Natriuretic peptides: their role in diagnosis and therapy

Cardiac natriuretic peptide hormones, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), are synthesized and secreted by the heart, producing several biological effects, such as natriuresis, vasorelaxation and hypotension. During the last decade these peptides, especially BNP, have received increasing attention as potential markers of cardiovascular disease. Their measurements can be used to diagnose heart failure, including diastolic dysfunction, and using them has been shown to save money. BNP levels can enable the differentiation between dyspnoic patients secondary to ventricular dysfunction and subjects with primary respiratory disorders. Moreover, there is good evidence that natriuretic peptides may have a diagnostic role in arterial hypertension, acute coronary syndromes, pulmonary hypertension, some valvular heart disease and some disorders affecting other systems (diabetes or thyroid disorders). In this paper we discuss the clinical utility of assessment of natriuretic peptide hormones in the diagnosis of various clinical conditions and their use as pharmacological agents.     

Interpretation of elevated plasma visfatin concentrations in patients with ST-elevation myocardial infarction

Visfatin is a cytokine that is expressed in many tissues, including the heart, and has been proposed to play a role in plaque destabilization leading to acute myocardial injury. The present study evaluates plasma levels of visfatin in acute ST-elevation myocardial infarction (STEMI) patients and examines the temporal changes in visfatin levels from the acute period to the subacute period to determine a correlation with the degree of myocardial ischemia. We evaluated 54 patients with STEMI. Circulating levels of visfatin and brain natriuretic peptide (BNP) were measured by ELISA. In addition, local expression of visfatin and BNP were detected by quantitative real-time polymerase chain reaction and immunohistochemical (IHC) analysis of left ventricular myocytes in a mouse model of myocardial infarction (MI). Plasma levels of visfatin were significantly increased in patients with STEMI on admission, relative to controls (effort angina patients and individuals without coronary artery disease). The visfatin levels reached a peak 24 h after percutaneous coronary intervention (PCI) and then decreased toward the control range during the first week after PCI. The basal plasma visfatin levels were found to correlate with peak troponin-I, peak creatine kinase-MB, total white blood cell count, and BNP levels. Trend analyses confirmed that visfatin levels correlated with the number of diseased coronary arteries. Further, in MI mice, mRNA levels of visfatin and BNP were found to be higher than in sham-treated mice. IHC analysis showed that visfatin and BNP immunoreactivity was diffusely observable in left ventricular myocytes of the MI mice. This study indicates that plasma visfatin levels are significantly higher in STEMI patients and that these higher visfatin levels correlate with elevated levels of cardiac enzymes, suggesting that increased plasma visfatin may be closely related to the degree of myocardial damage.     

The presence of brain natriuretic peptide of 12,000 daltons in porcine heart

Brain natriuretic peptide (BNP) and its N-terminally six amino acid extended form (BNP-32) have been identified in porcine brain. These peptides exert diuretic-natriuretic and hypotensive effects, and have remarkably high sequence homology to atrial natriuretic peptide (ANP). We have set up a radioimmunoassay system specific to BNP and surveyed immunoreactive (ir-) BNP in peripheral tissue. In porcine cardiac atrium, we found the highest concentration of ir-BNP. By using gel filtration and reverse phase high performance liquid chromatography, ir-BNP was characterized. Most of ir-BNP in the atrium was found to exist as a high molecular weight form of 12,000 daltons; less than 15% of the total ir-BNP exist as low molecular weight forms such as BNP and BNP-32. These results suggest that BNP functions as a circulating hormone in addition to the neuropeptide function in brain.     

脑钠肽与急性心肌梗死的研究进展

脑钠肽是心肌细胞分泌的一种循环激素。左心室的牵张和心室壁张力的增加对BNP的合成和分泌起主要调节作用;心肌缺血也是BNP释放的重要触发因素之一。对BNP水平进行分级能够很好的对急性心肌梗死进行危险分层,对诊断、预后的评估有重要意义。本文就脑钠肽的特性及与心肌梗死的关系做一综述。     

Flow cytometric analysis of peroxidative activity in granulocytes from coronary and peripheral blood in acute myocardial ischemia and reperfusion in dogs: protective effect of methionine.

