Thesis (M.S.)--Bowling Green State University, 2008. / Document formatted into pages; contains ix, 57 p. Includes bibliographical references.

Thesis (M.S.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on April 3, 2009) Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin, 1971. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (doctoral)--University of Tampere, 1984. / Includes previously published articles. Includes bibliographical references (p. 47-56 (1st group)).

Thesis (Ph. D.)--University of Nevada, Reno, 2008. / "December, 2008." Includes bibliographical references. Online version available on the World Wide Web.

The endogenous catecholamines and their metabolites play an integral role in establishing the presence or absence of a suspected sympatho-adrenal tumor. Highly elevated metabolites excreted in the urine are indicative of a tumor. For this reason numerous analytical methods has been developed to accurately quantify the levels of these compounds. However, current methods usually make use of conventional HPLC methods. Although effective, these methods require tedious sample preparation and are usually plagued by interferences. It was the aim of this work to develop a gas chromatographic – mass spectrometric (GC-MS) method that allow for the simultaneous analysis of the endogenous catecholamines, their basic and acidic metabolites using a single extraction procedure (which is easy to use and not tedious) with minimal derivatization steps. Furthermore, to develop GC-MS methods which do not require tedious sample preparation and yet be sensitive and accurate and allow for rapid analysis in the clinical pathology laboratory. Four different gas chromatographic - mass spectrometric methods were developed for the analysis of the catecholamines and their metabolites and are discussed in detail. / Dissertation (MSc)--University of Pretoria, 2009. / Chemical Pathology / unrestricted

Plasma catecholamines have been measured in chronically adrenalectomised (ADX) ducks, in chronically adrenal denervated ducks (DNX), in their respective sham-operated controls (SH-adx, SH-dnx) as well as in intact ducks after 3 minutes forced submergence. The results showed that 100% of the plasma Epinephrine (EP) and 40 to 80% of plasma Norepinephrine (NE) released during the dive came from the adrenal glands. 20 to 60% of plasma NE came from endings of the autonomic vascular sympathetic nerves which are strongly stimulated during diving. Adrenal catecholamines were released by nerve activation only; non neural mechanisms did not play any role in their release. Maximum dive times (MDT) in chronically adrenalectomised ducks (ADX: 5 min. 19 ± 20 sec.) and in chronically adrenal denervated ducks (DNX: 7 min. 10 ± 13 sec.) were significantly lower than in sham-operated controls (respectively SH-adx: 9 min. 58 ± 45 sec., SH-dnx: 12 min. 10 ± 28 sec). Venous infusion of catecholamines in ADX and DNX during the dive increased MDT: MDT of DNX ducks perfused with catecholamines (9 min. 46 ± 20 sec.) were significantly higher than in DNX perfused with saline (7 min. 21 ± 17 sec.), but did not reach the MDT observed in the SH-dnx: other adrenal products must be involved. Diving heart rates of ADX and DNX (at 4 min. dive respectively: 62 ± 16 and 31 ± 2 beats/min.) were significantly higher than in their sham-operated controls (23 ± 3 and 17 ± 2 beats/min.) . Blood pressure during the dive was signifi- cantly lower in ADX and DNX (at 4 min. dive respectively: 93 ± 8 and 98 ± 4 mmHg) compared with their sham-operated controls (131 ± 12 and 118 ± 6 mmHg). Infusion of catecholamines in DNX raised blood pressure towards SH-dnx values, but there was no change in heart rate. PaO₂, CaO₂, pHa and lactate levels in DNX (respectively: 42 ± 2 mmHg, 4.5 ± 0.8 ml 02 /100ml blood, 7.233 ± 0.016, 3.1 + 0.3 mM) were significantly lower than in SH-dnx after 5 minutes submergence (53 ± 1 mmHg, 6.8 ± 0.4 ml 02 /100 ml blood, 7.301 ± 0.007, 4.8 + 0.4 mM). There was also a significant increase of plasma N⁺ (+ 5.4 ± 1.7 mEq/L) in SH-dnx after 5 minutes submergence, but this was not the case in DNX where it was K⁺ (+ 1.1 ± 0.4 mEq/L) which increased. This suggested that adrenal catecholamines increase tolerance to underwater submersion by enhancing peripheral vasoconstriction, thus preserving the O₂ stores for the heart and brain. Moreover, they may affect the acid-base equilibrium during diving by increasing the activity of the Na⁺K⁺ pump and may also have a direct effect on the rate of glycogenolysis. Preventing the actions of catecholamines on the heart by injecting beta-blocker during forced submersion did not decrease MDT; however the cardiovascular response was markedly affected. During beta-blockade, diving heart rate rose steadily from 24 ± 6 beats/minute after 2 minutes to 52 ± 8 beats/minute after 6 minutes diving. In contrast, heart rates remained close to the levels reached at 2 minutes (17 ± 3 and 19 ± 4 beats/minute) throughout the control dives. Perfusion pressure and blood flow have been recorded simultaneously in both hind limbs of ducks. One leg was perfused with different blood mixtures devoid of catecholamines (Test leg) and compared with the other, perfused with the ducks'own blood (autoperfused leg). This showed that hyper-capnia has a depressant effect on the neural component of the peripheral vasoconstriction. Perfusion of test legs with hypoxic-hypercapnic blood to which catecholamines were added, showed that circulating catecholamines are needed to increase peripheral vasoconstriction during diving. In summary, during forced submergence circulating catecholamines, released mainly by the adrenal glands, compensate for the depressant action of hypercapnia on the neural component of peripheral vasoconstriction. Maintenance of this peripheral vasoconstriction during forced diving ensures that O₂ stores are not wasted on peripheral tissues, and this explains how MDT is prolonged. / Science, Faculty of / Zoology, Department of / Graduate

