Calcium improves mechanical function and carbohydrate metabolism following ischemia in isolated Bi-ventricular working hearts from immature rabbits.
In the adult heart an increase in extracellular [Ca2+] can contribute to the severity of ischemic injury. While experimental studies have suggested that the immature heart is more resistant to ischemia than the mature heart, the reasons for this are unclear. In this study, we determined the effects of increasing perfusate [Ca2+] from 1.25 to 2.5 mM on reperfusion recovery of mechanical function and energy substrate metabolism following ischemia. Isolated bi-ventricular working hearts from 2-week-old rabbits were subjected to a 55-min period of global ischemia followed by 40 min of aerobic reperfusion. Perfusate contained 11 mM glucose, 0.5 mM lactate, and 1.2 mM palmitate, containing either: (i) 1.25 mM Ca2+ throughout the perfusion period (n = 22), (ii) 1.25 mM Ca2+ prior to and during ischemia and 2.5 mM Ca2+ following ischemia (n = 19), or (iii) 2.5 mM Ca2+ throughout the perfusion period (n = 18). In hearts perfused with 1.25 mM Ca2+ throughout, a 57% recovery of preischemic function was seen following ischemia. If [Ca2+] was increased to 2.5 mM during reperfusion a significant improvement of function was seen (hearts recovered 127% of preischemic function). A concentration of 2.5 mM Ca2+ throughout the perfusion resulted in an increase in both pre- and post-ischemic function compared to hearts perfused with 1.25 mM Ca2+ throughout. In both experimental groups reperfused with 2.5 mM Ca2+ a greater than 200% increase in both glucose and lactate oxidation was seen during reperfusion. Fatty acid oxidation rates also returned to pre-ischemic levels in both groups reperfused with 2.5 mM Ca2+, while rates returned to only 53% in hearts reperfused with 1.25 mM Ca2+. As a result, increasing [Ca2+] from 1.25 to 2.5 mM resulted in a 100% increase in ATP production rates during reperfusion. In conclusion, this study demonstrates that increasing [Ca2+] significantly improves post-ischemic recovery of function in isolated bi-ventricular working immature rabbit hearts subjected to a 55-min period of ischemia. The beneficial effects of Ca2+ in these immature hearts may be due to both a direct inotropic effect and a marked increase in carbohydrate oxidation and ATP production during reperfusion.
Itoi
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Cardiovascular Disease Research Group, University of Alberta, Edmonton, Canada.
Lopaschuk
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GD
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000494:pharmacology*; D003999:Dichloroacetic Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate; D006352:Heart Ventricles; D019344:Lactic Acid / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D015425:Myocardial Reperfusion / Q000379:methods; D009206:Myocardium / Q000378:metabolism*; D010168:Palmitates / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D011817:Rabbits
D005227:Fatty Acids; D010168:Palmitates; D010710:Phosphates; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen; D003999:Dichloroacetic Acid; D005947:Glucose; D002118:Calcium