Remodeling occurs in both ventricle and atrium in dilated cardiomyopathy and heart failure. However, the alteration of atrial extracellular matrix components during remodeling and its effect on the ...electrical remodeling and atrial arrhythmia have never been explored.
Atrial tissue samples of 53 explanted hearts from patients with dilated cardiomyopathy and end-stage heart failure who underwent heart transplantation were examined. Nineteen patients had permanent atrial fibrillation (PmAF), 18 had persistent AF (PsAF), and 16 had no documented AF (NAF). Sixteen donor left atria (LA) were used as controls (CNs). Western Blot analysis revealed a selective downregulation of tissue inhibitor of metalloproteinase (TIMP)-2 in PmAF and PsAF groups compared with the NAF and CN groups and an upregulation of atrial metalloproteinase (MMP)-2 that was most pronounced in the PmAF group followed by the PsAF and NAF groups. Immunofluorescent staining revealed that in the LA, type I collagen volume fraction (CVF-I) increased significantly in the PmAF group followed by the PsAF and NAF groups compared with that in CN. LA CVF-I significantly correlated with LA dimension and TIMP-2 to MMP-2 ratio. In the PsAF group, CVF-I/CVF-III ratio was significantly correlated with AF duration and the frequency of AF recurrence.
Atrial extracellular matrix remodeling manifested by the selective downregulation of TIMP-2 along with upregulation of MMP-2 and CVF-I in the atrium is associated with the development of sustained atrial fibrillation in patients with cardiomyopathy and heart failure.
Objective Inhaled nitric oxide has been shown to reduce pulmonary vascular resistance in patients undergoing cardiothoracic surgery, but it is limited by toxicity, the need for special monitoring, ...and cost. Inhaled prostacyclin also decreases pulmonary artery pressure, is relatively free of toxicity, requires no specific monitoring, and is less expensive. The objective of this study was to compare nitric oxide and prostacyclin in the treatment of pulmonary hypertension, refractory hypoxemia, and right ventricular dysfunction in thoracic transplant recipients in a prospective, randomized, crossover pilot trial. Methods Heart transplant and lung transplant recipients were randomized to nitric oxide or prostacyclin as initial treatment, followed by a crossover to the other agent after 6 hours. Pulmonary vasodilators were initiated in the operating room for pulmonary hypertension, refractory hypoxemia, or right ventricular dysfunction. Nitric oxide was administered at 20 ppm, and prostacyclin was administered at 20,000 ng/mL. Hemodynamic and oxygenation parameters were recorded before and after initiation of pulmonary vasodilator therapy. At 6 hours, the hemodynamic and oxygenation parameters were recorded again, just before discontinuing the initial agent. Crossover baseline parameters were measured 30 minutes after the initial agent had been stopped. The crossover agent was then started, and the hemodynamic and oxygenation parameters were measured again 30 minutes later. Results Heart transplant and lung transplant recipients (n = 25) were randomized by initial treatment (nitric oxide, n = 14; prostacyclin, n = 11). Nitric oxide and prostacyclin both reduced pulmonary artery pressure and central venous pressure, and improved cardiac index and mixed venous oxygen saturation on initiation of therapy. More importantly, at the 6-hour crossover trial, there were no significant differences between nitric oxide and prostacyclin in the reduction of pulmonary artery pressures or central venous pressure, or in improvement in cardiac index or mixed venous oxygen saturation. Nitric oxide and prostacyclin did not affect the oxygenation index or systemic blood pressure. There were no complications associated with nitric oxide or prostacyclin. Conclusion In heart transplant and lung transplant recipients, nitric oxide and prostacyclin similarly reduce pulmonary artery pressures and central venous pressure, and improve cardiac index and mixed venous oxygen saturation. Inhaled prostacyclin may offer an alternative to nitric oxide in the treatment of pulmonary hypertension in thoracic transplantation.
Reconstituting the immune response will be critical for the survival of HIV-infected individuals once viral load is brought under control. While the adult thymus was previously thought to be ...relatively inactive, new data suggest it may play a role in T cell reconstitution. We examined thymopoiesis in adults up to 56 years of age and found active T cell receptor (TCR) rearrangement, generating a diverse TCR Vβ repertoire. The resulting thymocytes are functional and are capable of responding to costimulatory signals. These data demonstrate that the adult thymus remains active late in life and contributes functional T cells to the peripheral lymphoid pool.
The ability of high-density lipoprotein (HDL) to promote cholesterol efflux is an important component of its ability to protect against cardiovascular disease. In addition, the anti-inflammatory ...properties of HDL are important as well. As part of the innate immune system, HDL appears to have evolved to increase inflammation in the presence of an acute phase response but to inhibit inflammation in the absence of an acute phase response. In a study of humans with coronary heart disease, it was found that the patients who had proinflammatory HDL prior to statin therapy (and half of them despite a profound decrease in plasma lipids following statin therapy) continued to have proinflammatory HDL. Anti-inflammatory HDL was effective in promoting cholesterol efflux whereas proinflammatory HDL was relatively weak in its ability to promote cholesterol efflux. Oxidative alterations of the main protein of HDL, apolipoprotein A-I, impaired its capacity to promote cholesterol efflux from monocyte macrophages. Therefore, HDL composition, structure, and function appear to be more crucial than HDL cholesterol concentrations in determining risk for cardiovascular disorders.
