Abstract
Central baroreflex interruption, cardiac toxicity, and sudden death
The FASEB journal, Vol.20(4), pp.A738-A738
03/2006
DOI: 10.1096/fasebj.20.4.A738-c
Abstract
Killing nucleus tractus solitarii (NTS) neurons expressing neurokinin‐1 (NK‐1) receptors attenuates baroreflex responses and leads to sudden death within 2 weeks in 33% of treated rats. We hypothesized that cardiac toxicity appears after development of arterial pressure (AP) lability, an index of baroreflex dysfunction. To test the hypothesis we injected stabilized substance P‐saporin (SSP‐SAP; N=9) or vehicle (N=4) bilaterally into the NTS of anesthetized rats that were instrumented to continuously monitor AP, electrocardiographic activity (ECG), body temperature, and motility. Lability of AP, present one day postoperatively, reached a maximum by day 7. One rat died suddenly on day 9. Its ECG was normal until 8 minutes prior to death when it evolved through T wave abnormalities, ventricular ectopic beats, and finally asystole. Its motor activity and temperature changed only at the time of the final cardiac arrhythmia. In other animals at day 10 we performed echocardiography, which revealed normal cardiac output and no segmental defects in cardiac motility. Pathologic examination of hearts revealed multifocal small areas of acute coagulation necrosis and larger areas of more advanced subendocardial necrosis. Coronary arteries were patent and unrelated to cardiac changes. The cardiac changes found in this rat model mimic those seen in humans with central lesions.
Support: NIH HLR01‐59593 and VA Merit Review.
Details
- Title: Subtitle
- Central baroreflex interruption, cardiac toxicity, and sudden death
- Creators
- Ameya P Nayate - NeurologySteven A Moore - PathologyRobert M Weiss - University of IowaLi‐Hsien Lin - NeurologyWilliam T Talman - Neurology
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.20(4), pp.A738-A738
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.20.4.A738-c
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Grant note
- VA Merit Review NIH (HLR01‐59593)
- Language
- English
- Date published
- 03/2006
- Academic Unit
- Neurology; Cardiovascular Medicine; Internal Medicine; Pathology
- Record Identifier
- 9984363438502771
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