Abstract:
:The clinical use of positive inotropic agents has been associated with increased mortality, with proarrhythmia speculated to be a contributing factor. This study compares the arrhythmogenic potentials of six positive inotropic agents representing different mechanistic classes: the beta-adrenergic agonist dobutamine, the adenylyl cyclase activator forskolin, the phosphodiesterase-III inhibitor milrinone, the cardiac glycoside ouabain, and the sodium channel agonists DPI 201-106 and BDF 9148. These agents were studied in dogs with anterior myocardial infarction using lower and higher dose i.v. regimens targeted to elicit 20-40% and 70-90% increases in LV+dP/dt, respectively. Precipitation of new ventricular arrhythmia by programmed ventricular stimulation was observed in all treatment groups. Incidences of new arrhythmia were comparable in the lower dose regimens, ranging from 16.7% (3/18 animals with BDF 9148) to 31.6% (6/19 animals with DPI 201-106), and in the higher dose regimens, ranging from 10.0% (1/10 animals with milrinone) to 27.7% (5/18 animals with DPI 201-106). The overall incidence of new ventricular arrhythmia ranged from 27.3% (3/11 animals with ouabain) to 47.4% (9/19 animals with DPI 201-106). No differences were observed in underlying infarct size or time from infarction to electrophysiologic study between subgroups of animals in which new arrhythmias were precipitated vs. those remaining non-responsive in any treatment group. The positive inotropic agents tested displayed diverse total group effects on heart rate, electrocardiographic intervals including QTc and ventricular refractoriness. Within individual treatment comparisons revealed a general but not universal pattern of greater ventricular refractory period values in newly inducible vs. non-inducible subgroups in the DPI 201-106, BDF 9148 and ouabain (low and high dose); milrinone and dobutamine (high dose) treatment groups. These findings indicate that regardless of underlying cellular mechanism of action, the six positive inotropic agents tested all displayed comparable proarrhythmic potentials unrelated to underlying infarct size and time from infarction. This observation suggests the general shared property of increased myocardial contractility, potentially adversely affecting myocardial oxygen balance, myocardial perfusion and electrical stability in the setting of previous myocardial infarction, to be a common underlying cause for arrhythmogenesis. Additionally, alterations in ventricular refractoriness and repolarization may contribute significantly to proarrhythmia with some positive inotropic interventions.
journal_name
Basic Res Cardioljournal_title
Basic research in cardiologyauthors
Stump GL,Wallace AA,Gilberto DB,Gehret JR,Lynch JJ Jrdoi
10.1007/s003950050181keywords:
subject
Has Abstractpub_date
2000-06-01 00:00:00pages
186-98issue
3eissn
0300-8428issn
1435-1803journal_volume
95pub_type
杂志文章abstract::The isolated working rabbit heart preparation was used to study whether the "contractile machinery" remains unchanged in globally stunned myocardium. The function of the heart has been measured in nonischemic and postischemic conditions. The effect of isoprenaline or calcium chloride administration in both conditions ...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF02190601
更新日期:1991-05-01 00:00:00
abstract::The quantitative predominance of free and total cholesterol over the amount of mural calcium is a most significant criterion of healthy human coronary arteries during the whole life span (0-90 years). However, this normal ratio increasingly changes as soon as arteriosclerotic alterations of the coronary walls set in. ...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/978-3-642-85660-0_15
更新日期:1994-01-01 00:00:00
abstract::Increased activity of the sympathetic system is an important feature contributing to the pathogenesis and progression of chronic heart failure. While the mechanisms and consequences of enhanced norepinephrine release from sympathetic nerves have been intensely studied, the role of the adrenal gland in the development ...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-011-0166-z
更新日期:2011-06-01 00:00:00
abstract::The sympathetic and parasympathetic nervous system play a powerful role in controlling cardiac function by activating adrenergic and muscarinic receptors. In the human heart there exist alpha1-, beta1- and beta2-adrenoceptors and M2-muscarinic receptors and possibly also (prejunctional) alpha2-adrenoceptors. Beta1- an...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/s003950170003
更新日期:2001-11-01 00:00:00
