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Amelioration of ischemic calcium overload correlates with high-energy phosphates in senescent myocardium
T Tsukube1, J D McCully, K R Metz
1Division of Cardiothoracic Surgery, New England Deaconess Hospital, Boston, Massachusetts, USA.
Insights
Potassium and magnesium (K-Mg) cardioplegia improves aged heart function after ischemia by preserving high-energy phosphates. This K-Mg solution enhances recovery and reduces calcium buildup in the aged myocardium.
Area of Science:
- Cardiology
- Cardiovascular Physiology
- Biochemistry
Background:
- Potassium and magnesium (K-Mg) cardioplegia previously improved aged heart function post-ischemia.
- K-Mg cardioplegia enhanced mitochondrial activity and suggested high-energy phosphate preservation.
- Cytosolic calcium accumulation was ameliorated by K-Mg cardioplegia.
Purpose of the Study:
- To investigate the hypothesis that K-Mg cardioplegia preserves high-energy phosphates.
- To assess the effects of K-Mg cardioplegia on energy metabolism during ischemia and reperfusion in aged hearts.
- To correlate metabolic changes with functional recovery and calcium handling.
Main Methods:
- Langendorff-perfused, aged rabbit hearts (135 wk) were used.
- 31P nuclear magnetic resonance spectroscopy measured phosphocreatine (PCr), inorganic phosphate, nucleoside triphosphate (NTP), intracellular free magnesium (Mgf), and intracellular pH (pHi).
- Hearts underwent preischemia, 30 min global ischemia, and 30 min reperfusion.
Main Results:
- K-Mg cardioplegia significantly retarded PCr depletion (P < 0.05).
- NTP preservation was significantly enhanced (P < 0.05) during ischemia and reperfusion.
- K-Mg cardioplegia attenuated the increase in Mgf during ischemia (P < 0.05).
- Metabolic improvements correlated with ameliorated cytosolic calcium ([Ca2+]i) accumulation and preserved left ventricular function.
Conclusions:
- K-Mg cardioplegia effectively preserves high-energy phosphates during ischemia and reperfusion in aged hearts.
- K-Mg cardioplegia attenuates intracellular magnesium increase and calcium accumulation.
- K-Mg cardioplegia provides optimal functional recovery from surgically induced ischemia in the aged myocardium.
Abstract:
Previously, we have shown that potassium and magnesium (K-Mg, 20 mM each) cardioplegia ameliorated cytosolic calcium ([Ca2+]i) accumulation and was associated with enhanced functional recovery after surgically induced global ischemia in the aged heart. K-Mg cardioplegia was also shown to enhance cytosolic cytochrome oxidase I activity and mRNA levels, suggesting that enhanced functional recovery may involve the preservation of high-energy phosphates. To investigate this hypothesis, 31P nuclear magnetic resonance was used to measure serial alterations in phosphocreatine (PCr), inorganic phosphate, nucleoside triphosphate (NTP), intracellular free magnesium (Mgf), and intracellular pH (pHi) in Langendorff-perfused, aged (135 wk) rabbit hearts during preischemia, global ischemia (30 min), and reperfusion (30 min). K-Mg cardioplegia retarded PCr depletion (P < 0.05) and significantly enhanced NTP preservation (P < 0.05) during ischemia and reperfusion. K-Mg cardioplegia also attenuated the increase in Mgf during ischemia (P < 0.05). These results were correlated with amelioration of [Ca2+]i accumulation during ischemia and preservation of left ventricular function after reperfusion and suggest that optimal functional recovery from surgically induced ischemia is provided by K-Mg cardioplegia in the aged myocardium.