BACKGROUND: Methionine has shown protective effects in experimental models of myocardial infarction and is highly reactive to oxidative compounds produced by polymorphonuclear leukocytes (PMN), which in turn have been associated with myocardial damage. We have investigated the effect of methionine administration on spontaneous leukocyte peroxidative activity in myocardial ischemia and reperfusion. METHODS: In anesthetized dogs, with coronary occlusion (90 min) and reperfusion (90 min), PMN activation was measured by flow cytometric determination of H(2)O(2) with dihydrorhodamine 123, and correlated to hemodynamic parameters and infarct presence. To assess a possible direct effect of methionine, H(2)O(2) and superoxide were measured by flow cytometry in dog leukocyte suspensions following in vitro stimulation with f-MLP. RESULTS: PMN peroxidative activity in saline-treated dogs increased significantly after coronary occlusion and after reperfusion. These changes were greater in coronary venous blood than in femoral blood. Methionine administration (150 mg/kg, i.v.) before occlusion totally suppressed PMN activation, both after occlusion and reperfusion. CONCLUSIONS: PMN are promptly activated in myocardial ischemia, and methionine administration prevents such activation. However, methionine has no direct effect on spontaneous peroxidative activity, and f-MLP induced peroxidative activity. These in vivo effects of methionine, may additionally contribute to explain its protective role in experimental -788-877-7QQ8-8-7-88-8-8778--8Q78-----8--8-Q-7-Q7----- --------------8888 888888-7777777777777777777777777777777----------------888888888888888888 8877777--87--------8-----------------7-8888-887-----------8----8-8-87777 7777777------------------------------------------------------T7OW     

急性心肌梗死患者脑钠肽水平与血管病变的关系

目的:探讨急性心肌梗死患者血浆脑钠肽(BNP)水平与梗死相关动脉及病变血管的关系。方法:选取2010.7-2011.7于上海市第一人民医院诊断为急性心肌梗死的患者。分为ST抬高型心梗患者和非ST抬高型心梗患者两组,比较BNP水平与血管病变的关系。结果:(1)两组患者的年龄、男女比例、高血压病与糖尿病患病率、吸烟患者比例之间无显著差异。NSTEMI患者中,既往心梗和既往经皮冠状动脉成形术(PTCA)的比例和左室射血分数明显高于STEMI患者。(2)NSTEMI患者多支血管病变比例显著高于STEMI患者并且梗死相关动脉为左回旋支(LCX)的比例显著高于STEMI患者。(3)病变血管支数与心梗患者BNP水平无关,STEMI患者左冠状动脉前降支(LAD)为IRA的患者BNP水平显著高于LCX和右冠状动脉(RCA)分别为IRA的患者。NSTEMI患者LAD、LCX和RCA分别为IRA的患者其BNP水平无显著差异。结论:STEMI患者前壁心梗BNP水平较高,NSTEMI患者BNP水平对血管病变支数和IRA无预测价值。     

Increased plasma levels of intermedin and brain natriuretic peptide associated with severity of coronary stenosis in acute coronary syndrome

Intermedin (IMD) is a newly discovered peptide with increased levels in plasma and cardiac tissue in mice with ischemia/reperfusion. Continuous administration of low dose IMD markedly elevated the mRNA abundance of myocardial BNP in rats. Plasma BNP levels may reflect the severity of degree of coronary stenosis in patients with acute coronary syndrome (ACS). However, the role of circulating IMD in coronary heart disease remains unclear. We aimed to examine the plasma content of IMD and brain natriuretic peptide (BNP) and its clinical significance in patients with ACS. We collected plasma samples from 41 patients with ACS and 31 controls and measured IMD and BNP levels by radioimmunoassay. The severity of coronary artery stenosis for patients with ACS was measured by coronary angiography. Plasma IMD and BNP levels were markedly higher in ACS patients than that in controls (P < 0.05). The increased plasma IMD and BNP were positively correlated with degree of coronary stenosis in ACS patients (r = 0.263 and r = 0.238, respectively, both P < 0.05). In addition, plasma levels of IMD were positively correlated with BNP levels.     