abstract::Elucidation of the subcellular mechanism of myocardial ischemic preconditioning should be facilitated by precise knowledge of the biology of the cardioprotective response. Any proposed molecular mechanism for preconditioning must be initiated during the required ischemic stress period. The studies reported in this pap...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00805571
更新日期:1997-04-01 00:00:00
abstract::At 36 degrees C and 2 mM [Ca2+]o, single guinea-pig ventricular myocytes were voltage clamped with patch electrodes. When paired pulsing had potentiated the contraction to the maximum, the cells were shock-frozen for electron probe microanalysis (EPMA). Shock-freezing was timed at the end of diastole (-80 mV) or at di...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/978-3-662-30769-4_9
更新日期:1991-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00788518
更新日期:1997-08-01 00:00:00
abstract::The genetic defect in the cardiomyopathic (CM) hamster is a mutation in the glycoprotein-sarcoglycan (a component of the dystrophin-glycoprotein complex). Apoptosis has been identified in skeletal muscle of dystrophin-deficient mice, and therefore the role of myocardial apoptosis in relation to oncosis in causing myoc...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s395-002-8389-4
更新日期:2002-01-01 00:00:00
abstract::Diseases accompanied by severe cardiac impairment like sepsis and chronic uremia are frequently linked to an increase in cytokine release. In order to investigate possible toxic effects of the immune mediators on myocardial cells, we studied the contractility of cardiac myocytes and the de novo formation of stress pro...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00795385
更新日期:1992-01-01 00:00:00
abstract::Isolated cells obtained from adult myocardium are proving invaluable for a wide range of studies concerned with the mechanisms underlying many important cardiological processes. Although care must always be taken to ensure that the single myocyte is an appropriate model for the particular question to be researched, it...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:
更新日期:1985-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/978-3-642-72461-9_18
更新日期:1991-01-01 00:00:00
abstract::Delta-opioid receptors are known to participate in the protection found following ischemic preconditioning (IPC), but the role of kappa-receptors in IPC is currently controversial. Langendorff-perfused rat hearts received 35 min regional ischemia and 2 h reperfusion. PC (2 cycles 5 min global ischemia) substantially r...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s003950050001
更新日期:2000-02-01 00:00:00
abstract::Since the discovery of a novel mechanism of cell death that differs from traditional necrosis, i.e., apoptosis, there have been numerous studies concluding that increased apoptosis augments myocardial infarction and heart failure and that limiting apoptosis protects the heart. Importantly, the vast majority of cells i...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/s00395-016-0549-2
更新日期:2016-05-01 00:00:00
abstract::Complete length-tension diagrams of myocardium were measured on isolated papillary muscles of cat right ventricle. These diagrams clearly demonstrate that irrespective of loading conditions there is no uniform maxima curve. As a function of preload the curves of afterloaded isotonic maxima obey totally separate nonlin...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907862
更新日期:1985-11-01 00:00:00
abstract::8 mm long sections of common carotid arteries of conscious, freely moving rabbits were electrically stimulated with DC-impulses by chronically implanted gold-electrodes daily for 1/2 h or two times 1/2 h per day for 4--6 weeks. The electrodes were arranged in such a way that the wall was stimulated transmurally, In th...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907681
更新日期:1979-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-004-0482-7
更新日期:2004-09-01 00:00:00
abstract::Autologous bone marrow mononuclear cell (BM-MNC) therapy for patients with ST-segment elevation myocardial infarction (STEMI) has produced inconsistent results, possibly due to BM-MNC product heterogeneity. Patient-specific cardiovascular risk factors (CRFs) may contribute to variations in BM-MNC composition. We sough...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-016-0592-z
更新日期:2017-01-01 00:00:00
abstract::From January 2020, coronavirus disease (COVID-19) originated in China has spread around the world. The disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The presence of myocarditis, cardiac arrest, and acute heart failure in COVID-19 patients suggests the existence of a relationshi...
