Contact sensitivity in the mouse. IV. The role of lymphocytes and macrophages in passive transfer and the mechanism of their interaction.

Contact sensitivity skin reactions were produced in mice by immunization with 2-phenyl-4-ethoxymethylene oxazolone (oxazolone) and detected by the increase in ear thickness after challenging the ears with 2% oxazolone. These skin reactions can be transferred from immunized donors to irradiated recipients by peritoneal exudate cells induced by thioglycollate. The peritoneal exudate cells were separated into purified macrophage and purified lymphocyte populations. Both cell populations transferred skin reactions. However, their time course was different. The reactions produced by lymphocytes were greater at 24 hr than at 12 hr while the reactions produced by macrophages declined slightly between 12 and 24 hr. The working hypothesis was formed that the peritoneal lymphocytes conveyed a factor (presumptive cytophilic antibody) to peritoneal macrophages which enabled them to transfer ear reactions. Experiment showed that peritoneal and lymph node lymphocytes from sensitized donors within a Millipore chamber conveyed a factor to macrophages outside the chamber which enabled them to transfer ear reactions. In contrast, peritoneal macrophages (from sensitized donors) within the chamber and peritoneal lymphocytes outside the chamber were inactive. These findings suggested that there are three modes of immunological tissue damage: hypersensitivity mediated by lymphocytes (classical delayed hypersensitivity), hypersensitivity mediated by circulating antibody (classical immediate type hypersensitivity), and hypersensitivity mediated by macrophages which have passively acquired a factor (macrophage-mediated hypersensitivity).

Intermediary role of macrophages in the passage of suppressor signals between T-cell subsets.

We have examined the ability of macrophages (Mphi) to transmit T-cell derived suppressor signals to other T cells. The suppressor signal studied is an antigen-specific factor which suppresses the ability of adoptively transferred, sensitized lymphocytes to express contact hypersensitivity in normal recipients. We have found that this factor binds to peritoneal exudate Mphi via cell surface structures which can be blocked with heat-aggregated gamma globulin. Dead (HK) Mphi bind the factor but fail to present it in a functional way to assay (immune) T cells, whereas live (L) Mphi perform both functions. Further, L Mphi can retrieve the factor in an active form from the surfaces of HK Mphi. Based on these and other findings (1-5), we discuss the possibility that Mphi may play as important a role in presenting T-cell communication signals to the cells of the immune system as they do in presenting antigen.

Survival benefit in heart transplant recipients who have coronary artery disease confirmed using angiography and are receiving sirolimus.

INTRODUCTION: The aim of this study was to assess efficacy and safety of sirolimus (SIR) in heart transplant recipients to prevent further development of coronary artery disease (TxCAD) already confirmed by using coronary angiography. MATERIAL AND METHODS: We performed a retrospective case-control study involving all 60 heart transplant recipients receiving SIR in a number of combinations with other immunosuppressive drugs, and 60 matched individuals after heart transplantation treated without SIR. TxCAD was diagnosed using elective coronary angiography in 9 subjects in the study group (8 males and 1 female) of mean age 44 +/- 11 years, including ischemic cardiomyopathy in 4 members. The control group of 15 individuals 15 males of mean age 47 +/- 7 years, including ischemic cardiomyopathy in 8. We compared time to develop significant TxCAD and death caused by TxCAD, and all-cause deaths. Significance was assessed using log-rank and chi-square tests, when applicable. RESULTS: Significant TxCAD (critical coronary lesions, myocardial infarction or death) was observed in 5 (56%) patients receiving SIR and 11 (73%) without SIR (P = not significant [NS]). Time to develop significant TxCAD was comparable. There were 2 (22%) deaths in the SIR group and 8 (53%) in the control group (P = NS). Survival time was significantly longer among subjects receiving SIR (P = .02). None of deaths in the study group was caused by TxCAD compared with 6 (40%) deaths among controls (P = .09). Time of freedom from death caused by TxCAD was significantly longer in the study group (P = .023). CONCLUSION: SIR prolonged survival in heart transplant recipients with TxCAD confirmed using coronary angiography.