Angiotensin II receptor antagonism reverts the selective cardiac BNP upregulation and secretion observed in myocarditis

The cardiac natriuretic peptides atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) are discoordinately regulated in myocardial inflammation associated with acute allograft rejection in humans and during in vitro exposure of cardiocyte cultures to some proinflammatory cytokines. We used experimental autoimmune myocarditis (EAM) to determine whether the discoordinate regulation of ANF and BNP was specific to the situations above or was generally associated with other types of myocardial inflammation. The dependency of this process to angiotensin signaling was also determined, given that previous work demonstrated beneficial effects of the angiotensin receptor blocker olmesartan in myocarditis. Histopathological changes, plasma and cardiac ANF, BNP, and selected cytokines gene expression as well as plasma cytokine levels using a cytokine array were determined in EAM, angiotensin receptor blocker-treated, and control rats. It was found that EAM specifically increases BNP but not ANF circulating levels, thus mimicking the findings in acute cardiac allograft rejection and the effect of some proinflammatory cytokines on cardiocyte cultures in vitro. Plasma cytokine array and real-time PCR revealed that lipopolysaccharide-induced CXC chemokine, monocyte chemotactic protein-1, and tissue inhibitor of metalloproteinase-1 were increased in plasma and in the myocardium of EAM rats. Olmesartan treatment reversed virtually all neuroendocrine and histopathological cardiac changes induced by EAM, thus providing a mechanistic insight into this phenomenon. It is concluded that the inflammatory process contributes specific cytokines, leading to the disregulation of cardiac ANF and BNP production observed during myocardial inflammation, and that this process is angiotensin receptor 1 dependent.     

Augmented secretion of brain natriuretic peptide in acute myocardial infarction.

In order to elucidate biosynthesis and secretion of natriuretic peptides in the early phase of acute myocardial infarction (AMI), we measured the plasma level of brain natriuretic peptide (BNP), a novel cardiac hormone secreted from the ventricle, in patients with AMI and compared with that of atrial natriuretic peptide (ANP). The plasma level of BNP increased rapidly (within hours from the onset of AMI) and markedly (greater than 100 times the normal level) as compared to that of ANP. The plasma ANP level correlated with pulmonary capillary wedge pressure (PCWP), whereas the plasma BNP level did not correlate with PCWP but highly correlated inversely with cardiac index. These results indicate that BNP is secreted from the heart much more acutely and prominently than ANP in the early phase of AMI, in association with left ventricular dysfunction.     

C型利钠利尿肽对犬冠脉循环的作用

Ｃ型利钠利尿肽（ＣＮＰ）是新近发现的一种由内皮细胞分泌的利钠利尿肽,本研究采用冠脉内给药方法对比观察了ＣＮＰ、心房利钠尿肽（ＡＮＰ）对犬正常及心肌缺血后冠脉循环的作用,并应用常规离体血管灌流的方法测定了离体冠脉对ＣＮＰ、ＡＮＰ的舒张反应。结果显示：（１）对正常犬,ＣＮＰ、ＡＮＰ均可降低平均动脉压（ＭＡＰ）、远端小冠脉压和大、小冠脉阻力,增加冠脉流量,而不影响心率;（２）心肌缺血后,ＣＮＰ的上述作用依然存在,但ＡＮＰ降低ＭＡＰ的作用基本消失。（３）离体心外膜冠状动脉对ＣＮＰ、ＡＮＰ均呈剂量依赖性舒张反应。结果提示ＣＮＰ、ＡＮＰ均可舒张冠状动脉而改善冠脉循环,并可能对急性心肌缺血的治疗有益     

脑利钠肽后处理对兔急性心肌梗死的保护作用

目的：脑利钠肽后处理对兔急性心肌梗死的保护作用及可能机制。方法：30 只兔随机分为3 组,每组10 只,左冠状动脉的左 室支缺血30 分钟,再灌注120 分钟。AMI（急性心肌梗死）组：再灌注期间静脉滴注生理盐水;BNP（脑利钠肽）组：再灌注期间静脉 滴注rhBNP(重组人脑利钠肽);BNP+GLY（脑利钠肽+格列苯脲）组：再灌注期间静脉滴注rhBNP,同时舌下静脉注射GLY 。连续 监测心电变化,统计再灌注120 min 室性心动过速(VT)、心室颤动(VF)的发生率。心肌再灌注120 min 后,分别测定SOD(超氧化 物歧化酶)、MDA（丙二醛）、cTnI（肌钙蛋白I）、CK-MB（肌酸激酶同工酶）。各组随机抽取2 只兔,分别于再灌注1 小时和2 小时末 取心尖组织,HE 染色。结果：（1）再灌注心律失常：BNP 组与AMI组比较,VT 和VF发生率均明显升高（均为P<0.01）;BNP+GLY 组与BNP 组比较,VT 和VF 发生率均明显升高（均为P<0.01）。（2）SOD、MDA、cTnI 和CK-MB 水平：BNP 组与AMI 组比较, MDA、cTnI 和CK-MB 均明显降低（均为P<0.01）,而SOD 明显升高（P<0.01）;BNP+GLY 组与BNP 组比较,MDA、cTnI 和 CK-MB 均明显升高（分别为P<0.01,P<0.05和P<0.01）,而SOD明显降低（P<0.01）。（3）心肌HE 染色：AMI组和BNP+GLY 组心 肌损伤明显,BNP 组心肌损伤轻微。结论：脑利钠肽后处理对兔急性心肌梗死（缺血- 再灌注损伤）具有保护作用,可能与KATP 通道相关。     

