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Background: In Poland, lung transplantation (LTx) as a routine method began in 2004, and since then, the Silesian Center for Heart Disease in Zabrze 85 LTx has performed (54 single-lung transplantations, 30 double-lung transplantations, and 1 heart-lung) transplantation. The recommendation to take vitamin supplements (without specific indication of the iodine content) does not apply to another iodine prophylaxis in patients after lung transplantation, excluding patients with known thyroid disease. The aim of this study was to assess thyroid gland function based on hormones and urinary iodine (UI) concentration in patients after LTx., Material and Methods: UI analysis was performed in 19 lung recipients (12 men and 7 women; mean age: 46.2 ± 12.47 years, BMI: 21 ± 2.25) and compared to TSH, free T3, and free T4., Results: Sufficient UI was observed only in 2 (9%) samples. In 12 samples (54.5%), mild iodine deficiency was recorded, in 4 samples (18.2%) moderate iodine deficiency was noted, and in 3 (13.6%) severe iodine deficiency was found. No correlation between BMI and UI, as well as hormones concentration, was observed. No correlation was revealed when analyzed samples were divided by patient sex., Conclusions: Although thyroid gland hormones were in the normal range, we found moderate, mild, and severe iodine deficiency in the majority of analyzed samples. Measurements of urinary iodine in lung transplant recipients should accompany thyroid hormone measurements as an iodine deficiency test and in order to prevent iodine deficiency disorders.

Background: Gingival hyperplasia is a common complication of immunosuppressive therapy with cyclosporine A (CyA). However, the association of CyA with increased tissue concentrations of TGF- β(1), a potential causative factor of hyperplasia, remains unknown. The aim of the study was to assess the impact of TGF- β(1) and IL-2 on the development and maintenance of gingival hyperplasia in patients treated with CyA after orthotopic heart transplantation (OHT)., Material/methods: Gingival hyperplasia was indexed in 60 patients, in accordance with McGraw and Potter scale. Patients were divided and comparisons were made among 3 groups: Group A (18 patients; 49.0 ± 12.1 y/o) after OHT with gingival hyperplasia (score 1, 2, 3), Group B (12 patients; 40.0 ± 15.1 y/o) after OHT without gingival hyperplasia (score 0), and Group C - the control group - (30 patients; 42.0 ± 10.8 y/o) with clinically healthy paradentium. Cytokines (TGF- β(1) and IL-2) were marked in gingival tissue homogenate. The concentration of CyA was marked in the patients' blood (Groups A and B)., Results: The highest mean concentration of TGF- β(1) was obtained in Group A and the lowest concentration was in the control group. A positive correlation was found between TGF- β(1) in gingival tissue and CyA blood concentration in Groups A and B., Conclusions: TGF- β(1) is associated with gingival hyperplasia in patients treated with CyA after OHT procedure.

Background: Non-enzymatic coupling of protein and lipid cellular structures with glucose leading to the formation of advanced glycation end products (AGE) plays a role in aging and the development of diabetic complications, but its contribution to myocardial pathology is unclear. We aimed to assess the role of heart failure on AGE formation in patients with or without diabetes mellitus type 2 (DM2)., Material/methods: Heart tissue specimens from 136 patients undergoing transplantation were grouped as follows: 14 cases of ischemic cardiomyopathy (ICM) and DM2, 8 cases of dilated cardiomyopathy (DCM) and DM2, 67 cases of ICM without DM2, and 47 cases of DCM without DM2. Fourteen heart samples were from the autopsies of patients with DM2 without heart disease, and 20 heart samples were from organ donors in whom the heart was wasted. AGE deposits were localized immunohistochemically counted using a semiquantitative scale and characterized by their staining pattern., Results: Positive staining was present in all samples from both cardiomyopathy groups with DM2, in 71% of healthy hearts from the DM2 subjects, in 51% of ICM non-diabetic hearts, and in 38% of DCM non-diabetic hearts, and in only 15% of the organ donors. Mixed-diffuse and granular AGE patterns were characteristic for DM2, while a diffuse pattern was more frequently observed in heart failure patients without diabetes. The semiquantitative results supported increased AGE accumulation in patients with DM2 and/or cardiomyopathy., Conclusions: The amount of AGE in cardiomyocytes increases significantly in both diabetes and heart failure, with a staining pattern typical for each condition.

