Effects of diltiazem on phosphate metabolism in ischemic and reperfused myocardium using phosphorus31 nuclear magnetic resonance spectroscopy in vivo.
Diltiazem may provide a protective effect to ischemic and reperfused myocardium through preservation of high-energy phosphate metabolism. To test this hypothesis, rabbits had a 1.3 cm solenoidal coil placed over the myocardium to be rendered ischemic. Data were acquired with a 22 cm bore nuclear magnetic resonance spectrometer at 2.0 T. Animals were treated with diltiazem (200 micrograms/kg intravenous bolus of drug followed by a 15 micrograms/kg/min continuous intravenous infusion, n = 10) or by an equal volume of saline (n = 6). The left circumflex artery was occluded and reperfused using a reversible snare while electrocardiogram-gated spectra were accumulated. Levels of phosphocreatine were decreased during occlusion in both groups; however, this decrease was attenuated in the diltiazem treated animals compared to control (in relative percent area: 7.8 +/- 1.0 to 2.5 +/- 0.5, p less than 0.01). Levels of phosphocreatine promptly returned to baseline following reperfusion and there was no difference between the two groups. The inorganic phosphate metabolites of high-energy phosphate consumption increased with occlusion, though more so in the control group compared with the diltiazem-treated rabbits (in relative percent area: 72.5 +/- 0.9 to 55.4 +/- 1.3, p less than 0.01). With reperfusion, levels of inorganic phosphates returned toward baseline in both groups; however, the diltiazem group had a more complete recovery relative to control (in relative percent area: 38.8 +/- 2.1 to 47.6 +/- 2.7, p less than 0.05). Levels of adenosine triphosphate decreased in both groups relative to baseline; however, the amount of decrease was similar in the two groups. With reperfusion there was a definite though incomplete recovery of levels of adenosine triphosphate in the diltiazem-treated group (in relative percent area: 10.7 +/- 1.0 at occlusion, 12.3 +/- 0.4 during reperfusion, p less than 0.05), but in the control group levels of adenosine triphosphate remained depressed (in relative percent area: 9.8 +/- 0.6 at occlusion, 9.8 +/- 0.8 during reperfusion, p = NS). During ischemia there was a trend toward attenuation of intracellular acidosis in the diltiazem group; however, this trend did not reach statistical significance. These data indicate that diltiazem provides a protective effect on myocardial high-energy phosphate metabolism during regional ischemia and reperfusion in the intact animal.
Kavanaugh
K M
KM
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109.
Aisen
A M
AM
Fechner
K P
KP
Wroblewski
L
L
Chenevert
T L
TL
Buda
A J
AJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D015425:Myocardial Reperfusion; D010710:Phosphates / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D011817:Rabbits
D010710:Phosphates; D010725:Phosphocreatine; D010758:Phosphorus; D000255:Adenosine Triphosphate; D004110:Diltiazem