Distribution and molecular forms of brain natriuretic peptide in porcine heart and blood

Although brain natriuretic peptide (BNP) is a novel natriuretic peptide originally identified in porcine brain, recent investigation has verified the presence of BNP in porcine heart. In order to identify BNP as a circulating hormone, we analyzed the regional distribution and molecular form of immunoreactive (ir-) BNP in heart and blood. Tissue concentration of ir-BNP was high in atrium, but low in ventricle, in a manner similar to that of atrial natriuretic peptide (ANP). However, the concentration of ir-BNP in atrium was only about 1/50 that of ir-ANP. In plasma, ir-BNP was found at a concentration of 1-3 fmol/ml, which was about 1/20 that of ir-ANP. Both ir-BNP and ir-ANP were present as low molecular weight forms. Three forms of ir-BNP of about 3K daltons, including BNP-26, BNP-29 and BNP-32, are thought to circulate in blood.     

利钠肽家族基因与心血管疾病研究新进展

利钠肽家族是一组由心肌细胞分泌的激素, 主要包括A型、B型和C型利钠肽, 具有相似的基因结构和生理学效应, 可对心血管系统产生血压调节、抗心肌肥厚、抗心肌纤维化和抗心肌弛缓等保护作用。利钠肽受体A、B和C亦介导多种生理活性, 调节心血管稳态。利钠肽受体A选择性结合A型、B型利钠肽。利钠肽受体B结合C型利钠肽。利钠肽受体C结合各型利钠肽, 通过受体介导的内化和退化作用清除血液循环中利钠肽。对利钠肽家族及其受体基因单核甘酸多态性及功能研究显示, 其与多种心血管疾病(房颤、高血压、心力衰竭等)的易感性相关。利钠肽家族及其受体基因缺失的转基因小鼠表现为心肌肥厚、心肌纤维化, 与高血压、心肌病及心力衰竭的发生发展相关。各种导致心肌肥厚和缺血性损伤的刺激均参与利钠肽及其受体基因的表达调控。临床将脑钠肽作为左室功能障碍和心力衰竭失代偿的一个预测指标。静脉注射重组脑钠肽已经成为治疗急性心力衰竭的有效手段。深入了解利钠肽家族基因变异及其信号调控有助于探索心血管疾病的病理生理机制, 为临床诊疗开辟新思路。     

Increased prolactin in acute coronary syndromes as putative Co-activator of ADP-stimulated P-selectin expression.

Prolactin and leptin are newly recognized platelet co-stimulators due to enhancement of ADP-induced platelet aggregation. The aim of our study was to assess whether both hormones prolactin and leptin play a role as co-activators of platelet activation in patients with acute coronary syndromes. Twenty-one patients with acute coronary syndromes, 10 with stable angina pectoris and 10 controls were studied. Patients with acute coronary syndromes showed significantly higher prolactin and leptin values and a significant increased P-selectin expression on platelets compared to patients with stable angina pectoris or controls. However, patients with acute myocardial infarction as a subgroup of acute coronary syndromes showed the highest prolactin levels as well as ADP stimulated P-selectin expression. In the myocardial infarction subgroup prolactin values showed a significant correlation to ADP stimulated P-selectin expression on platelets (r (2)=0.41; p=0.025), whereas leptin was not correlated. Our data indicate an association between increased prolactin values and enhanced P-selectin expression on platelets in patients with acute coronary syndromes. Therefore, the stress hormone prolactin could be a co-stimulator of platelet activation in these patients. In contrast, the putative platelet activator leptin does not seem to play a major role in acute coronary syndromes.     

