JACC March 6, 2002 sire piatelet and fibrin-rich thrombus was seen. Neither the subendothelial infiltrate nor the large platelet clusters and thrombi were seen in the non-infected apo E -/- or in the wild-type infected mice. Conclusion: This study shows for the first time that influenza infection promotes inflam- mation, growth, and thrombosis of atherosclerotic plaques without involvement of the vessel media. Histopathologic changes as those observed in the present study have not been previously reported in human or animal atherasclerotic plaques. Possible mecha- nisms include massive production of cytokines in the lungs that are released into the cir- culation, influenza virus-induced deposition of immune-oomplexes in the plaque, virus presence in the plaque, thrombotic diathesis, endothelial apoptosis, endothelial dysfunc- tion, oxidative stress. This model may also prove useful for studying the roles of infection and inflammation in atherogenesis. 11:00 a.m. 892-3 Acute Chlamydia Pneumonise Infection Causes Diffuse Coronary Endothelial Dysfunction in Pigs Petru Liuba, Erkki Pesonen, Ilari Paakkari, Anders Forslid, Stafan Sandstrom, Lurid University Hospital, Lurid, Sweden. Background-We investigated whether acute Chlamydia pneumoniae infection, which has been epidemiologically associated with acute coronary syndromes (ACS), could alter the coronary endothelial vasomotor function in pigs. Methods-Eighteec pigs, 7-9-kg weight, were inoculated intratrecheally with C pneumo- niae (n=10) or saline (n=8). Half of animals from each group were investigated after 3 days and 2 weeks, respectively. The endothelium-dependent reactivity of coronary microcirculatioo was investigated at both time points by measuring peak coronary flow velocity (CFV) in response to bradykinin, an endothelium-dependent vasodilator, before and after infusions with glutathione, an antioxidant, and L-arginine, a substrate to nitric oxide synthase (NOS). Endothelial vasomotor function of prostaglandin F2(~ (PGF2c{)- precontracted LAD coronary rings was investigated in response to bradykinin at 3 days in the absence and presence of NG-nitro-L-arginine- methyl-ester (L-NAME), a NOS inhibi- tor. Results- CFV after bradykinin was significantly less in infected animals at both time points (Fig 1). At 2 weeks, both glutathione and L-arginine significantly improved CFV after bradykinin. CFV in response to sodium nitroprusside, an endothelium-independent vasodilator, was similar in both groups. At 3 days, in vitro, PGF2-induced contractions and bradykinin-induced relaxations of LAD coronary rings were significantly less in infected animals. L-NAME had significantly greater inhibitory effect on bradykinin- induced relaxation in infected animals. Plasma nitrate/nitrite and fibrinogen, and NOS activity from frozen LAD coronary samples, were significantly increased in infected ani- mals. Conclusion-Acute C pneumoniae infection causes profound endothelial dysfunction of both conduit and resistance coronary vessels. The findings support the role of C pneu- moniae in the pathogenesis of ACS. 11:15 a.m. 892-4 Antibodies to Chlamydial Heat Shock Protein 60 Is Associated With Coronary Artery Disease but Antibodies to Human Heat Shock Protein 60 and Escherlchia Coil Homologs Are Not ~laimatu S.M. Mahdi, Benjamin D. Home, Kelly Muellen, Joseph B. Muhlestein, Gerald I. Byrne, University Of Wisconsin, Madison, Wisconsin, LDS Hospital, Salt Lake City, Utah. Background: There is evidence for associations between Chlamydia pneumoniae (Cpn) infection and coronary artery disease (CAD), heat shock protein (Hsp) and chlamydial disease pathogenesis, and Hsp and CAD. Our aim was to determine whether immuno- logic responses to chlamydial Hsp may also be involved in CAD pathogenesis. Methods: Patients were recruited in a case-control study, in which 250 cases had anglo- graphic significant CAD (stenosis >_70%),and 250 controls had normal coronaries (steno- sis <10%). Risk factor data were available for each subject. ELISA was used to test serum IgG reactivity to Hsp antigens (recombinant human chaperonin 10 and Hsp60, E. coil GroES and GroEL, chlamydial Hspl0 (crisp10) and crisp60, and Cpn elementary bodies (EBs)). ANOVA evaluated the association of seroreactivity to each antigen to the presence of CAD. Multivariate logistic regression was used to predict CAD. Results: Multivariate analysis confirmed that known risk factors of CAD were indepen- dent predictors: age (P<0.001, odds ratio [OR]=l.6/decade), male gender (P<0.001, OR=3.4), diabetes (P=0.04, OR=1.8), family history of early CAD (P=0.01, OR=1.8), hyperlipidaemia (P=0.002, OR=2.0), hypertension (P=0.18, OR=1.4), smoking (P=0.09, OR=1.6), and CRP concentration (P=0.03, OR=1.2 per mg,'dL). Univariate analysis of seroreactivity to Hsps and Cpn showed that reactivity to crisp60, crisp10, E. coil GroEL and Cpn EBs (P=0.001, 0.045, 0.04 and 0.03, respectively) were significantly different between cases and controls. Multivariate analysis evaluating the predictive value of infectious factors for CAD found that only crisp60 seroreactivity remained a significant predictor for CAD, after controlling