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by Kwok-keung Chan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (p. 177-195). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Physiology / Master / Master of Philosophy

To determine differences in A1- and A2-selective adenosine effects on coronary endothelium, isolated rabbit hearts (n = 18) were perfused with erythrocyte-enriched buffer at constant left ventricular volume and physiologic flow rates. After 10-20 minutes of stabilization, the perfusate was changed to contain an A1-selective agonist (N6-cyclopentyladenosine, CPA; high dose, 4.26 X 10-7M or low dose, 10-8M), or an A2-selective agonist ((5'-(N-cyclopropyl) carboxaminoadenosine, CPCA; high dose, 4.45 X 10-6M or low dose 10-7 M). Before and during each treatment period of 1-15 minutes aortic and left ventricular pressures and rates of change were recorded. Hearts were then perfused intravascularly with ruthenium red stain (RR) dissolved in filtered 2.5% glutaraldehyde, and processed by routine electron microscopic methods for ultrastructural examination. Of the hemodynamic parameters measured only aortic pressure increased with CPA, and decreased with CPCA, indicating the expected pharmacologic efficacy at the doses used. However, no observable differences in RR uptake was noted between hearts that received no adenosine agonist and either low- or high-dose CPA. CPCA-treated hearts had noticeable RR uptake into endothelium with both low and high dose levels, with a marked uptake in hearts receiving high doses of this A2 agonist. These results provide direct morphological evidence that supports the concept that endothelial macromolecular uptake is an adenosine A2-mediated process.

The effect of carbonylcyanide m-chlorophenylhydrazone (CCCP) on the performance of isolated retrograde-perfused rabbit hearts was investigated in the present study. CCCP was first investigated as the blocking agent of photosynthesis. CCCP is also commonly used as the metabolic inhibitor of energy production. The animals were heparinized and anesthetized, the hearts were quickly removed and perfused with Krebs-Henseleit buffer in Langendorff's mode. Two parallel perfusion systems were used to distinguish the control and the treated heart. Two different concentrations of CCCP, low-dose (0.1 μM) and high-dose (0.5 μM), were used to study the dose-dependent relationship. The hemodynamic parameters used in the present study are aortic pressure (AOP), end diastolic pressure (EDP), peak systolic pressure (PSP), left ventricular developed pressure (LVDP), the rate of change of left ventricular pressure (positive dP/dt & negative dP/dt), and heart rate (HR). In general, CCCP impaired the mechanical performance of the heart by decreasing cardiac contractility. Positive and negative dP/dt were decreased 49.4% and 55.6%, respectively, by the low-dose of CCCP. High-doses of CCCP also decreased positive dP/dt and negative dP/dt by 81.4% and 88.9%, respectively. In addition, low-dose CCCP caused decreases of peak systolic pressure and left ventricular pressure developed by 50.4% and 61.6%. Similarly, high-dose CCCP decreased PSP and LVDP by 74.8% and 92.5%, respectively. The end diastolic pressure was increased 66.8% by low-dose CCCP. CCCP had no significant effects on aortic pressure and the heart rate. In conclusion, CCCP impaired the mechanical performance of the isolated perfused hearts as evidenced by decreasing PSP, LVDP, positive dP/dt and negative dP/dt. This degradation of myocardial performance showed a dose-dependent relationship. CCCP also caused a higher incidence rate of arrhythmia. Because CCCP uncoupled the electron transport from the ATP production in the mitochondria, the present study suggested that the development of contracture and heart failure was due to the energy depletion by CCCP.

