Mechanical circulatory assist devices (MCADs) are increasingly utilized independently of cardiac transplantation in the management of heart failure. Though MCAD use incorporates inherent mechanical risks, the inevitable onset of chronic anemia, with its associated morbidity and mortality, is also a significant concern. MCAD support has been correlated with elevated plasma levels of inflammatory cytokines TNF-alpha, IL-1beta, and IL-6, which have separately been found to inhibit erythropoietin (Epo)-induced erythrocyte (RBC) maturation. Previous analysis of hematological parameters for MCAD-supported patients concluded that an amplified inflammatory response impedes RBC proliferation and recovery from hemolytic anemia. Additional analysis may bolster this assertion. Hemoglobin concentration (HC), RBC distribution width (RDW), mean cell volume (MCV), and cardiac index were retrospectively analysed for 78 MCAD-supported patients implanted for greater than 30 days at the University of Arizona Health Sciences Center from 1996 to 2002. Analysis confirms that the HC, a conventional marker for anemia, declines with MCAD placement and remains below the clinically defined, minimum normal value. Inversely, the RDW rises above maximum normal measure, signifying an increased fraction of juvenile RBCs. The MCV remains unchanged and within normal limits, demonstrating adequate substrate for RBC formation. MCAD performance also stabilizes as adequate perfusion returns. These results further support our previously published conclusion that a sufficient response of erythropoiesis occurs in reaction to the onset of anemia by an increased production of immature RBCs. However, the cells never fully mature and join circulation. The patient's inflammatory cytokine response to the implanted device most likely mediates the chronic MCAD-induced anemia by inhibition of Epo effects.

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Our study compared left ventricular (LV) function between senescent and young adult mice through in situ pressure-volume loop analysis. Two groups of mice (n = 9 each), 6-mo-old and 16-mo-old (senescent) mice, were anesthetized with urethan and alpha-chloralose, and their LV were instrumented with a Millar 1.4-Fr conductance micromanometer catheter for the acquisition of the pressure-volume loops. The senescent mice had a significantly decreased contractile function related to load-dependent parameters, including stroke volume index, ejection fraction, cardiac output index, stroke work index, and maximum derivative of change in systolic pressure over time. The load-independent parameters, preload recruitable stroke work and the slope (end-systolic volume elastance) of the end-systolic pressure-volume relationship, were significantly decreased in the senescent mice. Heart rate and arterial elastance were not different between the two groups; however, the ventricular-to-vascular coupling ratio (ratio of elastance of artery to end-systolic volume elastance) was increased by threefold in the senescent mice (P < 0. 001). Thus there were significant decreases in contractile function in the senescent mouse heart that appeared to be related to reduced mechanical efficiency but not related to arterial elastance.

Abstract-Cardiac remodeling in response to pressure overload involves reorganization of the myocytes and extracellular matrix (ECM). Neurohormonal pathways have been described as effector pathways in left ventricular ECM reorganization in response to pressure overload; we now are assessing the role of the T lymphocyte in this process. Mice with defined differences in T-lymphocyte function (C57BL/6 SCID, C57BL/6 WT, and BALB/c) were treated with 50 mg/L of N G -nitro-L-arginine methyl ester in their drinking water for 30 days. The immune function of C57BL/6 WT mice was T-helper type 1 (TH1), BALB/c was TH2, and C57BL/6 SCID was null. The arterial blood pressure increased by 30% in all of the strains of mice. However, ventricular stiffness significantly decreased in the C57 SCID, significantly increased in the BALB/c, and did not change in the C57 WT. The characterization of matrix metalloproteinase induction and activation on day 30 was associated with T-lymphocyte function. The total cardiac fibrillar collagen, percentage of fibrillar collagen cross-linking, and the activity of the cross-linking enzyme lysyl oxidase-like-3 (LOXL-3) significantly decreased in the C57 SCID, significantly increased in the BALB/c, and did not change in the C57 WT. This study revealed that the LOXL-3 pathway, namely, gene expression, enzymatic activities, and LOXL-3-mediated collagen cross-linking, was associated with ventricular stiffness and incongruence with lymphocyte function. These data support the concept that the T lymphocytes may play a fundamental regulatory role in cardiac ECM composition through modulation of collagen synthesis, degradation, and cross-linking. Key Words: lymphocytes Ⅲ ventricular function Ⅲ collagen I n response to hypertension, the myocardium undergoes a series of changes, including adaptation of the extracellular matrix (ECM) composition. ECM remodeling leading to heart failure is characterized by disproportionate ECM fibrillar collagen synthesis and degradation 1 and collagen crosslinking by the enzyme lysyl oxidase (LOX). 2 These processes are mediated primarily by the cardiac fibroblast (CF), and, therefore, factors that modulate CF function will determine the nature of ECM remodeling in response to increased wall stress. It is understood that the CF function is under local as well as neurohormonal control. 3 We suggest that CF function is also affected by T-lymphocyte function.T lymphocytes participate in a regulatory role of virtually all immune responses and most nonlymphoid tissues. Several lines of evidence have shown that T lymphocytes are an essential component in the remodeling processes of noncardiac tissues, 4,5 and others have suggested a role in cardiovascular remodeling and heart failure. 2,6 The cytokine profile that has been used to describe subtypes of T-helper (CD4 ϩ ) lymphocytes is namely TH1 and TH2. 7 It is accepted that a pathological increase in neuroendocrine mediators and wall stress induce cardiac remodeling, and we proposed that, in a similar manner, a difference in TH1/TH2...