Stimulatory effect of gangliosides on phagocytosis, phagosome–lysosome fusion, and intracellular signal transduction system by human polymorphonuclear leukocytes

Gangliosides are known to be differentiation-inducing molecules in mammalian stem cells. We studied the interaction between the molecular structure of glycosphingolipids (GSLs) and their promoting mechanisms of the phagocytic processes in human polymorphonuclear leukocytes (PMN). The effect of various gangliosides from mammalian tissues on adhesion, phagocytosis, phagosome–lysosome (P–L) fusion and superoxide anion production was examined by human PMN using heat-killed cells of Staphylococcus aureus coated with GSLs. Gangliosides GM3, GD1a, GD3 and GT1b showed a marked stimulatory effect on the phagocytosis and P–L fusion in a dose-dependent manner, while ganglioside GM1, asialo GM1 and neutral GSLs did not. The relative phagocytic rate of ganglioside GM3-coated S. aureus was the highest among the tested GSLs. Both P–L fusion rate and phagocytosis of S. aureus were elevated significantly when coated with ganglioside GD1a, GD3 or GT1b, and GT1b gave a five times higher rate than that of the non-coated control. These results suggest that the terminal sialic acid moiety is essential for the enhancement of phagocytosis and that the number of sialic acid molecules in the ganglioside is related to the enhancement of the P–L fusion process. On the other hand, the superoxide anion release from PMN was not affected by ganglioside GM2, GM3, GD1a or GT1b. Furthermore, to clarify the trigger or the signal transduction mechanism of phagocytic processes, we examined the effect of protein kinase inhibitors such as H-7, staurosporine (protein kinase C inhibitor), H-89 (protein kinase A inhibitor), genistein (tyrosine kinase inhibitor), ML-7 (myosin light chain kinase inhibitor), and KN-62 (Ca2+/calmodulin-dependent protein kinase II inhibitor) on ganglioside-induced phagocytosis. H-7, staurosporine and KN-62 inhibited ganglioside-induced phagocytosis in the range of concentration without cell damage, while H-89, genistein and ML-7 did not. Moreover, H-7 and KN-62 inhibited ganglioside-induced P–L fusion. These results suggest that protein kinase C and Ca2+/calmodulin-dependent protein kinase II may be involved in the induction of phagocytosis and P–L fusion stimulated by gangliosides. This revised version was published online in November 2006 with corrections to the Cover Date.     

利钠肽家族基因与心血管疾病研究新进展

利钠肽家族是一组由心肌细胞分泌的激素,主要包括A型、B型和C型利钠肽,具有相似的基因结构和生理学效应,可对心血管系统产生血压调节、抗心肌肥厚、抗心肌纤维化和抗心肌弛缓等保护作用。利钠肽受体A、B和C亦介导多种生理活性,调节心血管稳态。利钠肽受体A选择性结合A型、B型利钠肽。利钠肽受体B结合C型利钠肽。利钠肽受体C结合各型利钠肽,通过受体介导的内化和退化作用清除血液循环中利钠肽。对利钠肽家族及其受体基因单核甘酸多态性及功能研究显示,其与多种心血管疾病(房颤、高血压、心力衰竭等)的易感性相关。利钠肽家族及其受体基因缺失的转基因小鼠表现为心肌肥厚、心肌纤维化,与高血压、心肌病及心力衰竭的发生发展相关。各种导致心肌肥厚和缺血性损伤的刺激均参与利钠肽及其受体基因的表达调控。临床将脑钠肽作为左室功能障碍和心力衰竭失代偿的一个预测指标。静脉注射重组脑钠肽已经成为治疗急性心力衰竭的有效手段。深入了解利钠肽家族基因变异及其信号调控有助于探索心血管疾病的病理生理机制,为临床诊疗开辟新思路。     

Circulating heat shock proteins and inflammatory markers in patients with idiopathic left ventricular dysfunction: their relationships with myocardial and microvascular impairment

