Living Kidney Donation Is Recipient Age Sensitive and Has a High Rate of Donor Organ Disqualifications.

BACKGROUND: Living donor kidney transplantation (LDKT) is the best therapy for patients with chronic renal failure. Its advantages, compared with cadaveric transplantation, include the possibility of avoiding dialysis, the likelihood of best outcome, and donor pool expansion. Careful assessment of potential donors is important to minimize the risks and ensure success. However, the proportion of donors disqualified has been poorly investigated. The aim of this work is to describe our experience and present the main reasons for missed donation. METHODS: This was a single-center, retrospective study of all potential donors and recipients evaluated for LDKT between January 2008 and December 2017. RESULTS: During the period of study, 81 donor-recipient pairs were evaluated. Of these, 45.7% were disqualified and 37 LDKTs were carried out. LDKT was the first choice in 68% of cases and preemptive in 20%; 60% of transplants were among family members. Sex distribution revealed a prevalence of females in the donor group (69%) and males in the recipient group (70%). The mean living donor age was 53 ± 9.5 years; the mean recipient age was lower in recipients listed in the living transplant program than those listed for cadaver transplantation (45.8 ± 13.4 vs 54.2 ± 11.08; P < .0001). Reasons for denial included hypertension (18.9%), deceased donor transplant performed during the study period (16.2%), urologic pathology (13.5%), incompatibility (13.5%), withdrawal of consent by donor or recipient (13.5%), psychological unsuitability (8.1%), donor cancer (5.4%), and reduced renal clearance (2.7%). CONCLUSION: LDKT is considered an option especially for younger recipients. Of the potential kidney living donors, 45.7% were disqualified during the evaluation, with medical reasons being the primary cause.

Sirolimus prevents short-term renal changes induced by ischemia-reperfusion injury in rats.

BACKGROUND: Ischemia-reperfusion (I/R) is present at various degrees in kidney transplants. I/R plays a major role in early function and long-term survival of renal allograft. The purpose of our study was to determine if immunosuppressants modulate I/R in a model that separates I/R from all immune responses. METHODS: Sprague-Dawley rats with monolateral renal I/R received daily cyclosporine (A), tacrolimus (B), sirolimus (C) or saline (D). Sham-operated rats received saline (E). After 30 days, glomerular filtration rate for each kidney was measured by inulin clearance. Kidney injury was examined, and TGF-ß, fibronectin and metalloproteases were evaluated by real-time PCR, Western blot and zymography. RESULTS: Sirolimus, but not cyclosporine and tacrolimus, prevented a glomerular filtration rate decrease in I/R kidneys (403 ± 303 vs. 1,006 ± 484 µl/min, p < 0.05; 126 ± 170 vs. 567 ± 374 µl/min, p < 0.05; 633 ± 293 vs. 786 ± 255; A, B and C group, respectively, I/R vs. contralateral kidneys). Sirolimus reduced ED-1+ cell infiltrate, interstitial fibrosis and intimal thickening of small vessels observed in I/R kidneys of controls and calcineurin inhibitor-treated rats. Tacrolimus and cyclosporine increased fibronectin and TGF-ß expression and matrix deposition. Only sirolimus increased metalloprotease activity. CONCLUSIONS: Sirolimus but not calcineurin inhibitors prevented I/R-induced kidney injury.

[Hepatocyte growth factor and kidney]. / Hepatocyte Growth Factor (HGF): ruolo nella embriogenesi e nella fibrosi renale.

