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Surgical revascularization of left main and/or three-vessel coronary artery disease (CAD) is associated with improved survival in patients with left ventricular dysfunction when compared to medical therapy and can result in improved left ventricular ejection fraction (LVEF) [1]. Multivessel percutaneous coronary intervention (PCI) is equivalent to surgery regarding short and intermediate term mortality, and left main PCI has emerged as a safe and effective alternate to surgical revascularization [2]. However, outcomes of unprotected left main PCI in patients with severely depressed LVEF have not been examined. We report a patient with left main chronic total occlusion, multivessel CAD, and dilated cardiomyopathy, in whom complete revascularization via PCI resulted in decreased left ventricular size and improved LVEF., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Erythropoietin mitigates myocardial damage and improves ventricular performance after experimental ischemic injury. This study assessed safety and efficacy markers relevant to the biological activity of recombinant human erythropoietin (rHuEpo) in patients with acute myocardial infarction (MI)., Methods: We conducted a prospective, placebo-controlled, randomized, double-blind trial to determine the effects of intravenous rHuEpo (200 U/kg daily for 3 consecutive days) on measures of platelet and endothelial cell activation, soluble Fas ligand, and peripheral blood mononuclear cell (PBMC) expression of angiogenesis signaling proteins in 44 subjects with acute MI treated with aspirin and clopidogrel after successful percutaneous coronary intervention., Results: Recombinant human erythropoietin did not alter bleeding time, platelet function assay closure time, von Willebrand factor levels, soluble P-selectin, or soluble Fas ligand levels when compared with placebo. By contrast, rHuEpo significantly increased expression of erythropoietin receptor, vascular endothelial growth factor receptor Flt-1, and phosphorylated phosphatidylinositol 3-kinase in PBMCs when compared with placebo (all Ps < .05)., Conclusions: In acute MI patients treated with aspirin and clopidogrel, short-term administration of rHuEpo did not alter markers of platelet and endothelial cell activation associated with thrombosis, yet did increase expression of angiogenesis signaling proteins in PBMCs when compared with placebo. These data provide preliminary evidence of safety and biologic activity of rHuEpo at this dosing and support continued enrollment in ongoing efficacy trials.

Background: Atherosclerosis is an inflammatory disease in which interferon (IFN)-gamma, the signature cytokine of Th1 cells, plays a central role. We investigated whether interleukin (IL)-17, the signature cytokine of Th17 cells, is also associated with human coronary atherosclerosis., Methods and Results: Circulating IL-17 and IFN-gamma were detected in a subset of patients with coronary atherosclerosis and in referent outpatients of similar age without cardiac disease but not in young healthy individuals. IL-17 plasma levels correlated closely with those of the IL-12/IFN-gamma/CXCL10 cytokine axis but not with known Th17 inducers such as IL-1beta, IL-6, and IL-23. Both IL-17 and IFN-gamma were produced at higher levels by T cells within cultured atherosclerotic coronary arteries after polyclonal activation than within nondiseased vessels. Combinations of proinflammatory cytokines induced IFN-gamma but not IL-17 secretion. Blockade of IFN-gamma signaling increased IL-17 synthesis, whereas neutralization of IL-17 responses decreased IFN-gamma synthesis; production of both cytokines was inhibited by transforming growth factor-beta1. Approximately 10-fold fewer coronary artery-infiltrating T helper cells were IL-17 producers than IFN-gamma producers, and unexpectedly, IL-17/IFN-gamma double producers were readily detectable within the artery wall. Although IL-17 did not modulate the growth or survival of cultured vascular smooth muscle cells, IL-17 interacted cooperatively with IFN-gamma to enhance IL-6, CXCL8, and CXCL10 secretion., Conclusions: Our findings demonstrate that IL-17 is produced concomitantly with IFN-gamma by coronary artery-infiltrating T cells and that these cytokines act synergistically to induce proinflammatory responses in vascular smooth muscle cells.