Fluctuations of exercise capacity in patients after kidney transplantation.

INTRODUCTION: The aim of this study was to assess changes in the exercise capacity in subjects with end-stage renal failure undergoing kidney transplantation. MATERIALS AND METHODS: The study group consisted of 16 subjects (9 males and 7 females) of mean age 43.3 +/- 11 years. The control group was composed of 7 healthy subjects (4 males and 3 females) of mean age 43.9 +/- 10 years. The first visit took place at 4-8 weeks after transplantation. Consecutive visits were scheduled for months 4, 10, 16, 24, 36, and 48 thereafter. Heart function was assessed using echocardiography and, an exercise test with analysis of peak oxygen consumption (VO(2)max). Results were correlated with VO(2)max (Pearson). The Mann-Whitney U test was used to compare study and control groups. RESULTS: The results of eligible VO(2)max tests were as follows (medians and ranges): 1 month (n = 15), 19.5 (8.8-27.5) mL/kg/min; 4 months (n = 9), 21.7 (16.0-29.3) mL/kg/min; 10 months (n = 8), 23.3 (13.1-30.0) mL/kg/min; 16 months (n = 9), 26.6 (18.3- 36.0) mL/kg/min; 24 months (n = 9), 22.3 (14.1-35.0) mL/kg/min; 36 months (n = 9) 20.9 (16.4-32.1) mL/kg/min; 48 months (n = 5), 19.7 (17.0-30.9) mL/kg/min; versus 26.8 (26.5-42.5) mL/kg/min in the control group. VO(2)max results achieved by the study group were significantly lower than that in the control group, except for months 16, 24, and 48. VO(2)max was significantly negatively correlated with the following ultrasound parameters: interventricular septum diastolic and systolic diameter, and left ventricle systolic volume. CONCLUSION: The exercise capacity of recipients seemed to be negatively affected by poor blood pressure control, resulting in heart muscle hypertrophy.

Advanced glycation end products in the development of ischemic and dilated cardiomyopathy in patients with diabetes mellitus type 2.

INTRODUCTION: Hyperglycemia intensifies nonenzymatic glucose coupling to tissues, resulting in myocardial stiffness and formation of advanced glycation end products (AGE). The aim of this study was to assess seeking AGE in the myocardium from patients with type 2 diabetes (DM2) subjected to orthotopic heart transplantation (OHT), seeking to establish whether AGE play a role in the development of cardiomyopathies leading to OHT. MATERIAL: The 2 studied groups consisted of 11 hearts explanted from patients with ischemic cardiomyopathy+DM2 (ICM+DM2, 55 +/- 6.5 years) and 8 from dilated cardiomyopathy+DM2 (DCM+DM2, 49.6 +/- 4.5 years). Comparative subgroups were composed of nondiabetic explanted hearts, 41 with ICM (52.8 +/- 5.8 years) and 41 with DCM (52.7 +/- 4.2 years). All patients were males. METHODS: We examined immunohistochemical localization of AGE using a semiquantitative scale of reaction intensity in cardiomyocytes, fibroblasts, capillaries, arterioles, and arteries. Additionally, we calculated the scores for cardiocytes (AGE(Cardiocyte)) and all left ventricular components (AGE(LV)). RESULTS: The cytoplasmic AGE deposits in cardiomyocytes were predominantly diffuse-granular in DM2 groups, whereas nondiabetic groups showed a lack of a reaction or a diffuse pattern. There were no differences in the reaction intensity between the 2 studied groups, or 2 comparative groups. All myocardial constituents showed higher AGE intensity in DM2 than nondiabetic groups. Only in the ICM+DM2 group did the DM2 duration correlate with AGE staining in selected myocardial layers and with AGE(Cardiocyte) and AGE(LV). CONCLUSIONS: The presence of AGE in the hearts of patients requiring transplantation was related to the duration of DM2. The deposition of AGE in left ventricular myocardium was enhanced by DM2 particularly in patients with ICM.

Cardiocyte nuclear chromatin density correlates with transplanted heart left ventricular mass.