HGF is a multifunctional polypeptide with mitogenic, motogenic and morphogenic effects. These effects are mediated by c-met, a specific receptor of HGF and a member of the receptor tyrosine kinase superfamily, virtually expressed in every type of kidney cell. HGF has a central role during embryogenesis since it stimulates epithelial differentiation of metanephric mesenchymal cells and induces branching tubules, as experiments in epithelial cells cultures demonstrated. Several studies have shown also that HGF accelerates the recovery from toxic-ischemic acute renal failure. This effect seems to be mediated by the inhibition of programmed cell death and an increased cell survival. HGF inhibits apoptosis by upregulating the protooncogene Bcl-2 and downregulating Bax. Since HGF can modulate extracellular matrix turnover, authors suggest its beneficial role in tissue remodelling and particularly in chronic renal diseases. Several studies reported a key role for HGF in reducing interstitial fibrosis and glomerular sclerosis, both in in vivo and in vitro models. This protective effect is secondary to HGF antagonizing the profibrotic action of TGF-beta. HGF modulates the balance between synthesis and degradation of extracellular matrix, increasing the expression of metalloproteases and reducing the production of their specific inhibitors TIMPs. Furthermore HGF suppresses the effect of TGF-beta by blocking the axis TGF-beta/Smad. Last, the antifibrotic effect of HGF might be modulated by the proliferative status of target cells. To sum up, the supplementation of exogenous HGF or the induction of endogenous HGF expression may provide an effective therapeutic strategy for combating chronic renal diseases.

Effect of calcineurin inhibitors on extracellular matrix turnover in isolated human glomeruli.

INTRODUCTION: Although chronic cyclosporine toxicity is mainly characterized by tubular atrophy and interstitial fibrosis, glomerular injury with expansion of mesangial matrix and sclerosis is not uncommon. Tacrolimus is a newer calcineurin inhibitor that has been used in renal transplant recipients as primary or rescue therapy. Clinical trials suggest an improved long-term graft survival among patients treated with tacrolimus. Recently we have shown that tacrolimus and cyclosporine have similar effects on extracellular matrix turnover in cultured cells. The present study was performed to investigate the effects of the calcineurin inhibitors on whole glomeruli extracellular matrix turnover. METHODS: Human glomeruli isolated from kidney biopsies just before transplantation were incubated with culture media containing either cyclosporine (200 ng/mL) or tacrolimus (10 ng/mL) for 24 hours. Glomeruli incubated only with culture medium were used as control. RESULTS: The expressions of (alpha2)IV collagen, metalloprotease 9 (MMP9), tissue inhibitors of metalloproteases 2 (TIMP-2), and TGFbeta were evaluated by in situ reverse transcription and polymerase chain reactions (RT-PCR). beta-actin was used as a control gene. Cyclosporine (but not tacrolimus) increased the expression of (alpha2)IV collagen and TIMP2 in isolated glomeruli. TGF-beta was markedly increased by cyclosporine. MMP9 expression was not affected by the calcineurin inhibitors. By light microscopy kidney biopsies did not show pathologic changes. CONCLUSION: Cyclosporine treatment modulates extracellular matrix turnover in isolated human glomeruli, inducing an imbalance between synthesis and degradation. This effect, not observed in tacrolimus-treated human glomeruli, may induce the extracellular matrix deposition and sclerosis characteristic of chronic cyclosporine toxicity.

Hyperkalemia-induced ECG abnormalities in patients with reduced renal function.

Hyperkalemia is a potentially lethal condition to be aware of in the presence of ECG abnormalities especially in patients with reduced renal function. However, ECG abnormalities are not always dependent on the degree ofhyperkalemia but may be aggravated by the rapidity of the development of hyperkalemia and by associated electrolyte disorders. We describe 3 patients with renal failure and different ECG changes induced by hyperkalemia. More severe changes were observed when hyperkalemia developed rapidly, but not in presence of electrolyte disorders. Even minor ECG abnormalities must alarm physicians in patients with renal failure since severe hyperkalemia is not always associated with critical ECG changes.

[Hepatocyte growth factor (HGF) reduces the expression of profibrotic factors in human isolated glomeruli]. / Hepatocyte growth factor (HGF) riduce l'espressione di fattori profibrotici in glomeruli umani isolati.

