The role of platelet aggregation and release in fragment D-induced pulmonary dysfunction.
The plasma concentration of fibrinogen degradation product D (fragmentt D) is markedly incrased following major burn or traumatic injury. Purified human fragment D infused into awake, restrained, nontraumatized rabbits (100 micrograms/ml blood) causes progressive thrombocytopenia, pulmonary dysfunction, vascular leak, and interstitial neutrophilia. Rabbits treated with the antihistamine diphenhydramine (Benadryl) prior to fragment D infusion fail to develop these symptoms. This study examined platelet aggregation, platelet ATP secretion, and platelet malondialdehyde release in rabbits which received fragmen D alone or fragment D following diphenhydramine pretreatment. Platelet-rich plasma was prepared from citrated blood drawn from femoral arterial catheters at 0, 2 1/2, and 4 hours postinfusion. Platelet aggregation was stimulated with either collagen or ADP. Malondialdehyde, a byproduct of thromboxane synthesis, was measured by colorimetry. Platelet aggregation and function (stimulated with collagen) were enhanced in fragment D platelet-rich plasma, since all response times decreased. Total ATP and MDA release incresed. Diphenhydramine pretreatment inhibited fragment D-enhanced aggregation, ATP release and prostaglandin (thromboxane) synthesis. No animal pretreated with diphenhydramine exhibited thrombocytopenia or respiratory dysfunction. Stimulation of platelet aggregation and release may represent one mechanism by which fragment D induces pulmonary dysfunction. Diphenhydramine inhibits these responses and may prove therapeutic in posttraumtic pulmonary complications.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D004155:Diphenhydramine / Q000627:therapeutic use; D004347:Drug Interactions; D005338:Fibrin Fibrinogen Degradation Products / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D008315:Malondialdehyde / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D011292:Premedication; D011817:Rabbits; D012131:Respiratory Insufficiency / Q000209:etiology* / Q000517:prevention & control; D013921:Thrombocytopenia / Q000209:etiology / Q000517:prevention & control
D005338:Fibrin Fibrinogen Degradation Products; C015214:fibrinogen D fragment; D008315:Malondialdehyde; D000244:Adenosine Diphosphate; D004155:Diphenhydramine; D000255:Adenosine Triphosphate; D003094:Collagen