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(Circulation. 1995;92:405-412.)
© 1995 American Heart Association, Inc.

Articles

Magnesium Cardioplegia Enhances mRNA Levels and the Maximal Velocity of Cytochrome Oxidase I in the Senescent Myocardium During Global Ischemia

Presented at the 67th Scientific Sessions of the American Heart Association, Nov 14-17, 1994, Dallas, Tex.

Elizabeth A. Faulk, MD; James D. McCully, PhD; Narelle C. Hadlow, MD; Takuro Tsukube, MD; Irvin B. Krukenkamp, MD; Micheline Federman, PhD; Sidney Levitsky, MD

From the Division of Cardiothoracic Surgery and the Department of Pathology, New England Deaconess Hospital and Harvard Medical School, Boston, Mass.

Correspondence to Sidney Levitsky, MD, Division of Cardiothoracic Surgery, New England Deaconess Hospital, 110 Francis St, Suite 2C, Boston, MA 02215.

Background The aged myocardium accumulates significantly more cytosolic calcium [Ca²⁺]_i during ischemia, and functional recovery is more severely compromised as compared with the mature heart. Cardioplegia ameliorates these phenomena. The mechanism by which increased calcium accumulation reduces functional recovery in the senescent myocardium is unknown, but it has been suggested that futile calcium cycling in the mitochondria leading to depletion of ATP stores during normothermic global ischemia may be involved.

Methods and Results To investigate the effect of cardioplegia on mitochondrial calcium ([Ca²⁺]_mt) accumulation and the expression of cytochrome oxidase I (COX I) during global ischemia, mitochondria were isolated from mature (age, 15 to 20 weeks) and aged (age >130 weeks) rabbit hearts after Langendorff perfusion. Five perfused heart groups were investigated: 30 minutes of global ischemia without treatment (control), with potassium (K, 20 mmol/L), magnesium (Mg, 20 mmol/L), or potassium and magnesium (K/Mg) cardioplegia. No significant difference in [Ca²⁺]_mt was evident in mature hearts with any protocol. In aged hearts, [Ca²⁺]_mt was increased in global ischemia but was ameliorated with Mg and K/Mg cardioplegia. COX I mRNA levels in aged hearts were lower in both control and global ischemia but were increased with cardioplegia. Maximal velocities for COX I were significantly increased with Mg cardioplegia both in the mature and the aged myocardium.

Conclusions K and/or Mg cardioplegia ameliorates [Ca²⁺]_mt accumulation in aged hearts during normothermic global ischemia and increases COX I mRNA levels to a level not significantly different from that found in mature hearts.

Key Words: cardioplegia • calcium • aging

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