INTRODUCTION: Cardiocyte hypertrophy is accompanied by polyploidy, seen as a decrease in chromatin density in the enlarged nucleus. Repeated biopsies of a transplanted heart offer the possibility of a dynamic evaluation of these phenomena. The aim of this work was an evaluation of cardiocyte nuclear chromatin density in transplanted hearts during long-term follow-up. MATERIALS AND METHODS: The material encompassed myocardial biopsy specimens taken during the first week, first month, and then on an annual basis up to 10 years after surgery. Only biopsy specimens with no rejection were considered (grade "0" International Society for Heart and Lung Transplantation [ISHLT] 122 biopsy specimens). The control group consisted of 7 donor heart specimens. We evaluated the optical density-mean gray level-of cardiomyocyte nuclear chromatin. We determined correlations of this index with the nuclear area, and with left ventricle ultrasound measurements, using correlation analysis. RESULTS: The chromatin mean gray level decreased with time, correlating positively with interventricular septum thickness, left ventricle posterior wall diameter, and left ventricular mass. Analysis of individual periods showed a significant positive correlation of the mean grey level with the cardiocyte nuclear surface in year 3, 4, and 9 after transplantation, thereby suggesting the occurrence of polyploidy at those times. The significant negative correlation of these values (1 week and 1 year) indicated normalization of early cardiocyte hypertrophy. CONCLUSIONS: With the passage of time chromatin condenses, leading to pyknosis. The activity of cardiocyte chromatin correlated with left ventricular hypertrophy. Compensatory cardiomyocyte polyploidy is a periodical phenomenon.

Peripheral blood CD14high CD16+ monocytes are main producers of IL-10.

Based on CD14 and CD16 expression, human peripheral blood monocytes (MO) can be divided into a major CD14(high) CD16(-) population and two minor CD14(high) CD16(+) and CD14(dim) CD16(+) subpopulations. CD14(dim) CD16(+) MO are well characterized and regarded as pro-inflammatory because upon stimulation produce TNF-alpha but little, if any, IL-10. By contrast, little is known about CD14(high) CD16(+) MO. We investigated the surface expression of selected determinants by CD16(+) MO subpopulations, cytokine production, phagocytosis and antigen presentation. We found that both CD16(+) subpopulations had a higher expression of HLA-DR, CD86, CD54 and a lower expression of CD64 than CD14(high) CD16(-) population. In addition, CD14(high) CD16(+) MO showed a higher expression of CD11b and TLR4 than CD14(dim) CD16(+) and CD14(high) CD16(-) subpopulations. CD14(high) CD16(+) MO exhibited an increased phagocytic activity and a decreased antigen presentation in comparison with CD14(dim) CD16(+). As expected, lipopolysaccharide (LPS)-stimulated CD14(dim) CD16(+) MO produced TNF-alpha but little IL-10. By contrast, LPS-stimulated CD14(high) CD16(+) subpopulation produced significantly more IL-10 than CD14(dim) CD16(+) and CD14(high) CD16(-) MO. In conclusion, our data show that human peripheral blood CD16(+) MO are heterogeneous in function and consist of two subpopulations: CD14(dim) CD16(+) pro-inflammatory and CD14(high) CD16(+) with anti-inflammatory potential.

Role of Pro-Brain Natriuretic Peptide Serum Concentration in the Detection of Pulmonary Hypertension in Patients With End-Stage Lung Diseases Referred for Lung Transplantation.

BACKGROUND: Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration is elevated in patients with pulmonary hypertension (PH); however, its role in the detection of PH associated with lung disease is not well established. AIM: The aim of this study was to assess the value of NT-proBNP in the detection of PH in patients with end-stage lung disease (esLD) referred for lung transplantation. MATERIALS AND METHODS: The study population consisted of 65 patients: 37 with idiopathic pulmonary fibrosis (IPF), 20 with chronic obstructive pulmonary disease, and 8 patients with other interstitial lung diseases (75% men, mean age 53.3 ± 9.5 years). Serum concentration of NT-proBNP was assessed with an immunoradiometric assay kit. The mean pulmonary artery pressure (mPAP) was measured using a Swan-Ganz catheter. PH was defined as mPAP ≥ 25 mm Hg. RESULTS: Median NT-proBNP concentrations were significantly higher in patients with PH than in patients without PH: 139 (49-1236) pg/mL vs 67 (38-116) pg/mL, respectively; P = .016. Receiver operating characteristic (ROC) analysis revealed that NT-proBNP concentration higher than 131.5 pg/mL was a predictor of PH with good specificity (81%) and positive predictive value (78.9%) but low sensitivity (55.6%) and negative predictive value (58.6%). The area under the ROC curve of serum NT-proBNP concentration for PH was 0.71 (95% confidence interval 0.57-0.85, P = .039). CONCLUSION: Serum concentration of NT-proBNP may be useful in the diagnosis of PH in patients with esLD referred for lung transplantation.

