Normalization of impaired response of platelets to prostaglandin E1/I2 and synthesis of prostacyclin by insulin in unstable angina pectoris and in acute myocardial infarction.
The minimal inhibitory concentration of prostaglandin E1 (used as a probe for prostacyclin [PGI2]) needed to inhibit platelet aggregation (36 +/- 16 nM) in normal volunteers (n = 40) increased (64 +/- 30 nM) in patients (n = 46) with acute coronary artery disease. Bolus injection of insulin in 20 patients, 0.1 U/kg body weight 4 times a day (every 6 hours) for 7 days decreased the minimal inhibitory concentration of prostaglandin E1 from 64 +/- 30 to 26 +/- 12 nM (p less than 0.001). Twenty other patients who received only saline solution had no decrease in minimal inhibitory concentration of the prostanoid. The bolus injection of insulin also increased the plasma level of PGI2 (9 +/- 2 pM) two-fold in these patients (28 +/- 10 pM). Administration of aspirin inhibited the insulin-induced increase of plasma prostanoid level. Patients in the placebo group had no increase in plasma PGI2 level. The bolus injection of insulin administered only once to another group of patients (n = 6) demonstrated that the hormonal effects were maximally increased within an hour of insulin administration, and were directly related to the increased insulin level in plasma. These results indicated the feasibility of using physiologic quantities of insulin for controlling of platelet aggregation through resensitization of platelet response to prostaglandin and increased synthesis of PGI2 in vivo in acute coronary artery disease.
Kahn
N N
NN
Division of Cardiology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York 10467.
Najeeb
M A
MA
Ishaq
M
M
Rahim
A
A
Sinha
A K
AK
D000789:Angina, Unstable / Q000097:blood / Q000188:drug therapy*; D015232:Dinoprostone / Q000502:physiology*; D011464:Epoprostenol / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*
D007328:Insulin; D010975:Platelet Aggregation Inhibitors; D011464:Epoprostenol; D015232:Dinoprostone