Background: Cardiac surgery is supposed to be a risk factor of PRA formation, however the role of PRA presence in non-transplant subjects is not known. Aim of the study was to assess PRA occurrence in patients undergoing elective cardiosurgery procedures and to evaluate its influence on the perioperative course., Material and Methods: Blood samples were obtained before operation in 44 subjects (36M/8F; 55.9 +/- 8.1 y/o) undergoing primary elective cardiosurgery procedures--CABG (n = 30), CABG + valve (n = 2) or valve procedure (n = 12). PRA results were obtained after the discharge, and patients were retrospectively divided into: Group A (n = 18) with PRA > 1%, and Group B (n = 26) with PRA. < or = 1%. PRA screening was repeated 3 months after the procedure in 41 subjects. They were divided into Group I (n = 13) with PRA > 1%, and Group II (n = 28) with PRA < or = 1%. Comparison was performed of Groups A vs. B, and I vs. II., Results: Differences in pre-operative characteristics and procedure type distribution were insignificant. Post-operative complications were more frequent in Groups A and I (pulmonary hypertension in Group I vs. II: 38 vs. 4%; p = 0.01). Duration of post-operative ICU stay was longer in Group I vs. 11 (2.9 vs. 1.9d.; p = 0.01). Overall hospital stay was longer in Group A vs. B (10.1 vs. 7.8d.; p = 0.054). Increase of PRA titers was observed in 10 subjects (3 pts. /17% from Group A, and 7 pts. /27% from Group B), exceeding 10% in 2 females after valve replacement. 6 months after procedure, detectable PRA was still observed in 7 patients., Conclusions: Cardiac surgery is not a strong causative factor of PRA formation. The presence of perceptible PRA level may be associated with increased incidence of complications and consequently prolonged in-hospital stay. Influence of PRA on peri-operative course is not dependent on the source of its increased level.

Aim of the Study: Was to estimate an influence of acute cellular rejection on electrophysiologic parameters of allograft and remnants of recipient's heart, in patients after orthotopic heart transplantation (OHT)., Patients and Methods: Analysis was performed in 25 OHT recipients (24M/1F, age 48.4 +/- 9 y., ischemic time 197 +/- 51 min., donor age 30 +/- 9 y.), who underwent electrophysiological study (EPS), along with elective endomyocardial biopsy (EMB), scheduled for the 1st month after the surgery. Results of EPS were correlated with a degree of rejection, assessed with the ISHLT grading system. Grades > or =3A were considered a significant cellular rejection., Results: ISHLT grade 0 was observed in 8 patients, grade 1A or 1B in 12 patients, and 3A in 5 patients. Frequency of transplanted heart rhythm (TH-R) was 691.3+/- 37 ms in patients with ISHLT grade 0, 690.4 +/- 41 ms in patients with grade 1A or 1B, and 744.4 +/- 668 ms in individuals with 3A rejection (p < 0.04, for difference between 0 and 3A groups). Intraatrial conduction time (IntrtaCT) was significantly shorter in grade 3A group (20.4 +/- 1.6 ms), when compared with patients without rejection (36.2 +/- 4.9 ms, p < 0.03), or with 1A or 1B rejection (41.5 +/- 13 ms, p < 0.032). Also interatrial conduction time (InterCT) was the shortest in patients with 3A rejection (53.8 +/- 4.3 ms), when compared with ISHLT grade 0 group (78.5 +/- 7.6 ms, p < 0.02) and 1A/1B group (74.1 +/- 12 ms, p < 0.023). The other characteristics of atria, ventricles and AV-junction performance were comparable in all patients., Conclusions: TH-R, IntraCT and InterCT should be considered as the markers of significant cellular rejection in patients after OHT. Further analysis involving higher number of patients is warranted.