Speckle-Tracking Echocardiography for Monitoring Acute Rejection in Transplanted Heart.

BACKGROUND: The diagnosis of acute cellular rejection (ACR) is a major objective in the management of heart transplant recipients. The aim of this study was to assess the utility of speckle-tracking derived parameters in identifying patients at risk of graft rejection. METHODS: A prospective, single-center study was carried out involving 45 consecutive heart transplant patients who underwent a total of 220 routine endomyocardial biopsies (EMBs) with correlative echocardiographic examination. RESULTS: No significant ACR (grade 0-1R) was seen in 190 biopsies (81.2% of the ACR-free group), and moderate ACR requiring specific treatment (grade 2R) was detected in 30 biopsies (13.6% of the ACR group). Grade 3R was not observed. All longitudinal left ventricular (LV) and right ventricular (RV) strain parameters were greater in the ACR-free group than in patients with ACR, while no differences were observed between radial and circumferential strain parameters. In our analysis, we selected RV free wall longitudinal strain (RV FW) ≤ 16.8% and 4-chamber longitudinal strain (4CH LS) ≤ 13.8%, which related to the presence of ACR requiring treatment. We assigned 1 point for each parameter (minimum 0, maximum 2 points) and derived a new echocardiographic index, the Strain Rejection Score (SRS). Our proposed approach-a combination of the 2 abovementioned indices-for screening patients at risk of ACR ≥ 2R, when expressed by a score 2 points, showed good specificity, strong negative predictive value, and the highest area under the curve. CONCLUSIONS: Our study demonstrated that combination of 4CH LS and RV FW as a new echocardiographic index, the Strain Rejection Score, can be useful as a noninvasive assessment of ACR during the first year of follow-up after heart transplant.

Predictive Value of Models for End-Stage Liver Disease Score in Patients With Pulsatile Flow POLVAD MEV Left Ventricular Assist Device Support.

BACKGROUND: Model for End-Stage Liver Disease (MELD) score predicts multisystem dysfunction and death in patients with heart failure (HF). Left ventricular assist devices (LVADs) have been used for the treatment of end-stage HF. AIM OF THE STUDY: We evaluated the prognostic values of MELD, MELD-XI, and MELD-Na scores in patients with POLVAD MEV LVAD. MATERIALS AND METHODS: We retrospectively analyzed data of 25 consecutive pulsatile flow POLVAD MEV LVAD patients (22 men and 3 women) divided in 2 groups: Group S (survivors), 20 patients (18 men and 2 women), and Group NS (nonsurvivors), 5 patients (4 men and 1 woman). Patients were qualified in INTERMACS class 1 (7 patients) and class 2 (18 patients). Clinical data and laboratory parameters for MELD, MELD-XI, and MELD-Na score calculation were obtained on postoperative days 1, 2, and 3. Study endpoints were mortality or 30 days survival. MELD scores and complications were compared between Groups S and NS. RESULTS: 20 patients survived, and 5 (4 men and 1 woman) died during observation. Demographics did not differ. MELD scores were insignificantly higher in patients who died (Group 2). Values were as follows: 1. MELD preoperatively (21.71 vs 15.28, P = .225) in day 1 (22.03 vs 17.14, P = .126), day 2 (20.52 vs 17.03, P = .296); 2. MELD-XI preoperatively (19.28 vs 16.39, P = .48), day 1 (21.55 vs 18.14, P = .2662), day 2 (20.45 vs 17.2, P = .461); and 3. MELD-Na preoperatively (20.78 vs 18.7, P = .46), day 1 23.68 vs 18.12, P = .083), day 2 (22.00 vs 19.19, P = .295) consecutively. CONCLUSIONS: The MELD scores do not identify patients with pulsatile LVAD at high risk for mortality in our series. Further investigation is needed.

