Effects of imipramine, fluvoxamine and depressive mood on autonomic cardiac functioning in major depressive disorder.

OBJECTIVE: Diminished HR variability is considered to be associated with depression and the increased risk of cardiovascular disease. The pharmacological effects of antidepressants and depressive mood itself may contribute to alterations in autonomic cardiac functioning, but a limited amount of data is available. We studied the effects of two different types of antidepressant treatments (imipramine and fluvoxamine), in addition to the effect of depressive mood, on the cardiovascular system in depressed patients. METHODS: Depressed inpatients were studied during a drug-free period and after 4 weeks of adequate treatment with imipramine (n = 17) or fluvoxamine (n = 24). Heart rate variability, blood pressure variability, and a baroreflex sensitivity index during supine rest and orthostatic challenge were analyzed by means of spectral techniques to obtain noninvasive parameters of sympathetic and parasympathetic activity. RESULTS: Both imipramine and fluvoxamine reduced sympathetic and parasympathetic activity, although the effects of imipramine were much more pronounced. Severity of depression was positively related to mean levels of heart rate and blood pressure in the total patient group. There was no convincing evidence that these relationships differed between depressed patients treated with imipramine and those treated with fluvoxamine. CONCLUSION: Our findings suggest that alterations in mean heart rate and blood pressure in depressed patients after antidepressant treatment are the result of a combined effect of pharmacological actions of antidepressants and improvement of depressive mood state. The present study did not confirm the relationship between clinical state and cardiovascular variability or baroreflex sensitivity.

Autologous pericardium for ventricular septal defect closure.

BACKGROUND AND AIMS OF THE STUDY: The use of living, untreated autologous pericardium for patch repair in the left ventricular outflow tract was considered attractive in children. METHODS: Ventricular septal defect (VSD) closure with an untreated autologous pericardial patch was performed in 102 children of mean age 13.4 months (range: 1 to 73 months). Postoperative transthoracic Doppler echocardiography was performed in all children at a mean of nine weeks (range: one day to 50 weeks) after surgery. One pericardial patch, which was explanted at autopsy two months after surgery, was studied microscopically. RESULTS: At short-term follow up, no or only minor residual VSD was found in 97 patients, moderate VSD in two and severe VSD in one patient. One patient was reoperated for residual VSD and an aneurysmic patch first diagnosed seven days after surgery. Two more patients showed ballooning of the patch without VSD after five and seven days respectively. All aneurysmic patches were attributed to intraoperative patch oversizing. Patch integrity was confirmed in all other patients. No inflammatory or degenerative changes were observed at microscopy, rather a remodeling response had caused the patch to thicken, indicating an adaptation of the living tissue. CONCLUSIONS: The untreated autologous pericardial patch has shown to be a safe alternative for VSD closure, provided that the patch is properly sized.

Analysis of T cell lines from rejecting renal allografts.

Acute rejection after renal allotransplantation is characterized by the presence of a mononuclear cell infiltrate in the interstitium with involvement of tubuli. In a previous study on renal histology we showed that tubular damage by graft infiltrating cells (GIC) is a sign of clinically significant rejection. We cultured proximal tubular epithelial cells (PTEC) and T cells bearing the interleukin 2 (IL-2) receptor from biopsies after transplantation. In vitro outgrowth of T cells from the biopsy was significantly (P = 0.0014) related to histological signs of graft rejection. Of the T cell lines generated from 25 biopsies, only five lines showed no or low cytotoxicity against donor PTEC. Three cell lines were cytotoxic towards donor PTEC, but not against PHA stimulated donor splenocytes, suggesting tissue specificity of GIC. Treatment of PTEC with interferon (IFN) gamma for 72 hours to upregulate MHC class I and to induce MHC class II expression did not necessarily result in an increased susceptibility to lysis. However, three PTEC lines displayed an increment of susceptibility to lysis after IFN gamma treatment. Analysis of one T cell line from the same graft revealed a high percentage of CD4 positive cells, compatible with a class II restricted cytotoxicity. This was confirmed by blocking experiments using anti-CD4, anti-CD8, anti-class I, and anti-class II antibodies. Blocking experiments were done with 12 of these 25 lines. Anti-CD3 and anti-CD18 antibodies inhibited cytotoxicity in every case, showing that cytotoxicity was T cell mediated.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal allograft-infiltrated lymphocytes and proximal tubular cells: further analysis of donor-specific lysis.

We obtained both graft-infiltrating cells of host origin and proximal tubular epithelial cells (PTEC) of donor origin (using a selective serum-free medium) simultaneously from biopsies of rejecting renal allografts. The identity of PTEC cultures was established with monoclonal antibodies. Major histocompatibility complex class I expression could be upregulated and major histocompatibility complex class II expression induced on PTEC by 24- to 48-hr incubation with 200 U interferon-gamma. Graft-infiltrating cells were shown to lyse PTEC grown from the corresponding biopsy and not PTEC from biopsies from other patients. Therefore the lytic activity appeared to be donor-specific. Preincubation of PTEC with interferon-gamma did not consistently increase PTEC lysis. Lysis by graft-infiltrating cells obtained from four patients could be blocked by target-preincubation with anti-class I monoclonal antibodies, in one case both anti-class I and anti-class II monoclonal antibodies could block PTEC lysis. Blocking could also be obtained with anti-CD3 monoclonal antibody. PTEC lysis occurred only with graft-infiltrating cells cultured from biopsies with cellular interstitial rejection. So, PTEC seem to be a target in renal allograft rejection both in vivo and in vitro. This model system may be useful for further studies of cellular interactions between graft-infiltrating cells and their targets.