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The purpose of this thesis investigation was to evaluate the effectiveness of dynamic strength training as an additional mode of exercise rehabilitation, in patients with coronary artery disease and well documented evidence of a previous myocardial infarction. The effects of 10 weeks (20 sessions) of combined weightlifting and aerobic training (WtAer) (n=10) were compared with aerobic training (Aer) (n=8) alone, on indices of strength and aerobic exercise capacity in 18 male patients with coronary artery disease (CAD). Initial test(s) performance was similar between groups. Post Aer, the maximum weightlifting strength (1RM) in single-arm curl, single-leg press, and single-knee extension exercises increased by 13% (x = 11.8 to 13.3 kg; P < 0.01), 4% (x = 97 to 101 kg; N.S.), and 5% (x = 28.2 to 29.7 kg; N.S.) respectively; corresponding gains with AerWt were 43% (x = 12.2 to 17.4 kg; P < 0.01), 21% (x = 99 to 120 kg; P <0.01) , and 24% (x = 29 to 36 kg; P < 0.01) . Following Aer the initial 1RM could be lifted an average of 4 times, compared to 14 times after AerWt. Neither Aer nor AerWt showed significant improvements in peak torque in either isokinetic single-knee extension at 90°/s and 180°/s or single-leg press exercise at 30°/s and 75°/s. Maximum progressive incremental cycle ergometer performance (Wmax)increased by 2% with Aer (x = 1088 to 1113 kpm/min; N.S.) and by 15% (x = 1030 to 1180 kpm/min; P < 0.05) with AerWt.Cycling time at 80% of initial Wmax before attaining a Borg RPE of 7 for the legs, increased by 11% (x = 604 to 672s; N.S.) and by 109% (x = 541 to 1128s; P < 0.05) with Aer and AerWt respectively. In these patients with CAD, AerWt was a more effective method of increasing aerobic performance and strength than Aer alone. In order for cardiac exercise rehabilitation therapy to optimize the strength and functional capacities of CAD patients it may be useful to incorporate appropriately monitored weightlifting training into the traditional aerobic exercise regimen. / Thesis / Master of Science (MS)

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13584号 / 論医博第2304号 / 新制||医||1070(附属図書館) / (主査)教授 江木 盛時, 教授 湊谷 謙司, 教授 江藤 浩之 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

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<p>Background: Genome wide association studies (GWAS) performed in Caucasian populations have identified several single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD), although their cumulative impact in other ethnicities is unknown. Using a genetic risk score (GRS), we examined the impact of CAD related SNPs on myocardial infarction (MI) in a multi-ethnic population.</p> <p>Methods: We included 4083 MI cases and 4473 controls from the INTERHEART case: control study, stratified by six ethnic groups: European, South Asian, other Asian, Arab, Latin American, and African. We created a GRS comprised of 25 SNPS, and tested its association with MI in individual ethnicities using logistic regression, and across ethnic groups through meta-analyses. Results were adjusted for age, sex, and modifiable risk factors.</p> <p>Results: The GRS was significantly associated with MI in Europeans (odds ratio [OR] = 1.08, 95% confidence interval [CI] 1.04-1.12 per risk allele), South Asians (OR = 1.09, 95% CI 1.05-1.14), other Asians (OR = 1.09, 95% CI 1.04-1.15), and Arabs (OR = 1.07, 95% CI 1.03-1.12). In Latin Americans and Africans the GRS was not significant. Meta-analysis of ethnic groups demonstrated a 1.06 (95% CI 1.03-1.09) increase in the odds of MI with the GRS per risk allele. Significant heterogeneity was observed, which was reduced by exclusion of Latin Americans (I2=63% to 0%). Above clinical risk factors, the GRS modestly increased population attributable risk (PAR) (0.92 to 0.94), concordance statistic (0.73 to 0.74), net reclassification improvement (0.14), and integrated discriminatory improvement (0.007).</p> <p>Conclusions:<strong> </strong>The GRS was associated with a significant increase in the odds of MI in multiple ethnic groups. Improvements in PAR, discrimination and reclassification were modest above clinical factors.</p> / Master of Science (MSc)

Ascorbate (Asc) is a key antioxidant in preventing cardiovascular dysfunction during diseases exacerbated by altered shear stress. According to the literature endothelial responses to hypotonic shock share some characteristics with those induced by shear stress. Thus to study the physiological responses of endothelium to shear stress, the characterization of the Asc release by pig coronary artery endothelial cells in response to hypotonic shock was performed. The pig coronary artery endothelial cells that had been loaded with ^14C Asc and ^3H deoxyglucose, were exposed to buffers of varying osmolality for different time periods and the release of ^14C Asc and ^3H deoxyglucose was examined. Based on various parameters like relative release of ^14C Asc and ^3H deoxyglucose, their rate of release and protein loss, it was decided to use buffer of .67 percent osmolality for 2 min for these characterization studies. The Asc release was authentic and not a result of membrane damage. The hypotonic shock induced Asc release was not due to endogenously released ATP. The inhibition of ATP induced release by anion channel inhibitors niflumic acid and NPPB was complete but only partial in case of hypotonic shock induced release. The release was not inhibited under nominally Ca^2+ free conditions. Additive release by hypotonic shock and ATP or hypotonic shock and Ca^2+ ionophore A23187 suggests that there are two independent Asc release pathways. Asc release by two different mechanisms may help endothelial cells deal with stressful conditions efficiently and preserve endothelial function. / Thesis / Master of Science (MS)