Carbohydrate Antigen 19-9 Level in Patients with Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent monogenic renal disease, responsible for 10% of the patients on renal replacement therapy, including kidney transplantation. Recently, it was reported that the serum CA 19-9 level is significantly elevated in ADPKD patients without malignancy. Exclusion of malignancy, including tumor marker analysis, is essential in pretransplant evaluation, as well as in assessment of kidney transplantation recipients. METHODS: In this study the serum CA 19-9 level in ADPKD patients without malignancy was retrospectively analyzed. The mean level of CA 19-9 was 30.3 U/mL (0.8 U/L-612 U/L). RESULTS: Overall, in 24 patients (18.8%) the serum CA 19-9 level was increased above the normal level found in the general population (35 U/L), and 5 of them (4.2%) did not experience polycystic liver disease. In 4 patients (3.4%) CA 19-9 level was increased 2-fold above the norm and in 3 of them (2.5%) 3-fold over the norm and higher. A statistically significant negative correlation between serum CA 19-9 level and estimated glomerular filtration rate, both in patients with and without hepatic cysts was observed. In nearly 1 in 5 patients with ADPKD, serum CA 19-9 level should be expected to be above the norm found in the general population, despite the lack of coexistence of a tumor or cholangitis. CONCLUSION: This finding should be considered during transplantation qualification and in follow-up examination after kidney transplantation.

Intracranial aneurysms in autosomal dominant polycystic kidney disease.

BACKGROUND AND PURPOSE: ADPKD correlates with an increased frequency of ICANs, but universal screening for ICANs in patients with ADPKD is not currently recommended. The aim of our study was to determine which groups might benefit from screening by determining the prevalence of ICANs in the Polish ADPKD population and identifying any subgroups with an increased risk for ICANs. MATERIALS AND METHODS: Eighty-three adult, predialysis-phase patients with ADPKD underwent screening for ICANs with MRA of the brain. RESULTS: The prevalence of ICANs in the studied population was 16.9%, with 6% of the screened group requiring neurosurgical intervention. We also found that the frequency of ICANs increases with age, reaching 22.4% in patients older than 45 years. All diagnosed ICANs were small (< 9 mm) and were localized in the anterior circulation. In addition, MR imaging revealed arachnoid cysts in 4.8% of patients with ADPKD. CONCLUSIONS: We suggest that patients older than 45 years with ADPKD be considered as candidates for screening for ICANs, and we propose a clinical algorithm for this subgroup. However, we could not find risk factors for ICANs in younger patients with ADPKD.

Human peripheral blood CD8+ CD28- T cells of renal allograft recipients do not express FOXP3 protein.

INTRODUCTION: In recent studies, the FOXP3 molecule has been suggested to be a marker of a suppressor subset of human CD8+ CD28- T cells based on correlations between the level of its mRNA and allograft function. Because this transcriptional factor produces a protein, we suggest that these correlations should focus on the FOXP3 protein. The aim of our study was to evaluate whether FOXP3 protein was present in cells of the CD8+ CD28- population in the peripheral blood of renal allograft recipients and whether the level of CD8+ CD28- FOXP3+ cells correlated with allograft function. METHODS: The study was performed on 30 renal allograft recipients with uneventful stable courses (n=18) or biopsy-proven chronic rejection (n=12). The immunosuppression was based on cyclosporine (n=12) or rapamycin (n=9). Peripheral blood mononuclear cells isolated from recipient blood samples were labeled with anti-CD8 and anti-CD28 MAbs conjugated with fluorochromes. After incubation, washing, and labeling using a PE anti-human FOXP3 Kit, we determined the percentage of cells by flow cytometry. RESULTS: FOXP3 protein expression was not observed either in the CD8+ CD28- population, or the whole populations of CD8+ or CD28- cells among patient groups. CONCLUSIONS: The expression of FOXP3 protein in CD8+ CD28- cells seems to be of a questionable value as a diagnostic tool for allograft function, it is probably not a marker for the CD8+ CD28- T cell subset.

Intestine as source of cytokines and growth factors.