BACKGROUND: The imbalance between the synthesis and degradation of the mesangial matrix causes glomerulosclerosis and ultimately leads to chronic renal failure. HGF is a pleiotropic cytokine involved in angiogenesis, morphogenesis, organogenesis, and bone remodeling. Recently, we and other investigators have shown that HGF has a central role in the recovery of acute renal failure. Furthermore, HGF treatment halts the progression of kidney disease in a murine model of chronic renal failure. The aim of the present study was to evaluate the effect of HGF on the mRNA levels of molecules involved in the extracellular matrix turnover and of the c-met receptor in isolated human glomeruli. METHODS: Human glomeruli were isolated by microdissection from donor kidney biopsies just before transplantation. Glomeruli were extensively washed and incubated with culture media containing HGF (50 ng/mL) for 24 h at 37 C. Glomeruli incubated without HGF were used as controls. After 24 h, glomeruli were washed and freezed and thawed three times. The expression of c-met, (alpha2) IV collagen, TGF-beta, metalloproteases 9 (MMP9), and of the inhibitor of metalloproteases-1, TIMP-1 was evaluated by in situ reverse transcription (RT) and polymerase chain reaction (PCR). beta-actin was used as a housekeeping gene. RESULTS: The (alpha2)IV collagen mRNA level was decreased by HGF in human glomeruli. TGF-beta and TIMP-1 gene expression was markedly reduced by HGF treatment, whereas the expression of MMP-9 and c-met did not change. Under light-microscopic examination, kidney biopsies showed neither glomerular hypercellularity nor mesangial expansion. CONCLUSIONS: HGF treatment reduces the expression of extracellular matrix components and of profibrotic factors in human glomeruli. Our results confirm a protective role of HGF in glomerulosclerosis.

Long-term exposure to high glucose up-regulates VCAM-induced endothelial cell adhesiveness to PBMC.

BACKGROUND: The changes induced on endothelial cells by a long-term exposure to high glucose, a situation that mimics the hyperglycemia of diabetics, have not yet been determined. We compared short- and long-term effects of elevated glucose on macrovascular and microvascular endothelial cells. METHODS: Endothelial cells were grown in high-glucose media for 24 hours and for 8 weeks. Cell proliferation was evaluated by cell counting, apoptosis and expression of adhesion molecules by flow cytometry; nitric oxide (NO) by measuring the concentration of nitrite/nitrate in the cell supernatant; alpha 2(IV) collagen mRNA and protein by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The adhesion of peripheral blood mononuclear cells (PBMCs) to endothelial cells was evaluated by adhesion assay. In some experiments, endothelial cells were preincubated with anti-vascular cell adhesion molecule-1 (VCAM-1) and anti-receptor for advanced glycation end product (RAGE) blocking antibodies. RESULTS: At 24 hours, but not at 8 weeks, high glucose increased endothelial cell proliferation and apoptosis. High glucose did not modify NO synthesis at 24 hours and 8 weeks. Collagen production and expression were increased only after eight weeks. VCAM-1 but not intercellular adhesion molecule-1 was up-regulated after 8 weeks, a change not observed after 24 hours. The adhesion of PBMCs was significantly increased at eight weeks and was completely abrogated by anti--VCAM-1 and by anti-RAGE antibodies. After 24 hours, there was a modest increase of PBMC adhesion that was not blunted by anti-RAGE antibodies. CONCLUSIONS: Increased adhesion of PBMCs, caused by up-regulation of VCAM-1 with a mechanism involving advanced glycation end product (AGE) adducts, and augmented collagen deposition are critical effects of long-term high glucose on endothelial cells, and may eventually promote the atherosclerotic process.

Arterial switch operation after left ventricular retraining in the adult.

Retraining the morphological left ventricle in transposition of the great arteries has been successfully reported in infancy, while older age seems to be a contraindication. A 23-year-old woman with ¿S,D,D¿ transposition of the great arteries and ventricular septal defect developed severe right systemic ventricular dysfunction 22 years after Mustard procedure and ventricular septal defect closure. Hemodynamic investigation revealed moderate pulmonary hypertension and preserved left ventricular function. A pulmonary artery band was applied to obtain a left-right ventricular pressure ratio of 0.91. Her postoperative course was characterized by biventricular failure, treated effectively with inotropic support. Six months later, she underwent a Mustard baffle takedown and arterial switch procedure. Her postoperative course was uneventful. She was discharged home on postoperative day 15. At 24-months follow-up, she is in excellent clinical condition; echocardiographic evaluation shows good left ventricular function (ejection fraction: 0.69) with left ventricular volume within normal limits (70 ml/m2). Our experience demonstrates that, despite adult age, a staged arterial switch operation can be performed successfully in selected patients when left ventricular function is preserved.

