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Effects of diltiazem on platelet activation and cytosolic calcium during percutaneous transluminal coronary angioplasty

Department of Cardiology, First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China

Correspondence to:
Correspondence to:
Dr Jianhua Zhu, Department of Cardiology, First Affiliated Hospital of Zhejiang University, No 79 Qingchun Road, Hangzhou, Zhejiang 310003, China;
zjh_john{at}sina.com

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 B₂, 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 B₂ 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 [Ca²⁺]_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 [Ca²⁺]_i and may only be achieved in higher than therapeutic concentrations.

Keywords: angioplasty; platelets; diltiazem; calcium

Abbreviations: FITC, fluorescein isothiocyanate; GP, glycoprotein; PTCA, percutaneous transluminal coronary angioplasty