Left Ventricular Assist Device Implantation in Patients With Optimal and Borderline Echocardiographic Assessment of Right Ventricle Function.

BACKGROUND: Left ventricular assist devices (LVADs) are used for treatment of end-stage heart failure. Outcomes are dependent on right ventricle (RV) function. Prediction of RV function after LVAD implantation is crucial for device selection and patient outcome. The aim of our study was to compare early LVAD course in patients with optimal and borderline echocardiographic parameters of RV function. MATERIAL AND METHODS: We retrospectively reviewed 24 male patients with LVAD implantation. The following echocardiographic data of RV function were collected: FAC (fractional area change) with optimal value > 20%, tricuspid annulus plane systolic excursion >15 mm, RV diameter < 50mm, and right-to-left ventricle ratio < 0.57 (RV/LV). Patients were divided into group 1 (12 patients) with transthoracic echocardiography parameters in optimal ranges and group 2 (12 patients) with suboptimal transthoracic echocardiography findings. Study endpoints were mortality, discharge from the intensive care unit, and RV dysfunction. Demographics, postoperative clinical outcomes, comorbidities, complications, and results in a 30-day period were analyzed between groups. RESULTS: Echocardiography parameters differed significantly between groups 1 and 2 according to FAC (31.8% vs 24.08%; P = .005), RV4 (45.08 mm vs 51.69 mm; P = .02), and RV/LV ratio (0.6 vs 0.7; P = .009). Patients did not differ according to course of disease, comorbidities before implantation, or complications. One patient from each group died. Patients in group 2 experienced more pulmonary hypertension, required increased doses of catecholamines, and stayed in the intensive care unit longer. No RV dysfunction was noted. CONCLUSIONS: Borderline FAC, tricuspid annulus plane systolic excursion, and RV4 add RV/LV ratio prolonged recovery after LVAD implantation even with no RV failure. Parameters chosen for qualification are in safe ranges.

Red Blood Cell Distribution Width in End-Stage Heart Failure Patients Is Independently Associated With All-Cause Mortality After Orthotopic Heart Transplantation.

BACKGROUND: Red blood cell markers (RBCM) have been found to be predictors of mortality in various populations. However, there is no information regarding the association between the values of RBCM and long-term outcomes after orthotopic heart transplantation (OHT). The aim of this study was to assess whether the values of inflammatory markers and RBCM obtained directly before OHT are associated with mortality in patients diagnosed as having end-stage heart failure undergoing OHT. METHODS: We retrospectively analyzed data of 173 nonanemic adult patients diagnosed as having end-stage heart failure undergoing primary OHT between 2007 and 2014. Clinical and laboratory data were obtained at the time of admission for the OHT. RBCM were analyzed using an automated blood counter (Sysmex XS-1000i and XE-2100, Sysmex Corporation, Kobe, Japan). RESULTS: Mean age of the patients was 54 (41-59) and 72% of them were male. During the observation period, the mortality rate was 32%. Multivariable analysis of Cox proportional hazard confirmed that elevated pretransplantation red blood cell distribution width value (hazard ratio [HR], 1.38 [1.25-1.48], P < .001) was the sole independent predictor of death during long-term follow-up. Other red blood cell distribution width such as mean corpuscular volume, mean corpuscular hemoglobin concentration, and mean corpuscular hemoglobin (HR, 0.88 [0.84-0.91]; P < .001; HR, 0.75 [0.53-1.05]; P < .05; HR, 0.78 [0.64-0.96]; P < .05, respectively) had predictive value in univariable analysis. CONCLUSIONS: In summary, we have demonstrated that elevated red blood cell distribution width immediately before OHT is an independent predictor of all-cause mortality in heart transplant recipients. Other factors associated with posttransplantation mortality include lower values of mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration.

