Role of activated platelets in excitation of cardiac afferents during myocardial ischemia in cats.
Myocardial ischemia activates cardiac spinal afferents that mediate chest pain and excitatory reflex cardiovascular responses. Platelets are activated during myocardial ischemia and release 5-hydroxytryptamine, which stimulates abdominal spinal afferents. This study investigated the role of activated platelets in excitation of cardiac spinal afferents during ischemia. Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were obtained from cats and incubated with collagen (2 mg/ml) or thrombin (5 U/ml). We observed reduction of platelets in PRP indicative of platelet activation by collagen and thrombin, respectively. Activity of single-unit, ischemia-sensitive cardiac spinal afferents was recorded from the left sympathetic chain in anesthetized cats. Injection of 1.5 ml PRP + collagen (activated platelets) into the left atrium (LA) stimulated 12 of 13 cardiac afferents. PRP + saline (nonactivated platelets, LA) and PPP + collagen did not alter activity of these afferents. PRP + thrombin (1.5 ml, LA) stimulated eight of nine other cardiac afferents, whereas PPP + thrombin did not stimulate any of the nine afferents. Antiplatelet immune serum (1 ml/kg iv) significantly decreased circulating platelets as well as neutrophils (polymorphonuclear leukocytes, PMNs) in eight other cats, and in each animal, attenuated the ischemia-related increase in activity of cardiac afferents. Conversely, responses of five separate cardiac afferents to ischemia were not diminished after treatment with anti-PMN immune serum when concentration of circulating platelets was maintained by infusion of donated PRP despite the decrease in circulating PMNs. These data indicate activated platelets stimulate ischemia-sensitive cardiac spinal afferents and contribute to activation of these afferents during ischemia.
Fu
Liang-Wu
LW
Department of Medicine, College of Medicine, C240 Medical Sciences I, University of California, Irvine, CA 92697-4075, USA. kwfu@uci.edu
Longhurst
John C
JC
D000344:Afferent Pathways / Q000503:physiopathology*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002415:Cats; D003094:Collagen / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006321:Heart / Q000294:innervation*; D007106:Immune Sera / Q000494:pharmacology; D007958:Leukocyte Count; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000503:physiopathology*; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D015539:Platelet Activation; D010976:Platelet Count; D011817:Rabbits; D012701:Serotonin / Q000097:blood; D013116:Spinal Cord / Q000503:physiopathology; D013917:Thrombin / Q000494:pharmacology
D007106:Immune Sera; D012701:Serotonin; D003094:Collagen; D013917:Thrombin