心臓の交感および副交感神経分布は部位により異なるため, PTCA中に神経反射によりもたらされる心拍数 (HR) 変動も閉塞枝により異なると考えられる.PTCA中, 心電図でST上昇を認めた62例において, RCA群 (18例) ではBezold-Jarisch反射によると考えられるHR低下を認めたが, LCX群 (10例) は有意なHR変化を認めなかった.一方, LAD群 (34例) はHR単調増加型 (I型) とHR非増加型 (NI型) に分類できた.I型とNI型では年齢・性別・前胸部誘導ST上昇の総和ΣST (mm) に有意差を認めなかったが, I型はNI型よりも有意に心機能が低く, 対側心筋梗塞の合併率・PTCA中の不整脈出現率は有意に高かった.LAD群のHR変化は, 交感および副交感神経の分布の相違と, 虚血・梗塞巣の広がりの相対的関係に依存して, Bezold-Jarisch反射が誘発されたり抑制されたりするためと考えられる.

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We previously reported a clinical study in which (1) Probucol prevented restenosis after coronary angioplasty and (2) Pravastatin reduced the risk of restenosis associated with plasma cholesterol concentration. To examine these mechanism, we analyzed the effect of probucol and pravastatin on the intimal proliferation, the cellular makeup of lesion and the expression of PDGF after balloon injury in rabbits. Probucol study: Probucol was given orally 1.3 g/day from 2 weeks prior to carotid balloon injury to the time of killing (2 or 4 weeks after balloon injury). Probucol remarkably decreased intimal area by 70%, the number of Smooth Muscle Cell (SMC) and Proliferating Cell Nuclear Antigen (PCNA)-labeled cells in the intima. The expression of PDGF-A mRNA was markedly suppressed with probucol treatment. However, probucol did not suppress SMemb expression. SMemb is a good molecular marker for de-differentiated SMC. Probucol is effective in preventing SMC proliferation, which is possibly due to a decrease in the expression of PDGF.
Pravastatin study: Pravastatin was received orally 20mg/day with 0.5% cholestrol diet 2 weeks before iliac balloon injury. After 2 or 4 weeks, the rabbits were killed. Pravastatin reduced plasma cholesterol concentration, neointimal macrophage content and intimal area. The neointimal area was related to macrophage content. Moreover, macrophage content was correlated to plasma cholesterol level. Pravastatin effectively inhibits myointimal proliferation, which may be partly explained by its hypocholesterolemic activity.

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Nonalcoholic fatty liver disease (NAFLD) is a common disease in humans having a broad spectrum of liver histology from simple fatty liver to mixed inflammatory cell infiltration and fibrosis (nonalcoholic steatohepatitis, NASH), which is a more severe and progressing form. NASH/NAFLD is significantly associated with lifestyle such as diet and exercise, obesity, insulin resistance, type 2 diabetes, dyslipidemia and hypertension. Age and gender are also associated with the development. On the other hand, NAFLD has been found in a high percentage of nonobese individuals in the Asia-Pacific area. Some characteristic animal models of NAFLD/NASH have been developed to clarify the pathogenesis of human NAFLD/NASH. We have recently developed a novel NASH rat model (stroke-prone spontaneously hypertensive rats, SHRSP5/Dmcr), which showed hepatic steatosis and inflammation at 2 weeks, ballooning, macrovesicular steatosis and fibrosis at 8 weeks, and bridging fibrosis at 14 weeks by feeding of high-fat and -cholesterol (HFC) diet alone. This animal model does not have obesity, insulin resistance or diabetes. Therefore, this may be an excellent animal model of human NASH/NAFLD without obesity and diabetes. Sex and strain differences observed in fibrogenesis by the HFC diet in SHRSP5/Dmcr may be associated with the sensitivity to detoxification enzymes in the liver, because the levels of UGP-glucuronosyltransferase and sulfotransferase and their regulating nuclear receptors only decreased in male SHRSP5/Dmcr rats, but not in female and SHRSP rats. This suggests the importance of phase II reactions of drug-metabolizing enzymes in NASH progression. Importantly, SHRSP5/Dmcr rats are spontaneously hypertensive; therefore, when we use the original strain Wistar Kyoto, which has normal blood pressure, the involvement of blood pressure in the development of human NASH/NAFLD may also be clarified.

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