Evaluation of the effect of metoprolol on energy metabolism in the ischaemic myocardium in relation to regional myocardial blood flow.
To evaluate the effect of beta blockade on energy metabolism in ischaemic myocardium metoprolol tartrate in doses of 0.2 or 0.5 mg.kg-1 or saline was injected into 24 anaesthetised dogs 20 min after coronary ligation. Regional myocardial blood flow was measured by the hydrogen gas clearance method, and the heart rate and aortic pressure were recorded. After 60 min coronary occlusion myocardial biopsy specimens were removed from five areas where myocardial blood flow had been recorded to determine their content of adenosine-5'-triphosphate (ATP). Respiratory function and acyl-coenzyme A contents of mitochondria isolated from ischaemic and non-ischaemic myocardium were also measured. In the control group the ATP content in severely ischaemic myocardium where myocardial blood flow was less than 20 ml.min-1.100 g-1 was decreased to 27.5% of that in the non-ischaemic area, whereas the administration of metoprolol 0.5 mg.kg-1 maintained ATP content at 46.3%. In ischaemic myocardium metoprolol inhibited the accumulation of long chain acyl-coenzyme A in mitochondria and significantly preserved their respiratory function. In contrast, metoprolol did not affect myocardial blood flow in myocardium where flow was less than 60 ml.min-1.100 g-1. Heart rate was decreased by metoprolol in proportion to the dose, whereas mean aortic pressure was not changed. These results suggest that beta blockade had beneficial effects on the energy metabolism of ischaemic myocardium and that such effects might be due not only to a reduction in cardiac work but also to a reduction in the vicious circle of fatty acid metabolism in ischaemic myocardium.
Nanki
M
M
Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Itoh
K
K
Matsubara
T
T
Nishimura
K
K
Kambe
T
T
Sugiyama
S
S
Ozawa
T
T
Sakamoto
N
N
D000214:Acyl Coenzyme A / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects
D000214:Acyl Coenzyme A; D000255:Adenosine Triphosphate; D008790:Metoprolol