Release of platelet-activating factor from rabbit heart perfused in vitro by sera with transplantation alloantibodies.
During "hyperacute rejection" of rabbit heart perfused with transplantation alloantibodies, platelet activating factor (PAF) was released into the coronary effluent, which appeared to have physicochemical and functional properties similar to the 1-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (synthetic PAF) and to PAF obtained from IgE-sensitized rabbit basophils. The release of PAF was associated with an early tachycardia, followed by increasing bradycardia and conduction arrhythmias, as well as decrease of coronary flow and of amplitude of electrogram. The heart stopped beating within 30 min. The release of PAF as well as the "rejection" required the presence of fresh rabbit serum as a source of complement. The PAF receptor antagonist SRI 63-072 in a dose of 0.6 mg, reversed by 70% the reduction of coronary flow within 2-4 min after its addition to the perfusate; ED50 was 0.4 mg. Bradycardia and arrhythmia were reduced; however, the normal electrical activity was only occasionally restored. The cessation of heart action was delayed up to 50 min after the beginning of perfusion with transplantation alloantibodies and complement, but it was not prevented. These results suggest that PAF is released during "rejection" of the heart perfused in vitro with serum containing transplantation alloantibodies in the absence of inflammatory cells and that this mediator is at least in part responsible for the deterioration of cardiac function.
Camussi
G
G
Niesen
N
N
Tetta
C
C
Saunders
R N
RN
Milgrom
F
F
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D005260:Female; D006084:Graft Rejection; D006321:Heart / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D007518:Isoantibodies / Q000008:administration & dosage*; D010477:Perfusion; D010972:Platelet Activating Factor / Q000378:metabolism*; D011817:Rabbits; D016038:Skin Transplantation; D013844:Thiazoles / Q000494:pharmacology
D007518:Isoantibodies; D010972:Platelet Activating Factor; D013844:Thiazoles; C049820:SRI 63072