Substrate enhancement of cardioplegic solution: experimental studies and clinical evaluation.
BACKGROUND
The development of myocardial protective strategies depends on a complete understanding of the pathophysiology of myocardial ischemia and reperfusion. This article reviews the rationale for inclusion of metabolic substrates in cardioplegic solutions on the basis of our current understanding of the underlying pathophysiologic pathways and speculates on the inclusion of future additives that await further investigation.


METHODS
The pathophysiology of myocardial ischemia and reperfusion was evaluated from an extensive review of the pertinent literature. Experimental and clinical studies supporting the inclusion of metabolic substrates in clinical cardioplegic solutions were reviewed and summarized. Speculation on possible future additives to these formulas was made on the basis of encouraging, albeit preliminary, experimental data.


RESULTS
Sound experimental and clinical evidence supports the inclusion of glucose, amino acids, calcium chelators, and oxygen as fundamental substrate additives to current cardioplegic solutions. Antioxidants, calcium-channel blockers, and tricarboxylic acid cycle intermediates may be of value. Adenosine, potassium-adenosine triphosphate channel modulators, and nitric oxide may join these lists after further research.


CONCLUSIONS
Substrate enhancement of clinical cardioplegic solutions is based on physiologic principles that have been confirmed in the clinical setting. Further definition of the intricacies of myocardial ischemia and reperfusion promises to expand the current list of additives.
Rosenkranz
E R
ER
Division of Cardiothoracic Surgery, Children's Hospital of Buffalo, NY 14222, USA.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D000975:Antioxidants / Q000032:analysis; D002118:Calcium / Q000032:analysis; D002121:Calcium Channel Blockers / Q000032:analysis; D002314:Cardioplegic Solutions / Q000032:analysis* / Q000378:metabolism; D005947:Glucose / Q000032:analysis; D006801:Humans; D017202:Myocardial Ischemia / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000032:analysis; D014233:Tricarboxylic Acids / Q000032:analysis
D000596:Amino Acids; D000975:Antioxidants; D002121:Calcium Channel Blockers; D002314:Cardioplegic Solutions; D017382:Reactive Oxygen Species; D014233:Tricarboxylic Acids; D005947:Glucose; D002118:Calcium