Recipient pulmonary hypertension due to chronic congestive heart failure is a major cause of right ventricular (RV) dysfunction after heart transplantation. We hypothesized that inhaled nitric oxide ...(NO), in the postoperative period, would a) selectively reduce pulmonary vascular resistance and improve RV hemodynamics and b) reduce the incidence of RV dysfunction compared with a matched historical group.
Sixteen consecutive adult heart transplant recipients with lowest mean pulmonary artery (PA) pressures >25 mmHg were prospectively enrolled. Inhaled NO at 20 parts per million (ppm) was initiated before termination of cardiopulmonary bypass (CPB). At 6 and 12 hours after CPB, NO was stopped for 15 minutes and systemic and pulmonary hemodynamics were measured. RV dysfunction was defined as central venous pressure >15 mmHg and consistent echocardiographic findings. The incidence of RV dysfunction and 30-day survival in this group was compared with a historical cohort of 16 patients matched for pulmonary hypertension.
Discontinuation of NO for 15 minutes at 6 hours after transplantation resulted in a significant rise in mean PA pressure, pulmonary vascular resistance (PVR), and RV stroke work index. Systemic hemodynamics were not affected by NO therapy. One patient in the NO-treated group, compared with 6 patients in the historical cohort group, developed RV dysfunction (P< .05). The 30-day survival in the NO-treated group and the historical cohort group were 100% and 81%, respectively (P> .05).
In heart transplant recipients with pulmonary hypertension, inhaled NO in the postoperative period selectively reduces PVR and enhances RV stroke work. Furthermore, NO reduces the incidence of RV dysfunction in this group of patients when compared with a historical cohort matched for pulmonary hypertension. Inhaled NO is a useful adjunct to the postoperative treatment protocol of heart transplant patients with pulmonary hypertension.
The reluctance to use organs from donors who have died from severe infections is based on the potential transmission of an infectious agent to the recipient and on the uncertainty about allograft ...function in the setting of severe donor sepsis.
From 1999 to 2007, donor hospital records were reviewed which focused on microbiology cultures and sensitivity results; type and duration of antimicrobial therapy; hemodynamic data, results of echocardiogram, and imaging studies. Preliminary positive and negative results from pre-harvest blood, respiratory, urine, and cerebrospinal fluid cultures were verified with the procurement agency. The harvesting surgeon performed gross inspection of donor valvular structures.
Nine donor hearts were transplanted from patients who expired from community onset infections with severe septic shock, meningitis, and/or pneumonia caused by Streptococcus pneumoniae (n = 4), Streptococcus milleri (n = 2), Neisseria meningitidis (n = 2), and unidentified gram- positive cocci (n = 1). Four donors had probable infection-induced intracranial hemorrhage, and all donors were vasopressor-dependent before organ procurement. No evidence of donor-transmitted infection, sepsis, or rejection was observed, and long-term function remained excellent; allograft dysfunction in three patients resolved after transplant. Our series of nine donors represents approximately 1.3% of successfully transplanted cardiac allografts during the respective period of review.
Patients succumbing to severe infections (meningitis, pneumonia, and septic shock) should not be arbitrarily excluded for possible heart donation. Assessing the suitability of donors with severe infections requires flawless communication between the donor and transplant facility, including a comprehensive evaluation of donor infection and pathogen(s), severity of sepsis, adequacy of antimicrobial treatment, and the degree of sepsis-induced myocardial dysfunction.
Mechanical circulatory support is a highly effective technology to maintain organ perfusion in patients with cardiogenic shock as a bridge to transplantation. Although implantation of a left ...ventricular assist device alone is often the preferred configuration, patients with biventricular failure and significant end-organ dysfunction often require biventricular assistance.
Between January 2000 and September 2008, 80 patients with severe biventricular failure were accepted for heart transplantation and received a pneumatic biventricular assist devices as a bridge to transplant. Patients were retrospectively divided into 2 groups: those successfully bridged to transplant (Group A) and those who died (Group B). Patients were also divided into 2 periods of implantation: Group X (2000-2005) and Group Y (2006-2008, which used a multidiscipline selection process).
Overall success rate to transplantation was 71.3%, with Group Y demonstrating an 82% success to transplant rate vs 63% in Group X. One-year actuarial survival after transplant was 89% compared with 92% in patients without a ventricular assist device. There were no statistically significant laboratory parameters between Groups A and B identifying potential risk factors for poor outcome.
Biventricular assist device therapy represents an effective and reliable means of supporting selected Interagency Registry for Mechanically Assisted Circulatory Support profile 1 patients as a bridge to transplantation, with excellent success to transplant rates and post-transplant survival.
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