A novel mechanism of bradycardia and the character of acetylcholine in the heart.

UNLABELLED: At first the aim of our study was to observe the simultaneous responses of two hearts after intraarterial (into a. femoralis) adrenaline administration, in the rat with its own heart and a transplanted one--hence non-innervated. After these, some next experiments were performed: in some rats the His bundle of the heterotopically transplanted heart was damaged before transplantation. In all experiments the heart rate was observed on ECG and simultaneously, the arterial blood pressure was recorded from femoral artery in Vetbutal-anaesthetized rats. RESULTS: 1) both the heterotopically transplanted, non-innervated heart and the animal's own heart reacted to adrenaline administeration by producing bradycardia, 2) the heterotopically transplanted heart with the damaged His bundle--hence with a ventricular block reacted to adrenaline administration by raising the heart rate, whereas at the same time and in the same animal its own heart reacted by producing bradycardia. CONCLUSIONS: 1) the cause of bradycardia after adrenaline administration does not lie in the reflex from the arcus aortae, since we observed bradycardia after adrenaline administration also in the transplanted, non-innervated heart; therefore the baroreceptor reflex is not the cause of bradycardia after adrenaline administration; 2) bradycardia after adrenaline occurs in both the proper heart and the transplanted, non-innervated one, as a result of an interaction between two cholinergic centres which must be situated above and below the point of the His bundle interruption. The role of acetylcholine in the heart results from the interaction between these two centres.

[Risk of hypertension after heart transplantation in the follow-up period]. / Ryzyko nadcisnienia tetniczego po przeszczepieniu serca w obserwacji odleglej.

From October 1988 to March 2000, 58 patients underwent orthotopic heart transplantation (HTX). Data of 220 heart recipients with the follow up > or = 3 months after HTX were analyzed using the average values of blood pressure measured with the sphigmo-manometer. 65% of patients were diagnosed with the hypertension (HA). 39.9% of those patients (NTA group) had the systolic blood pressure < or = 140 mmHg and diastolic blood pressure < or = 90 mmHg during pharmacotherapy. 60.1% of hypertensive patients (NTB group) had the systolic pressure > 140 mmHg and/or diastolic pressure > 90 mmHg despite pharmacotherapy. 35% of all patients had normal blood pressure after HTX (HNA group). Patients with hypertension were older and the end stage ischemic cardiomyopathy was more frequently indication for HTX. Significantly more females were in NTA group. We observed no influence of the daily dose of cyclosporine or other immunosuppressive drugs on HA. The average blood concentration of cyclosporine A and mycophenolate mofetil was similar in all groups. The calcium channel blockers and inhibitors of angiotensin converting enzyme were main tool of pharmacotherapy used. In NTA group calcium channels blockers were used more frequently. In NTB group there was a statistically significant higher blood level of creatinine. After HTX there is a high risk of HA, which: increases with age, with the ischemic cardiomyopathy as indication to HTX, is significantly higher in males, there is no correlation between HA and the dosage and blood level of cyclosporine, increases with kidney insufficiency. In monotherapy calcium channel blockers seem to be especially effective.

Giant cell myocarditis--a case report.

The authors described a case of giant cell myocarditis treated by heart transplantation.

[Epstein-Barr virus infection in patients after bone marrow and heart transplantation]. / Zakazenie wirusem Epsteina-Barr u pacjentów po przeszczepie szpiku kostnego i serca.

UNLABELLED: Epstein-Barr virus (EBV) infections in immunosuppressed patients cause the severe clinical problems. Posttransplant lymphoproliferative disease (PTLD) might occur as a result of the latent EBV activation. OBJECTIVE: Occurrence of active EBV infection in heart and bone marrow transplant patients. METHODS: 68 serum samples obtained from 13 allogenic bone marrow and 20 heart transplant patients were tested by IF and ELISA methods. Antibodies against VCA, EA and EBNA antigens were measured. RESULTS: All patients showed the presence of anti-VCA IgG antibodies, thus all were seropositive. Three patients (9%) showed primary EBV infection while in 12 (36%) patients virus reactivation or reinfection was confirmed. CONCLUSIONS: 1. EBV infection in immunosuppressed patients is mainly caused by latent virus reactivation. 2. Type of EBV infection can be confirmed serologically only by the detection of specific anti-VCA, EA and EBNA antibodies. 3. The risk of PTLD in transplant patients creates the need for frequent monitoring.

Effects of cyclosporin A on contractile activity and cytoskeleton in chick embryo cardiomyocytes.

The effects of cyclosporin A (CsA), a clinically used immunosupressive drug, on contractile activity of chick cardiomyocytes grown as small aggregates or explants suspended on a network of elastic glass fibres or cultured in a monolayer were analysed in vitro with computer-aided image cytometry methods. At therapeutic concentrations (200-1500 ng/mL), CsA induced changes in the frequency and amplitude of the beating activity of cardiomyocytes 15 min after application. Longer treatment of cardiomyocytes, for 20-24 h, additionally induced changes in their shape and cytoskeleton organization (F-actin and alpha-actinin distribution). These results indicate that CsA is able to affect directly the contractile activity, morphology, and cytoskeleton architecture of heart cells.

