ABSTRACT
In vitro studies show serotonin has a profound vasospastic effect on human mesenteric arteries. A similar response has been shown in vivo in atherosclerotic primates. If platelet serotonin stores are released as a consequence of platelet activation during colorectal surgery, a similar effect may significantly alter the perfusion of newly formed anastomoses leading to ischaemia and anastomotic breakdown. Here we have studied the effects of surgery and anaesthesia on intraplatelet and plasma serotonin levels during the peri- and postoperative period following colorectal surgery. A series of six consecutive patients undergoing colorectal resection and anastomosis were selected. Peripheral venous blood samples, taken at specified times before and after surgery and prepared in a platelet stabilizing buffer solution, were analysed using a validated enzyme immunoassay technique. Intraplatelet serotonin levels were seen to fall post-operatively, whilst plasma serotonin levels were shown to rise, implying significant platelet activation and serotonin during the peri-operative period. This study demonstrates the increased bioavailability of serotonin during the peri-operative period in colorectal surgery patients. If the in vitro effects of this amine are mirrored in vivo, increased plasma levels of serotonin may have an important role in anastomotic dehiscence secondary to ischaemia.
ABSTRACT
Milrinone (MIL; a cAMP-specific phosphodiesterase type-III inhibitor), added in vitro to achieve concentrations below the therapeutic levels, inhibited agonist-induced platelet shape change (PSC). Arachidonic acid (AA)-induced PSC was significantly more inhibited by a combination of MIL and indomethacin (INDO; a cyclooxygenase inhibitor) than by either alone. PSC induced by 5-hydroxytryptamine was inhibited by MIL but not by INDO; and this effect of MIL was not augmented by INDO. Whole blood-platelet aggregation (WB-PA) and platelet-rich plasma aggregation induced by potent stimulators of thromboxane A2 (TXA2) synthesis such as AA and calcium ionophore and by less potent agonists (e.g. ADP and U46619) were inhibited by MIL at or near therapeutic concentrations. WB-PA induced by collagen was significantly more inhibited by the MIL and INDO combination than by either of these agents alone whereas with ADP-induced WB-PA no additional effect could be shown when both MIL and INDO were co-incubated. MIL and similar types of drugs may be of benefit in conditions associated with platelet hyperactivity and some of these effects may be enhanced by cyclooxygenase inhibitors.
