Changes in lymphocyte subsets and mitogen responsiveness following open-heart surgery and possible therapeutic approaches.
Septic multi-organ failure represents a common cause for operative mortality following open-heart surgery. One major reason might be the depression of cell-mediated immunity. The purpose of this prospective randomized trial was to quantify and specify the effects of open-heart surgery on cell-mediated immune mechanisms. In addition, the immunorestorative potential of a combined immunomodulatory therapy with the cyclooxygenase inhibitor indomethacin and the thymomimetic substance Thymopentin versus single drug administration of indomethacin was investigated. Twenty patients were given indomethacin for the first 5 postoperative days (group A). Another 20 patients also received Thymopentin perioperatively and on the second and fourth postoperative days (group B), while 20 patients underwent conventional therapy (group C). Cell-mediated immune response was quantified in vitro by measuring CD3+ T-lymphocytes and their subsets, CD4+ T-helper and CD8+ T-suppressor cells. Lymphocyte responsiveness to a specific (Antigen-Cocktail) and non-specific mitogen (phytohemagglutinin) provided information about the quality of cell-mediated immune response. On the first postoperative day CD3+ T-lymphocyte counts and Antigen-Cocktail-induced lymphocyte proliferation decreased significantly in all groups. The number of CD4+ T-Helper cells fell significantly only in groups A and C, while the decrease in group B was not statistically significant; the same applied to phytohemagglutinin-induced lymphocyte response. The CD4+/CD8+ ratio was significantly depressed only in group C, decreased slightly in group A and did not change as compared to baseline values in group B. All investigated parameters remained significantly depressed until the seventh postoperative day in group C.(ABSTRACT TRUNCATED AT 250 WORDS)
Markewitz
A
A
Department of Cardiac Surgery, University of Munich-Grosshadern, Germany.
Faist
E
E
Niesel
T
T
Lang
S
S
Weinhold
C
C
Reichart
B
B
D000368:Aged; D016516:CD4-CD8 Ratio; D006348:Cardiac Surgical Procedures; D004359:Drug Therapy, Combination; D005112:Extracorporeal Circulation; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology; D007213:Indomethacin / Q000494:pharmacology* / Q000627:therapeutic use; D007958:Leukocyte Count; D016131:Lymphocyte Subsets / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy / Q000276:immunology*; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016305:Thymopentin / Q000494:pharmacology* / Q000627:therapeutic use
D016305:Thymopentin; D007213:Indomethacin