Endotoxin-Induced Myocardial Tumor Necrosis Factor-α Synthesis Depresses Contractility of Isolated Rat Hearts

Grandel, Ulrich; Fink, Ludger; Blum, Andreas; Heep, Martina; Buerke, Michael; Kraemer, Hans-Joachim; Mayer, Konstantin; Bohle, Rainer M.; Seeger, Werner; Grimminger, Friedrich; Sibelius, Ulf

doi:10.1161/01.cir.102.22.2758

Cited by 114 publications

(46 citation statements)

References 31 publications

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“…18 A COX-2-induced tumor necrosis factor-␣ overexpression has been suggested to be involved in cardiac alteration in septic heart, via its cardiodepressant action. 24 The rapid effect of indomethacin on myocardial relaxation seen in the present study, however, favors a direct and immediate action of COX-2 products in the regulation of cardiac performance in septic hearts.…”

Section: Discussioncontrasting

confidence: 43%

Activation of Cardiac Endothelium as a Compensatory Component in Endotoxin-Induced Cardiomyopathy

et al. 2001

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Background-In view of growing evidence of an important endothelial paracrine regulation of cardiac function, the present study investigated the role of cardiac endothelium-derived endothelin-1 (ET-1), prostaglandins, and nitric oxide (NO) during endotoxin-induced cardiomyopathy in rabbits. Methods and Results-Immunohistochemical studies showed a marked transient coinduction of the inducible isoforms of NO synthase (NOS-2) and cyclooxygenase (COX-2) in endocardial endothelium and coronary arteriolar endothelium of hearts 12 hours after intravenous administration of lipopolysaccharide (LPSϩ12h); staining for both isoforms was much weaker 24 hours later (LPSϩ36h). Nitrotyrosine localization was similar to that of NOS-2, suggesting a NOS-2-related endothelial formation of peroxynitrite in septic hearts. Contractile performance of papillary muscles was depressed in both LPS-treated groups. In the LPSϩ12h group, however, isometric twitches were significantly prolonged (482Ϯ14 versus 420Ϯ14 ms in the saline-treated group, PϽ0.005). This twitch prolongation was completely reversed by simultaneous administration of BQ-123 and indomethacin to block endogenous ET-1 and prostaglandins, respectively. In addition, in the LPSϩ12h group, myocardial inotropic responsiveness to exogenous ET-1 was enhanced (PϽ0.01). Conclusions-Cardiac

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Section: Discussioncontrasting

confidence: 43%

Activation of Cardiac Endothelium as a Compensatory Component in Endotoxin-Induced Cardiomyopathy

et al. 2001

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“…Furthermore, the contractile abnormalities seen in this model were not restored in the present of NOS inhibitors, L-NMMA and L-nitroarginine (L-NA) [104]. These findings were supported by similar finding in two other studies following treatment with LPS in adult guinea pig cardiac myocytes and isolated perfused rat hearts [105,106].…”

Section: Effects Of No and Cytokines On Contraction In Isolated Cardisupporting

confidence: 86%

The complex role of iNOS in acutely rejecting cardiac transplants

Pieper

Roza

2008

Free Radical Biology and Medicine

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This review summarizes the evidence for a detrimental role of nitric oxide (NO) derived from inducible NO synthase (iNOS) and/or reactive nitrogen species such as peroxynitrite in acutelyrejecting cardiac transplants. In chronic cardiac transplant rejection, iNOS may have an opposing beneficial component. The purpose of this review is primarily to address issues related to acute rejection which is a recognized risk factor for chronic rejection. The evidence for a detrimental role is based upon strategies involving non-selective NOS inhibitors, NO neutralizers, selective iNOS inhibitors and iNOS gene deletion in rodent models of cardiac rejection. The review is discussed in the context of the impact on various components including graft survival, histological rejection and cardiac function which may contribute in toto to the process of graft rejection. Possible limitations of each strategy are discussed in order to understand better the variance in published findings including issues related to the potential importance of cell localization of iNOS expression. Finally, the concept of a dual role of NO and its down-stream product, peroxynitrite, in rejection vs. immune regulation is discussed.

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“…32,40,74,75 In isolated adult feline LVs and cardiomyocytes, Yokoyama et al 74 demonstrated that TNF-␣-dependent immediate reductions in contractility and Ca 2ϩ transients were not accompanied by increased NO oxidation products or cGMP production. Furthermore, the contractile dysfunction was not prevented by two different pharmacological NOS inhibitors.…”

Section: E-c Couplingmentioning

confidence: 99%

Cytokine-Induced Modulation of Cardiac Function

Prabhu

2004

Circulation Research

345

267

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Abstract-Cytokines act in an autocrine and/or paracrine fashion to induce a diverse variety of biological responses.Several cardiac diseases are associated with cytokine activation, and such activation significantly influences several physiologic parameters, including cardiac mechanical function. This review summarizes the current concepts regarding the modulation of myocardial function by cytokines and provides rationale for the sometimes-conflicting results in the literature regarding underlying mechanisms and patterns of dysfunction. Although traditionally considered cardiodepressant mediators, contractile responses are complex and bimodal, with an early response (within minutes) of variable direction, stimulatory or depressant, depending on the ambient physiologic milieu and relative contributions of the underlying signaling pathways that are activated. These pathways include sphingomyelinase-, nitric oxide (NO)-, and phospholipase A2-dependent signaling with resultant combined effects on contraction and the Ca 2ϩ transient. This is subsequently followed by a profoundly cardiodepressant late response lasting hours to days, depending on the production of secondary mediators and the combined influence of NO generated from inducible NO synthase, reactive oxygen species, and alterations in ␤-adrenergic receptor signaling. The interrelationships between these pathways and the time-dependence of their activation are important considerations in the evaluation of cytokine-dependent dysfunction during both acute cardiac injury and chronic cardiac pathologies.

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Endotoxin-Induced Myocardial Tumor Necrosis Factor-α Synthesis Depresses Contractility of Isolated Rat Hearts

Cited by 114 publications

References 31 publications

Activation of Cardiac Endothelium as a Compensatory Component in Endotoxin-Induced Cardiomyopathy

Activation of Cardiac Endothelium as a Compensatory Component in Endotoxin-Induced Cardiomyopathy

The complex role of iNOS in acutely rejecting cardiac transplants

Cytokine-Induced Modulation of Cardiac Function

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