[The clinical course of end stage heart disease in 152 patients qualified for heart transplantation in a four year observation]. / Przebieg krancowej choroby serca u 152 chorych zakwalifikowanych do transplantacji serca w obserwacji czteroletniej.

UNLABELLED: The aim of the study was to analyse the clinical course of pts with end stage disease (ESD) in the period of four years. The study population consisted of 152 pts (132 males, 20 females) at the age of 17-66 years (mean = 48.8 year SD = 9.1) primarily qualified to the heart transplantation (HTX). We analysed the ethiology of cardiac failure, the NYHA class of circulation insufficiency, frequency of occurrence of cardiac arrhythmias and conduction system disturbances in 24-hour ecg monitoring, and the pharmacotherapy efficacy. An ischemic ethiology of cardiac failure we found in 102 pts, cardiomyopathy (idiopathic, hypertrophic or postinfectious) in 46 and unoperable valvular disease--in 4. Ten pts were in II NYHA class, 112 in III, and 30 in IV. Left ventricular ejection fraction (echo assessed) ranged from 11% to 40%(mean = 24.9%), LVEDd = 46-111 mm (mean = 80.9 mm), LVESd = 34-83.5 mm(mean = 63 mm). We found IVa class by Lown ventricular arrhythmias (in Holter monitoring) in 38 pts and IVb in 78. Fifty six pts were treated with amiodarone, 10--with beta-blockers and 11 with sotalol. 19 pts were treated by permanent cardiac pacing during the waiting period, 2 ones--by PTCA, 2--by CABG, three ones--by dynamic cardiomyoplasty, and one--by partial aneurysmectomy. One pt was treated by CABG and automatic cardioverter-defibrilator implantation. In 5 cases HTX was delayed because of the positive effect of pharmacotherapy. In assessed period HTX were performed in 64 cases, 31 pts died and 43 are still waiting for the procedure. CONCLUSIONS: During the 4-year period HTX were performed in 42% of waiting pts. Mortality in this group was 38.2%. In 9 pts (5.9%) the alternative methods of surgical treatment were applicable. In 5 pts (3.9) the decision about HTX was delayed because of the positive change of the clinical status. This fact confirms the necessity of the waiting list verification.

The incidence of malignancy in heart transplant recipients.

OBJECTIVES AND METHODS: 219 heart transplant recipients with survival over 3 months were retro- and prospectively analysed for the incidence of primary neoplasms. Patients received immunosuppressive drugs (cyclosporine A, azathioprine, steroids) with a 4-5 days induction course of Rabbit Anti-Thymocyte Immunoglobulin (RATG) or monoclonal antibodies induction /OKT3/ in some cases. Anti-rejection treatment consisted of pulse doses of methyloprednisolon or RATG. RESULTS: 9 cases of malignancy (4.1%) with one case of pre-malignant liver condition (dysplasia gigantocellulare, 0.45%) were found (8M; 1F; age: 45-67 y.o., x57.7). Symptoms of neoplasms occurred 7-79 months (x31.4) postoperatively. Skin carcinomas: planoepitheliale, spinocellulare, soft tissue neoplasms/mesenchymal sarcoma, larynx Ca planoepitheliale, lung: adenocarcinoma and Ca microcellulare, kidney Ca clarocellulare and post transplant non-Hodgkin lymphoma were diagnosed. Chemo- and radiotherapy, surgery and reduction of immunosuppression did not change the outcome of malignancy in 6 pts.; (regression-1 pt was., remission-2 pts). Patients died 7-86 months after Htx (x41), 4-25 mos. (x12.5) after suffering from first symptoms and 0-10 months (x4.9) after pathology-based diagnosis of neoplasm. CONCLUSIONS: Heart transplant recipients have an increased risk of carcinogenesis. The incidence of malignancies in the studied group is similar or even lower than in other reports.

[Coronary bypass grafting after failed percutaneous angioplasty (PTCA)]. / Pilne pomostowanie tetnic wiencowych po powiklanych angioplastykach wiencowych (PTCA).

Between January 1991 and September 1997, in the Cardiovascular Surgery Department of the Institute of Cardiology of Jagiellonian University Medical School, 23 patients underwent emergency CABG due to acute myocardial ischaemia in result of failed PTCA. Over the same period of time invasive cardiologists performed 1883 PTCAs out of which 23 (1.2%) were emergency cardiosurgical procedures, and in 38 patients, stents were implanted in the damaged coronary arteries. The patients' age ranged from 37 to 67 years (median 52.2). In all patients good left ventricular function was preserved, median ejection fraction being 64%. Two patients required IABP to support left ventricular function. 1-4 bypass grafts were implanted (median 1.9 per patient). In one patient, internal mammary artery was collected and then implanted into anterior interventricular branch. The most common complication was myocardial infarction which occurred in 12 patients (52%). In ten patients low output was observed postoperatively. One operated patient (a female died (4.3%). The mean time of hospitalization was 11 days. Emergency myocardial revascularisation procedures performed after failed PTCA, bring higher risk of mortality and dangerous postoperative complications.

