TY - JOUR
T1 - Substrate regulation of the nucleotide pool during regional ischaemia and reperfusion in an isolated rat heart preparation
T2 - A phosphorus-31 magnetic resonance spectroscopy analysis
AU - Camacho, S. Albert
AU - Parmley, William W.
AU - James, Thomas L.
AU - Abe, Hiroyuki
AU - Wu, Shao T.
AU - Botvinick, Elias H.
AU - Watters, Thomas A.
AU - Schiller, Nelson
AU - Sievers, Richard
AU - Wikman-Coffelt, Joan
N1 - Funding Information:
This study was supported in part by American Heart Association, California Affiliate Grant-in-Aid Award, 86-N103,th e Susan and Don Schleicher Fund, and the George D Smith Fund. SAC is supported by NHLBI Institutional NRSA Grant in Heart and Vascular Diseases. We thank Walter Hauck, for advice on statistical analysis.
PY - 1988/3
Y1 - 1988/3
N2 - Isolated rat heart preparations were studied to characterise the alterations in high energy phosphates that occur during reversible regional ischaemia and to determine whether pyruvate, as the sole exogenous energy substrate, would attenuate the ischaemia induced depletion of the nucleotide pool when compared with glucose. Using phosphorus-31 magnetic resonance spectroscopy baseline concentrations of adenosine triphosphate, phosphocreatine, inorganic phosphate, and intracellular pH were compared with values during 30 min of left coronary artery occlusion followed by 30 min of reperfusion. These variables were related to changes in developed pressure, coronary flow, and oxygen consumption. In addition, the total nucleotide pool was evaluated by biochemical analysis of myocardial tissue extracts and coronary effluent. The ischaemic region was characterised by a dye staining technique and cross sectional echocardiographic measurements of regional myocardial wall thinning. In both glucose and pyruvate perfused groups, coronary flow and oxygen consumption decreased to 50-60% of control within 1 min of ischaemia and returned to baseline values with reflow. Developed pressure decreased to 50(9) and 74(8)% (mean(SEM)) of control after 30 min of ischaemia in glucose and pyruvate perfused groups respectively. Reperfusion resulted in complete recovery of developed pressure in hearts perfused with pyruvate but not in the glucose group. Glucose perfused hearts had a greater decrease in intracellular pH during ischaemia (7.07(0.01) to 6.36(0.1)) than pyruvate perfused hearts (7.06(0.02) to 6.83(0.04)). Reperfusion resulted in a rapid return to baseline intracellular pH in both groups. During ischaemia, adenosine triphosphate values decreased to a greater degree in glucose than in pyruvate perfused hearts (57(4) and 79(5)% of baseline respectively). Thirty minutes of reperfusion did not significantly improve adenosine triphosphate concentrations in either group. Phosphocreatine concentrations decreased to 52(7) and 75(6)% of baseline in glucose and pyruvate perfused groups respectively after the ischaemic period. Reperfusion resulted in normalisation of phosphocreatine values in the pyruvate but not in the glucose perfused group. Biochemical analysis of myocardial tissue extracts confirmed the spectroscopy data and showed that pyruvate inhibits the efflux of adenine nucleotide derivatives. Tissue concentrations of adenosine monophosphate were three times greater and adenosine 50% less after 30 min of ischaemia in the pyruvate perfused group. Coronary effluent inosine and hypoxanthine losses were 50% lower during both ischaemia and reperfusion in the pyruvate perfused hearts.It is concluded that the use of pyruvate, when compared with that of glucose, as the sole exogenous substrate results in greater functional and biochemical recovery after 30 rnin of ischaemia and 30 min of reflow. Pyruvate's beneficial effect is associated with amelioration of the observed intracellular acidosis during ischaemia and preservation of the total nucleotide pool.
AB - Isolated rat heart preparations were studied to characterise the alterations in high energy phosphates that occur during reversible regional ischaemia and to determine whether pyruvate, as the sole exogenous energy substrate, would attenuate the ischaemia induced depletion of the nucleotide pool when compared with glucose. Using phosphorus-31 magnetic resonance spectroscopy baseline concentrations of adenosine triphosphate, phosphocreatine, inorganic phosphate, and intracellular pH were compared with values during 30 min of left coronary artery occlusion followed by 30 min of reperfusion. These variables were related to changes in developed pressure, coronary flow, and oxygen consumption. In addition, the total nucleotide pool was evaluated by biochemical analysis of myocardial tissue extracts and coronary effluent. The ischaemic region was characterised by a dye staining technique and cross sectional echocardiographic measurements of regional myocardial wall thinning. In both glucose and pyruvate perfused groups, coronary flow and oxygen consumption decreased to 50-60% of control within 1 min of ischaemia and returned to baseline values with reflow. Developed pressure decreased to 50(9) and 74(8)% (mean(SEM)) of control after 30 min of ischaemia in glucose and pyruvate perfused groups respectively. Reperfusion resulted in complete recovery of developed pressure in hearts perfused with pyruvate but not in the glucose group. Glucose perfused hearts had a greater decrease in intracellular pH during ischaemia (7.07(0.01) to 6.36(0.1)) than pyruvate perfused hearts (7.06(0.02) to 6.83(0.04)). Reperfusion resulted in a rapid return to baseline intracellular pH in both groups. During ischaemia, adenosine triphosphate values decreased to a greater degree in glucose than in pyruvate perfused hearts (57(4) and 79(5)% of baseline respectively). Thirty minutes of reperfusion did not significantly improve adenosine triphosphate concentrations in either group. Phosphocreatine concentrations decreased to 52(7) and 75(6)% of baseline in glucose and pyruvate perfused groups respectively after the ischaemic period. Reperfusion resulted in normalisation of phosphocreatine values in the pyruvate but not in the glucose perfused group. Biochemical analysis of myocardial tissue extracts confirmed the spectroscopy data and showed that pyruvate inhibits the efflux of adenine nucleotide derivatives. Tissue concentrations of adenosine monophosphate were three times greater and adenosine 50% less after 30 min of ischaemia in the pyruvate perfused group. Coronary effluent inosine and hypoxanthine losses were 50% lower during both ischaemia and reperfusion in the pyruvate perfused hearts.It is concluded that the use of pyruvate, when compared with that of glucose, as the sole exogenous substrate results in greater functional and biochemical recovery after 30 rnin of ischaemia and 30 min of reflow. Pyruvate's beneficial effect is associated with amelioration of the observed intracellular acidosis during ischaemia and preservation of the total nucleotide pool.
KW - Adenosine triphosphate, pH
KW - Ischaemia
KW - Nuclear magnetic resonance
KW - Nucleotide pool
KW - Pyruvate
KW - Spectroscopy
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U2 - 10.1093/cvr/22.3.193
DO - 10.1093/cvr/22.3.193
M3 - Review article
C2 - 3167943
AN - SCOPUS:85047676643
SN - 0008-6363
VL - 22
SP - 193
EP - 203
JO - Cardiovascular research
JF - Cardiovascular research
IS - 3
ER -