Role of activated platelets in excitation of cardiac afferents during myocardial ischemia in cats

Abstract

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.

Disruption of the nonneuronal tph1 gene demonstrates the importance of peripheral serotonin in cardiac function

“…A regulatory role of the sympathetic system could provide an explanation of the cardiac dysfunction. The drop in the circulating 5-HT may lead to a decrease or lack of reflex stimulation by sensory nerves and thus result in a loss of contractility, such as that displayed by the tph1 Ϫ/Ϫ mice (49). Therefore, a decompensated state develops which leads to severe heart failure.…”

Bradykinin and thromboxane A2reciprocally interact to synergistically stimulate cardiac spinal afferents during myocardial ischemia

“…Single-unit activity of cardiac afferents was recorded as previously described (8,9). In brief, a midline sternotomy was performed, and the first to seventh left ribs and the left lung were removed.…”

“…Conduction time was determined by measuring the time interval from electrical stimulation to the evoked action potential. Conduction distance was estimated by measuring the length of a wet thread between the receptive field and the recording electrode along the supposed afferent pathway (8,9). Unmyelinated C-fibers and finely myelinated A␦-fibers were classified as those with CVs of Ͻ2.5 and 2.5-30 m/s, respectively.…”

Determinants of baroreflex sensitivity in health and disease:

“…These sites of activation position the activated platelets near baroreceptor and cardiac receptor nerve endings in carotid sinus and heart. Consequently, experimental studies have focused on these sensory nerves as possible sites of action of platelet factors [5,6,[17][18][19][20].…”

“…Serotonin released from platelets activates "sympathetic" afferents innervating the left ventricle [5,6] leading to increased efferent sympathetic activity and decreased arterial BRS [26].…”