Abstract-Matrix metalloproteinase-1 (MMP-1), also called interstitial collagenase, may play an important role in the pathogenesis of atherosclerosis and atherosclerotic plaque rupture. We investigated the effects of fluvastatin on MMP-1 expression in human vascular endothelial cells (ECs). The addition of fluvastatin decreased the basal MMP-1 levels in the culture media of ECs in a time-dependent (0 to 48 hours) and dose-dependent (10 Ϫ8 to 10 Ϫ5 mol/L) manner. On the other hand, fluvastatin did not affect tissue inhibitor of metalloproteinase-1 levels. Collagenolytic activity in conditioned media of ECs was also dose-dependently reduced by fluvastatin. The effect of fluvastatin on MMP-1 expression was completely reversed in the presence of mevalonate or geranylgeranyl-pyrophosphate, but not in the presence of squalene. Key Words: atherosclerosis Ⅲ nitric oxide Ⅲ extracellular matrix Ⅲ collagen U nstable atherosclerotic plaque rupture is an important event that triggers acute coronary syndrome. Plaque rupture is frequently correlated with loss of the extracellular matrix at certain locations, often in the shoulder areas of the plaque. Focal destruction of the extracellular matrix renders the plaques less resistant to the mechanical stresses imposed during systole and therefore vulnerable to rupture. 1-3 Recent studies have suggested that matrix metalloproteinases (MMPs) may contribute to the vulnerability of atherosclerotic plaques by degrading the components of the fibrous cup: collagens, elastin, fibronectin, and proteoglycans. 4 Immunocytochemistry studies have demonstrated that MMP-1, MMP-9, and MMP-3 are expressed by cells present in atheromas, including luminal and neovascular endothelial cells, macrophages, and smooth muscle cells, but not by cells present in the walls of normal arteries. 5 Studies including in situ zymography and enzymatic activity assays showed a significantly enhanced collagenase activity in atherosclerotic plaques. 6 -8 The expression of MMP-1, also called interstitial collagenase, in atherosclerotic lesions warrants special attention because this enzyme is involved in the initial cleavage of collagens, mainly type I collagen. Type I collagen is the predominant protein in atherosclerotic plaques that confers strength to the fibrous cap. MMP-1 is also the only enzyme able to initiate the degradation of collagen at neutral pH.Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been widely used for treatment of hyperlipidemia. They may also directly interfere with the major processes of atherogenesis occurring in the arterial wall. 9 Smooth muscle cell migration and proliferation are inhibited by HMG-CoA reductase inhibitors, 10,11 and cholesterol accumulation is prevented in macrophages by reducing modified-LDL endocytosis. 12 All of these cellular effects are mediated by inhibition of the isoprenoid pathway. If HMGCoA reductase inhibitors affect MMP activity, they could influence plaque stability and disease progression of coronary artery diseases. Recently,...

Electrical storm (ES) was observed in an 82-year-old man with recent myocardial infarction. Conventional therapy, including amiodarone, could not suppress the ES. After more than 100 electrical defibrillations, we were finally able to control the ES with the administration of landiolol. It is known that landiolol can inhibit ES. However, we hesitate to use landiolol in patients with low cardiac output. We would like to emphasize that careful use of landiolol should be considered in patients with refractory ES after myocardial infarction, although cardiac output is severely reduced.

Results suggest that ANP affects TdP in the rabbit model, and that this anti-arrhythmic effect of ANP is not necessarily shared by other vasodilating agents.

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Background: Anesthesia sometimes suppresses ventricular tachyarrhythmias (VT) resistant to conventional pharmacological treatment. Methods and Results:To know (1) whether deep anesthesia inhibits abnormal repolarization-related VT and (2) if α2-adrenoreceptor (AR) agonistic action is associated with the antiarrhythmic effect of anesthetics, the incidence of VT in a rabbit model of acquired long QT syndrome using different anesthetic regimen was assessed. In Study 1 (n=30), 15 rabbits were lightly anesthetized with ketamine (123±46 mg/kg) and an α2-AR agonist, xylazine (9.4±3.0 mg/kg), while combination of these anesthetics at high doses were used in the other 15 rabbits (343±78 mg/kg and 38.9±3.0 mg/kg). Administration of α1-AR stimulant, methoxamine and nifekalant (Ikr blocker) caused VT in all lightly anesthetized rabbits. In contrast, VT was observed only in 1 of the 15 deeply anesthetized rabbits (P<0.01). In Study 2 (n=15), 10 rabbits were anesthetized with high-dose ketamine and low-dose xylazine. In the other 5 rabbits, low-dose ketamine and high-dose xylazine were used. QTc interval in the latter was longer than that of the former (399±56 ms vs. 494±57 ms, P<0.01). Although no VT appeared in high/low-rabbits, VT occurred in 3 out of 5 low/high-rabbits (P<0.05). Conclusions:These results suggest that (1) deep anesthesia suppresses abnormal repolarization-related VT and (2) antiarrhythmic effect of anesthesia on this type of VT is not dependent on α2-AR agonistic action. (Circ J 2011; 75: 89 - 93)