BACKGROUND: The activation status of intestinal immune system cells is much higher than that of analogous peripheral cells. Increased serum concentrations of proinflammatory cytokines have been reported in various pathologic conditions; however, the source of these mediators has not been elucidated. OBJECTIVE: To assess the role of the human intestine and its lymphatic system in production of growth factors and proinflammatory cytokines. MATERIAL AND METHODS: Twenty liver transplant recipients and 20 donors were included in the study. Blood samples were obtained from the artery supplying the intestine, the portal vein, and a peripheral vein during liver harvesting in donors and after transplantation in recipients. An enzyme-linked immunosorbent assay was used to assess serum concentrations of IL-6, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and hepatocyte growth factor (HGF). RESULTS: In transplant recipients, IL-6 concentration in arterial blood was lower than that in portal blood (P < .049), whereas in donors, there was no significant difference in these concentrations. Neither recipients nor donors demonstrated significant differences in arterial or portal blood concentrations of TNF-alpha, TGF-beta, or HGF. CONCLUSIONS: In healthy human beings, the intestine is not a substantial source of IL-6, TNF-alpha, TGF-beta, or HGF. However, in patients with liver cirrhosis, the intestine is an important source of IL-6 but not of the other studied growth factors and cytokines.

The influence of immuosuppressive therapy on the development of CD4+CD25+ T cells after renal transplantation.

A growing number of studies suggest that CD4(+)CD25(+) T regulatory (Treg) cells play a significant role to downregulate the immune response to alloantigens. In this study, we investigated the possible influence of immunosuppressive therapy, including cyclosporine (CsA) or rapamycin (sirolimus), on the level of CD4(+)CD25(+), CD4(+)CD25(+)FOXP3(+), and CD4(+)CD25(+)CTLA-4(+) T cells in the peripheral blood of renal allograft recipients. The study was performed on renal allograft recipients who displayed uneventful stable courses (RAR-S; n = 15) versus biopsy-proven chronic rejection (RAR-CH; n = 12). The patients were divided based on the immunosuppressive protocol: group 1 (prednisone+CsA+Aza) and group II (prednisone+sirolimus). The control group consisted of 10 healthy blood donors. We examined the expression of CD4, CD25, CTLA-4, and Foxp3 in peripheral blood T cells. Flow cytometry was performed with a FACSCalibur (BD Biosciences) instrument with data analyzed using Cell Quest software. The percentage of CD4(+)CD25(+)Foxp3(+) T cells in rapamycin (sirolimus) treated patients did not differ from that observed in healthy individuals, but was significantly higher compared with CsA-treated patients. CsA therapy resulted in a reduction in the percentage of CD4(+)CD25(+)CTLA-4(+) and CD4(+)CD25(+)Foxp3(+) regulatory T cells after renal transplantation in both groups (RAR-S and RAR-CH) compared with patients treated with rapamycin or to healthy donors. The type of immunosuppressive therapy (with or without calcineurin inhibitors) may have an important role in tolerance induction and graft function.

Results of a 6-month, multicenter, open-label, prospective study concerning efficacy and safety of mycophenolate sodium in de novo kidney transplant recipients.

BACKGROUND: Mycophenolate sodium (MPS) was designed to reduce the gastrointestinal side effects of mycophenolic acid. The aim of our study was to determine the safety and efficacy of MPS in de novo renal transplant recipients. PATIENTS AND METHODS: This 6-month, multicenter, open-label, single-arm, prospective study was carried out in three centers in Poland. Thirty patients were recruited. Immunosuppressive regimen contained of MPS and cyclosporine (CsA) with or without steroids. RESULTS: The 6-month graft and patient survival was 100%. The incidence of suspected acute rejection episodes (ARE) was 5/30 (16.7%), including biopsy-proven ARE in 2 (6.7%) cases. ARE reversed after therapy. At month 6, the mean serum creatinine level was 1.4 mg/dL, and the mean creatinine clearance (according to the Cockroft-Gault formula) was >70 mL/min. The most frequent adverse effects included diarrhea, delayed graft function, anemia, and lymphocele. Among infections, most common were infections of urinary tract, cytomegalovirus infections, and infections of respiratory tract. Only three patients (10.0%) terminated the study prematurely, including two who discontinuated because of an adverse event, and one because of noncompliance. CONCLUSIONS: An immunosuppressive regimen, including MPS and CsA, with or without steroids, provided effective antirejecton prophylaxis and was well tolerated.

Economic evaluation of sirolimus-based immunosuppressive regimens in kidney graft recipients.