In Mycobacterium marinum, the homologue of Rv1500 of M. tuberculosis encodes a glycosyltransferase. Initially, it was suggested that this gene is involved in the synthesis of phosphatidylinositol mannosides (PIMs), generating Ac(2)PIM(7) from Ac(2)PIM(5). Phosphatidylinositol mannoside and its related compounds lipomannan (LM) and lipoarabinomannan (LAM) have been shown to modulate the host response to an infection with M. tuberculosis. Here, we generated a deletion mutant of Rv1500 in M. tuberculosis H37Rv, and analyzed the mutant using a biochemical approach as well as in vitro and in vivo infection models. Inactivation of Rv1500 did not lead to an altered expression pattern of PIMs in M. tuberculosis H37Rv. We found phosphatidylinositol (PI), PIM(2), AcPIM(2), Ac(2)PIM(2), and AcPIM(6) in both strains, but were unable to detect Ac(2)PIM(7) or Ac(2)PIM(5) either in the wild type or the mutant strain. Uptake and growth of H37Rv and Rv1500 mutant strains in murine bone marrow-derived macrophages was identical, and TNFalpha and IL-12p40 production in mouse macrophages and dendritic cells was induced to similar levels following infection with either strain. Aerosol challenge of mice showed that wild type and Rv1500 mutant strains had identical growth rates in infected organs over time. We verified mRNA expression of Rv1500 in H37Rv and conclude that Rv1500 must serve a redundant role in viability and virulence of M. tuberculosis.

Inflammation is associated with the pathogenesis of coronary atherosclerosis, although the mechanisms remain unclear. We investigated whether cytokine secretion by innate immune responses could contribute to the production of proarteriosclerotic Th1-type cytokines in human coronary atherosclerosis. Cytokines were measured by ELISA in the plasma of patients with coronary atherosclerosis undergoing cardiac catheterization. IL-18 was detected in all subjects, whereas a subset of patients demonstrated a coordinated induction of other IFN-gamma-related cytokines. Specifically, elevated plasma levels of IL-12 correlated with that of IFN-gamma and IFN-gamma-inducible chemokines, defining an IFN-gamma axis that was activated independently of IL-6 or C-reactive protein. Systemic inflammation triggered by cardiopulmonary bypass increased plasma levels of the IFN-gamma axis, but not that of IL-18. Activation of the IFN-gamma axis was not associated with acute coronary syndromes, but portended increased morbidity and mortality after 1-year follow-up. IL-12 and IL-18, but not other monokines, elicited secretion of IFN-gamma and IFN-gamma-inducible chemokines in human atherosclerotic coronary arteries maintained in organ culture. T cells were the principal source of IFN-gamma in response to IL-12/IL-18 within the arterial wall. This inflammatory response did not require, but was synergistic with and primed for TCR signals. IL-12/IL-18-stimulated T cells displayed a cytokine-producing, nonproliferating, and noncytolytic phenotype, consistent with previous descriptions of lymphocytes in stable plaques. In contrast to cognate stimuli, IL-12/IL-18-dependent IFN-gamma secretion was prevented by a p38 MAPK inhibitor and not by cyclosporine. In conclusion, circulating IL-12 may provide a mechanistic link between inflammation and Th1-type cytokine production in coronary atherosclerosis.

Intravascular brachytherapy is the primary treatment for coronary in-stent restenosis. Variations in dose in the treated artery may represent a potential cause of treatment failure. We compared dose distributions in patients who had developed recurrent restenosis (treatment failure) with those in patients who remained event free at 9 months (treatment success). We followed 140 patients who were receiving brachytherapy for in-stent restenosis with 4 radiation delivery devices to identify treatment failures and successes. Through a nested case-control construct, treatment failures (n = 14) were compared 1:2 with treatment successes (n = 28) matched by radiation delivery system and in-stent restenosis lesion pattern. The dose absorbed by 90% of the artery encompassed by the external elastic membrane (D(90)EEM) was calculated by applying intravascular ultrasound at 2-mm intervals along the treated lesion. Dose calculations were performed using dose kernel integration techniques generated from Monte Carlo simulations. The mean minimum D(90)EEM in treatment failures was 7.46 +/- 1.98 Gy, and that in treatment successes was 8.87 +/- 1.13 Gy (p = 0.007). Using a minimum dose threshold of 8.4 Gy, a minimum D(90)EEM

