma membrane integrity. Inulin is excluded from the ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.57.6.864
更新日期:1985-12-01 00:00:00
abstract::We have previously studied the relation between long-chain fatty acid and pyruvate metabolism in reperfused myocardium and noted a rapid return of fatty acid oxidation to at least preischemic values accompanied by a marked decrease in pyruvate oxidation. The purpose of the present report is to further characterize car...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.4.1094
更新日期:1989-10-01 00:00:00
abstract:RATIONALE:Activation of the mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) has been implicated in the mechanism of cardiac ischemic preconditioning, yet its molecular composition is unknown. OBJECTIVE:To use an unbiased proteomic analysis of the mitochondrial inner membrane to identify the mitochondrial K(...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.112.266445
更新日期:2012-08-03 00:00:00
abstract::Hypertrophic (HCM) and dilated (DCM) cardiomyopathies are inherited diseases with a high incidence of death due to electric abnormalities or outflow tract obstruction. In many of the families afflicted with either disease, causative mutations have been identified in various sarcomeric proteins. In this review, we focu...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.110.223842
更新日期:2012-07-20 00:00:00
abstract::The endothelial cell membrane glycoprotein thrombomodulin (TM) plays a critical role in the regulation of coagulation. TM is an essential cofactor in protein C activation by thrombin, and a direct inhibitor of thrombin-induced platelet activation and fibrinogen clotting. Protease nexin-1 (PN-1) is a serpin synthesized...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000265066.92923.ee
更新日期:2007-04-27 00:00:00
abstract:RATIONALE:Kawasaki disease (KD), an acute febrile vasculitis, is the most common cause of acquired heart disease in childhood; however, diagnosing KD can be difficult. OBJECTIVE:To identify unique proteomic biomarkers that can be used to facilitate earlier diagnosis of KD. METHODS AND RESULTS:We enrolled 214 children...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.305834
更新日期:2015-02-27 00:00:00
abstract::Heparin inhibits the development of intimal thickening after carotid injury in the rat; however, the specific cellular events responsible for this effect have not been defined. In this study, smooth muscle cell growth fraction and migration into the intima were quantitatively measured in heparin-treated animals. All r...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.58.6.839
更新日期:1986-06-01 00:00:00
abstract::We have investigated the actions of vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) on the pacemaker current (I(f)) in canine Purkinje fibers. On voltage pulses to the middle of the I(f) activation range, VIP reversibly increases I(f), whereas NPY reversibly decreases I(f). A three-pulse voltage protocol ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.1.157
更新日期:1994-01-01 00:00:00
abstract::We report the cloning of cDNAs encoding two different human nonmuscle myosin heavy chains designated NMMHC-A and NMMHC-B. The mRNAs encoding NMMHC-A and NMMHC-B are both 7.5 kb in size but are shown to be the products of different genes, which are localized to chromosome 22q11.2 and chromosome 17q13, respectively. In ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.2.530
更新日期:1991-08-01 00:00:00
abstract::Complete knowledge of myocardial structure, metabolism, and function is crucial to understanding the response of the heart to injury such as ischemia. Increasingly, this type of knowledge is required at multiple levels, from that of the isolated myocyte to the functioning organism, to provide basic scientists and clin...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000103863.40055.E8
更新日期:2003-12-12 00:00:00
abstract::To elucidate the mechanisms responsible for the increase in alpha 1-adrenergic receptors during ischemia in vivo, we developed a procedure for measuring alpha 1-adrenergic receptors in isolated, calcium-tolerant adult canine myocytes. Specific [3H]prazosin binding was rapid, saturable, reversible, and demonstrated the...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.5.735
更新日期:1987-11-01 00:00:00
abstract::Canine cardiac Purkinje cells contain both L- and T-type calcium currents, yet the single Ca2+ channels have not been characterized from these cells. Additionally, previous studies have shown an overlap between the steady-state inactivation and activations curves for L-type Ca2+ currents, suggesting the presence of L-...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.3.456
更新日期:1992-03-01 00:00:00
abstract::The role of the central nervous system in the mechanism(s) involved in acute carotid baroreflex resetting was studied in six conscious, chronically instrumented, aortic-denervated dogs. Dogs were prepared for reversible vascular isolation of the carotid sinuses. Acute baroreflex resetting was induced by holding the le...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.1.63
更新日期:1989-07-01 00:00:00
abstract::We designed this study to test the hypothesis that in acute mitral regurgitation the mitral regurgitant area (MRA) is a dynamic quantity which varies with the time variation of ventricular volume. Mitral insufficiency was created in five open-chest dogs in which a portion of the anterior leaflet was excised. Phasic ao...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.45.5.677
更新日期:1979-11-01 00:00:00
abstract::Selective troponin I (TnI) modification has been demonstrated to be in part responsible for the contractile dysfunction observed with myocardial ischemia/reperfusion injury. We have isolated and characterized modified TnI products in isolated rat hearts after 0, 15, or 60 minutes of ischemia followed by 45 minutes of ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.1.9
更新日期:1999-01-08 00:00:00
abstract::This study investigated the possible roles of strongly binding myosin crossbridges in determining loaded shortening and power output in cardiac myocytes. Single skinned cardiac myocytes were attached between a force transducer and position motor, and shortening velocities were measured over a range of loads during var...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.9.768
更新日期:2000-10-27 00:00:00
abstract::To determine if intestinal microvascular growth is impaired in diabetic juvenile animals, a segment of the terminal ileum was marked and the microvasculature of this segment observed at the age of 5 weeks and again at the age of 10-11 weeks in normal and diabetic Sprague Dawley rats. Diabetes was induced by streptozot...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.2.429
更新日期:1988-08-01 00:00:00