Role of protons in activation of cardiac sympathetic C‐fibre afferents during ischaemia in cats

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Abstract
1 Chest pain caused by myocardial ischaemia is mediated by cardiac sympathetic afferents. The mechanisms of activation of cardiac afferents during ischaemia remain poorly understood. Increased lactic acid production is associated closely with myocardial ischaemia. The present study examined the role of protons generated during ischaemia in activation of cardiac sympathetic C-fibre afferents. 2 Single-unit activity of cardiac afferents innervating both ventricles was recorded from the left sympathetic chain in anaesthetized cats. Epicardial tissue pH was measured within 1-1.5 mm of the surface by a pH-sensitive needle electrode. Responses of cardiac afferents to myocardial ischaemia, lactic acid, sodium lactate, acidic phosphate buffer and hypercapnia were determined. 3 Occlusion of the coronary artery for 5 min decreased epicardial tissue pH from 7.35 ± 0.21 to 6.98 ± 0.22 (P < 0.05). Epicardial placement of isotonic neutral phosphate buffer, but not saline, prevented the ischaemia-induced decrease in epicardial pH. This manoeuvre significantly attenuated the response of 16 afferents to 5 min of ischaemia (1.56 ± 0.23 pre-treatment vs. 0.67 ± 0.18 impulses s−1). Topical application of 10-100 μg ml−1 of lactic acid, but not sodium lactate, concentration-dependently stimulated 18 cardiac afferents. Inhalation with high-CO2 gas failed to activate 12 separate cardiac afferents. Furthermore, lactic acid stimulated cardiac afferents to a greater extent than acidic phosphate buffer solution, applied at a similar pH to the same afferents. 4 Collectively, this study provides important in vivo evidence that protons contribute to activation/sensitization of cardiac sympathetic C-fibre afferents during myocardial ischaemia.