INTRODUCTION: The aim of this study was an economic evaluation of three sirolimus (SRL)-based regimens in the first 2 years after renal transplantation. MATERIALS AND METHODS: The three SRL-based immunosuppressive regimens in renal transplant patients between June 2000 and September 2002 were: (1) SRL + steroids + cyclosporine (CsA) permanently; (2) SRL + steroids + tacrolimus (Tac); and (3) SRL + steroids + CsA, with CsA discontinuation at 3 months posttransplant. Ten patients were included in each group in an intent-to-treat analysis. Cost was calculated according to the hospital price list and recast into euros (EUR) with a 5% discount rate. RESULTS: The number of patients free of an acute rejection episode during 2 years posttransplant were 6, 8, and 5, with 2-year graft and patient survivals of 9, 10, and 9 for regimens 1, 2, and 3, respectively. As differences in clinical effects were not statistically significant, cost analysis was appropriate instead of cost-effectiveness analysis. The mean cost of the 2-year treatment was 15,759 EUR; 25,593 EUR; and 21,197 EUR per patient for regimens 1, 2, and 3, respectively. Sensitivity analysis for the main variables confirmed that the results were not dependent on changes in costs. CONCLUSIONS: Regimen 1 was the most economical immunosuppressive therapy during the 2 years after kidney transplantation. Studies on a larger group of longer observation would be more useful for clinical analysis.

Liver transplantation in hepatitis C virus-related cirrhosis.

End-stage liver disease associated with HCV infection has become one of the leading indications for liver transplantation and it is the most common disease recurring after liver transplantation. The aim of this retrospective study was to asses factors potentially affecting outcome in patients transplanted for HCV-related liver disease. Among 164 adult patients who underwent orthotopic liver transplantation from December 1994 to December 2002, 134 survived >2 months, including 25 with HCV-related liver disease. Mean follow-up after LTx was 24.8 months (range, 2.1-99.4). Anti-HCV was negative in all donors. The parameters considered in our analysis were: the course, outcome, and liver function tests at 1-year follow-up after HCV reinfection: the potential impact of maintenance and induction immunosuppressive regimens; and episodes of acute rejection. Deterioration of graft function because of HCV reinfection occurred in 16 patients (64%). Mean time for deterioration of liver function related to reinfection was 4.5 months (range, 0.83-23). Induction and maintenance immunosuppression did not affect outcome of HCV-infected liver transplant recipients. Aminotransferases were significantly higher among HCV-infected recipients than among the other patients in our series. There was a slight tendency for earlier recurrence of HCV hepatitis among patients treated with high-dose steroids because of acute rejection.

PAF-receptor in inflammatory versus non inflammatory human epidermis, cell cultures and embryonal cells.

OBJECTIVE: PAF-R (platelet activating factor-receptor) has been found on human keratinocytes to bind PAF, a proinflammatory phospholipid. We aimed to study PAF-R in a range of dermal cell lines and in samples of normal and psoriatic human skin to learn about its further role in humans. METHODS: PAF-R was labeled immunocytochemically, histochemically and additionally studied with western blotting in human keratinocytes, human fibroblasts, embryonal keratinocytes, tumor cell lines and samples of normal and psoriatic human skin. RESULTS: Keratinocytes from adult and embryonal epidermis of the 20th week of pregnancy showed a low level of labeling for PAF-R, but 3 +/- 0.05% of plantar keratinocytes from adults were positive as were 4.2 +/- 0.05% of embryonal plantar keratinocytes from the 21st week of pregnancy. In fibroblasts from adult and embryonal epidermis the protein was expressed at low levels. Western blotting revealed PAF-R positive bands at 67 k.Da in normal human skin and psoriasis, in psoriasis additionally at 45 k.Da. A 68 k.Da band was found in the colon cancer line HT 29 (control), and HaCaT cells, in embryonal keratinocytes additionally at 116 k.Da. CONCLUSIONS: PAF-R seems not to be important for embryonal or adult fibroblasts. In embryonal keratinocytes it is turned on after the 21st pregnancy week in a few cells seen as a band of 67 k.Da and at 116 k.Da, the latter is not found in adult keratinocytes. An additional 45 k.Da band of PAF-R was found in psoriasis that might stand for a truncated receptor. In the epithelial tumor cell line HaCaT and the HT29 colon cancer cell line PAF-R characterizes the anti-apoptotic effect of this receptor propagating tumor proliferation.

