Effect of anti-CD18 antibody on myocardial neutrophil accumulation and infarct size after ischemia and reperfusion in dogs.

Tanaka, Masaru; Brooks, S E; Richard, Vincent; FitzHarris, G P; Stoler, Robert C.; Jennings, Robert B.; Arfors, K. E.; Reimer, Keith A.

doi:10.1161/01.cir.87.2.526

Cited by 110 publications

(50 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although several experimental studies have shown that inhibition of leukocyte adhesion by treatment with an anti-CD18 antibody can reduce myocardial infarct size, 24,25 a recent report in humans did not show the effect of anti-CD18 antibody treatment on infarct size. 26 The discrepancy between the results of the experimental and human studies may be attributed to the optimal timing or dosage of administration.…”

Section: Discussionmentioning

confidence: 96%

Relation Between White Blood Cell Counts and Myocardial Reperfusion in Patients With Recanalized Anterior Acute Myocardial Infarction

Kosuge

Kimura

Ishikawa

et al. 2004

Circ J

View full text Add to dashboard Cite

he white blood cell (WBC) count on admission is a strong and independent predictor of increased morbidity and mortality in patients with acute myocardial infarction (AMI), 1-3 although the mechanism underlying these observations is unclear. Recent studies have reported that an elevated WBC count on admission is associated with a larger infarct size, 2,4 but whether it is the cause or the result of the large infarct remains to be determined. The development of ischemic myocardial damage may time-dependently elevate the WBC count in patients with AMI, 4 suggesting that the WBC count during the acute phase of AMI may be affected by the duration of the ischemia. Previous studies have assessed the relation between the WBC count and infarct size, without examining ischemic time, so the present study sought to clarify the relation of the WBC count on admission to infarct size and myocardial reperfusion according to ischemic time in patients with a recanalized anterior AMI. Methods Study GroupThe study group comprised 135 consecutive patients (mean age 59±11 years; 111 men, 24 women) with an AMI who fulfilled the following criteria: (1) no history of myocardial infarction; (2) complete occlusion (TIMI grade 0 flow) 5 of the left anterior descending (LAD) coronary artery on admission with achievement of TIMI grade 3 flow as confirmed by coronary angiography within 6 h of symptom onset; (3) electrocardiograms (ECGs) obtained before and after recanalization; (4) adequate assessment of myocardial blush grade after recanalization; (5) a patent LAD coronary artery as confirmed by predischarge coronary angiography, performed a mean of 14 days after AMI; and (6) no concomitant noncardiac diseases, such as inflammatory disorders, malignancy, or infection. The diagnosis of anterior AMI was based on typical chest pain lasting more than 30 min, ST-segment elevation of at least 2 mm in at least 2 contiguous precordial leads, and a subsequent increase in the serum creatine kinase (CK) concentration to more than twice the upper limit of normal. Coronary AngiographyCoronary angiography was performed immediately after admission. The grade of collateral filling in the LAD coronary artery was evaluated as described by Rentrop et al. 6 A good collateral channel was defined as grade 2 or 3, and a poor collateral channel as grade 0 or 1. The allocation of recanalization therapy was left to the attending doctor's discretion. 7,8 Recanalization was defined as the establishment of TIMI grade 3 flow. In the right coronary artery and the left circumflex coronary artery, stenosis was considered clinically significant if the lumen diameter was narrowed by 75% or more in any projection. Myocardial blush was Background The clinical significance of the white blood cell (WBC) count on admission in relation to the duration of ischemia in acute myocardial infarction (AMI) remains unclear. Methods and ResultsThe relationship of the WBC count on admission to myocardial reperfusion was examined in 135 patients with recanalization of an anterior AMI within 6...

show abstract

Section: Discussionmentioning

confidence: 96%

Relation Between White Blood Cell Counts and Myocardial Reperfusion in Patients With Recanalized Anterior Acute Myocardial Infarction

