Date of Graduation


Document Type


Degree Type



School of Medicine


Physiology, Pharmacology & Neuroscience

Committee Chair

David A. Taylor.


After much early debate, it is now well recognized that the origin of the heart beat is myogenic, or intrinsic, to the heart. It has been felt that the intrinsic heart rate (IHR) is constant and that the observed heart rate is controlled by tonal alterations in the activity of the autonomic nervous system in response to various stimuli. Some investigators have recognized, however, that the intrinsic heart rate (IHR) can be altered in certain conditions. Sepsis, or the host response to bacterial infection, is recognized as a stress to the host that results in decreased myocardial contractility and tachycardia. Some previous work has suggested that this tachycardia may exist outside the tonal regulation of the autonomic nervous system, raising the possibility of an elevation of the IHR. Utilizing an E. coli lipopolysaccharide (LPS) endotoxin model of sepsis in the rat, this work demonstrates an elevation of the IHR in sepsis. The experimental evidence further suggests that the beta-adrenoceptor participates in the induction of the elevation in IHR early in the septic process. By sixteen hours after LPS administration the beta-adrenoceptor is, however, no longer required for the ongoing elevation of IHR. It is also demonstrated that the elevation in IHR is more prolonged than the contractile dysfunction induced by LPS.