Prognostic Value of Mean, Diastolic, and Systolic Pulmonary Artery Pressure in Patients With End-stage Lung Disease Referred for Lung Transplantation.

BACKGROUND: Pulmonary hypertension (PH) is a common complication in end-stage lung disease (esLD). The aim of this study was to establish the best threshold values for mean, systolic, and diastolic artery pressure (mPAP, dPAP, and sPAP, respectively) to identify patients with esLD referred for lung transplantation and to predict 1-year prognosis. METHODS: Sixty-five patients were enrolled in the study (75% men) with a mean age of 53.3 ± 9.5 years; 31% had chronic obstructive pulmonary disease (COPD), 57% had idiopathic pulmonary fibrosis (IPF), and 12% had interstitial lung diseases (ILDs). The mean period of observation was 14.4 ± 5 months. We assessed invasively mPAP, dPAP, and sPAP, as well as pulmonary capillary wedge pressure (PCWP), using a Swan-Ganz catheter. Receiver-operating characteristic (ROC) curves were constructed to identify the best cutoff points for mPAP, dPAP, and sPAP to predict survival. The study endpoint was defined as 1-year mortality before transplantation. Survival analysis was completed according to the Kaplan-Meier method. RESULTS: During follow-up, 30 (46.1%) patients died and 19 (29%) underwent lung transplantation. Based on ROC curve analysis, we estimated mPAP ≥30 mm Hg, dPAP ≥20 mm Hg, and sPAP ≥44 mm Hg as the best threshold values with the highest sensitivity (70%, 70%, and 73%, respectively) and specificity (76%, 69%, and 72%, respectively) and the acceptable area under curve (0.67, 0.68, and 0.72, respectively). The negative predictive values for mPAP, dPAP, and sPAP were higher than the positive predictive values (79%, 77%, and 81% vs 67%, 61%, and 64%, respectively). We also constructed Kaplan-Meier curves for mPAP, dPAP, and sPAP threshold values. There were significant differences in 1-year survival between patients with and without PH for mPAP, dPAP, and sPAP threshold values (P = .005, P = .035, and P < .001; respectively). CONCLUSION: Elevated mPAP, dPAP, and sPAP are related to worse prognosis in patients with esLD referred for lung transplantation.

Exhaled nitric oxide concentration in patients after heart transplantation.

Nitric oxide (NO) is present in exhaled air in humans and its level may decrease in heart diseases. In the present study we prospectively investigated how heart transplantation treated with oral immunosuppresive drugs based on ciclosporine A influences the exhaled NO concentration (exNO). The study was performed in 17 patients after heart transplantation in various time after procedure and 15 nonsmoking healthy volunteers as a control group. Patients after heart transplantation were free of clinical signs of rejection. End-tidal concentration of exNO was measured by the use of a chemiluminescence method. We found no statistically significant differences in the exNO level between patients after heart transplantation and healthy controls (6.81+/-2.70 part per billion (ppb) in the transplant group vs. 6.01+/-3.43 ppb in the control group). We conclude that heart transplantation and immunosuppresive therapy do not influence the exhaled NO concentration.

Left ventricular dysfunction in patients with interstitial lung diseases referred for lung transplantation.

The objective of this study was to determine the prevalence of left ventricular (LV) dysfunction in patients with advanced interstitial lung disease (ILD) and the relationship between LV function and factors limiting physical activity. In 2005-2006, 40 patients with end stage ILD were admitted with qualifications for lung transplantation (LT). From this group, 18 patients (7 women, 11 men) were referred for LT (active list), 22 patients (8 women, 14 men), who did not meet the ATS/ERS criteria for LT were excluded from this procedure (waiting list). All patients had echocardiography, spirometry, 6-min walking test (6MW), and gas exchange measurements. The following main echocariographic data that describe the LV function and morphology were taken into account: LVs, LVd, LVPWd, LVPWs, Ao, LA, ESV, EDV, and EF. We noted significant differences in LVPWd (P=0.01), ESV (P=0.01), and EDV (P=0.02), which presented lower values in patients on the active list compared with those on the waiting list. A positive correlation was found between 6MW and LVs (r=0.41), LA (r=0.45), ESV (r=0.62), and EDV (r=0.68). Correlations between spirometric, gas exchange, and left ventricle echocardiographic data were also observed. We conclude that patients on active list for lung transplantation present a decrease in the diameter and volume of the left ventricle. The latter change may influence the functional ability of interstitial lung disease patients.