Background: The effectiveness of brachytherapy for the treatment of in-stent restenosis (ISR) has been established in a number of large randomized controlled trials. Efficacy of this therapy in general population is less well established., Methods and Materials: We report our experience of 207 patients, 236 coronary lesions, treated with brachytherapy between November 2000 and November 2002. All commercially available brachytherapy devices, as well as one investigational device, were utilized. This cohort was followed over 9 months and clinical outcomes were obtained with subsequent analysis of patient and lesion-specific characteristics., Results: Average treatment age was 62.5 years; 73% were male and the most frequent presentation was unstable angina (74%). All patients had successful delivery of radiation, with no in-hospital deaths. Novoste BetaCath device was used for 163 (65%) lesions, Cordis Checkmate for 56 (24%) lesions, Interventional Therapies device in 13 (8%) lesions, and Guidant Galileo in 4 lesions (3%). At a mean follow-up of 9.1 months, 78.7% were free of major adverse cardiac event (MACE). Twenty-one patients required repeat PTCA (10.1%), 19 had CABG (9.2%), 3 had MI (1.4%), and there was 1 death (0.5%). Unadjusted MACE rates for each device were 21% for Novoste, 28% for Checkmate, 8% for Interventional Therapies, and 50% for Galileo. Lesion length, minimal lumen diameter, renal failure, diabetes, and smoking did not predict treatment failure; only age was inversely correlated with MACE (P=.002)., Conclusion: When applied across a spectrum of patients, lesions, and devices, brachytherapy retains its effectiveness with outcomes similar to those reported in randomized clinical trials.

Background: The PlA2 polymorphism of platelet glycoprotein IIIa has been identified as a prothrombotic risk factor in a number of cardiovascular settings. The aim of this study was to determine whether the PlA2 polymorphism of platelet glycoprotein IIIa and degree of platelet activation were associated with more severe myocardial injury as indicated by troponin I release following cardiopulmonary bypass., Methods: The PlA2 genotype was determined in 66 patients undergoing elective coronary artery bypass grafting requiring cardiopulmonary bypass. Troponin I concentrations and the percentage of circulating, activated (CD62P+) platelets were measured at predetermined intervals perioperatively., Results: Forty-six patients were Pl(A1,A1), and 20 were Pl(A1,A2) or Pl(A2,A2). Patients with at least one PlA2 allele had significantly greater postoperative troponin I concentrations than PlA1 homozygotes (P = 0.006, analysis of variance). Peak troponin I concentrations also correlated significantly with the increase in circulating, activated platelets (P = 0.02, Spearman rank correlation)., Conclusions: The PlA2 allele of platelet glycoprotein IIIa is associated with higher troponin I concentrations following cardiopulmonary bypass surgery, suggesting that this platelet polymorphism contributes to perioperative myocardial injury.

Background: Although activation of the complement system in myocardial infarction and cardiopulmonary bypass has been shown to contribute to myocardial injury, its role in congestive heart failure (CHF) is unknown. The purpose of this study was to determine the presence of terminal complement activation and its relation to clinical outcomes in patients with CHF., Methods: We measured serum levels of the terminal complement complex C5b-9 in 36 patients with symptomatic heart failure and left ventricular ejection fraction <40%. We compared the serum C5b-9 levels of these patients with CHF with a group of 12 age-matched control patients. Combined clinical outcomes (death, urgent heart transplantation, or hospitalization with worsening heart failure) at 6 months were determined., Results: The serum C5b-9 [median (25th to 75th percentiles)] levels in 36 patients with CHF [101.5 ng/mL (40 to 164)] were significantly (P =.003) higher than in the 12 control patients [36.5 ng/mL (22 to 50)]. Significantly more of the patients with CHF with the highest levels of C5b-9 (highest 50th percentile) had New York Heart Association class IV symptoms (67% vs 33%; P =.04) and adverse clinical outcomes by 6 months (56% vs 17%; P =.02) compared with the patients with CHF with lower levels (lowest 50th percentile)., Conclusions: We have described a significant elevation in circulating C5b-9, the terminal complement complex, in patients with symptomatic heart failure and have observed an association between high levels of C5b-9 and near-term adverse events.

