Date of Award
Doctor of Philosophy (PhD)
Trauma is the leading cause of death of young people in the United States. Most such deaths result either from the initial blood loss or from secondary reperfusion injury following resuscitation.
Currently, the standard treatments for hypovolemic shock include volume resuscitation and using of vasoconstrictors to raise pressure. However, these treatments can exacerbate reperfusion injury, and require technical care when apply to patients. Therefore, novel therapies that can safely restore perfusion pressure are needed.
Our lab has found that 5-HT1A-receptor agonist, 8-OH-DPAT, increases perfusion pressure and improves acid-base balance in hypovolemic rats by stimulation of sympathetic-mediated increases in venous tone. These data suggest that 8-OH-DPAT may be a promising adjuvant agent in resuscitation. We have also found that 8-OH-DPAT administered into the IVth cerebroventricle in the vicinity of the nucleus tractus solitarius (NTS) rapidly increases normal perfusion pressure following hemorrhage in unanaesthetized rats. This result indicates that 8-OH-DPAT may act in the NTS to mediate its effect. Studies have also shown that serotonin neurons are activated and promoted ventilatory responses during hemorrhage. However, it was not known if endogenous serotonin influenced sympathetic and ventilatory responses to hemorrhage.
This dissertation was to investigate the overall hypothesis that hindbrain serotonergic neurons activate 5-HT1A receptors in the nucleus tractus solitarius (NTS) to modulate sympathetic recovery following hypotensive hemorrhage. Aim one was to determine if caudal hindbrain serotonin neurons are necessary for normal sympathetic and ventilatory responses during hemorrhage. We found that central serotonin neurons maintaining cardiac output and suppressing increases in peripheral resistance similarly as 8-OH-DPAT was found to do. The second aim was to determine if 8-OH-DPAT acted on the 5-HT1A autoreceptors to exert its effect. Instead, we found that the drug acts on post-synaptic receptors since the effects of the drug were exactly the same in serotonin lesion and sham-lesioned rats. In the third aim we determined if serotonin nerve terminals in the NTS were necessary for normal sympathetic and ventilatory responses to blood loss. We found that selective serotonin nerve terminals lesion in the NTS suppressed both sympathetic and ventilatory responses to hemorrhage and as well as to hypoxia.
Kung, Ling-Hsuan, "Hindbrain Serotonin Neurons Activate 5-HT1A Receptors in the Nucleus Tractus Solitarius (NTS) to Modulate Sympathetic and Ventilatory Recovery Following Hypotensive Hemorrhage" (2010). Dissertations. 189.
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Copyright © 2010 Ling-Hsuan Kung