journal_title:Basic research in cardiology
pub_type: 社论
doi:10.1007/s00395-020-0791-5
更新日期:2020-04-09 00:00:00
abstract::This paper reviews the recent data concerning the force-frequency relations in experimental animals with heart failure. After a brief overview of the nature of these relations, which are induced by 2 opposite phenomena, the potentiation of force of contraction by heart rate and the restitution process, the paper revie...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/s003950050212
更新日期:1998-01-01 00:00:00
abstract::Affinity labelling of the digitalis receptor has indicated that it is situated on the N-terminal part of the alpha-subunit of the (Na+,K+)ATPase. Biochemical and pharmacological properties of the (Na+,K+)ATPase studied on intact chick embryonic hearts and under heart cell culture conditions have indicated the existenc...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/978-3-642-72376-6_15
更新日期:1984-01-01 00:00:00
abstract::Dopexamine is a newly developed sympathetic catecholamine which combines dopaminergic (DA-1) and beta 2-adrenergic agonist activity with only minor beta 1-adrenergic action. Thereby, this compound exerts systemic and preferential renal vasodilation, causing afterload reduction, increases in cardiac output, and improve...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/BF02650357
更新日期:1989-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
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更新日期:2005-11-01 00:00:00
abstract::Cardiac glycosides like ouabain are used in the therapy of heart failure and atrial fibrillation. They exert a positive inotropic effect on cardiomyocytes by inhibiting the plasma membrane sodium pump (Na,K-ATPase), decreasing the Ca-extrusion by the sarcolemmal cardiac sodium/calcium exchanger (NCX) and increasing th...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-003-0396-9
更新日期:2003-03-01 00:00:00
abstract::In order to clarify the genesis of the characteristic pressure and flow pulse contours of the common carotid artery of man, at first transcutaneous pulse recordings were carried out on healthy resting subjects during breathing of room air and of a mixture of 95% O2 and 5% CO2 (Carbogen). The latter was used to cause v...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907041
更新日期:1977-11-01 00:00:00
abstract::Six dogs were subjected to an acute stenosis of the left anterior descending coronary artery. The mean aortic pressure was fixed with a windkessel and an occluder on four different levels. A significant decrease of coronary blood flow and poststenotic coronary pressure was closely related to the level of mean aortic ...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01906456
更新日期:1976-05-01 00:00:00
abstract::The molecular mechanisms through which ghrelin exerts its cardioprotective effects during cardiac remodeling post-myocardial infarction (MI) are poorly understood. The aim of this study was to investigate whether the cardioprotection mechanisms are mediated by modulation of JAK/STAT signaling and what triggers this mo...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-018-0671-4
更新日期:2018-02-01 00:00:00
abstract::X-ray microanalysis was used to compare chemically untreated cryosections of quick-frozen myocardial tissue in "caffeine contracture" with cryosections of normal muscle. Our goal was to find out if it is possible by means of this method to detect changes in the calcium compartmentalization of the myocardial cell occur...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF02001396
更新日期:1980-01-01 00:00:00
abstract::A rapid change in length of cat papillary muscle induces two reciprocal diastolic and systolic processes: stretching causes a viscoelastic relaxation of the muscle. The opposite behavior is observed after abrupt releases when - subsequent to an increase in resting tension - diastolic force attains its new equilibrium....
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01910780
更新日期:1976-07-01 00:00:00
abstract::Cardiac hypertrophy which occurs during chronic mechanical overload is one of the numerous examples of biological adaptation to environmental requirements. As such, it is obtained at random by trial and error, and adaptation represents the sum of various modifications in gene expression, including the shift in isoform...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/978-3-642-72474-9_15
更新日期:1992-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00