Cyclosporine induces different responses in human epithelial, endothelial and fibroblast cell cultures.

BACKGROUND: Nephrotoxicity, accelerated atherosclerosis, and graft vascular disease are common complications of cyclosporine long-term treatment characterized by a wide disruption of organ architecture with increased interstitial areas and accumulation of extracellular matrix (ECM). How cyclosporine induces these changes is not clear, but it is conceivable that they are the sum of changes induced at the cell level. METHODS: We studied the effects of cyclosporine on human endothelial (HEC), epithelial (HK-2), and fibroblast (MRC5) cells. Cell proliferation was evaluated by cell counting, apoptosis and collagen production by enzyme-linked immunosorbent assay, and nitric oxide by measuring the concentration of nitrite/nitrate in the cell supernatant. (alpha1)I and (alpha2)IV collagen, matrix metalloprotease-9 (MMP9), and tissue inhibitors of metalloprotease-1 (TIMP-1) mRNA levels were measured by reverse transcription-polymerase chain reaction. Proteolytic activity was evaluated by zymography. RESULTS: Cyclosporine showed a marked antiproliferative and proapoptotic effect on endothelial and epithelial cells. Fibroblast growth was not affected by cyclosporine. Nitric oxide was up-regulated by cyclosporine in epithelial cells and fibroblasts but not in endothelial cells. (alpha1)I and (alpha2)IV collagen synthesis was increased in cyclosporine-treated endothelial and epithelial cells, respectively. Proteolytic activity was increased in endothelial and epithelial cells. TIMP-1 mRNA was up-regulated by cyclosporine in fibroblasts. CONCLUSIONS: Our results demonstrate that cyclosporine exhibits an antiproliferative effect on endothelial and epithelial cells. This effect is associated with induction of apoptosis probably via nitric oxide up-regulation in epithelial cell cultures. Cyclosporine treatment induces ECM accumulation by increasing collagen synthesis in endothelial and epithelial cells and reducing its degradation by up-regulating TIMP-1 expression in fibroblasts. We conclude that cyclosporine affects cell types differently and that the disruption of organ architecture is the result of multiple effects at the cell level.

Risk factors for chronic renal dysfunction in cardiac allograft recipients.

Renal dysfunction is one of the most common and threatening complications in heart transplant recipients. Even if ciclosporin seems to play a central role in inducing renal damage, other factors may concur or predispose to renal injury. In order to identify factors responsible for renal dysfunction, we retrospectively studied a cohort of 114 cardiac transplant recipients during a follow-up period of at least 3 years. The patients had a normal renal function before and 0.5 months after heart transplantation. Doubling of baseline serum creatinine or attainment of serum creatinine steadily above 176.8 micromol/l (2.0 mg/dl) was used as criterion to define the end-point renal dysfunction. A series of clinical and laboratory variables were obtained from the patients' charts at different time intervals, and their prognostic value for the occurrence of renal dysfunction was calculated by Cox proportional hazards models. 23 out of 114 patients reached the end point after a median time period of 21 months. High serum triglyceride, alanine aminotransferase, alkaline phosphatase, ciclosporin, urea, glucose, and hemoglobin levels were shown to be associated with the development of renal dysfunction. Four variables, i.e., triglyceride, ciclosporin, urea, and alkaline phosphatase, had an independent prognostic value. Our results confirm a role for ciclosporin in inducing renal dysfunction and identify hyperlipidemia and an increased plasma urea level as risk factors for renal dysfunction in heart transplant recipients.

Henoch-Schönlein purpura in a chronic hemodialysis patient.

We describe a patient on maintenance hemodialysis who developed purpura, abdominal pain with bloody stool, and gross hematuria. A skin biopsy revealed leukocytoclastic vasculitis with IgA deposits. This is the first report of Henoch-Schönlein purpura in a hemodialysis patient.

Early reduction in plasma norepinephrine during beta-blocking therapy with metoprolol in chronic heart failure.