Role of N-acetylcysteine on renal function in patients after orthotopic heart transplantation undergoing coronary angiography.

INTRODUCTION: The aim of this study was to assess nephroprotective influence of intravenous N-acetylcysteine (NAC) on renal function after radiocontrast use in calcineurin inhibitor-treated patients after orthotopic heart transplantation (OHT). MATERIALS AND METHODS: We analyzed the results of 112 consecutive coronary angiography examinations (CAG). All patients received intravenous 500 mL multielectrolyte fluid (PWE) before catheterization. Group I of 55 randomly selected cases in addition were treated with 300 mg of NAC. The other 57 cases (group II) received only hydration. After catheterization, we administered 500 mL 0.9% saline with 20 mg furosemide. A nonionic, low-osmolality contrast agent (OPTIRAY) was used for all catheterizations. All patients underwent measurements of serum creatinine and creatinine clearance levels before and after the procedure (CREA0, CREA1, CC0, and CC1, respectively). We assessed the influence of NAC on CREA1 and the relative change of CREA1/CREA0 and CC1/CC0 ratios. RESULTS: In groups I and II we noticed decreased CC0 in 17 versus 22 cases (31% vs 39%), a relative change of CREA1/CREA0 ratio of 0% versus -3.95% and of CC1/CC0 ratio 0% versus 4, 11%, respectively. CIN was not recognized in any patient. None of the differences was significant. CONCLUSION: Intravenous NAC (300 mg) along with hydration before radiocontrast use had no impact on renal function in OHT patients undergoing CAG. It seems that there is no need for an additional preventive strategy apart from hydration and a small volume of low osmolar contrast in the majority of patients.

Use of sildenafil in heart transplant recipients with pulmonary hypertension may prevent right heart failure.

PURPOSE: We performed a short-term outcome analysis of orthotopic heart transplantation (OHT) in patients with pulmonary hypertension (PH) treated perioperatively with oral sildenafil. METHODS: PH (pulmonary vascular resistance > 2.5 Wood units, and/or transpulmonary gradient > 12 mmHg) was diagnosed in 6 of 25 (group A) heart transplant recipients operated in 2006. This group of patients underwent a modified medication protocol including perioperative administration of oral sildenafil: 50 mg before followed by 50 or 25 mg TID after heart transplantation. Sildenafil treatment was discontinued 10 to 14 days post OHT, after stepwise dose reduction. During the ICU stay all patients underwent circulatory monitoring of pulmonary and systemic pressures and resistance as well as transthoracic echocardiogram (TTE) evaluation. RESULTS: Perioperative oral sildenafil administration in PH patients undergoing OHT was associated with good short-term outcomes in the majority of transplanted patients (4/6). Sildenafil treatment reduced pulmonary resistance and pressures with a low rate of hemodynamic instability among OHT patients. CONCLUSIONS: Pharmacologic perioperative reduction of PH improves the short-term prognosis for successful OHT. One may speculate whether sildenafil treatment transplant recipients with PH would be associated with long-term improvement of pulmonary vascular status, therefore leading to extended life-expectancy and improved outcomes.

Anti-ox-LDL and anticardiolipin autoantibodies in patients after cardiac transplantation.