Unlabelled: The purpose of this study was to assess the clinical utility of mycophenolic acid (MPA) trough concentration monitoring in heart transplant recipients., Methods: We reviewed 456 MPA plasma level measurements (EMIT/Dade-Behring) which were performed in 76 pts. after orthotopic heart transplantation (OHT): 57 M and 21 F, age 41.9 +/- 16, time after OHT (months) 17.6 +/- 24. Daily dose of mycophenolate mofetil (MMF) was 2-3 g before MPA measurement introduction, then it was adjusted to achieve MPA trough levels (TL) of 2-4 microg/ml. Additionally pts. received either cyclosporine-A (CyA) or tacrolimus and prednisone. We analyzed first MPA levels obtained in pts. without previous monitoring, then we looked for a relation between CyA or tacrolimus and MPA level, and finally we checked for a relation between MPA level and the side-effects of MMF RESULTS: In a group of 59 pts. without earlier MPA level monitoring we found that 36 pts. (61%) had MPA level below, 19 pts. (32%) within, and 4 pts. (7%) above target TL. We identified a group of 11 pts. (characterized by unstable CyA TLs and liver impairment) with a significant positive correlation between CyA and MPA level. For the remaining group of pts. we found a non-significant negative correlation between CyA and MPA concentrations. Target MPA TL was achieved in 40% of cases in pts. with CyA TL below 200 ng/ml (Axsym/Abbott), in 40% of cases in pts. with CyA TL 200-300 ng/ml, and in 27% of cases in pts. with CyA TL over 300 ng/ml. There was no correlation between tacrolimus and MPA level. MPA TL over 4 microg/ml occurred in 22% of results from pts. receiving tacrolimus (n=6) and 11% of pts. on CyA (n=17, p = 0.011). 90% of these pts. had symptoms of GI irritation, 33%--leucopoenia, and 14%--anemia., Conclusions: It is uncommon to achieve MPA TL of 2-4 microg/ml with typical doses of MMF, especially with concomitant high CyA TL. Typical side effects of MMF should be an indication to check MPA TL.

Diabetes mellitus is a very well recognized risk factor for coronary artery disease in non-transplant patients. With the introduction of new immunosuppressive agents in solid organ recipients, there is an interest in medical complications of immunosuppressive therapy. An influence of long-term cyclosporine-A (CyA) therapy on glucose metabolism was analyzed in a group of 122 heart transplant recipients who developed hyperglycemia after heart transplantation. Based on WHO criteria for diagnosis of diabetes two groups were identified: group 1 (102 pts) included pts with impaired glycemic control and group 2 (20 pts) with clinical diabetes. Fasting insulin, proinsulin, C-peptide, HbA1c and cyclosporine-A trough levels were determined 12-18 months post surgery in clinically stable period without transplant rejection. The immunosuppressive treatment in both groups was the same and consisted of cyclosporine A, azathioprine and prednisone. We observed a statistically significant negative correlation between CyA concentration and insulin in both groups, a statistically significant negative correlation between CyA concentration and proinsulin, C-peptide blood level in group 1 and statistically significant positive correlation between CyA and glucose blood level in both groups.

Objectives: Aim of the study was to assess frequency and risk factors of steroid resistant cellular rejection (SRR) in heart transplant recipients, to determine methods of its treatment, and to evaluate influence of steroid resistant rejection and method of its treatment on short- and long-term results., Methods: All pts. received cyclosporine-A, azathioprine and prednisone. Biopsy results > or = 3A (ISHLT) were considered a significant rejection, requiring treatment with 1 g i.v. methylprednizolone for 3 days followed by oral prednisone. SRR was recognized in case of biopsy-proven progression of rejection, lack of improvement in 2 consecutive biopsies, or increasing hemodynamic compromise despite treatment of biopsy-proven rejection. 146 pts. eligible for the study were divided into: study group--15 pts. with SRR (10%), and control group--131 pts. SRR was treated with: cytolytic therapy--ATG (10 pts.), mycophenolate mofetil (3 pts.) or steroids (2 pts.). Number of biopsies > or = 3A, cumulative biopsy score, average biopsy result, effectiveness of SRR treatment, side effects of therapy, and survival were analysed., Results: All parameters characterizing rejection were significantly higher in the study group. No risk factors of SRR were found. In 6 pts. with SRR and hemodynamic compromise (all treated with ATG) improvement was observed in 4 pts, while death occurred in 2 pts. There were no deaths in pts. without hemodynamic compromise--none of 3 methods of treatment was superior, however ATG increased the infection risk. Survival in the 1st year was significantly lower in the study group (67% vs. 89% in the control group)., Conclusions: SRR is recognized in about 10% of heart transplant recipients, increasing risk of death in the 1st year after surgery. Cytolytic therapy increases risk of infection, and should be avoided in pts. without hemodynamic compromise.