Kosuge

Kimura

Ishikawa

et al. 2004

Circ J

View full text Add to dashboard Cite

show abstract

“…Evidence from several lines of investigation suggests that inflammation is an important functional contributor to the pathogenesis of ischemic myocardial injury. For example, in animal models, neutrophil depletion with antibodies (128) or physical filtering (34,61), as well as the inhibition of neutrophil adhesion with anti-CD18 monoclonal antibody (142), all substantially reduce injury after reperfusion. In addition, interventions targeted at a variety of specific inflammatory mediators have demonstrated benefits in I/R injury, including complement depletion (96) or lipoxygenase inhibitors (133), or antibodies to the proinflammatory cytokine IL-1 (60).…”

Section: Tlr Signaling Mediates Myocardial I/r Injurymentioning

confidence: 99%

Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart

Chao¹

2009

American Journal of Physiology-Heart and Circulatory Physiology

212

166

View full text Add to dashboard Cite

Toll-like receptors (TLRs) represent the first line of host defense against microbial infection and play a pivotal role in both innate and adaptive immunity. TLRs recognize invading pathogens through molecular pattern recognition, transduce signals via distinct intracellular pathways involving a unique set of adaptor proteins and kinases, and ultimately lead to the activation of transcription factors and inflammatory responses. Among 10 TLRs identified in humans, at least two exist in the heart, i.e., TLR2 and TLR4. In addition to the critical role of these in mediating cardiac dysfunction in septic conditions, emerging evidence suggests that the TLRs can also recognize endogenous ligands and may play an important role in modulating cardiomyocyte survival and in ischemic myocardial injury. In animal models of ischemia-reperfusion injury or in hypoxic cardiomyocytes in vitro, the administration of a sublethal dose of lipopolysaccharide, which signals through TLR4, reduces subsequent myocardial infarction, improves cardiac functions, and attenuates cardiomyocyte apoptosis. By contrast, a systemic deficiency of TLR2, TLR4, or myeloid differentiation primary-response gene 88, an adaptor critical for all TLR signaling, except TLR3, leads to an attenuated myocardial inflammation, a smaller infarction size, a better preserved ventricular function, and a reduced ventricular remodeling after ischemic injury. These loss-of-function studies suggest that both TLRs contribute to myocardial inflammation and ischemic injury in the heart although the exact contribution of cardiac (vs. circulatory cell) TLRs remains to be defined. These recent studies demonstrate an emerging role for TLRs as a critical modulator in both cell survival and tissue injury in the heart.

show abstract

“…Accordingly, early bolus application of adhesion antagonists, eg CD18 antibodies or selectin antagonists, reduces myocardial detriment after 3-6 h of reperfusion. 4,5 However, improvement of myocardial function after anti-adhesive therapy fades over time, and is maintained only in animals receiving continuous antiadhesive treatment. 6,7 Consistent with these observations, postischemic PMN adhesion occurs in an immediate or delayed manner:…”

Section: Introductionmentioning

confidence: 99%

Retroinfusion of NFκB decoy oligonucleotide extends cardioprotection achieved by CD18 inhibition in a preclinical study of myocardial ischemia and retroinfusion in pigs

Kupatt¹,

Wichels²,

Deiss³

et al. 2002

Gene Ther

View full text Add to dashboard Cite

show abstract

Effect of anti-CD18 antibody on myocardial neutrophil accumulation and infarct size after ischemia and reperfusion in dogs.

Abstract: Although PMN accumulation contributed to reduced postischemic microvascular perfusion, it caused insufficient additional myocardial cell death to measurably affect infarct size in this model.

Cited by 110 publications

References 39 publications

Relation Between White Blood Cell Counts and Myocardial Reperfusion in Patients With Recanalized Anterior Acute Myocardial Infarction

Relation Between White Blood Cell Counts and Myocardial Reperfusion in Patients With Recanalized Anterior Acute Myocardial Infarction

Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart

Retroinfusion of NFκB decoy oligonucleotide extends cardioprotection achieved by CD18 inhibition in a preclinical study of myocardial ischemia and retroinfusion in pigs

Contact Info

Product

Resources

About