Myocardial Dysfunction With Coronary Microembolization

Abstract

Abstract-Coronary microembolization results in progressive myocardial dysfunction, with causal involvement of tumor necrosis factor-␣ (TNF-␣). TNF-␣ uses a signal transduction involving nitric oxide (NO) and/or sphingosine. Therefore, we induced coronary microembolization in anesthetized dogs and studied the role and sequence of NO, TNF-␣, and sphingosine for the evolving contractile dysfunction. Four sham-operated dogs served as controls (group 1). Eleven dogs received placebo (group 2), 6 dogs received the NO synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME, group 3), and 6 dogs received the ceramidase inhibitor N-oleoylethanolamine (NOE, group 4) before microembolization was induced by infusion of 3000 microspheres (42-m diameter) per milliliter inflow into the left circumflex coronary artery. Posterior systolic wall thickening (PWT) remained unchanged in group 1 but decreased progressively in group 2 from 20.6Ϯ4.9% (meanϮSD) at baseline to 4.1Ϯ3.7% at 8 hours after microembolization. Leukocyte count, TNF-␣, and sphingosine contents were increased in the microembolized posterior myocardium. In group 3, PWT remained unchanged (20.3Ϯ2.6% at baseline) with intracoronary administration of L-NAME (20.8Ϯ3.4%) and 17.7Ϯ2.3% at 8 hours after microembolization; TNF-␣ and sphingosine contents were not increased. In group 4, PWT also remained unchanged (20.7Ϯ4.6% at baseline) with intravenous administration of NOE (19.5Ϯ5.7%) and 16.4Ϯ6.3% at 8 hours after microembolization; TNF-␣, but not sphingosine content, was increased. In all groups, systemic hemodynamics, anterior systolic wall thickening, and regional myocardial blood flow remained unchanged throughout the protocols. A signal transduction cascade of NO, TNF-␣, and sphingosine is causally involved in the coronary microembolizationinduced progressive contractile dysfunction.

Effect of metoprolol on myocardial apoptosis after coronary microembolization in rats

“…Using DMR+Q550 pathological image pattern analysis instrument to analyze slices stained by HBFP, five microscopic visual fields (×100) were randomly sampled from each slice for observation, using Leica Qwin analysis software (Germany) and the planar area method to measure the infraction zone, expressing as area percent of bulk analysis slice and averaging. [13]…”

“…[10] Clinical findings show that metoprolol could play its roles of anti-inflammation and anti-apoptosis to improve cardiac function in condition of ischemic cardiomyopathy. [8,11,12] The function of metoprolol in the treatment of CME is not entirely clear, but myocardial apoptosis certainly occurs after CME[13] and metoprolol can inhibit myocardial apoptosis. Therefore, this study aims to observe the effect of metoprolol on myocardial apoptosis and caspase-3 activation after CME in rats, and to explore how metoprolol can prevent myocardial injury caused by CME, and to provide theoretical basis for the clinical prevention and treatment of CME.…”

The Involvement of Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN) in the Regulation of Inflammation Following Coronary Microembolization

“…Previous studies have demonstrated that the aggregate amount of infarction involved a small area (<5%) of microembolized myocardium in pigs or dogs, as indicated by the typical inflammatory responses with increases in TNF-α expression and leukocyte infiltration [6,7,20,21]. Our preliminary studies showed that a post-CME inflammatory response occurred as a result of the upregulation of TNF-α expression in the myocardium [10,11].…”

“…Our preliminary studies showed that a post-CME inflammatory response occurred as a result of the upregulation of TNF-α expression in the myocardium [10,11]. It has been well established that excessive TNF-α expression is derived from the surviving cardiomyocytes surrounding microinfarcts in autocrine or paracrine patterns [6] and is responsible for the detrimental effect on progressive contractile dysfunction [6,7,8,20,22]. …”

“…Accordingly, the resulting coronary microcirculation dysfunction might be determined by perfusion-contraction mismatch, reactive hyperemia, and regional myocardial contractile dysfunction; however, myocardial function partially recovers within minutes [4,5]. Many studies have shown that CME-induced microinfarcts initiate an inflammatory reaction with increased tumor necrosis factor-α (TNF-α) expression [6,7], resulting in damage to the myocardium and deterioration of myocardial systolic function [8,9]. Moreover, our previous studies also verified that microinfarction and ischemia in microembolized myocardium cause a severe inflammatory response with increased TNF-α expression in concert with the impairment of cardiac function [10,11].…”