Cardiac acidosis triggers sympathoexcitation in mice

Cardiac ischemia triggers sympathoexcitation, which is detrimental to the ischemic heart. Acid‐Sensing Ion Channels (ASICs) are highly expressed in cardiac sensory neurons, where they may sense pH changes associated with myocardial ischemia. We propose to use an in vivo murine model to test the role of ASICs in cardiac pH/ischemia‐induced sympathoexcitation. WT mice (C57BL/6, age 8–11 weeks) were anesthetized with sodium pentobarbital, ventilated, and the heart was exposed via thoracotomy. In a first set of experiments, we induced myocardial ischemia by coronary artery ligation and recorded pH on the left ventricle using a micro‐pH probe. After ligation, the pH dropped from 7.4 to an average of 7.0 over 2–3 minutes. In a second set of experiments, saline solutions (50 μL) of varying pH were injected in the pericardium, while blood pressure (BP) was recorded via a carotid artery catheter. Solutions containing a mix of 1μM bradykinin, serotonin, adenosine, histamine and PgE2 (“soup”) at pH 7.4 were used as a positive control. Application of pH 5 increased BP (6.3 ± 0.9 SEM mmHg) when compared to pH 7.4 (1.8 ± 0.3 mmHg, n = 8).“Soup” increased BP by 14.3 ± 2.2 mmHg. Preliminary studies with TRPV1 KO mice showed no significant difference in responses as compared to wild type: BP increased 6.2 ± 1.2 with pH 5, 1.2 ± 0.6 with pH 7.4, and 25.2 ± 4.9 mmHg with “soup”. We present an in vivo murine model to study reflexive hemodynamic changes associated with cardiac acidosis. This model shows reproducible increases in BP with pH 5 application to the heart in WT mice, and will be applied to ASIC KO mice to determine the role of ASICs in cardiac afferent activation and subsequent sympathoexcitation in the setting of myocardial ischemia.