Cilostazol, a novel cyclic AMP phosphodiesterase inhibitor, prevents reocclusion after coronary arterial thrombolysis with recombinant tissue-type plasminogen activator.

Abstract

Inhibitors of cyclic nucleotide phosphodiesterase hydrolysis of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate are known to inhibit platelet aggregation, which plays an important role in acute reocclusion after thrombolysis in acute myocardial infarction. In the present study of a canine preparation of coronary artery thrombosis superimposed on high-grade stenosis, we tested whether the antithrombotic agent cilostazol, an inhibitor of cAMP phosphodiesterase, could prevent acute reocclusion or sustain coronary blood flow after thrombolysis when used with recombinant tissue-type plasminogen activator (rt-PAJ and heparin. Intravenous infusion of rt-PA (0.5 mg/kg body wt for 30 minutes) and heparin (a 150 11)/kg body wt i.v. bolus and then 25 IU/kg body wt per hour i.v.) was combined with cilostazol (0.6 or 1.8 mg/kg body wt for 60 minutes). Without cilostazol, reperfusion was observed in seven of eight dogs, but reocclusion occurred in six of these seven dogs after 9±2 minutes. After administration of 1.8 mg/kg body wt cilostazol (group B-2; a 120-minute observation after the start of rt-PA infusion), reperfusion occurred in all seven dogs (p<0.05 versus control group), and brief cyclic reocclusion was observed in only one dog 63 minutes after reperfusion. At the same dose of cilostazol (group B-2L; a 240-minute observation after the start of rt-PA infusion), reperfusion occurred in all five dogs (p<0.05 versus control group), and coronary blood flow was well maintained except for one short reocclusion in one dog. Cilostazol inhibited cyclic flow reduction in a dose-dependent fashion. We conclude that cilostazol is a new potent antiplatelet agent for preventing reocclusion after coronary thrombolysis, when used in combination with rt-PA and heparin. (

The Cardioprotective Effect of a Statin and Cilostazol Combination: Relationship to Akt and Endothelial Nitric Oxide Synthase Activation

“…Studies in animals showed that CIL suppresses atherosclerosis formation in low-density lipoprotein receptor (Ldlr)-null mice by suppressing superoxide and TNF-α formation, and thereby reducing NF-κB activation/transcription, VCAM-1/MCP-1 expressions, and monocyte recruitments [65]. In the dog, CIL prevented coronary re-thrombosis following thrombolysis in a model of coronary artery thrombosis superimposed on high-grade stenosis [66].…”

Anti‐platelet therapy in small animal medicine

“…In cats, cilostazol is not only an effective anti-platelet therapy, but is also a marked vasodilator (Tanaka et al, 1989;Suzuki et al, 1998). While there are no clinical studies evaluating the effects of cilostazol in hypercoagulable dogs and cats, the drug demonstrates potential as an effective anti-platelet therapy when used in models of human disease (Kimura et al, 1985;Tanaka et al, 1989;Saitoh et al, 1993). Other PDE3 inhibitors, such as milrinone, are primarily used in patients with congestive heart failure (Keister et al, 1990).…”

Characteristics of Heparin-Induced Platelet Aggregates in Chronic Hemodialysis with Long-Term Heparin Use

“…, an antiplatelet agent which acts as an inhibitor of cyclic AMP phosphodiesterase and thereby increases the cAMP concentration in platelets [11], or aspirin were added to PRP from normal subjects with heparin-induced small aggregate formation. Inhibition of heparin-induced small aggregates by each drug was measured as the difference between the light intensity before and after addition of the drug.…”