Objectives: Aim of this study was to find features characteristic for steroid resistant cellular rejection (SRR) of the transplanted heart, using phenotypic identification of cells creating infiltrates in endomyocardial biopsies (EMBs) obtained before and after high dose steroids treatment., Methods: 146 heart transplant recipients, treated with cyclosporine-A, azathioprine and prednisone, were taken under consideration. EMB results > or = 3A (ISHLT) were considered significant rejection, requiring treatment with 1 g i.v. methylprednizolone for 3 days followed by oral prednisone. SRR was diagnosed in case of increased grade of rejection in control EMB, lack of improvement in 2 consecutive EMBs or increasing hemodynamic compromise. SRR was found in 15 pts. (study group). Control group consisted of remaining 131 pts. Paraffin-embedded blocks containing EMB samples from 9 pts. from study group and randomly chosen 14 pts. from control group were used (2 EMBs per pt.). Significant rejection was present in the first EMB, the second EMB was performed 7 days after beginning of the treatment. In the study group, first 2 EMBs creating a sequence of SRR were analysed. Following antigens were identified: CD45RO (T-cells), CD8 (cytotoxic T-cells), CD20 (B-cells), and CD95 (marker of apoptosis). DR expression and macrophages presence were also quantified., Results: CD45RO was predominant phenotype before and after treatment in both groups. Higher quantity of CD20 cells were observed in study group, however its number increased after treatment in control group. CDB-cells and macrophages were present in low amounts, that did not react to treatment. CD95 positive cells were present only in 3 EMBs. None of above differences was statistically significant. DR expression staining showed no difference either in biopsies taken before steroid treatment or after completing of high dose steroid therapy., Conclusion: Phenotype identification of cells infiltrating myocardium of the transplanted heart was not sufficient to predict or characterise steroid resistant rejection.

A retrospective analysis was performed on the records of 95 pts who underwent heart transplantation at Dept. Of Cardiac Surgery & Transplantation in 1999 and 2000 y. In 34 pts lower respiratory tract infections were observed. In all cases bacterial factor was detected in sputum or bronchoalveolar lavage. In study population we analysed influence of such factors as age of the patients, the intensity and duration of immunosuppression, pre-existing diseases and timing after transplantation on the incidence of infection. Most often, in 43 pts gram negative stains bacteria was detected. Pseudomonas aeruginosa (15 pts), Acinetobacter baumanii (7 pts) and Enterobacter cloacae (6 pts) were predominant. Gram positive stains bacteria was detected only in two cases (Streptococcus pneumoniae and Staphylococcus aureus). In 1 pt we observed lung tuberculosis and in 2 pts Pneumocystis carinii pneumonia. Older recipient age was the only risk factor leading to occurrence of respiratory tract infections in patients after heart transplantation.

Pulmonary infections remain the leading cause of death in patients after heart transplantation. Lung tuberculosis is more common in transplant recipients than in general population. Two cases of tuberculosis are presented in patients after heart transplantation. Regarding to influence of rifampicin on immunosuppressive therapy, those patients were treated with antimycobacterial drugs except rifampicin. A cure without recurrence can be achieved with a scheme of treatment regimes without rifampicin.