BACKGROUND: The possible role exerted by modulation of sympathetic outflow in the clinical effects of beta-blockade in chronic heart failure was tested during short- and long-term treatment. METHODS AND RESULTS: Oral metoprolol (30-150 mg/day) was added to conventional therapy in 14 patients with idiopathic dilated cardiomyopathy, left ventricular ejection fraction (LVEF) of <0.45, and New York Heart Association class II or III. Norepinephrine plasma levels, which are an index of sympathetic activation, decreased by 27.57 +/- 18.03% after 1 month (P < .005), but returned to pretreatment levels after 6 months. LVEF increased by 7.7 +/- 6.0 ejection fraction units after 6 months (P < .005 vs baseline and P < .05 vs 1 month). Long-term beta-blockade resulted in nonsignificant improvements in functional class, symptom score, and oxygen consumption at peak exercise. After 1 month, the reduction in plasma norepinephrine levels and the changes in LVEF were inversely correlated (P < .01). No other correlation emerged during short- or long-term treatment. CONCLUSION: In conclusion, the reduction in plasma norepinephrine levels during short-term beta-blockade was not proportional to the clinical benefits and may have been attributed to the direct inhibition of sympathetic outflow. The early reduction in circulating norepinephrine levels may decrease cardiac performance through withdrawal of sympathetic support when the favorable effects of beta-blockade have not had time to occur. The role that sympathetic modulation may exert in the long-term clinical benefits of metoprolol deserves further investigation.

Postextrasystolic potentiation echocardiography in predicting reversible myocardial dysfunction by surgical coronary revascularization.

Sustained inotropic stimulation, such as dobutamine infusion, has the potential to cause an additional contractile deterioration in viable but chronically hypoperfused and dysfunctioning myocardium, by inducing ischemia. Postextrasystolic potentiation (PESP) represents a potent inotropic stimulus without risk of provoking ischemia, as it is instantaneous. In this study, we assessed the role of PESP-echocardiographic examination in predicting the recovery of regional contractility after coronary revascularization. We examined 105 consecutive patients with multivessel coronary artery disease who were candidates for bypass surgery; 79 were included in this prospective study. Preoperative reversibility of contractile dysfunction in asynergic myocardial regions was determined by PESP, with a coupling interval of 500 msec decreasing to 300 msec, with a progressive decrease by 10 msec. The examination was accompanied by continuous 2-dimensional (2D) echocardiographic monitoring. The assessed sensitivity and specificity were 92% and 87%, respectively; the predictive accuracy was 90%. These results demonstrated that PESP echocardiography is a useful and cost-effective method for identifying viable myocardium in patients undergoing myocardial revascularization.

Myocardial dysfunction and adrenergic cardiac innervation in patients with insulin-dependent diabetes mellitus.

BACKGROUND: Insulin-dependent diabetes mellitus (IDDM) is associated with an increased incidence of heart failure due to several factors, and in some cases a specific cardiomyopathy has been suggested. OBJECTIVES: This study sought to assess the mechanisms of exercise-induced left ventricular (LV) dysfunction in asymptomatic patients with IDDM in the absence of hypertensive or coronary artery disease. METHODS: Fourteen consecutive patients with IDDM were enrolled (10 men, 4 women; mean [+/- SD] age 28.5 +/- 6 years); 10 healthy subjects matched for gender (7 men, 3 women) and age (28.5 +/- 3 years) constituted the control group. LV volume, LV ejection fraction (LVEF) and end-systolic wall stress were calculated by two-dimensional echocardiography at rest and during isometric exercise. LV contractile reserve was assessed by post-extrasystolic potentiation (PESP) obtained by transesophageal cardiac electrical stimulation and dobutamine infusion. Myocardial iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed to assess adrenergic cardiac innervation. RESULTS: Diabetic patients were classified into group A (n = 7), with an abnormal LVEF response to handgrip (42 +/- 7%), and group B (n = 7), with a normal response (72 +/- 8%). Baseline LVEF was normal in both group A and B patients (60 +/- 6% vs. 61 +/- 7%, p = NS). In group A patients, the LV circumferential wall stress-LVEF relation showed an impairment in LVEF disproportionate to the level of LV afterload. No significant changes in LVEF occurred during dobutamine (60 +/- 6% vs. 64 +/- 10%, p = NS), whereas PESP significantly increased LVEF (60 +/- 6% vs. 74 +/- 6%, p < 0.001); PESP at peak handgrip normalized the abnormal LVEF (42 +/- 7% vs. 72 +/- 5%, p < 0.001); and MIBG uptake normalized for body weight or for LV mass was lower than that in normal subjects (1.69 +/- 0.30 vs. 2.98 +/- 0.82 cpm/MBq per g, p = 0.01) and group B diabetic patients (vs. 2.79 +/- 0.94 cpm/MBq per g, p = 0.01). Finally, a strong linear correlation between LVEF at peak handgrip and myocardial MIBG uptake normalized for LV mass was demonstrated in the study patients. CONCLUSIONS: Despite normal contractile reserve, a defective blunted recruitment of myocardial contractility plays an important role in determining exercise LV dysfunction in the early phase of diabetic cardiomyopathy. This abnormal response to exercise is strongly related to an impairment of cardiac sympathetic innervation.

