DISSERTATION (PH.D.)--THE UNIVERSITY OF MICHIGAN / CHAIRMAN: VINCENT G. ZANNONI

DISSERTATION (PH.D.)--THE UNIVERSITY OF MICHIGAN

DISSERTATION (PH.D.)--THE UNIVERSITY OF MICHIGAN

Thesis (Ph.D.)--University of California, San Francisco, 2010. / Source: Dissertation Abstracts International, Volume: 71-02, Section: B, page: . Adviser: Leslie Z. Benet.

DISSERTATION (PH.D.)--THE UNIVERSITY OF MICHIGAN

DISSERTATION (PH.D.)--THE UNIVERSITY OF MICHIGAN / CHAIR: JOHN G. WAGNER

DISSERTATION (PH.D.)--THE UNIVERSITY OF MICHIGAN

A major determinant of myocardial infarct size (IS) is the amount of myocardium at risk of infarcting (AAR). When determined in vivo, AAR size depends upon the size of the normal perfusion territory of the occluded bed and upon collateral flow. We tested the hypothesis that AAR size can change spontaneously or after therapy. $\sp{\rm 99m}$Tc macroaggregates (MAC) or Monastral Blue Dye (MBD) were used to define the AAR. After MBD, the hearts were excised, sliced, photographed and incubated in Nitro-Blue tetrazolium to identify the infarct. After rephotographing, the slices were autoradiographed. The two sets of photographs and autoradiographs were used for planimetery of the AAR as defined by MBD, infarct size, and AAR as defined by MAC respectively. In all 3 groups there was a correlation between the AAR sizes as determined by the two techniques. In this model, the AAR size does not change either spontaneously or following Nicardipine. Nicardipine also does not appear to substantially limit infarct size. (Abstract shortened by UMI.)

We investigated in Wistar rats (1) the effectiveness of peripheral administration of two AT1-receptor blockers (losartan and embusartan) to cause central AT1-receptor blockade, and (2) whether chronic peripheral treatment with losartan or embursartan can exert sufficient central effects to prevent the central effects of ouabain and sodium. In the first set of experiments, losartan or embursartan at 30 and 100 mg/kg were administered subcutaneously (sc) as a single dose or 1 dose daily for 6 days. The BP responses to intracerebroventricular (icv) injection of Ang II, icv infusion of Na +-rich aCSF (0.3 M NaCl) and intravenous (iv) injection of Ang II were then measured. In the second set of experiments, losartan or embusartan (both at 100mg/kg/day) were given se once daily for 16 days. Ouabain or sodium-rich aCSF were given in these groups of rats by osmotic minipump for 13--14 days. The mean arterial pressure (MAP) at rest and in response to air stress, and icv injection of guanabenz (75 mug/7.5 mul, and 25 mug/2.5 mul), Ang II (30 ng/3 mul) and ouabain (0.5 mug/2 mul) at a 10 minutes interval were then measured. (Abstract shortened by UMI.)

The ethnopharmacological use of Panax quinquefolius L. (American ginseng) led to assessment of the immunostimulating properties of this eastern North American herb, and to investigate the phytochemical variation in its associated North American Araliaceae relatives. An analysis of the effect of different processing methods on ginsenoside content, a determination of the bioactive compounds in ginseng, and testing of an HPLC method were also undertaken in this thesis. A survey of wild North American P. quinquefolius populations showed phytochemical variation exemplified by differences in the levels of major ginsenosides between populations. The investigation of the phytochemical variation in eastern North American Araliaceae revealed the presence of ginsenosides in Aralia nudicaulis L. (Wild sarsaparilla) and Aralia racemosa L. (Spikenard). Major ginsenosides were also quantified in P. quinquefolius stem, and the ginsenoside-Rb2 was shown to be a significant saponin in P. quinquefolius leaves. Although the results obtained for system suitability, intea-laboratory repeatability, and inter-laboratory reproducibility were generally consistent among the collaborators, the HPLC method was held not to be rigorous enough for the analysis of Rg1 and Re. The second investigation of ginsenoside analyses examined the effect of different processing methods. The results for this investigation indicated that the most promising processing method for obtaining the highest levels of total ginsenoside content and the best quantities of Rb1, Rg1 and Rd was drying at high temperature, as performed to obtain white ginseng. A pre-steam treatment before drying to obtain red ginseng and particularly freeze-drying yielded lower ginsenoside levels. Aqueous extracts from a four-year old cultivated root significantly stimulated the release of immunoreactive tumour necrosis factor alpha (TNFalpha) in culture. The crude extractable polysaccharide fraction was analysed, and was found to contain glucose, uronic acid, galactose, arabinose, rhamnose, fucose and mannose. (Abstract shortened by UMI.)