Little information is available on peripheral levels of Hsp72, Hsp60, and anti-Hsp60 antibodies in patients with left ventricular (LV) dysfunction due to non-atherosclerotic cardiac disease. In this study, serum Hsp72, Hsp60 and anti-Hsp60 antibodies, IL-6, and C-reactive protein (CRP) were measured in 44 healthy controls and in 82 patients with angiographically normal coronary arteries (LV ejection fraction [EF] > or = 50%, n=22; -35% to <50%, n=32; <35%, n=28). Patients with more severe disease (more depressed myocardial blood flow at rest and during dipyridamole, indicative of coronary microvascular impairment) showed more elevated circulating Hsp60 and auto-antibodies, Hsp72, and CRP levels. IL-6 was increased progressively as a function of severity of LV dysfunction. Anti-Hsp60 antibodies, Hsp72, and IL-6 were significantly correlated with brain natriuretic peptide (BNP) levels and LV end-diastolic dimensions (LVEDD) values. IL-6 tended to be related with Hsp72 in particular in patients with more severe disease (r = 0.45, P = 0.021). Hsp60 and Hsp72 activation and inflammatory markers were correlated with the extent of cardiac and microvascular dysfunction in patients with angiographycally normal coronary arteries. These results suggest a pathogenic role of infective-metabolic insult and inflammatory reaction in the development of vascular and myocardial damage in patients with heart failure even in the absence of overt coronary artery disease.     

NT-proBNP、BNP及hs-CRP在老年急性非ST段抬高型心肌梗死患者血浆中的表达及临床意义

目的:探讨N末端前体脑钠肽(NT-proBNP)、脑钠肽(BNP)及超敏C-反应蛋白(hs-CRP)在老年急性非ST段抬高型心肌梗死患者血浆中的表达及临床意义。方法:选择2015年2月～2018年7月在我院进行诊治的老年急性非ST段抬高型心肌梗死患者200例为观察组,选择同期在我院进行诊治的非冠脉综合征患者100例为对照组。入院后次日检测所有患者的血浆中的NT-proBNP、BNP及hs-CRP等指标的水平,并对比两组患者以及观察组中不同血管病变支数患者上述指标水平。两组患者均随访6个月,观察心血管不良事件的发生率。结果:观察组患者的NT-proBNP、BNP及hs-CRP水平均显著高于对照组,组间比较差异有统计学意义(P0.05)。观察组内单支血管病变、双支血管病变、三支血管病变患者间NT-proBNP、BNP及hs-CRP水平比较差异有统计学意义(P0.05),各项指标水平随着血管病变支数增加而升高(P0.05)。观察组在出院后为期6个月随访期间心血管不良事件发生率为16.50%,高于对照组心血管不良事件发生率为6.00%,组间比较差异有统计学意义(P0.05)。患者冠脉血管病变支数与血浆NT-proBNP、BNP及hs-CRP水平间呈正相关(P0.05)。结论:血浆NT-proBNP、BNP及hs-CRP水平在老年急性非ST段抬高型心肌梗死患者中显著升高,且随着患者血管病变程度的增加而升高,对患者预后心血管不良事件判断有较好的预测作用。     

Essential fatty acid deficiency inhibits early but not late leukocyte infiltration in rabbit myocardial infarcts

Essential fatty acid (EFA) deficiency, induced by elimination of the dietary (n-6) fatty acids, has been shown to limit inflammatory cell influx and consequent enhanced eicosanoid production in experimental glomerulonephritis and hydronephrosis. To determine whether EFA-deficiency exerts anti-inflammatory effects following left ventricular myocardial infarction (LVMI), male weanling rabbits were fed EFA-deficient diet for 3 months prior to 60 minutes of distal left circumflex coronary artery occlusion followed by reperfusion. One and 4 days later, corresponding to infiltration of cardiac tissue with polymorphonuclear (PMN) and mononuclear leukocytes respectively, infarcted hearts were buffer perfused and stimulated to produce eicosanoids with f-met-leu-phe or bradykinin. One day following LVMI, the hearts of EFA-deficient rabbits demonstrated a marked suppression of PMN infiltration and eicosanoid production relative to controls. Four days following myocardial infarction, no differences were observed in mononuclear cell invasion, collagen deposition, or eicosanoid production between EFA-deficient and normal hearts. Our data show that EFA-deficiency inhibits PMN influx and consequent enhanced eicosanoid production without affecting the later appearance of mononuclear cells, collagen deposition, or eicosanoid production. Recent studies have shown that suppression of PMN invasion limits the extent of tissue damage following LVMI. Selective inhibition of PMN infiltration is possible and may be useful in the management of acute myocardial infarction.