[Electrical instability of the heart in patients with left ventricular hypertrophy in the course of hypertension]. / Niestabilnosc elektryczna serca u chorych z przerostem lewej komory w przebiegu nadcisnienia tetniczego.

UNLABELLED: Left ventricular hypertrophy (LVH) in course of the systemic hypertension (HT) is found as independent risk factor for ventricular arrhythmia and sudden cardiac death. OBJECTS: The aim of the study was to evaluate the relationship between occurrence of LVH and electrical instability. Study group included 64 patients (pts) with mild to moderate HT, without clinical signs of coronary artery disease. Pts were divided into two group: with and without LVH (LVH was diagnosed by echocardiography (ECHO) when left ventricular mass index (LVMI) was > 106 g/m2 for women, and > 111 g/m2 for men). By 12-lead ECG QTc, dispersion QT (QTd) were calculated. From SAECG the QRS duration (tQRS), the root mean square of the last 40 ms of the filtered QRS complex (RMS40) and the duration of the terminal low amplitude QRS signal < 40 microV (LAS 40) were calculated. Ventricular arrhythmias were recorded during 24 hour Holter monitoring and classified into the Lown classification. RESULTS: No difference in QTd between two groups was observed. Nobody has nonsustained ventricular tachycardia in 24-hour Holter monitoring. In group with LVH tQRS was longer and RMS higher in SAECG than in group without LVH. CONCLUSION: LVH in hypertensive pts influences the increase of electrical instability that is evaluated by SAECG.

[Simultaneous use of different nuclear medical examinations in Klippel-Trenaunay syndrome--vs. Proteus syndrome]. / Simultaner Einsatz verschiedener nuklearmedizinischer Verfahren bei Klippel-Trenaunay-Syndrom--vs. Proteus-Syndrom.

A three-year-old male patient presented already at his birth a disproportion macrosomia of the left foot and a large, nodular nevus flammeus in the left hip region, which led to the tentative diagnosis of a Klippel-Trenaunay syndrome. In the following years, both changes showed a continuous progression, with distinct soft-tissue swelling as well as papillomatous and verruciform vegetations of the nevus. Additionally, large, plain subcutaneous masses developed under the right shoulder, and a macrodactyly of the first and second left toe could be observed. Although several examinations had been performed in the meantime, the tentative diagnosis could not be confirmed up to that time. On the occasion of a severe local infection in the hip region, which led to the consideration of a surgical therapy, a radionuclide lymphography, a blood pool scintigraphy including dynamic phlebography and ventriculography as well as a bone scintigraphy were performed. These examinations were done simultaneously at one day in order to avoid a longer period of immobilization. The findings led to the diagnosis of a large lymphangioma, which could be confirmed histologically after surgery. In consideration of all results, the basic disorder seems to be the rare proteus syndrome rather than a Klippel-Trenaunay syndrome.

[Prognostic value of an early peak CK-MB in plasma of patients treated with streptokinase for acute myocardial infarction]. / Wartosc prognostyczna wczesnego szczytu aktywnosci CK-MB w surowicy u chorych leczonych streptokinaza w ostrym zawale serca.

111 patients below 70 years old, with the first acute myocardial infarctions, 6 hours since the pain occurred--have been treated with streptokinase i.v. In 102 patients we obtained full curve of CK-MB activity. Early peak of CK-MB activity < 15 hours after onset of symptoms we have observed in 59 patients, and late peak of CK-MB activity > 15 hours in 43 patients. There was not any significant statistics differences between early and late groups in frequency of: early ventricular fibrillation (< 48 hours), complex ventricular arrhythmia (in 21 day), heart failure and in-hospital mortality. 1 patient died in hospital in early group and in late group also died 1 patient. The follow-up period was from 10 to 48 months (av. 26 +/- 13). 100 patients left the hospital and the full informations we have obtained in 97 cases. No one died in that time. In the group with early peak CK-MB activity we observed more often the unstable angina and the new myocardial infarction (21%) than in the group with late peak of CK-MB activity (15%), but these differences were nonsignificant. In conclusion our results don't confirm that the early peak of CK-MB activity is the positive risk factor of unstable angina and the new myocardial infarction.