The role of ascending catecholamine systems in the punishing and reinforcing properties of some opiates and stimulant drugs was investigated. In one series of experiments, the reinforcing properties were evaluated through the use of intravenous self-administration procedures while the punishing properties were evaluated through the conditioned taste aversion procedure. In one experiment fifteen rats were trained to press a lever to receive an intravenous injection of cocaine and after this behaviour had stabilized, each rat received bilateral intracerebral injections of the neurotoxin 6-hydroxydopamine (6-OHDA) into the n. accumbens. These lesions produced a marked disruption of cocaine self-administration which in most cases returned to baseline rates after 1-3 weeks. This recovery was found to be negatively correlated with the levels of dopamine (DA) remaining in the n. accumbens (r=-.81). The animals with the severest depletion of DA failed to show recovery of cocaine intake. This disruption of cocaine self-administration behaviour was shown not to be due to a non-specific effect on operant responding, because the same animals which failed to self-administer cocaine continued to self-administer apomorphine at pre-lesion rates. To evaluate whether noradrenergic (NA) mechanisms serve a critical role in cocaine self-administration, four rats received two bilateral injections of 6-OHDA aimed at the dorsal and ventral NA bundles. Despite causing near total depletion of forebrain NA, these lesions did not significantly affect the rate or pattern of cocaine self-administration. These data do not support the hypothesis that forebrain NA mechanisms subserve stimulant-based reinforcement, and the evidence in favor of such a view is discussed. In a separate series of experiments, it was observed that depletion of central DA and NA by intraventricular injections of 6-OHDA severely attenuated a conditioned taste aversion (CTA) induced by amphetamine. This attenuation was not the result of a general learning deficit because animals with identical treatments acquired a CTA when LiCl was used as the punishing stimulus. Selective depletion of hippocampal and cortical NA through intracerebral infusions of 6-OHDA, which spare DA systems, has no effect on an amphetamine-induced CTA. It is, therefore, argued that central DA, rather than NA, mechanisms are involved in the punishing property of amphetamine. The possibility that both the punishing and reinforcing effects of psychomotor stimulants may be mediated by the same systems in the brain is discussed. Depletion of forebrain NA was found to attenuate the CTA induced by 10 mg/kg morphine. This effect suggested some intriguing possibilities regarding NA and the reinforcing and punishing properties of opiates. Self-administration of heroin was not affected, however, by depletion of forebrain NA following 6-OHDA lesions, suggesting that forebrain NA does not play a critical role in opiate reinforcement. The DA receptor blocker, pimozide, was found to produce an apparent blockade of cocaine reinforcement, but pimozide had no effect on heroin self-administration. It therefore appears DA mechanisms are not critical to heroin reinforcement, and that there are multiple systems in the brain which can subserve drug reward. / Graduate and Postdoctoral Studies / Graduate

