1.
Effects of diltiazem on platelet activation and cytosolic calcium during percutaneous transluminal coronary angioplasty.
Dai, H, Chen, J, Tao, Q, Zhu, J, Zhang, F, Zheng, L, Qiu, Y
Postgraduate medical journal. 2003;(935):522-6
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Abstract
AIMS: To evaluate effects of diltiazem on platelet hyper-reactivity in situations associated with endothelial injury and their possible relationship to cytosolic calcium concentration. METHODS Blood samples were collected at seven time points from 35 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) who received combined diltiazem and aspirin/ticlopidine therapy or aspirin/ticlopidine therapy alone. Platelet expression of glycoprotein IIb/IIIa and P-selectin, production of thromboxane B(2), and cytosolic calcium concentration were measured, respectively, by whole blood flow cytometry, radioimmunoassay, and fluorospectrophotometry. The effects of diltiazem of different concentrations on expression of glycoprotein IIb/IIIa and P-selectin were also studied in vitro in blood samples from patients with chronic stable angina. RESULTS Of the two treatments, aspirin/ticlopidine therapy did not prevent an acute increase of expression of glycoprotein IIb/IIIa and P-selectin and plasma thromboxane B(2) five minutes and 10 minutes after first inflation and 10 minutes after PTCA, whereas combined diltiazem and aspirin/ticlopidine therapy had a significant inhibitory effect. In the group receiving aspirin/ticlopidine therapy, there was a short term increase of platelet [Ca(2+)](i) immediately after PTCA which was significantly reduced by diltiazem treatment. Expression of glycoprotein IIb/IIIa and P-selectin was significantly inhibited in vitro by diltiazem in the concentration of 200 ng/ml or higher, but not 50 ng/ml. CONCLUSIONS Combined diltiazem and aspirin/ticlopidine therapy significantly inhibited platelet activation that continued in the presence of conventional aspirin/ticlopidine treatment. Antiplatelet effects of diltiazem were probably a consequence of reduction of platelet [Ca(2+)](i) and may only be achieved in higher than therapeutic concentrations.
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Does diltiazem inhibit the inflammatory response in cardiopulmonary bypass?
Fansa, I, Gol, M, Nisanoglu, V, Yavas, S, Iscan, Z, Tasdemir, O
Medical science monitor : international medical journal of experimental and clinical research. 2003;(4):PI30-6
Abstract
BACKGROUND The objective of our study was to investigate the anti-inflammatory effect and inhibiting action of diltiazem, a calcium channel blocking agent, on the systemic inflammatory response seen after cardiopulmonary bypass (CPB) in humans, in a controlled prospective study. MATERIAL/METHODS Two groups of 15 candidates for coronary artery bypass graft were enrolled in the study. In the study group, 1 g/kg/min of diltiazem was infused during cardiopulmonary bypass, while the control group received saline. Interleukin-6 and 10 (IL-6, IL-10) levels were measured from systemic arterial blood at five time points. RESULTS The levels of IL-6, a marker of the severity of systemic inflammation, were significantly higher in the control group at the end of CPB and 3 hours later. At the end of CPB, the mean IL-6 level in the control group was significantly higher than in the diltiazem group (p=0.015), and at 3 hours after CPB the difference was even greater (p=0.002). The levels of IL-10, an anti-inflammatory cytokine that limits the effects of pro-inflammatory cytokines, were higher in the control group, but not statistically significant at any time point. CONCLUSIONS Diltiazem inhibits the release of the pro-inflammatory cytokine IL-6, which is strong evidence for its anti-inflammatory effect. It is clinically important to inhibit the inflammation that takes place during CPB and the inflammation of myocardium encountered after ischemia-reperfusion, since these effect the clinical status of the patient after CPB, as well as myocardial functions.