Translumbar puncture for access to the central arterial tree has been used for aortography and for selective coronary angiography in selected patients where conventional peripheral access is not possible. A single case report of coronary angioplasty through this access technique is available in the literature. We report a case of coronary stent placement using the translumbar approach to access the coronary arteries.

Objectives: The present study examined the association of estrogen (E2) and the inflammatory response of endothelium in coronary artery disease (CAD) by measuring circulating cellular adhesion molecules (cCAMs) in subjects with atherosclerosis., Background: Atherosclerotic plaque demonstrates features similar to inflammation. Endothelial cell activation by inflammatory cytokines induces expression of cellular adhesion molecules (CAMs), thereby perhaps augmenting leukocyte adhesion and recruitment and subsequent development of atherosclerosis. The incidence of CAD is lower in women; this may be due to the cardioprotective effects of E2., Methods: Consecutive eligible subjects with CAD admitted for cardiac catheterization were studied. The groups evaluated were men, postmenopausal women receiving E2 replacement therapy (ERT), postmenopausal women not receiving ERT and premenopausal women. Control groups included men and women without CAD. Preprocedural blood samples were drawn from all groups. Measurements of cCAMs, E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 were performed by enzyme-linked immunoabsorbant assay. E2 levels were assessed by radioimmunoassay., Results: We observed a statistically significant increase in all cCAMs in men with CAD and postmenopausal women with CAD not receiving ERT compared with postmenopausal women with CAD receiving ERT. Premenopausal women with CAD and postmenopausal women with CAD receiving ERT had a significant increase in VCAM-1 alone compared with the female control group., Conclusions: A possible mechanism by which E2 exerts one of its cardioprotective effects is by limiting the inflammatory response to injury by modulating the expression of CAMs from the endothelium.

It has been established that IL-8 triggers angiogenesis in vivo, but this effect may be mediated either by IL-8-recruited leukocytes or by direct actions of IL-8 upon endothelial cells (EC). We have approached this question by examining interactions of recombinant human IL-8 with cultured large vessel and microvascular human EC. We are unable to detect specific IL-8 binding to cultured human umbilical vein endothelial cells (HUVEC) or leukocyte-like IL-8 receptor mRNA expression by either cultured HUVEC or human dermal microvascular endothelial cells (DMEC). We find no alteration of cytoplasmic calcium concentration ([Ca2+]i) in either cell type in response to IL-8 treatment. Finally, we find no IL-8-induced change in EC proliferative rates in the presence or absence of endothelial cell growth factor. Our data favour an indirect action for IL-8 as an angiogenic factor.

Study Objective: The purpose of this study was to evaluate the effect of thermistor position with varying injectate temperatures on the reproducibility of thermodilution cardiac output determination. The key hypothesis to be tested was that the positioning of the proximal thermistor at the right atrial port would improve the reproducibility of thermodilution cardiac output determination, independent of injectate temperature., Design: Prospective randomized trial., Setting: The study was performed in the cardiac catheterization laboratory of the West Haven Veterans Affairs Medical Center., Participants: Twenty consecutive patients undergoing right and left heart catheterizations were enrolled in the study., Interventions: Each patient underwent triplicate determination of thermodilution cardiac output measurements under four experimental conditions: (1) ambient or room temperature injectate using an external thermistor in the injectate reservoir; (2) iced injectate using an external thermistor; (3) room temperature injectate using an internal right atrium (RA) thermistor; and (4) iced injectate using an RA thermistor. Reproducibility was assessed by the coefficient of variation (CV) and standard error of the mean percent (SEM%), of the triplicate measurements., Measurements and Results: Using an internal RA thermistor improved the reproducibility of cardiac output determinations independent of injectate temperature. Using room temperature injectate, the CV was 12.8 percent using an external thermistor and 7.9 percent using an internal RA thermistor (p < 0.05). Using iced injectate, the CV was 10.2 percent using an external thermistor and 5.5 percent using an internal RA thermistor (p < 0.05)., Conclusions: Reproducibility of thermodilution cardiac output determinations is improved when injectate temperature is measured internally, at the RA, as opposed to externally in the reservoir. This has clinical implications for determining significant changes in serial cardiac output determinations.