Chow Tsun Cheung, Louis. / "May 2000." / Thesis (M.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

The mechanical and biochemical effects of prostaglandins E₁ and F₁α were studied on rat heart using isolated right and left atria and the Langendorff perfused whole heart preparation. Preliminary experiments were performed to establish optimal perfusion conditions for the Langendorff preparation. Hearts were perfused at different perfusate temperatures and at different filling pressures. Heart rate and coronary flow rate were monitored at all combinations of perfusate temperature and filling pressure. A constant temperature water recirculating pump setting of 38°C and a filling pressure of 40 cm of H₂O were chosen as the optimal perfusion conditions. Hearts perfused under the above conditions responded normally to bolus injections of isoproterenol. Isoproterenol produced a dose dependent increase in the contractile force of the Langendorff preparation and the cyclic AMP increasing effect of isoproterenol preceeded the positive inotropic effect in a time course study. Prostaglandin E₁ (PGE₁) did not produce any effect on heart rate or tension development in the Langendorff preparation, when infused over a dose range of 0.03 Ug to 5.0 μg/min. Infusion of prostaglandin F₁α (PGF₁α) (0.1 to 5.0 μg/min) produced an increase in tension development which was associated with a negative chronotropic effect. The positive inotropic effect of PGF₁α was secondary to the drop in rate as the positive inotropic effect was completely abolished when the hearts were paced at 6 Hz. In the rat right atrium, PGE₁ produced a dose dependent increase in the rate which developed very slowly. PGE₁ had no effect on the tension development of the.rat left atrium. PGF₁α produced a slow, dose dependent positive chronotropic effect on the right atrium and a slight but not significant effect on the force of contraction of the left atrium. Both prostaglandins were equipotent in exerting their positive chronotropic effect on the right atrium. The PD₁ value for PGE₁ was 5.54 ±0.25 and for PG₁α 5.59 ± 0.18. In the right atrium 10⁻⁴ M PGE₁ increased the rate and cyclic AMP content without changing phosphorylase a activity or cyclic GMP content. PGE₁ (10⁻⁴M) slightly but not significantly increased the left atrial cyclic AMP con-; tent and did not change the cyclic GMP content. 10⁻⁴ M PGF₁α did not affect either right or left atrial cyclic AMP or cyclic GMP content. The effect of a 1 μg/min infusion of either PGE₁ or PGF₁α on the changes of cyclic AMP and cyclic GMP contents and phosphorylase a activity with time were studied in the Langendorff preparation. A 1 μg/min infusion of PGE₁ increased the myocardial cyclic AMP levels by about 57 per cent above control at 30 sees after starting the infusion and the cyclic AMP levels were still elevated by 50 per cent over control at the end of a one minute period of infusion. PGE₁ did not change cyclic GMP content or phos-phorylase a activity at any time point. A 1 ug/min infusion of PGF₁α did not alter cyclic AMP and cyclic GMP levels or phosphorylase a activity in the rat heart within one minute. These results supported the earlier reported observation that PGE₁ selectively increased rat myocardial cyclic AMP content without altering myocardial contractile force or phosphorylase a activity. PGE₁ might be selectively increasing a pool of cyclic AMP and activating a cyclic AMP-dependent protein kinase in the cardiac cells that is not associated with contractile force or phosphorylase activation. PGF₁α did not possess this selective effect of PGE₁. Cyclic GMP is not involved in the mediation of the actions of either PGE₁, or PGF₁α, on the rat heart. / Pharmaceutical Sciences, Faculty of / Graduate

