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.

MATERIALS AND 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: L Zhang, L Zhang, Y H Li, H Y Zhang, M L Chen, M-M Gao, A H Hu, H S Yang, H S Yang
• Journal: European journal of clinical investigation (Eur J Clin Invest) Vol. 35 Issue 3 Pg. 164-70 (Mar 2005) ISSN: 0014-2972 [Print] England
• PMID: 15733070 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cardioplegic Solutions
• FASLG protein, human
• Fas Ligand Protein
• Faslg protein, rat
• Insulin
• Membrane Glycoproteins
• Troponin I
• fas Receptor
• glucose-insulin-potassium cardioplegic solution
• Glucose
• Potassium

Topics

• Aged
• Angioplasty, Balloon, Coronary
• Apoptosis (drug effects)
• Biomarkers (blood)
• Cardioplegic Solutions (adverse effects, therapeutic use)
• Combined Modality Therapy
• Fas Ligand Protein
• Female
• Glucose (adverse effects, therapeutic use)
• Humans
• Insulin (adverse effects, therapeutic use)
• Male
• Membrane Glycoproteins (blood)
• Middle Aged
• Myocardial Infarction (blood, drug therapy, pathology)
• Myocardial Reperfusion Injury (prevention & control)
• Potassium (adverse effects, therapeutic use)
• Troponin I (blood)
• fas Receptor (blood)