for risk factors and seroreactivity by other antigens (P=0.01, OR=2.1 for 5th quartile). Conclusion: Of the antibodies tested, only the presence of crisp60 IgG Abs was signifi- cantly associated with CAD. This finding argues against previous suggestions that cross- reactivity or autoimmune responses may be responsible for the contribution of Hsp dis- ease progression. Therefore, it may be possible to use IgG antibody response to the chlamydial Hsp60 as a marker for severe CAD. ABSTRACTS - Hypertension, Vascular Disease, and Prevention 277A 11:30 a.m. 892-5 Chronic but Not Acute Perivasculer Infection With Chlamydia Pneumonise Resulted In Plaque Pormation In Vivo Markus G. Enoelmann, Constanze V. Redl, Jaroslav Pelisek, Corinna Barz, Juergen Heesemann, Sigrid Nikol, University of Munich, Grosshadem, Medical Department I. Munich, Germany, University of Munich, Max yon Pettenkofer Institute, Munich, Germany. Background and Aims: in recent years, the association of Chlamydia pneumoniae (CPn) with atherogenesis became evident. We established a hypercholesterolemic rabbit model, in which chronic and acute arterial infection by CPn were compared. Methods: NZW rabbits were fed a high cholesterol diet (0.5%) for 16 weeks. Arterial seg- ments (n=21) were infected in vivo using viable Chlamydia pneumoniae (strain AR-39) either chronically by repetitive perivascular application of the organism at week 3, 7. 11 or by a single infection at week 11. Control arteries (n=21) were treated equally using sodium chloride. After sacrification, vascular tissues were analyzed by computer- assisted morphometry determining intima-media-ratio (IMR) and plaque-area-index (PAl). CPn was detected by fluorascence-immunohistochemistry and nested PCR. Remote tissues, such as lymphatic, lung, and parenchymal tissues were analyzed to detect systemic spread. Results: After 16 weeks, chronic perivascular infection of CPn resulted in a significant increase in PAl (0.23±0.08) when compared to single infection and control (0.03±0.02, and 0.01±0.01, respectively, p<0.005). Chronic CPn infection induced an increased lesion formation when compared to single infection or control (9 lesions of 12 infected vessels vs 2/9, and 2/12, p<0.05). CPn-DNA could be detected in 20% of arterial seg- ments and weakly in lymphatic and lung tissues. Persistent CPn major outer membrane protein was detected in edventitial tissue as well as in macrophage-rich plaques. Conclusion: Significant increase in plaque formation occurad only after chronic local infection by CPn. Persistence of the microorganisms rather than acute infection may con- tribute to atherogenesis. 11:45 a.m. 892-6 Adenosine Deaminase Inhibition Attenuates the Inflammatory Response to Sepsis and Improves Survival Steven M. Hollenbero. Elliott S. Cohen, Kenneth Q. Cruz, Beth Nardulli, William R. Law, Joseph E. Parrillo, Rush Medical College, Chicago, Illinois, University of Illinois, Chicago, Illinois. Objective: Adhesion of activated neutrophils to the microvasculature and increased cap- illary permeability lead to tissue damage and organ failure in sepsis. Adenosine down- regulates leukocyte-endothelial interactions; to explore its role in sepsis, mice were treated with the adenosine deaminase inhibitor pentostatin (PS) to increase endogenous adenosine. Methods: Mice made septic by cecal ligation and puncture (CLP) were compared to con- trois that underwent sham ligation. PS (1 mg/kg, SC) was given to mice immediately post CLP. Leukocyte rolling and adhesion in cremasteric post-capillary venules and leakage of fluorescein-labeled albumin was studied 15-18 hours after CLP by in vivo videomicros- copy; blood was analyzed for IL-6, TNF, and soluble TNF receptors (sTNFR). Survival was assessed in septic mice resuscitated with fluids and antibiotics every 6 hours. PS was provided by Supergen. Results: Leukocyte rolling (6.02±0.09 vs 0.74±0.05 cells/min) and adhesion (2.07±-0.04 vs 0.63±0.07 cells/100pm/min) were increased in septic mice compared to controls and decreased significantly with PS treatment (to 1.71±0.12 ceUs/min and 0.62±0.05 cells/ 100pm/min, p<0.0Ol). Venular shear did not differ significantly between groups. Albumin leakage ratio was increased in septic mice compared to controls (0.42±0.05 vs 0.13±0.03) and also improved with PS (to 0.21±0.04, p<0.01). TNF and IL-6 were signifi- cantly elevated in septic animals compared to controls (128±27 vs 36±16 pg/ml for TNF and 11968±3853 vs 57±86 pg/ml for IL-6) and was significantly attenuated by PS treat- ment (to 20±15 and 5525±1435 pg/ml, p<0.05). Circulating levels of sTNFRI and II were significantly increased in septic mice, and PS decreased sTNFRII but not sTNFRI. PS improved survival at 48 hours in resuscitated septic mice from 38% to 56%, (n=48, p<0.01). Conclusions: Sepsis-induced increases in microvascular leukocyte roiling, adhesion cytokine production, and capillary permeability were reduced by adenosine deaminase inhibition in a clinically relevant septic model, and this translated into improved survival. Endogenous adenosine may play an important role in modulating microvascular abnor- malities in sepsis.