Influence of adenosine on basal myocardial function: observations in anaesthetised, domestic swine

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Abstract
Data from experiments in isolated cardiac muscle preparations indicate that adenosine in high concentration (10−3 mol·litre−1) exerts a negative inotropic effect on the myocardium under basal conditions. The following study was performed to test the hypothesis that adenosine exerts a similar negative inotropic effect when administered in an intact animal model in a dose sufficient to cause maximal coronary vasodilatation. Six open chest anaesthetised pigs were studied as follows. Ultrasonic length sensors were placed in the endocardium of the free wall of the left ventricle in a region perfused by the left anterior descending (LAD) coronary artery. Large increases in endocardial blood flow in response to adenosine administration, which could enhance segmental function (“garden hose effect”), were prevented by inserting an artificial stenosis (73% reduction in lumenal diameter) in the proximal third of the LAD. Measurements of haemodynamics, regional myocardial blood flow (microsphere technique), and regional systolic function were made at control 1, at the end of 10 min of intracoronary adenosine infusion (3.0 μmol·min−1) at a dose which exceeded that previously shown to cause maximal coronary vasodilatation and at second control 20 to 40 min after discontinuation of adenosine infusion. In response to drug infusion there was no significant change (versus control 1) in heart rate (82±15 to 90±17 min−1, mean±1 SD), systolic arterial pressure (132±20 to 128±16 mmHg [17.6±2.6 to 17.0±2.1 kPa]), mean left atrial pressure (6±2 to 8±4 mmHg [0.8±0.3 to 1.1±0.5 kPa]) and endocardial blood flow (0.94±0.24 to 1.06±0.46 ml·min−1·g−1). Adenosine in LAD plasma attained an estimated concentration of 1.09 × 10−4 ± 5.16 × 10−5 mol·litre−1 during infusion. Regional systolic function (assessed by fractional shortening (FS), mean velocity of circumferential fibre shortening (Vcf, s−1), and end diastolic length (EDL, mm)) did not change significantly versus control 1 in response to adenosine infusion. Values for each parameter (control 1 to adenosine) were as follows: FS=0.17±0.03 to 0.16±0.20; Vcf=0.43±0.09 to 0.43±0.10; and EDL=17.4±4.0 to 16.9±4.2. Thus, contrary to the proposed hypothesis, under basal conditions adenosine does not exert a negative inotropic effect on the myocardium of an intact animal when administered in a dose sufficient to cause maximal coronary vasodilatation.