The influence of statins on the free intracellular calcium concentration in human umbilical vein endothelial cells.

BACKGROUND: Statins are cholesterol-lowering drugs that are widely used to reduce the risk of cardiac infarction. Their beneficial clinical effects, however, are not restricted to their influence on cholesterol production. As several studies have shown that they have a potency of relaxing blood vessels. METHODS: We measured the effects of statins on the intracellular free calcium concentration ([Ca2+]i) in human umbilical vein endothelial cells (HUVEC) after acute application and 24-h-preincubation of statins. RESULTS: Incubation of the cells for 24 h with cerivastatin or fluvastatin significantly increased the resting [Ca2+]i. For cerivastatin this effect manifested at a concentration of 1 microM. Increase of resting [Ca2+]i in the presence of cerivastatin also occurred when the nitric oxide synthase was inhibited. Transient Ca2+ release induced by histamine was not affected. CONCLUSIONS: The increase of resting [Ca2+]i after incubation with cerivastatin or fluvastatin may provide an explanation for the direct effects of statins on the endothelial-dependent vasodilatation and restoration of endothelial activity in vivo.

Impaired acute collateral recruitment as a possible mechanism for increased cardiac adverse events in patients with diabetes mellitus.

BACKGROUND: The mortality of coronary artery disease is increased in diabetic patients. An impaired collateral function is considered a possible explanation. This study should assess the influence of diabetes on collaterals by direct invasive assessment of collateral function. METHODS: In 90 consecutive patients with a chronic coronary occlusion (TCO) of >2 weeks duration a recanalization was done. Thirty patients with diabetes (33%) were compared with 60 (67%) without diabetes. Blood flow velocity and pressure were measured distal to the occlusion by intracoronary Doppler and pressure wires before PTCA, and again after PTCA during a final balloon reocclusion to assess acute recruitment of collaterals. Resistance indexes for collaterals (R(Coll)) and peripheral microcirculation (R(P)) were calculated. RESULTS: The R(Coll)(diabetics: 8.1+/-6.8 vs nondiabetics: 8.7+/-6.7 mmHg cm(-1)s(-1); p=0.68) and R(P)(5.6+/-4.2 vs 6.6+/-3.8 mmHg cm(-1)s(-1); p=0.30) were similar in diabetic and nondiabetic patients before recanalization. During balloon reocclusion both R(Coll)and R(P)increased. This increase was significantly more pronounced in diabetic than in nondiabetic patients in TCOs <3 months duration. In TCOs of longer duration (> or =3 months) these differences were no longer detectable between both patient groups. CONCLUSIONS: Diabetic patients with TCOs have similarly developed collaterals as nondiabetic patients. However, in TCOs <3 months duration the acute recruitment of collaterals in case of reocclusion is impaired. This could explain some of the higher complication rate and mortality after coronary interventions in diabetic patients.

Angiographic assessment of collateral connections in comparison with invasively determined collateral function in chronic coronary occlusions.

BACKGROUND: The evaluation of new therapeutic modalities to induce collateral growth in coronary artery disease require improved methods of angiographic characterization of collaterals, which should be validated by quantitative assessment of collateral function. METHODS AND RESULTS: In 100 patients with total chronic occlusion of a major coronary artery (duration >2 weeks) collaterals were assessed angiographically by the Rentrop grading, by their anatomic location, and by a new grading of collateral connections (CC grade 0: no continuous connection, CC1: threadlike continuous connection, CC2: side branch-like connection). The interobserver variability was 10%. Collateral function was assessed by Doppler flow (average peak velocity) and pressure recordings distal to the occlusion before recanalization. A collateral resistance index (RColl) was calculated. Recruitable collateral flow was measured during a final balloon inflation >30 minutes after the baseline measurement. The comparison of the anatomic location, the Rentrop, and the collateral connection grade showed only for the latter an independent and significant relation with RColl. CC2 collaterals preserved regional left ventricular function better than did CC1 collaterals and provided a higher collateral flow reserve during adenosine infusion. CC0 collaterals were predominantly observed in recent occlusions of 2 to 4 weeks' duration, with the highest RColl. During balloon reocclusion, recruitable collateral function was best preserved with CC2 and least with CC0. CONCLUSIONS: The angiographic grading of collateral connections in total chronic occlusions could differentiate collaterals according to their functional capacity to preserve regional left ventricular function and was closely associated with invasively determined parameters of collateral hemodynamics.