Rats fed diets which contained 15% of casein and 0.620% of methionine with 0.0002, 0.02 and 0.42% of dietary inorganic sulfate had a dietary sulfate-related change in methionine metabolism. Rats fed the diets low in sulfate (0.0002%) had a 35% increase in methionine metabolism compared to rats fed the diets high in sulfate (0.42%). In contrast, rats fed the diet low in sulfate (0.0002%) had the lowest level of tissue S-adenosyl-methionine and the highest activity of phenylethanolamine-N-methyltransferase activity. Those animals fed the diet normal with respect to sulfate (0.02%) had intermediate levels of S-adenosylmethionine and phenylethanolamine-N-methyl transferase activity. Rats fed the diet high in sulfate (0.42%) had the highest level of tissue S-adenosyl-methionine and the lowest phenylethanol-amine-N-methyl transferase activity. Due to the inverse relationship between S-adenosylmethionine and phenylethanolamine-N-methyl transferase activity, it appears that the catecholamines may function as a methyl sink for the increase in the metabolism of methionine required to provide sulfate for rats fed diets low in sulfate.

Background-High catecholamine concentrations are cytotoxic to cardiac myocytes. We hypothesized that myocardial interstitial catecholamine levels are greatly elevated immediately after long-duration ventricular fibrillation (VF), defibrillation, and reperfusion and that the short-acting β-antagonist esmolol administered at reperfusion would protect against this catecholamine surge and improve survival. Methods and Results-In part 1 of this study, catecholamines from myocardial interstitial fluid (ISF) and aortic and coronary sinus plasma were quantified by use of 3H-labeled radioenzymatic assay in 8 open-chest, anesthetized pigs. Eight minutes of electrically induced VF was followed by internal defibrillation and reperfusion. By 4 minutes of VF, ISF norepinephrine increased significantly, from 1.3±0.3 to 7.4±2.4 ng/mL. Epinephrine increased significantly, from 0.4±0.2 to 1.5±0.7 ng/mL. ISF norepinephrine and epinephrine peaked at 219.2±92.1 and 63.7±25.1 ng/mL after defibrillation and reperfusion and decreased significantly to 12.2±3.5 and 6.7±3.1 ng/mL 23 minutes after defibrillation. Transcardiac catecholamine changes were similar. In part 2, 8 minutes of VF was followed by external defibrillation in anesthetized, closed-chest pigs. Animals received 1.0 mg/kg esmolol (n=8) or saline (n=8) intravenously at the start of cardiopulmonary resuscitation (CPR). Advanced cardiac life support, including CPR and epinephrine, was delivered to both groups. Esmolol before reperfusion improved return of spontaneous circulation and 4-hour survival (7/8 versus 3/8 survivors, χ2 P<0.05). Conclusions-Transcardiac and ISF norepinephrine and epinephrine levels are briefly massively elevated after 8 minutes of VF, defibrillation, and reperfusion. A short-acting β-antagonist administered immediately after defibrillation improves return of spontaneous circulation and 4-hour survival after this prolonged VF.