What has the baboon to offer as a model of experimental ischemia?

The greatest advantage of the baboon model is the phylogenetic closeness of the animal to man which may be of considerable importance when dealing with receptor-related events and with drug-specific therapy. The major disadvantage is the difficulty of dealing with awake baboons and the absence of any adequate model for coronary artery spasm.

Single administration of atenolol does not influence the kinetics of orally given isosorbide dinitrate.

In eight subjects, plasma concentrations of isosorbide dinitrate and its mononitrates after oral administration of 10 mg isosorbide dinitrate were measured on two occasions, once with and once without previous administration of a single dose of atenolol 100 mg. There were no significant changes either in plasma concentration at different times after administration, or in peak plasma concentrations or in area under the curve of the isosorbide dinitrate and mononitrates.

Bioavailability and saturation of the presystemic metabolism of oral lorcainide therapy initiated in three different dose regimens.

The feasibility of giving a supplementary starting dose of the antiarrhythmic drug lorcainide, in order to minimalize the impact of the extensive, but saturable first-pass metabolism, was evaluated. Twenty-five adult patients were given 100 mg lorcainide tablets according to one of 3 different dosage schedules: Eight patients took one tablet at 0, 12 and 24 h, 8 took 1 tablet at 0, 1, 12 and 24 h and 9 took 1 tablet at 0, 2, 12 and 24 h. Levels of lorcainide and its metabolite, nor-lorcainide, during treatment were determined by gas-liquid chromatography. The results show that giving a second tablet 1 or 2 h after the first may produce faster saturation of the pre-systemic metabolism of lorcainide in the liver.

Plasma concentrations of isosorbide dinitrate and mononitrates after acute and chronic oral administration of isosorbide dinitrate in man.

Isosorbide dinitrate (Cedocard) was given orally to patients in doses of either 5, 20 or 40 mg t.i.d. for 19 days, and the plasma concentrations of unchanged product and of its mononitrates were measured. While the concentration of isosorbide 2-mononitrate remained stable, the concentration of isosorbide dinitrate and of isosorbide 5-mononitrate in plasma increased gradually during the first days of administration. Decrease in presystemic or systemic clearance is probably responsible for this phenomenon.

Effects of glucose, insulin and potassium infusion on tissue metabolic changes within first hour of myocardial infarction in the baboon.

The effects of infusions of glucose, insulin and potassium (GIK) on the heart tissue metabolic changes found in adult baboons 60 min after coronary artery ligation were studied. Biopsies taken from 11 baboons without coronary artery ligation gave control values. A second group of 46 baboons had coronary artery ligation. A third group of 17 baboons received an infusion of KCl after coronary artery ligation. A fourth group of 26 baboons received infusion of GIK. Coronary artery ligation resulted in the expected fall of ATP, creatine phosphate, glycogen, tissue (K+/Na+) ratio, and tissue pH, and rise of inorganic phosphate, lactare, lactate/pyruvate ratio and alpha-glycerophosphate in the infarction zones. Compared with ligation, additional infusions of GIK approximately doubled the contents of creatine phosphate and glycogen in the infarct zones, increased the content of ATP in the central infarct zone, and decreased the content of inorganic phosphate in the peripheral infarct zone. Other GIK effects were that the tissue (K+/Na+) ratio rose in the peripheral infarct zone, and the content of both glycogen and lactate rose in the peri-infarct and non-ischemic zones; the pH of tissue homogenates did not decrease. KCl infusions had few effects compared with the ligation group. GIK infusions exerted a beneficial effect when compared with infusions of KCl in that tissue creatine phosphate rose in the peripheral infarct and nonischemic zones; the tissue K+/Na+ ratio rose in the peripheral infarct, peri-infarct, and nonischemic zones; and the lactate/pyruvate ratio fell in the infarct zone. It is proposed that GIK counteracted early tissue metabolic deterioration in the infarcting baboon heart.

Effect of early oral feeding on plasma free fatty acid concentrations in patients in a coronary care unit.

Forty-two consecutive patients with acute myocardial infarction were studied over the first 3 days of their illness to determine the effect of oral or intravenous calorie intake on the circulating free fatty acid values. Repeated sampling in 9 patients showed that free fatty acid levels above 1000 mumol/l were seldom found beyond the first 10 hours after admission. Oral calories, chiefly in the form of carbohydrate, reduced free fatty acid by an average of 145 mumol/l for each intake of 90 or more calories (378kF) on the first day. Oral calories (especially carbohydrate) should be considered as possible antilipolytic therapy if it be held desirable to reduce circulating free fatty acid concentrations in patients with acute mycoardial infarction.

Early ventricular fibrillation in the baboon: possible role of epicardial ST segment changes.

The changes in epicardial ST segment and the severity of the infarct defined by the onset of primary ventricular fibrillation were monitored in baboons after ligation of the anterior descending coronary artery. Although an increase in the ratio of the total ST segment elevation over the maximal drop of isoelectric baseline appeared to precede the onset of ventricular fibrillation, further data is needed for establishing a clear relation between these parameters.