Effects of serotonin and the 5-HT2/1C receptor agonist DOI on neurons of the cerebellar dentate/interpositus nuclei: possible involvement of a GABAergic interneuron.

The present study was designed to examine the effects of iontophoretically applied serotonin (5-HT) on neurons of the cerebellar dentate/interpositus nuclei in an in vitro slice preparation and to determine if the 5-HT2/1C receptor subtype could be responsible for mediating any effects noted with 5-HT. 5-HT and the 5-HT2/1C-selective agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) were iontophoretically applied alone and during superfusion of the 5-HT2/1C-selective antagonist, ritanserin. 5-HT and DOI elicited either inhibition or excitation of the spontaneous activity of dentate/interpositus neurons. An inhibitory response was induced by both compounds in the majority of cells responding. Ritanserin significantly attenuated the inhibitory response elicited by both 5-HT and DOI. In addition, the inhibitory response to DOI was significantly attenuated by the gamma-aminobutyric acid (GABA) antagonists, bicuculline and picrotoxin. Our results suggest that the 5-HT2/1C receptor subtype may be partially responsible for mediating 5-HT-induced inhibition of dentate/interpositus neurons, possibly via activation of GABAergic interneurons.

Platelet-rich plasma sequestration, with therapeutic platelet yields, reduces allogeneic transfusion in complex cardiac surgery.

UNLABELLED: Platelet dysfunction is the most common cause of nonsurgical bleeding after cardiopulmonary bypass (CPB). We hypothesized that reinfusion of a therapeutic quantity of platelets sequestered before CPB would decrease the need for allogeneic platelet transfusion, as well as decrease bleeding and total allogeneic transfusion, in cardiac surgery patients at moderately high risk for bleeding. Fifty-five patients undergoing either reoperative coronary artery bypass (CABG) or combined CABG and valve replacement were randomized to control or platelet-rich plasma sequestration (pheresis) groups. All patients received intraoperative epsilon-aminocaproic acid infusions. There was no significant difference between groups with respect to preoperative characteristics, duration of CPB, or target postoperative hematocrit. Mean platelet yields were 6.2 +/- 2.1 units (3.1 x 10(11) platelets). Mean pheresis time was 44 min. Allogeneic platelets (range = 6-12 units) were transfused to 28% of control patients, compared with 0% of pheresis patients (P < 0.01). Allogeneic packed red blood cells were transfused to 45% of control patients (1.2 units per patient) versus 31% of pheresis patients (0. 7 unit per patient) (P = 0.35). Total allogeneic units transfused were significantly reduced in the pheresis group (P < 0.02). Mediastinal chest tube drainage was not significantly decreased in the pheresis group. In this prospective, randomized study, therapeutic platelet yields were obtained before CPB. In contrast with recent studies with low platelet yields, these data support the conclusion that platelet-rich plasma sequestration is effective in reducing allogeneic platelet transfusions and total allogeneic units transfused in cardiac surgery patients at moderately high risk for post-CPB coagulopathy and bleeding. IMPLICATIONS: Transfusion of allogeneic blood products, including platelets, is common during complex cardiac surgical procedures. In the present prospective, randomized study, a significant reduction in allogeneic platelet transfusion and total allogeneic units transfused was observed after the reinfusion of a therapeutic quantity of autologous platelets sequestered before cardiopulmonary bypass.