Picosecond optical switching based on biphotonic excitation of an electron donor-acceptor-donor molecule.

An electron donor-acceptor-donor molecule consisting of two porphyrin donors rigidly attached to the two-electron acceptor N,N'-diphenyl-3,4,9,10-perylenebis(dicarboximide) acts as a light intensity-dependent molecular switch on a picosecond time scale. Excitation of the porphyrins within this molecule with subpicosecond laser pulses results in single or double reduction of the acceptor depending on the light intensity. The singly and doubly reduced electron acceptors absorb light strongly at 713 and 546 nanometers, respectively. Because these absorption changes are produced solely by electron transfers, this molecular switch effectively has no moving parts and switches significantly faster than photochromic molecules that must undergo changes in molecular structure.

[A method of averaged ECG signal does not identify patients with ventricular tachycardia in disorders of intraventricular conduction]. / Technika usredniania sygnalu EKG nie pozwala na wyodrebnienie chorych z czestoskurczem komorowym przy zaburzeniach przewodnictwa sródkomorowego.

Conduction defect are known to delay and fragment the ecg signal and may be expected to cause changes on the signal-averaged ecg that mimic ventricular late potentials. The aim of our study was to asses whether signal-averaged ECG (SAE) identify patients (pts) with sustained ventricular tachycardia (VT) after myocardial infarction (MI) who display right or left bundle branch block (RBBB or LBBB). We studied 23 pts with RBBB and 25 pts with LBBB. SEA was recorded with bidirectional filters at 25-250 HZ and 40-250 Hz using Simson method. The total filtered QRS duration (QRSd), root mean square voltage in the terminal 40ms of the QRS (RMS40) and low amplitude signal duration less than 40uV (LAS40)) were measured. Signal-averaged parameters with a filter at 25-250 Hz were: [table: see text] Signal-averaged parameters with a filter at 40-259 Hz were: [table: see text] In conclusion SAE parameters do not allow separation of pts with sustained VT from pts with RBBB or LBBB after MI. These data indicate that conduction defects have effects on signal-averaged ecg parameters and may result in masking of ventricular late potentials.

[Atrial natriuretic peptide level in acute myocardial infarction]. / Stezenie przedsionkowego peptydu natriuretycznego w swiezym zawale serca.

Concentration of atrial natriuretic peptide (ANP) was studied in acute myocardial infarction (AMI), its association with ventricular arrhythmias (VA), left ventricular dysfunction and infarct size. Plasma ANP concentrations were measured at time: 0, 4, 8, 16, 24, 48 and 72 hours after admission in 11 patients (pts) with first AMI, up to 6 hours after the first symptoms. Ventricular arrhythmia was assessed by 24 hour Holter monitoring, left ventricular dysfunction by echocardiography and infarct size by serial CK-MB measurement in first 72 hours of AMI. In subsequent measurements the average plasma concentration of ANP (mean +/- SEM) was elevated: 42.2 +/- 9.9, 35.3 +/- 12.5, 33.9 +/- 8.3, 42.3 +/- 8.3, 36.9 +/- 6.4, 60.7 +/- 9.3, 47.8 +/- 12.0 fmol/ml. The maximal plasma ANP concentration was significantly higher (p less than 0.01) in 4 pts with VA 4th grade acc. to Lown than in 7 pts without VA (102.6 +/- 17.9 vs 41.1 +/- 6.4). The maximal level of ANP--153.3 fmol/ml in a patient with paroxysmal supraventricular tachycardia was observed. There were no significant correlations between plasma ANP and infarct size, size of left atrium and contractility disturbances of left ventricle.

Effects of histamine H1-receptor blockade on respiratory and cardiac manifestation of systemic anaphylaxis.