Kwok, Ka Ming. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 124-146). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABSTRACT / In English --- p.ii / In Chinese --- p.v / LIST OF TABLES --- p.vii / LIST OF FIGURE --- p.ix / ABBREVIATIONS / For Units --- p.x / For Prefixes of the International System of Units --- p.x / For Terms Commonly Used --- p.xi / Role of research workers --- p.xv / Chapter CHAPTER 1 --- Overview of methylmercury / Chapter 1.1 --- Source of methylmercury --- p.1 / Chapter 1.2 --- Toxicokinetics --- p.3 / Chapter 1.2.1 --- Absorption and distribution --- p.3 / Chapter 1.2.2 --- Half-life --- p.5 / Chapter 1.2.3 --- Metabolism/Biotransformation --- p.5 / Chapter 1.2.4 --- Biochemical mechanism of toxicity --- p.7 / Chapter 1.3 --- Health effects of mercury exposure --- p.9 / Chapter 1.3.1 --- Adult central nervous system --- p.10 / Chapter 1.3.2 --- The developing central nervous system --- p.11 / Chapter 1.3.3 --- Cardiovascular effects --- p.13 / Chapter 1.3.4 --- Immunotoxicity --- p.14 / Chapter 1.4 --- Biomarkers for prenatal exposure --- p.15 / Chapter 1.5 --- MeHg exposure in high risk populations in Hong Kong --- p.17 / Chapter CHAPTER 2 --- Neurocognitive performance / Chapter 2.1 --- Introduction --- p.19 / Chapter 2.1.1 --- New Zealand --- p.20 / Chapter 2.1.2 --- Seychelles --- p.21 / Chapter 2.1.3 --- Faroe Islands --- p.22 / Chapter 2.1.4 --- The Hong Kong situation --- p.23 / Chapter 2.2 --- Method --- p.23 / Chapter 2.2.1 --- Subjects and study design --- p.23 / Chapter 2.2.2 --- Questionnaires --- p.24 / Chapter 2.2.3 --- Hg concentration measurement --- p.25 / Chapter 2.2.4 --- Neurocognitive measurements --- p.26 / Chapter 2.2.4.1 --- Hong Kong - Wechsler Intelligence Scale for Children --- p.27 / Chapter 2.2.4.2 --- Hong King List Learning Test --- p.28 / Chapter 2.2.4.3 --- Test of Everyday Attention for Children --- p.29 / Chapter 2.2.4.4 --- Boston Naming Test --- p.31 / Chapter 2.2.4.5 --- Grooved Pegboard Test --- p.31 / Chapter 2.2.5 --- Statistical analysis --- p.32 / Chapter 2.3 --- Results --- p.33 / Chapter 2.3.1 --- Subject characteristic --- p.33 / Chapter 2.3.2 --- Test results --- p.34 / Chapter 2.3.3 --- Statistical analysis results --- p.35 / Chapter 2.4 --- Discussion --- p.36 / Chapter CHAPTER 3 --- Cardiac autonomic function / Chapter 3.1 --- Introduction --- p.60 / Chapter 3.1.1 --- Mechanism --- p.60 / Chapter 3.1.2 --- The association between HRV and the ANS --- p.61 / Chapter 3.1.3 --- Clinical applications and related studies --- p.63 / Chapter 3.1.4 --- Associations between MeHg exposure & HRV --- p.64 / Chapter 3.2 --- Methods --- p.65 / Chapter 3.2.1 --- Subjects and study design --- p.65 / Chapter 3.2.2 --- Physical and HRV measurement --- p.66 / Chapter 3.2.3 --- Time domain analysis --- p.68 / Chapter 3.2.4 --- Frequency domain analysis --- p.68 / Chapter 3.2.5 --- Non-linear method --- p.69 / Chapter 3.2.6 --- Statistical analysis --- p.70 / Chapter 3.3 --- Results --- p.71 / Chapter 3.3.1 --- Subjects characteristics --- p.71 / Chapter 3.3.2 --- HRV and statistical analysis results --- p.71 / Chapter 3.4 --- Discussion --- p.73 / Chapter CHAPTER 4 --- Immuno-toxicity / Chapter 4.1 --- Introduction --- p.91 / Chapter 4.2 --- Methods --- p.96 / Chapter 4.2.1 --- Subjects and Study Design --- p.96 / Chapter 4.2.2 --- Cytokine measurement --- p.96 / Chapter 4.2.3 --- Reversibility --- p.98 / Chapter 4.2.4 --- Statistical Analysis --- p.99 / Chapter 4.3 --- Results --- p.101 / Chapter 4.3.1 --- Subject Characteristics --- p.101 / Chapter 4.3.2 --- Atopic and non-atopic diseases group --- p.101 / Chapter 4.3.3 --- Cytokine profiles --- p.102 / Chapter 4.3.4 --- Reversibility --- p.103 / Chapter 4.4 --- Discussion --- p.104 / Chapter CHAPTER 5 --- Conclusion --- p.119 / Reference List --- p.124

published_or_final_version / abstract / Physiology / Doctoral / Doctor of Philosophy