Unlabelled: Orthotopic heart transplantation (OHT) is most effective method for treatment of irreversible heart failure. Patients after OHT considered for permanent pacing consist still present a challenge for the implanting physician due to distorted atrial geometry and specific electrophysiological conditions of atrium. The aim of our study was to analyse the effectiveness of permanent atrial pacing in these patients., Patients and Methods: We implanted atrial lead in 37 SND pts., 2 months--7 years after OHT, (3 pts with coexisting AV block received ventricular lead). Only straight BP screw-in leads and manually formed stylets were used; we found satisfactory pacing/sensing conditions in 25 pts in RA appendage or anterior/lateral wall, in 10 pts--in CS ostium region and in 2--in proximal part of CS., Results: All implantations were successful and no patient received VVI pacing system. One dislodged lead required revision (1/37, 3%) but this was not related to endomyocardial biopsy. In 2 pts, due to unacceptable low RA potential and/or high PTh values atrial lead was implanted to CS for sensing/pacing of left atrium. The average acute value of A wave were 2.4 mV and chronic 2.2 mV; values of pacing threshold were 0.9 V and 1.6 V respectively. Only in 13/37 pts native A waves were recorded but with amplitude < 0.6 mV. Wenckebach point was 120/min only in 2 pts., in borders 130-160 bpm in 15 pts. and exceeded 170 bpm. in remained 20 pts. Retrograde VA conduction was intact in 33/37 pts, but in 4 pts exceeded 260/min. During long term follow-up in no patient we observed AV conduction disturbances. In 6 pts. treadmill exercise (Bruce's protocol) was repeated three times during: sinus (spontaneous) rhythm, AAI pacing 70/min, AAI-R (DDD-R) pacing. AAI 70 bpm did not influence significantly attained workload, heart rate on peak exercise or duration of exercise. But atrial rate modulated pacing increased values of examined parameters significantly., Conclusions: 1. Atrial pacing (and atrial based pacing modes) are possible in majority of transplanted heart patients. 2. Frequency of atrial lead dislocation, appearance of atrial sensing problems and AV conduction disturbances (all in about 3%) are comparable to non-transplanted patients. 3. In most patients with SND after OHT AV conduction remains within normal limits; it indicates safety of rate responsive pacing modes in these patients. 4. Rate modulated atrial pacing improves exercise tolerance in heart transplanted patients with SND. 5. High ("supra-normal") values of Wenckebach's point observed in most of patients with transplanted (dennervated) heart may have clinical importance in cases of atrial arrhythmias in these patients.

Unlabelled: Lower-Shumway technique (atrioatrial anastomosis) is the most frequently used technique for orthotopic heart transplantation and such a patient has two right atria and two sinus nodes. Sinus node dysfunction (SND) is a frequent finding in pts. after OHT; taking advantage of the frequency of innervated sinus node of recipient's atrial remnant as a natural biosensor for triggered pacing of donor atrium is an interesting option for these pts. THE AIMS OF OUR STUDY: 1. the analysis of possibility of utility of recipient atrial sinus node as natural biosensor for triggered donor atrium permanent pacing in transplanted patients with SND. 2. the evaluation of pacing and sensing conditions of the recipient's atrium in the some pts.. 3. long-term observation of effectiveness A2A2T(/D) pacing mode., Methods: 10 out of 37 pts. received A2A2T (8 pts.) and A2A2T/D (2 pts) pacing systems. In pts. with NSR of recipients atrium, we evaluated acceleration of its frequency during slight exercise and atropine., Results: In recipient's atrium among 37 pts we recognized NSR only in 15/37 pts.; in the remaining 22 pts. we found: sinus bradycardia--in 3, atrial flutter--in 3, low voltage AF--in 12 and no electrical activity--in 4 pts. Positive response to isometric exercise and atropine was observed in 12/15 pts. and 8 of them received A2A2T or A2A2T/D pacing system. We found much better sensing and pacing conditions in donor (A wave 2.1 mV, p. threshold 0.8 V) than in recipient atrium (1.1 mV and 1.4 V respectively). We observed some problems with sensing of recipient atrium in 4 of 10 pts. and changes SST to AAI-R mode solved the problem without loss of atrial resynchronization. 9 out of 10 pts. preferred AAT to AAI-R pacing program. One dislodged lead required revision during postoperative period (1/44, 2%). There was no dislodgement related to endomyocardial biopsy. In one patient, atrial flutter in recipient atria was transmitted to atrium of transplanted heart by pacing system with 2:1 conduction; arrhythmia was interrupted with drugs and did not return., Conclusions: 1. Atrial resynchronization is possible only in about 1/4 patients with SND after OHT due to frequently noted electrophysiological changes in recipient atrium. 2. In transplanted heart patients sensing and pacing conditions are much more favorable in donor's than recipient's atrium. 3. Atrial resynchronization can be subjectively (positively) recognised by most of patient after OHT and it still remains a promising pacing mode for selected patients after OHT with SND.