Successful full-term pregnancy in a patient three and a half years after a heart transplant.

The patient is a 28 year old woman who received a heart transplant in 1992 secondary to hypertrophic cardiomyopathy with unremarkable post-operative course. In the period immediately post transplantation the patient was on a four-drug immunosuppressive regimen which was subsequently changed to standard three-agent therapy. This therapy was continued until the patient became pregnant. In the first trimester only Cyclosporine (CsA) was used, and thereafter, the patient was continued on the previous three agent regimen. Toward the end of pregnancy a rise in systolic pressure was observed, but the child was delivered by spontaneous vaginal delivery without complications in the 38th week of pregnancy. The newborn weighed 3320 g and was in good health. A sharp fall in the newborn CsA blood levels was observed post delivery reaching zero level on the third day of life. At the present time, both mother and baby are in good health, 6 weeks after delivery.

The effect of neonatal immunoregulatory cells and cyclosporine on the heart allograft survival in rats.

Lymphoid neonatal cells from syngeneic donors are able to modulate the reactivity of recipient rats to MHC-incompatible vascular cardiac grafts. The suppressor splenocytes, obtained from one-day-old rats, may enhance the immunosuppressive effect of chronically administered low doses of cyclosporine (CsA).

Ultrastructure of donor heart muscle prior to transplantation.

Biopsy samples obtained from right ventricle (septum) of donor heart just at the moment of procurement and few hours later after implantation, was examined under electron microscopy. Our study revealed in both biopsy groups the presence of mild cytoplasmic changes similar in character but different in the intensity and extent. The anomalies are unspecific and similar in their character to changes described in disease states or toxic damage. Lack of damage to the membrane system in the cardiac myocytes indicates a reversible character of changes. Further studies are required to compare the present findings with ultrastructural myocardial features after reperfusion.

Microfocal myocardial lesions in cardiac allograft recipients.

Endomyocardial biopsy has been widely accepted as a method for diagnosing acute heart transplant rejection. However, disperse and microfocal changes due to a smaller specificity, cause difficulty in histological differential diagnosis. The purpose of the present study was to morphologically assess microfocal lesions, to determine their relative incidence and their specificity in relation to the time of onset after cardiac transplantation and to compare these data with those concerning more extensive changes. We examined 658 samples in 152 endomyocardial biopsies obtained from 45 posttransplant patients, including 311 samples identified as containing focal lesions of varying size, and 33 as containing diffuse lesions. Samples with focal and diffuse lesions (344 samples) were submitted for further studies which revealed that microfocal changes in the transplanted heart show more enhanced polymorphism in the composition of cellular infiltrates than more extensive changes. Furthermore they are frequently seen in biopsies in the first two months after transplantation and as single changes. Necrosis and cellular infiltrates at that time are more diversified than those seen in later biopsies. In our experience differential diagnosis of microfocal myocardial lesions in cardiac allograft recipients is difficult. Potentially microfocal lesions may be a result not only of acute rejection but also a result of myocardial alterations in the course of intensive therapy both in the donor and in the recipient, cold ischemia, reperfusion, and inflammation. The morphological picture in some cases is not sufficient to make an unequivocal diagnosis. This indicates the need for improvement of diagnostic methods and criteria on the one hand, and a suitable approach to the problem on the other hand. Our experience shows that a temporary solution could be establishing of a separate classification category for these types of changes and defining them as nonspecific microfocal lesions.

Histologic analysis of myocardial biopsies from donor hearts before transplantation.

Myocardial biopsy is an accepted diagnostic tool in the assessment of acute heart transplant rejection. An important element of this assessment is the so-called zero (0) biopsies. The purpose of the present study was histologic analysis and comparison of these biopsies. We examined biopsy specimens obtained from 35 hearts of donors aged 15-46 years. 0-1 biopsy was obtained during organ procurement and 0-2 biopsy immediately before coronary reperfusion after implantation. Histologic analysis of changes was carried out by two observers. 0 biopsies in 8 out of 35 cases were histologically normal. In 23 cases minute histologic changes were found. They included myocyte enlargement, perinuclear vacuolization, interstitial and perivascular edema and fibrosis. Sporadically (4 cases) we encountered also signs of cardiac myocyte damage (microfocal necrosis and/or myocyte disruption). Differences were seen both between individual donors as well as 0-1 and 0-2 biopsies obtained from the same donor. 0-1 and 0-2 biopsies differed more clearly in the appearance of interstitium and microvessels. Interstitial edema was more frequent in 0-2 than in 0-1 biopsy and it was usually more severe. Differences between 0-1 and 0-2 biopsies with respect to changes in cardiac myocytes and interstitium were as expected and may result from progress of changes due to hypoxia. In contrast, endothelial swelling was more frequent and more severe in 0-2 than in 0-1 biopsies. This phenomenon may be accounted for by easier penetration and greater effect of perfused preservation solutions on endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolongation of H--Y incompatible skin grafts in mice by neonatal spleen cells.

Prolongation of H--Y incompatible skin graft survival can be achieved by the injection of adult female recipients with neonatal spleen cells. The suppressive effect depends mainly on the sex of neonatal syngeneic and allogeneic donors.