Myocardial protection: heparin-induced free fatty acid elevation during cardiopulmonary bypass and its prevention.
Elevated serum free fatty acids (FFA) adversely affect the hypoxic or ischemic myocardium by impairing cardiac function, decreasing contractility, and increasing arrhythmogenicity . Heparin, an anticoagulant used routinely in cardiac surgery, elevates circulating FFA. The purpose of this study was to determine the magnitude of FFA elevation in cardiac surgery patients and to establish, in dogs, a dose-response of FFA to heparin and to test whether glucose-insulin-potassium (GIK) solution could prevent heparin-induced rise in FFA. In 52 patients undergoing cardiopulmonary bypass (CPB), serial blood samples were obtained for FFA determination before and after heparin (300 IU/kg) administration. Then in seven normal dogs, heparin at a dose of 80 or 300 IU/kg was given. In another group of five dogs either GIK solution or NaCl were infused, while intravenous heparin (300 IU/Kg) injection was given. Each dog acted as its own control. It was found that there was a twofold increase in circulating serum FFA after heparin administration during cardiac surgery in patients, reaching the toxicity level of greater than 0.80 meq/liter. One-third of these patients had elevations of FFA level above the arrhythmogenic threshold of greater than 1.20 meq/liter. In the canine experiments low-dose heparin (80 IU/Kg) resulted in milder elevations of FFA for a shorter duration. Dogs given saline and high-dose heparin (300 IU/Kg) had responses similar to those seen in human patients undergoing cardiac surgery, while GIK abolished the elevation of serum FFA in response to high-dose heparin, eventually reducing FFA to below preheparin levels.
D000328:Adult; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control; D002315:Cardiopulmonary Bypass; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005947:Glucose / Q000008:administration & dosage; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage; D007432:Intraoperative Period; D011184:Postoperative Period; D011188:Potassium / Q000008:administration & dosage; D012965:Sodium Chloride / Q000008:administration & dosage; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D005230:Fatty Acids, Nonesterified; D007328:Insulin; C030396:glucose-insulin-potassium cardioplegic solution; D012965:Sodium Chloride; D006493:Heparin; D005947:Glucose; D011188:Potassium