Anionic polymerizations of 2-[(trimethylsilyl)oxy]ethyl methacrylate (l), 2-[(tert-butyldimethylsilyl)oxy]ethy1 methacrylate (2), and 2-[(methoxymethyl)oxy]ethyl methacrylate (3), the protected forms of 2-hydroxyethyl methacrylate (HEMA), were carried out in THF at -78 "C with 1 ,l -diphenylhexyllithium or 1,l -diphenyl-3-methylpentyllithium in the presence of LiCl. The resulting poly(1-3)s were found to possess predictable molecular weights and very narrow molecular weight distributions. The sequential polymerizations of tert-butyl methacrylate with the anionic propagating ends of poly(1-3) gave block copolymers in quantitative efficiency. Thus, the anionic polymerizations of 1-3 proceeded without transfer and termination reactions to afford stable living polymers. Complete hydrolysis of the protective groups of poly(1-3)s produced linear poly(HEMA) quantitatively. Novel well-defined di-and triblock copolymers containing hydrophobic [polystyrene, poly(4-octylstyrene), polyisoprene] and hydrophilic segments [poly(HEMA)] were also prepared by sequential polymerization of the corresponding hydrophobic comonomers with 1, followed by deprotection.

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It has been shown that orally administered geranylgeranylacetone (GGA), an anti-ulcer drug, induces expression of heat shock protein 72 (HSP72) and provides protection against ischemia-reperfusion in rat hearts. The underlying protective mechanisms, however, remain unknown. Mitochondria have been shown to be a selective target for heat stress-induced cardioprotection. Therefore, we hypothesized that preservation of mitochondrial function, owing to an opening of a putative channel in the inner mitochondrial membrane, the mitochondrial ATP-sensitive potassium (mitoKATP) channel, could be involved in GGA- or heat stress-induced cardioprotection against ischemia-reperfusion. Rats were treated with oral GGA or vehicle. Twenty-four hours later, each heart was isolated and perfused with a Langendorff apparatus. GGA-treated hearts showed better functional recovery, and less creatine kinase was released during a 30-min reperfusion period, after 20 min of no-flow ischemia. Concomitant perfusion with 5-hydroxydecanoate (5-HD, 100 μM) or glibenclamide (10 μM) abolished the GGA-induced cardioprotective effect. GGA also showed preserved mitochondrial respiratory function, isolated at the end of the reperfusion period, which was abolished with 5-HD treatment. GGA prevented destruction of the mitochondrial structure by ischemia-reperfusion, as shown by electron microscopy. In cultured cardiomyocytes, GGA induced HSP72 expression and resulted in less damage to cells, including less apoptosis in response to hypoxia-reoxygenation. Treatment with 5-HD abolished the GGA-induced cardioprotective effects but did not affect HSP72 expression. Our results indicate that preserved mitochondrial respiratory function, owing to GGA-induced HSP72 expression, may, at least in part, have a role in cardioprotection against ischemia-reperfusion. These processes may involve opening of the mitoKATP channel.

Background: Cardiovascular autonomic neuropathy is a major complication in patients with diabetes mellitus (DM). However, the relationship between cardiovascular autonomic neuropathy and the incidence of cardiovascular events has been poorly investigated in type 2 DM. The present study aimed to assess the long-term cardiovascular predictive value of baroreflex sensitivity (BRS) in Japanese patients with type 2 DM without structural heart disease. Methods and Results:BRS was evaluated using the phenylephrine method in 210 patients with type 2 DM who did not have structural heart disease or other severe complications. BRS was considered depressed if <6 ms/mmHg. Accurate follow-up information for 3-10 years (mean 4.7 years) was obtained in 184 patients (90 females, 94 males; mean age 58±12 years). The initial onset of a major adverse cardiovascular event (MACE) was investigated. During follow-up, 19 patients presented with a MACE (4 cardiovascular deaths, 3 nonfatal myocardial infarctions, 4 coronary revascularizations, 5 strokes, 2 congestive heart failures). Cox proportional hazards regression analysis revealed that depressed BRS was independently associated with the incidence of MACE (hazard ratio 1.93, 95% confidence interval 1.09-3.82, P=0.0236). Conclusions:Depressed BRS at baseline has long-term cardiovascular predictive value in Japanese patients with type 2 DM without structural heart disease. (Circ J 2010; 74: 1379 - 1383