Production of oxidative products of nitric oxide in infarcted human heart

Akiyama, Koichiro; Kimura, Akio; Suzuki, Hiroshi; Takeyama, Youichi; Gluckman, Tracy L.; Terhakopian, Artin; Kubo, Takashi; Suh, Ki-Young; Roseto, James; Bing, Richard J.

doi:10.1016/s0735-1097(98)00270-8

Cited by 53 publications

(28 citation statements)

References 28 publications

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“…9 The understanding of the pathophysiology of cardiogenic shock complicating MI has recently evolved toward an appreciation of the role of systemic inflammation, including cytokine release and expression of inducible nitric oxide synthase (NOS). [10][11][12] Excessive NOS results in high levels of nitric oxide that, in turn, lead to inappropriate systemic vasodilatation, progressive systemic and coronary hypoperfusion, and myocardial depression. [10][11][12] Inhibition of NOS is a theoretically appealing approach to treatment of this high-risk population.…”

Section: The Triumph Randomized Controlled Trialmentioning

confidence: 99%

“…[10][11][12] Excessive NOS results in high levels of nitric oxide that, in turn, lead to inappropriate systemic vasodilatation, progressive systemic and coronary hypoperfusion, and myocardial depression. [10][11][12] Inhibition of NOS is a theoretically appealing approach to treatment of this high-risk population. Early singlecenter studies with isoform-nonselective NOS inhibitors were promising and suggested a substantial beneficial effect on survival.…”

Section: The Triumph Randomized Controlled Trialmentioning

confidence: 99%

“…A quarter of the pa- 55 (27) 50 (27) 105 (27) . (31) 134 (33) .49 Prior MI 60 (29) 49 (26) 109 (28) .48 Prior CABG 14 (6.8) 15 (7.9) 29 (7.3) .68 Prior heart failure 44 (22) 40 (21) 84 (21) .94 Among those with heart failure, highest NYHA class in 6 wk I 6 (14) 3 (8) 9 (11) .59 II 17 (39) 12 (32) 29 (35) III 12 (27) 11 (29) 23 (28) IV 9 (21) 12 (32) 21 (26 (28) 53 (28) 111 (28) .95 Left bundle-branch block 27 (13) 21 (11) 48 (12) .53 ST-segment depression 41 (20) 47 (25) 88 (22) .25…”

Section: Patient Populationmentioning

confidence: 99%

See 2 more Smart Citations

Effect of Tilarginine Acetate in Patients With Acute Myocardial Infarction and Cardiogenic Shock

Investigators

Alexander²,

Reynolds³

et al. 2007

JAMA

342

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Section: The Triumph Randomized Controlled Trialmentioning

confidence: 99%

Section: The Triumph Randomized Controlled Trialmentioning

confidence: 99%

Section: Patient Populationmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Tilarginine Acetate in Patients With Acute Myocardial Infarction and Cardiogenic Shock

Investigators

Alexander²,

Reynolds³

et al. 2007

JAMA

342

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“…NO originates from an L-arginine-dependent pathway [3]. In patients and animals with myocardial infarction, NO myocardial production increases its oxidation products (NO 2 and NO 3 : NOx) in coronary sinus blood [4,5]. Together with NO, there occurs an increase of prostacyclin (PGI 2 ) and thromboxane A 2 (TXA 2 ) in heart muscle as a result of activation of cyclooxygenase (COX) [6].…”

Section: Introductionmentioning

confidence: 99%

Effect of Cyclooxygenase-2 Inhibitor (Celecoxib) on the Infarcted Heart in situ

Yamamoto¹,

Kakar²,

Vina³

et al. 2001

Pharmacology

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Several attempts have been made to replace aspirin with compounds without gastric toxicity; a cyclooxygenase-2 (COX-2) inhibitor, celecoxib, and a nitric oxide-aspirin, NCX-4016, have been developed for this purpose. This paper compares effects of celecoxib, NCX-4016 and aspirin on production of prostacyclin (PGI₂) and thromboxane A₂ (TXA₂) and activation of the inducible form of nitric oxide synthase (iNOS) in infarcted heart in situ. Aspirin was most effective in reducing myocardial PGI₂ synthesis and formation of TXA₂. Myocardial effects of celecoxib resemble those of NCX-4016, although the two compounds have different modes of action.

