A rodent model of syncope: the effects of a CRH antagonist

Abstract

Vasovagal syncope is accompanied by profound bradycardia, hypotension, and subsequent unconsciousness. Male Sprague Dawley rats exhibited these cardiovascular changes in response to swim stress; 50% of rats exposed to a cylindrical tank filled with 30 cm of 25°C water sank below the surface and failed to rise, requiring rescue. Sinking rats exhibited more severe bradycardia within 30 minutes of water immersion compared with non-sinkers (average minimum HR (bpm) ±SEM; 143±13 vs. 247±14). Cardiac vagal activity, as measured by PR interval, was also elevated to a greater extent in rats that sank; PR (msec ±SEM) increased from 51±1 to 76±1.5 in non-sinking and to 95±3.5 in sinking rats. Blood pressure changes also suggest sinking may be a manifestation of experimentally-induced syncope in rodents; mean arterial pressure dropped by 40 (±6) mmHg 10 seconds prior to sinking, whereas this effect failed to occur in non-sinkers. Antalarmin (32 mg/kg), a non-peptidic CRH-1 receptor antagonist, produced extreme bradycardia (135±11 bpm) and elevated vagal activity (PR: 106±4 msec) during water exposure, leading to sinking in all rats. The cardiovascular and behavioral consequences that led to sinking in untreated and antalarmin-treated rats were blocked by methylatropine confirming a vagally-mediated action at the sinoatrial node. We conclude that antalarmin facilitates these syncope-like cardiovascular events, and we suggest that differences in CRH dynamics may be related to disposition to syncope. Research supported by USPHS Grants DA14349 and GM07767