title: High-dose glucose-insulin-potassium treatment reduces myocardial apoptosis in patients with acute myocardial infarction.
abstract: BACKGROUND
  Several clinical trials have suggested that a metabolic cocktail of glucose-insulin-potassium (GIK) decreases mortality rates in patients with acute myocardial infarction (AMI). It has also been reported that Fas-mediated apoptosis plays an important role in ischaemic/reperfusion injury in the rat model. This study was designed to evaluate the interaction of ischaemic/reperfusion and reperfusion therapy coadministered with high-dose GIK treatment on soluble Fas/APO-1 (sFas) and Fas ligand (sFasL) plasma concentration in patients with AMI.
  
  
  METHODS
  Seventy-four patients presenting with AMI who underwent reperfusion therapy were randomized into a GIK group (n = 35) receiving high-dose GIK for 24 h or a vehicle group (n = 39). Thirty-four control subjects were also enrolled in the present study. Strepavidin-biotin ELISA was used to determine the soluble sFas and sFasL plasma concentration at baseline, 24 h (h), 3 day (d), 7 d and 14 d.
  
  
  RESULTS
  Soluble Fas and sFas-L serum concentrations ([sFas] and [sFas-L]) of patients with AMI were significantly elevated at baseline as compared with normal controls (NCs; P < 0.01 vs. NC). The sFas in the GIK and vehicle groups markedly decreased 24 h after the GIK infusion (10.7-->5.9 ng mL(-1) and 9.7-->6.5 ng mL(-1); P < 0.01 vs. baseline) and then increased during the 3-7-d period (5.9-->12.1 ng mL(-1) and 6.5-->11.1 ng mL(-1); P < 0.01 vs. 24 h). The GIK group demonstrated reduced sFas (12.1-->5.9 ng mL(-1)) at 14 d (P < 0.01 vs. 7 d), with no concomitant changes in the vehicle group. The sFas-L in the GIK and vehicle groups was not significant different during the 14-d period.
  
  
  CONCLUSIONS
  These results indicate that the sFas and sFasL in patients with AMI increased significantly compared with NC. Owing to the cardioprotective effects reported here and by others, a high-dose GIK infusion co-administered with the timely re-establishment of nutritive perfusion should be strongly considered as a treatment of choice for AMI. Additionally, sFas may be a valuable marker of the physiological response to ischaemic/reperfusion injury and reperfusion associated with high-dose GIK treatment.
authors.affiliation: Heart Center, Institute of Cardiovascular Disease, Capital Medical University Chaoyang Hospital, 8 Baijiazhuang Road, 100-020 Beijing, China. linzhangpeking@hotmail.com
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: Y H
authors.initials: YH
authors.lastname: Li
authors.forename: H Y
authors.initials: HY
authors.lastname: Zhang
authors.forename: M L
authors.initials: ML
authors.lastname: Chen
authors.forename: M-M
authors.initials: MM
authors.lastname: Gao
authors.forename: A H
authors.initials: AH
authors.lastname: Hu
authors.forename: H S
authors.initials: HS
authors.lastname: Yang
authors.forename: H S
authors.initials: HS
authors.lastname: Yang
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D002314:Cardioplegic Solutions / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D053222:Fas Ligand Protein; D005260:Female; D005947:Glucose / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D011188:Potassium / Q000009:adverse effects / Q000627:therapeutic use*; D019210:Troponin I / Q000097:blood; D019014:fas Receptor / Q000097:blood
chemical_list: D015415:Biomarkers; D002314:Cardioplegic Solutions; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D007328:Insulin; D008562:Membrane Glycoproteins; D019210:Troponin I; D019014:fas Receptor; C030396:glucose-insulin-potassium cardioplegic solution; D005947:Glucose; D011188:Potassium