Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction

AbstractOBJECTIVESWe tested to find out whether pravastatin restores the infarct size (IS)-limiting effect of ischemic preconditioning (IP) and if it has any effect on the IP-induced activation of adenosine producing enzyme ecto-5′-nucleotidase which plays a key role in the IP-induced cardioprotection.BACKGROUNDThe IS-limiting effect of IP is blunted by hypercholesterolemia. Recently, HMG-CoA reductase inhibitors are shown to have direct cytoprotective effects.METHODSRabbits were fed with a normal or cholesterol (1%) added diet with or without pravastatin (5 mg/kg/day) treatment. Infarct size was measured after 30 min occlusion and 3 h reperfusion of circumflex coronary artery with or without the IP procedure (5 min occlusion and 10 min reperfusion). Additionally, ecto-5′-nucleotidase activities of ischemic and nonischemic myocardium were measured immediately after IP procedure.RESULTSThis dose of pravastatin did not normalize the increased level of serum cholesterol. The IS-limiting effect of preceding IP (IS reduced from 36.7% to 9.6%, p < 0.001) was abolished by hypercholesterolemia (from 46.1% to 31.3%, p = NS) and restored by pravastatin treatment (from 35.2% to 9.4%, p < 0.001). Pravastatin treatment did not affect IS or the effect of IP under normocholesterolemia. The activation of ecto-5′-nucleotidase presented as the activity ratio of ischemic to nonischemic myocardium (3.1-fold in normocholesterolemia) was blunted by hypercholesterolemia (1.8-fold, p < 0.05) and restored by pravastatin treatment (2.9-fold).CONCLUSIONSPravastatin, at the dose serum cholesterol was not normalized, restored the IS-limiting effect of IP and IP-induced ecto-5′-nucleotidase activation, which were both blunted by hypercholesterolemia. The activation of ecto-5′-nucleotidase may be worth further investigation as a possible mechanism for the hypercholesterolemia-induced retardation and pravastatin-mediated restoration of the cardioprotective effect of IP

Angioscopic Observation After Coronary Angioplasty for Chronic Coronary Occlusion Comparison With Severe Stenotic Lesion

Objectives To clarify the underlying mechanism for the high restenosis rate after the coronary angioplasty for the chronic total occlusion by using the coronary angioscope

キツエン シュウカンシャ ニ オケル リンゴポリフェノール ノ ケッカン ナイヒ キノウ カイゼン コウカ ニ カンスル ケンキュウ

【目的】抗酸化能が強いとされる縮合型タンニン(プロアントシアニン)を豊富に含有するリンゴポリフェノールに着目し、その抗酸化活性の生体内効果を明らかにするため前腕動脈血流(反応性充血)を非侵襲的に計測することにより解析した。【方法】被験者21名(喫煙者13名、非喫煙者8名)を対象にストレンゲージプレチスモグラフィーを用い、前腕動脈血流量を測定した。本法による血流測定の再現性について検討を行った上で、リンゴポリフェノール250mg投与1時間後(急性投与試験)と、250mg/日1週間連投後(慢性投与試験)の血流量変化を評価することにより、血管内皮機能改善効果を検討した。【結果】反応性充血ピーク流量から安静時血流量を減じた値をΔ0、遮断開放15秒後の血流量から安静時血流量を減じた値をΔ15、遮断解放後180秒までの15秒毎の血流量から安静時血流量を減じた値の総和をΔΣ、さらに反応性充血ピーク流量と安静時血流量の比をRH0/Basalflowとした。このうち、Δ0が最も再現性が保たれていたことから、これを個人の血管内皮依存性拡張能を反映する指標とみなし、ポリフェノールの生体内作用を追跡するマーカーとした。急性投与試験ではΔ0は24.9±5.6から26.7±7.8ml/min/100ml tissueへと増加を示したが、その変化は有意ではなかった。しかしながら、血管内皮が酸化障害に曝されていると考えられる喫煙者に対して慢性投与試験を行った結果、Δ0は24.9±5.6から35.2±8.6ml/min/100ml tissueへと著明に増加し血管内皮機能改善効果が顕著に現れた