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Exogenous calcium preconditions myocardium from patients taking oral sulfonylurea agents
B S Cain1, D R Meldrum, X Meng
1Department of Surgery, University of Colorado Health Sciences Center, Denver, Colorado, 80262, USA.
Insights
Exogenous calcium pretreatment can protect atrial trabeculae from patients taking oral sulfonylurea hypoglycemic agents against ischemia. This finding offers a potential therapeutic strategy for diabetic patients undergoing cardiac procedures.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Myocardial Ischemia
Background:
- Oral sulfonylurea hypoglycemic agents are associated with increased cardiovascular mortality.
- Previous research indicated atrial trabeculae from these patients cannot be preconditioned by transient ischemia.
- Exogenous calcium pretreatment was previously found to protect human atrial trabeculae from ischemia.
Purpose of the Study:
- To investigate if exogenous calcium pretreatment can confer ischemic protection to atrial trabeculae from patients taking oral sulfonylurea drugs.
- To test the hypothesis that exogenous calcium confers ischemic protection in this patient group.
Main Methods:
- Human atrial trabeculae were isolated and stimulated in organ baths.
- Trabeculae were subjected to ischemia/reperfusion (I/R) with or without calcium pretreatment.
- Developed force was measured as a percentage of baseline force (%BDF).
Main Results:
- Ischemia/reperfusion reduced contractility to 15.3% of baseline force in patients on oral hypoglycemics.
- Calcium pretreatment significantly increased post-ischemic developed force to 35.3% of baseline (P < 0.05).
Conclusions:
- Atrial muscle from patients taking oral hypoglycemic agents can be preconditioned with exogenous calcium.
- This calcium-based therapy may provide a clinically relevant method to precondition the myocardium in diabetic patients.
- Potential application in protecting diabetic patients undergoing interventions like coronary angioplasty or cardiac bypass.
Abstract:
We have previously reported that atrial trabeculae from patients taking oral sulfonylurea hypoglycemic agents cannot be preconditioned by transient ischemia, which may, in part, explain the increased cardiovascular mortality historically associated with the use of these agents (J. C. Cleveland et al., 1997, Circulation 96, 29-32). Recently, we reported that clinically accessible and acceptable exogenous Ca(2+) pretreatment protects human atrial trabeculae from subsequent ischemia (B. S. Cain et al., 1998, Ann. Thoracic Surg. 65, 1065-1070). It remains unknown whether this preconditioning strategy could confer protection to trabeculae from patients taking oral sulfonylurea drugs. We therefore hypothesized that exogenous Ca(2+) confers ischemic protection to trabeculae from patients taking oral sulfonylureas. Human atrial trabeculae were suspended in organ baths and field stimulated at 1 Hz, and force development was recorded. Following 90 min equilibration, trabeculae from patients taking oral sulfonylurea agents (n = 6 patients) were subjected to ischemia/reperfusion (I/R; 45/120 min) with or without Ca(2+) (1 mM increase x 5 min) 10 min prior to I/R. I/R decreased postischemic human myocardial contractility in trabeculae from patients on oral hypoglycemics to 15.3 +/- 2.0% baseline developed force (%BDF). Ca(2+) pretreatment increased postischemic human myocardial developed force to 35.3 +/- 2.9 %BDF in these patients (P < 0.05 vs I/R, ANOVA and Bonferroni/Dunn). We conclude that atrial muscle from patients taking oral hypoglycemic agents can be preconditioned with exogenous Ca(2+). This therapy may offer a clinically relevant means to precondition the myocardium of diabetics taking oral hypoglycemic agents prior to clinical interventions such as coronary angioplasty or cardiac bypass.