Beneficial effect of nipradilol (K-351) on acute myocardial ischemia. Study of the relationship between regional myocardial blood flow and energy metabolism.
To examine the effects of nipradilol on ischemic myocardium, experiments were performed on regional myocardial blood flow (MBF) and energy metabolism in anesthetized, open-chest dogs. Nipradilol at a dose of 0.3 mg/kg was i.v.-administered 10 min after coronary ligation. MBFs at various sites, including ischemic and non-ischemic areas, were determined by the hydrogen gas clearance method. The levels of ATP and creatine phosphate (CP) at the site of MBF determination were measured 60 min after ligation, and mitochondrial function (RCI, QO2) in the ischemic and non-ischemic areas was determined. Following nipradilol administration, aortic pressure and heart rate were significantly lowered. In ischemic areas with MBF below 40 ml/min/100 g, nipradilol had no influence on MBF. However, the tissue level of ATP in nipradilol treated hearts was significantly higher as compared with untreated hearts. In the area of mild ischemia with MBF of 40-60 ml/min/100 g, nipradilol preserved the tissue ATP and CP levels in spite of a decrease in MBF. Moreover, an inhibition of the decrease in mitochondrial respiratory function was observed in ischemic areas with MBF below 20 ml/min/100 g. Thus, nipradilol administered following ischemia preserved ATP content and mitochondrial function in the ischemic myocardium with reduction of heart rate and aortic pressure. This suggests that nipradilol exerts a cardioprotective effect in acute ischemia. It seems that the cardioprotective effect is due to a decrease in myocardial oxygen demand and preservation of mitochondrial function.
Okamoto
Y
Y
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Matsubara
T
T
Iyeda
N
N
Miyajima
K
K
Iida
K
K
Nishida
T
T
Kobayashi
S
S
Kakinuma
Y
Y
Itoh
K
K
Hibi
N
N
D000255:Adenosine Triphosphate / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects*; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010725:Phosphocreatine / Q000378:metabolism; D011412:Propanolamines / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; C036089:nipradilol