Evaluation of the efficacy and tolerability of nitrendipine in reducing both pressure and left ventricular mass in hypertensive type 2 diabetic patients.

OBJECTIVE: To evaluate the efficacy and tolerability of nitrendipine in comparison with captopril in hypertensive diabetic patients with left ventricular hypertrophy (LVH). RESEARCH DESIGN AND METHODS: A total of 75 patients enrolled in this study presented stable type 2 diabetes (not treated with insulin) and mild-to-moderate hypertension with a left ventricular mass > or = 75 g/m2 by two-dimensional echocardiography. After a 4-week washout period, 38 patients were assigned to treatment with captopril, and 37 patients to nitrendipine (random allocation). The duration of follow-up was 36 weeks. RESULTS: Patients of both groups were similar with regard to the duration of diabetes and hypertension, systolic and diastolic blood pressure at rest, degree of LVH, metabolic control, and albumin excretion rate (AER). Both drugs were equally effective in reducing systolic and diastolic blood pressure (captopril: from 165 +/- 13/100 +/- 4 to 147 +/- 11/87 +/- 4 mmHg; nitrendipine: from 167 +/- 17/100 +/- 5 to 143 +/- 9/86 +/- 4 mmHg; P < 0.05) and in reversing LVH (nitrendipine: from 87 +/- 2 to 81 +/- 1 g/m2; captopril: from 89 +/- 2 to 85 +/- 2 g/m2; P = 0.0001). Neither the left ventricular end-diastolic volume index nor the left ventricular ejection fraction changed significantly during the treatment period. CONCLUSION: Nitrendipine is as effective as captopril in reducing both systolic and diastolic blood pressure and in reversing LVH. Neither drug showed any negative side effects on fasting plasma glucose and glycated hemoglobin (HbA1c) levels, and both maintain constant AERs.

Postextrasystolic potentiation and dobutamine echocardiography in predicting recovery of myocardial function after coronary bypass revascularization.

BACKGROUND: Identification of viable but hibernating myocardium remains a relevant issue in the current era of myocardial revascularization. Echocardiography can be helpful in detecting reversible contractile dysfunction and optimizing the selection of patients for coronary bypass surgery. METHODS AND RESULTS: Eighty-four consecutive candidates for bypass surgery with chronic multivessel coronary artery disease were screened, and 60 were included in this prospective study. Preoperative evaluation of a reversible contractile dysfunction in asynergic myocardial regions was performed by dobutamine infusion at 5 (low dose) and 10 (intermediate dose) microg x kg(-1) x min(-1) with each stage lasting at least 5 minutes; postextrasystolic potentiation (PESP), with a coupling interval ranging from 500 to 300 ms with a progressive 10-ms decrease; or a combination of both dobutamine infusion and PESP. Sensitivity (92% versus 86%) and predictive accuracy (89% versus 84%) were higher with PESP than dobutamine (P=.009 and P=.001, respectively), but the combination did not improve sensitivity or accuracy. Dobutamine induced ischemic dysfunction in 15% of patients at the intermediate dose; however, the low dose resulted in loss of sensitivity. CONCLUSIONS: PESP echocardiography is a useful and cost-effective method to identify viable myocardium in patients with multivessel coronary disease undergoing revascularization and is more sensitive and accurate than dobutamine infusion.