INTRODUCTION: Among cardiac transplantation (OHT) of coronary arterial disease, the pathogenesis can be associated with autoimmunologic effects due to oxidative lipoprotein modification and their change in antigenicity. These factors may lead to lipoprotein vascular changes observed in antiphospholipid syndrome or systemic lupus erythematosus. The aim of the presented study was to evaluate anticardiolipin autoantibodies (ACA) and anti-ox-LDL (antibodies against oxidized LDL) levels in the plasma immunoglobulin IgG class. MATERIALS AND METHODS: The study group consisted of 90 OHT patients (79 men/11 women, age 44 +/- 13); 35 individuals were chosen as a control group. Blood samples were taken twice, in years 2002 and 2004. The investigated group was divided into 2 smaller groups: OHT patients in 2002 and OHT patients before 2002. RESULTS: OHT patients showed significantly higher ACA concentrations compared with the control group (3.53 vs 1.10 GPL U/mL), whereas anti-ox-LDL levels did not differ considerably (494 vs 385 mU/mL). During long-term observation the significant increase in ACA concentration was observed in both patients groups. Significant differences between the 2 OHT patient groups regarding anti-ox-LDL concentration were demonstrated among samples taken in 2002. CONCLUSIONS: The results may indicate the possible role of autoimmunological processes in OHT development. It is necessary to focus further research on the possibilities of developing secondary antiphospholipid syndrome.

Thymoglobulin administered early after heart transplantation reduces early myocardial hypertrophy assessed by morphometric studies.

UNLABELLED: The aim of this study was to assess the effects of early thymoglobulin administration on cardiocyte nuclear status in orthotopic heart transplant (OHT) recipients. MATERIAL AND METHODS: We investigated endomyocardial biopsies (EMBs) from 31 OHT recipients and 10 control cases. OHT patients were divided into the standard group who were treated without thymoglobuline; an ATG group who received thymoglobulin electively, and a standard+ATG group who were administered thymoglobulin upon a drop in renal function. We evaluated only EMBs obtained at 1 and 4 weeks after OHT showing no significant rejection (ISHLT grades 0 to 1B). The morphometric studies were performed using a computerized, automated Quantimet image analysis system. Overall, 1750 cardiocyte nuclei were quantitated for area, length, breadth, perimeter, chromatin median grey level, and fullness factor. Statistical analysis was performed using the Mann- Whitney U test, the Wilcoxon test, and discriminant analysis. RESULTS: All OHT groups showed significantly higher values (indicating nucleus enlargement) than the control group. All factors suggesting myocardial hypertrophy were significantly higher in the standard group; however, they decreased significantly with time. In contrast, the nuclear geometric parameters were significantly lower and stable throughout the study in the ATG group. The results of the standard+ATG group were intermediate, and their normalization as incomplete at the week 4 examination. Discriminant analysis revealed the closest Mahalanobis distance between control and ATG groups both at and weeks 1 and 4 after OHT. CONCLUSION: Thymoglobulin administered early after surgery protected cardiocyte hypertrophy in heart transplant recipients, mitigating graft ischemic damage.

Effectiveness and safety of treatment with sildenafil for secondary pulmonary hypertension in heart transplant candidates.

BACKGROUND: Pulmonary hypertension (PH) is a predictor of early death risk owing to right heart insufficiency after orthotopic heart transplantation (OHT). The aim of this study was to evaluate the effectiveness and safety of sildenafil therapy to decrease pulmonary vascular resistance (PVR) in patients with heart failure requiring transplantation, who may otherwise have been excluded because of PH. MATERIAL AND METHODS: We analyzed the hemodynamic results of six men (aged 47 to 61) with well-grounded OHT indications and PH diagnosed by a transpulmonary gradient (TPG) > 12 mmHg and/or PVR > 2.5 Wood units. Patients underwent a PH reversibility test with sodium nitroprusside (NPS) to achieve normal TPG and PVR results without a drop in systolic arterial pressure <85 mmHg. Unresponsiveness to NPS was shown in all subjects, who were subsequently qualified for sildenafil therapy (50 mg bid). RESULTS: After 1 month of sildenafil, three subjects achieved normal TPG and PVR, and acceptable responsiveness of PH to NPS in two other patients, all of whom qualified for OHT. Therapy was unsuccessful in one patient, which was confirmed also by right heart catheterization after 3 months of sildenafil use. Therapy was well tolerated in all patients, namely, no significant drop in arterial pressure on angiotensin-converting enzyme inhibitors. CONCLUSIONS: Sildenafil may be effectively used for treatment of secondary, irreversible PH in potential heart transplant recipients.