Browsing by Subject "cardiovascular system"
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Item Local Enkephalins Modulate Vagal Control of Heart Rate(2001-05-01) Jackson, Keith E.; James L. Caffrey; H. Fred Downey; Michael W. MartinJackson, Keith E., Local Enkephalins Modulate Vagal Control of Heart Rate. Doctor of Philosophy (Biomedical Sciences), May 2001; 112pp; 7 tables; 22 figures; bibliography, 99 titles. Endogenous opioids, such as enkephalins, were first investigated for their ability to modulate pain. A body of evidence now supports opioid actions in many facets of regulation, including the cardiovascular system. Our laboratory is particularly interested in the ability of opioids to modulate autonomic function. Specifically, the role of the endogenous encephalin, methionine-enkephalin-arginine-phenylalanine (MEAP) was investigated to determine its ability to modulate parasympathetic function in the canine. To investigate MEAP’s response in the sinoatrial (SA) node a novel application of microdialysis was employed, whereby microdialysis was employed, whereby microdialysis probes were fabricated as described by Dr. David Van Wylen (38), and implanted in the SA node. After implantation of the probe, there was a significant attenuation of vagal function during the nodal application of MEAP. Specifically, vagally mediated bradcardia was reduced as compared to control, during the nodal application of MEAP. This inhibition of the vagus by MEAP was blocked by naltrindole, a selective delta antagonist. These data suggested that the vagolytic effects of MEAP were elicited via a delta opioid receptor. To test the hypothesis that MEAP’s effects were elicited through a delta opioid receptor mechanism, selective agonists and antagonists for the opioid receptors were utilized. An attenuation of vagal bradycardia was only observed during the infusion of a very selective delta opioid receptor agonist, deltorphin. A mu and kappa agonist showed no significant differences from control. Deltorphin was observed to elicit vagolytic effects in a similar concentration range as MEAP. However, deltorphin was more efficacious that MEAP. There was a significant attenuation of the deltorphin and MEAP’s vagolytic effects, during the co-infusion of the selective delta antagonist, naltrindole. The mu and kappa antagonists were both ineffective. These data further demonstrate that the observed vagolytic effect is linked to a delta opioid receptor. Endogenous MEAP. A series of experiments were undertaken to determine if endogenous MEAP could be demonstrated in the SA node and is so, was it similarly vagolytic. A preconditioning-like protocol was performed to produce intermittent local nodal ischemia to increase the local concentration of endogenous MEAP. The resulting MEAP was measured and was observed to be elevated during the periods of local nodal ischemia and return to control during reperfusion. Contrary to expectations an augmentation of vagal function was observed, during vagal stimulation. The augmented vagal bradycardia was only observed during ischemia, when MEAP was elevated and returned to control during each subsequent reperfusion. Therefore, there was a correlation between elevated MEAP concentrations and augmented vagal bradycardia. The delta antagonist, naltrindole, prevented the augmented vagal response, during nodal ischemia Glibenclamide, a selective KATP channel blocker, partially reversed the augmented vagal response. These data confirm that delta opiate receptors are involved in the augmented vagal bradycardia and that the mechanism may involve the activation of a KATP channel.Item The Effect of Fitness on Cardiac Work with and without Metoprolol(2008-07-01) Hawkins, Megan Nicole; Peter Raven; Michael Smith; Robert MalletHawkins, Megan Nicole, The Effect of Fitness on Cardiac Work with and without Metoprolol. Doctor of Philosophy (Biomedical Science), July 2008; 128 pp; 3 tables; 17 figures; bibliography. Chronic endurance exercise adaptations of the cardiovascular and skeletal muscle systems. The mechanisms by which these adaptations occur, and their effect on the physiological response to exercise, have not been fully elucated. In addition, the classic concept of the role of maximal oxygen consumption (Vo2max) as a parametric index of cardiorespiratory capacity has been questioned. Therefore the purpose of the investigations presented within this dissertation was to: i)retrospectively analyze 156 incremental exercise stress tests and supramaximal exercise tests to verify that VO2 does indeed attain a maximal value; ii)evaluate the effects of cardioselective beta-adrenergic blockade on the ability to maintain cardiac work in average trained and endurance exercise trained subjects during moderate (45% VO2max) and heavy (70% Vo2max) intensity cycling exercise; and iii) determine the effect of aerobic fitness on resting and peak leg vascular conductance and the change in central blood volume observed during the onset of cycling exercise. In the first investigation we demonstrated that highly trained runners capable of maintaining supramaximal workloads achieved a VO2 that rarely exceeded the VO2max value obtained during an incremental exercise stress test. In the second investigation we demonstrated that acute β1-adrenergic receptor (βAR) inhibition reduced cardiac output, cardiac work and cardiac efficiency in endurance trained athletes during moderate and heavy intensity exercise. However, in average trained individuals these same variables were not affected during moderate exercise intensity, but were reduced at heavy intensity exercise. We concluded that βAR blockade impaired the more efficient Frank-Starling mechanism in endurance trained athletes but remained functional in average trained subjects during moderate exercise intensities. In the third investigation we demonstrated that endurance athletes responded to the onset of exercise with a larger increase in central blood volume than average trained individuals. In addition, resting and post-ischemic leg blood glow and leg vascular conductance were greater in the exercise training-induced adaptations of the skeletal muscle vasculature resulted in larger conductance capacity of the working muscle in response to increases in oxygen demand and enabled a greater increase in muscle blood flow from rest to exercise.