RESUMEN
Nausea is a common disease symptom, yet there is no consensus regarding its physiological markers. In contrast, the process of vomiting is well documented as sequential muscular contractions of the diaphragm and abdominal muscles and esophageal shortening. Nausea, like other self-reported perceptions, is difficult to distinguish in preclinical models, but based on human experience emesis is usually preceded by nausea. Here we focused on measuring gastrointestinal and cardiorespiratory changes prior to emesis to provide additional insights into markers for nausea. Felines were instrumented to chronically record heart rate, respiration, and electromyographic (EMG) activity from the stomach and duodenum before and after intragastric delivery of saline or copper sulfate (CuSO4, from 83 to 322 mg). CuSO4 is a prototypical emetic test agent that triggers vomiting primarily by action on GI vagal afferent fibers when administered intragastrically. CuSO4 infusion elicited a significant increase in heart rate, decrease in respiratory rate, and a disruption of gastric and intestinal EMG activity several minutes prior to emesis. The change in EMG activity was most consistent in the duodenum. Administration of the same volume of saline did not induce these effects. Increasing the dose of CuSO4 did not alter the physiologic changes induced by the treatment. It is postulated that the intestinal EMG activity was related to the retrograde movement of chyme from the intestine to the stomach demonstrated to occur prior to emesis by other investigators. These findings suggest that monitoring of intestinal EMG activity, perhaps in combination with heart rate, may provide the best indicator of the onset of nausea following treatments and in disease conditions, including GI disease, associated with emesis.
RESUMEN
Considerable evidence shows that the vestibular system contributes to adjusting sympathetic nervous system activity to maintain adequate blood pressure during movement and changes in posture. However, only a few prior experiments entailed recordings in conscious animals from brainstem neurons presumed to convey baroreceptor and vestibular inputs to neurons in the rostral ventrolateral medulla (RVLM) that provide inputs to sympathetic preganglionic neurons in the spinal cord. In this study, recordings were made in conscious felines from neurons in the medullary lateral tegmental field (LTF) and nucleus tractus solitarius (NTS) identified as regulating sympathetic nervous system activity by exhibiting changes in firing rate related to the cardiac cycle, or cardiac-related activity (CRA). Approximately 38% of LTF and NTS neurons responded to static 40° head up tilts with a change in firing rate (increase for 60% of the neurons, decrease for 40%) of ~50%. However, few of these neurons responded to 10° sinusoidal rotations in the pitch plane, in contrast to prior findings in decerebrate animals that the firing rates of both NTS and LTF neurons are modulated by small-amplitude body rotations. Thus, as previously demonstrated for RVLM neurons, in conscious animals NTS and LTF neurons only respond to large rotations that lead to changes in sympathetic nervous system activity. The similar responses to head-up rotations of LTF and NTS neurons with those documented for RVLM neurons suggest that LTF and NTS neurons are components of the vestibulo-sympathetic reflex pathway. However, a difference between NTS/LTF and RVLM neurons was variability in CRA over time. This variability was significantly greater for RVLM neurons, raising the hypothesis that the responsiveness of these neurons to baroreceptor input is adjusted based on the animal's vigilance and alertness.