Autoimmunity in myocarditis and dilated cardiomyopathy: cardiac autoantibody frequency and clinical correlates in a patient series from Italy.

BACKGROUND: Organ- and disease-specific cardiac autoantibodies, detected by indirect immunofluorescence, represent markers of autoimmunity in a subgroup (25-35%) of patients with dilated cardiomyopathy or myocarditis from Northern Europe and the United States of America. Autoantibody frequencies, as well as associations between clinical and immunological features, may vary in patients from different countries, due to ethnically related differences in genetic susceptibility to autoimmune disease. METHODS: We assessed the frequency of cardiac autoantibodies in a series from Italy, including 91 subjects with idiopathic dilated cardiomyopathy (61 male, aged 49 +/- 11 years) and 11 with biopsy-proven (Dallas criteria) myocarditis (7 male, aged 23 +/- 16), including 2 cases of giant cell myocarditis. Controls were 160 patients with other cardiac disease, 141 with ischemic heart failure and 270 normals Cardiac antibody test was performed blindly by indirect immunofluorescence on normal human myocardium and skeletal muscle. RESULTS: The frequency of organ-specific cardiac autoantibodies was higher (p = 0.0001) in myocarditis (45%) and in dilated cardiomyopathy (20%) than in other cardiac disease (1%), in ischemic heart failure (1%), or in normals (2.5%). Cross-reactive antibodies were detected in similar proportions of study patients and controls. Both patients with giant cell myocarditis were antibody positive. Myocarditis patients with cardiac antibodies had shorter duration of symptoms compared to those who were antibody negative (0.4 +/- 0.3 vs 4 +/- 1 months, p = 0.004). In dilated cardiomyopathy, antibody status was not associated with any clinical or diagnostic feature. CONCLUSIONS: Autoimmunity is involved in a subset of patients with myocarditis and with dilated cardiomyopathy, regardless of their geographical origin or immunogenetic background. The antibody frequency in our dilated cardiomyopathy series from Italy tended to be lower than in other countries. This may reflect reduced antibody levels with disease progression and/or the recognised feature that Mediterranean populations are often less susceptible to autoimmune disease.

Evidence of myocardial dysfunction in Bartter's syndrome.

Bartter's syndrome (BS) is characterized by arterial normohypotension despite biochemical and hormonal abnormalities generally associated with hypertension. An abnormal intracellular calcium homeostasis due to a reduced capacity to increase intracellular calcium has been demonstrated by us in BS and proposed as the main pathophysiological factor of the vascular hyporeactivity in BS. The present study was designed to assess whether this altered intracellular calcium homeostasis could also impair contractile recruitment at the myocyte level. Left-ventricular function of patients with BS and normal subjects (C) were studied by quantitative 2-D echocardiography at rest and by postextrasystolic potentiation (PESP), an inotropic stimulus able to recruit the maximal contractile reserve. A group of patients with hypokalemia other than BS (PB) was also included in the study to evaluate the effect of hypokalemia on myocardial contractile recruitment. Baseline left-ventricular end-diastolic volume (EDV) and ejection fraction (EF) did not differ in the 3 groups: EDV: 62 +/- 6 vs. 64 +/- 9 and 60 +/- 12 ml/m2; EF: 64 +/- 9 vs. 67 +/- 8 and 64 +/- 8%. PESP determines an increase of EF in C and PB: 82 +/- 5%, p < 0.01 and 76 +/- 6%, p < 0.01, while in BS it is unchanged: 69 +/- 9% and is reduced in comparison with the increment of myocardial function shown by C and PB (p < 0.01). This study is the first demonstration in BS of a depressed inotropic recruitment causing an exercise-induced left-ventricular dysfunction likely due to an abnormal intracellular calcium homeostasis in the myocytes.