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“…The interaction of ROS with membrane lipids and essential cellular biomolecule modification contribute to damage, leading to vasoconstriction and leukocyte adhesion on the endothelial surface (3,12,19). NO has been shown to be protective in I/R-induced damage by inhibiting platelet adhesion and aggregation and attenuating leukocyte adhesion (1,5,17,24). However, despite recent advances in therapeutics and the potential of antioxidant intervention, both the efficacy of ROS scavengers and the role of NO in the clinical setting remain undetermined (2,20,41).…”

mentioning

confidence: 99%

Antioxidant activity of nitro derivative of aspirin against ischemia-reperfusion in hamster cheek pouch microcirculation

Bertuglia¹,

Giusti²,

Soldato³

2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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oxidant activity of nitro derivative of aspirin against ischemia-reperfusion in hamster cheek pouch microcirculation. Am J Physiol Gastrointest Liver Physiol 286: G437-G443, 2004. First published October 16, 2003 10.1152/ajpgi.00339.2003.-Aspirin that has been chemically combined with a nitric oxide (NO) donor (NCX-4016) has been shown to inhibit cyclooxygenase and prostaglandin generation while maintaining the inhibitory effects of aspirin. The possible role of reactive oxygen species (ROS) in the action of NCX-4016 in ischemia-reperfusion (I/R) has not been studied. Furthermore, we were interested in comparing the effects of a conventional NO donor [2,2Ј-hydroxynitrosohydrazino-bis-etanamine (DETA/NO)] and NCX-4016 at the microvascular level in the hamster cheek pouch visualized by using an intravital fluorescent microscopy technique. Microvascular injury was assessed by measuring diameter change, the perfused capillary length (PCL), and leukocyte adhesion. Animals were treated with NCX-4016 (100 mg/kg or 30 mg⅐kg Ϫ1 ⅐day Ϫ1 for 5 days po) or DETA-NO (0.5 mg/kg). Mean arterial blood pressure increased slightly but significantly after NCX-4016 treatment. During 5-and 15-min reperfusion, lipid peroxides in the systemic blood increased by 72 and 89% vs. baseline, respectively, and were still higher than in basal conditions after 30-min reperfusion in the I/R group. Pretreatment with NCX-4016 maintained ROS at normal levels; increased arteriolar diameter, blood flow, and PCL; and decreased leukocyte adhesion (P Ͻ 0.05). DETA-NO decreased ROS during 30-min reperfusion; however, later there was a significant increase during reperfusion. DETA-NO decreased leukocyte adhesion (P Ͻ 0.05) but microvascular permeability increased after 30 min of reperfusion. In conclusion, NCX-4016 attenuates oxidative stress and prevents arteriolar constriction during I/R, whereas DETA-NO increases lipid peroxides in the systemic blood and permeability after reperfusion. oxidative stress; nitric oxide-aspirin; microcirculation; lipid peroxides RECENTLY, A NEW CLASS of anti-inflammatory drugs has been developed by adding nitric oxide (NO) moiety to aspirin . NO released from these compounds has been shown to suppress prostanoid synthesis and to inhibit pathogenetic events during endotoxic shock (22,27,38,39). NCX-4016 has a more pronounced anti-thrombotic activity than aspirin (25, 37) as shown by the fact that it protected mice from pulmonary embolism, whereas in rabbits it reduced platelet accumulation induced by thrombin in the pulmonary vasculature (22, 32). NCX-4016 reduced infarct size and suppressed arrhythmias after myocardial ischemia-reperfusion (I/R) in pigs (38) and rats (40). NCX-4016, but not aspirin alone, was found to reduce brain damage induced by focal cerebral ischemia in spontaneously hypertensive rats (11).On restoration of blood flow during I/R, the production of reactive oxygen species (ROS) increases and is strongly implicated in microvascular dysfunction in experimental conditions, as well as in patients with acu...

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Production of oxidative products of nitric oxide in infarcted human heart

Cited by 53 publications

References 28 publications

Effect of Tilarginine Acetate in Patients With Acute Myocardial Infarction and Cardiogenic Shock

Effect of Tilarginine Acetate in Patients With Acute Myocardial Infarction and Cardiogenic Shock

Effect of Cyclooxygenase-2 Inhibitor (Celecoxib) on the Infarcted Heart in situ

Antioxidant activity of nitro derivative of aspirin against ischemia-reperfusion in hamster cheek pouch microcirculation

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