In vivo anaphylaxis is associated with respiratory distress and cardiovascular failure. The present investigation was designed to further characterize respiratory and cardiac anaphylactic events. In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin together with Freund's adjuvant. Fourteen days after sensitization, the effects of an intravenous infusion of ovalbumin were tested in the anesthetized artificially ventilated guinea pigs. The renewed application of the antigen induced an initial increase of left ventricular pressure which was followed by a rapid decrease 5 min after antigenic challenge. Enddiastolic left ventricular pressure increased within 3 min, thus indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, heart rate steadily decreased. All animals died within 15 min. Simultaneously with cardiac anaphylactic malfunction, severe arterial hypoxia and carbon dioxide retention occurred, revealing respiratory distress. Histamine is known as a potent bronchoconstrictor via histamine H1-receptor stimulation. Administration of H1-receptor antagonists to improve respiration may therefore provide further information on the contribution of pulmonary malfunction to anaphylactic cardiovascular shock. Therefore, additional experiments were performed with sensitized guinea pigs pretreated with the histamine H1-receptor blocker mepyramine. In these experiments the antigenic challenge induced a dissociation of cardiac and respiratory manifestation of anaphylaxis. Despite inhibition of hypoxia and carbon dioxide retention, left ventricular pump failure and occurrence of myocardial ischemia were delayed but not suppressed. It is concluded that histamine is an important mediator of anaphylactic respiratory distress. However, vasoactive anaphylactic mediators other than histamine are primarily involved in anaphylactic cardiac malfunction occurring during the later phase of systemic anaphylaxis.

Effects of histamine H1- and H2-receptor antagonists on cardiovascular function during systemic anaphylaxis in guinea pigs.

The heart is a target organ of anaphylaxis. In isolated perfused hearts, an anaphylactic reaction is characterized by arrhythmias, coronary constriction and severe impairment of ventricular contractile force. Various mediators such as PAF, thromboxane A2 and leukotrienes are responsible for anaphylactic coronary constriction and negative inotropic effects. The cardiac effects of anaphylactic histamine release are related to the stimulation of two antagonistic receptor types. Histamine induces atrioventricular conduction delay and constriction of the epicardial coronary vessels via H1-receptor stimulation. H2-receptors, however, mediate coronary vasodilation and an increase in heart rate and myocardial contractility. It may therefore be concluded that administration of histamine H2-receptor antagonists is disadvantageous. During anaphylactic states, the cardiodepressive effects of the other mediators of anaphylaxis are unmasked, resulting in a sustained coronary constriction and impairment of myocardial contractility. To verify this speculation, we investigated the effects of H1- and H2-receptor antagonists on cardiovascular function of guinea pigs during systemic anaphylaxis. In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin. Fourteen days after sensitization, the effects of an intravenous infusion of ovalbumin were tested in the anesthetized artificially ventilated guinea pigs. The renewed administration of the antigen induced severe cardiac dysfunction. Within a few minutes, cardiac output markedly decreased and left ventricular end-diastolic pressure increased significantly, indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, arrhythmias occurred in terms of an atrioventricular block.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of platelet-activating factor on beta- and H2-receptor-mediated increase of myocardial contractile force in isolated perfused guinea pig hearts.

Platelet-activating factor (PAF) has been termed an important mediator of cardiovascular shock due to immunological reactions, including anaphylaxis and endotoxic reactions. Previous studies have shown that PAF is a potent cardiodepressive agent inducing a drastic coronary constriction and a sustained impairment of myocardial contractility. In this study, an attempt was made to further characterize the prolonged PAF effects on coronary circulation and myocardial contractile force in the isolated guinea pig heart perfused at constant pressure. An intracoronary PAF bolus (0.18 nmol, related to coronary flow rates of 1 ml/min) induced a precipitous decrease of coronary flow rates, left ventricular pressure, and left ventricular contraction (peak positive dP/dt), which was followed by a slow increase reaching new steady state after 15 min (-48%, -40%, -42% below baseline, respectively). If the specific PAF antagonist WEB 2086 (3.65 nmol/min, related to coronary flow rates of 1 ml/min) was infused 30 min after PAF administration, the prolonged PAF-mediated cardio-depressive effects were rapidly reversed. Several studies indicate that PAF induces a down regulation of beta-adrenoreceptors in different cell types, including human lung tissue. Therefore, a further objective of the study was to evaluate whether PAF selectively impairs the positive inotropic effects of beta-receptor agonists or also inhibits the contractile effects of inotropic drugs, which are known to enhance cardiac contractility independently of beta-receptors. In these experiments, the beta-agonist isoproterenol and the H2-agonist impromidine were administered as intracoronary boluses (0.35 nmol and 0.14 nmol, respectively, related to coronary flow rates of 1 ml/min) prior to PAF injection and 30 min after PAF.(ABSTRACT TRUNCATED AT 250 WORDS)