Effects of a Bradycardic Agent (DK-AH 269) on Haemodynamics and Oxygen Consumption of Isolated Blood-Perfused Rabbit Hearts

Journal of Clinical and Basic Cardiology 2000; 3 (3): 191-196

PDF    Summary    Figures   




Keywords: Bradykardie,  isoliertes durchblutetes Herz,  Kaninchen,  Sauerstoffverbrauch,  systolische und diastolische Funktion,  bradycardia,  isolated blood-perfused heart,  oxygen consumption,  rabbit,  systolic and diastolic function

Objectives: Pharmacologic bradycardia is a promising strategy to improve myocardial energetic balance. We evaluated the effects of the novel sinus node inhibitor DK-AH 269 (DK) on ventricular function and perfusion in isolated rabbit hearts. Methods: To differentiate between the effects of the negative force-frequency relation and a direct negative inotropic action of DK, measurements of haemodynamic and metabolic parameters were made during electrical pacing (EP), after application of DK (DK+EP), and after termination of pacing (DK-EP). Results: Heart rate was significantly reduced by DK (EP: 161 ± 20, DK+EP: 161 ± 19 min-1, DK-EP: 101 ± 32 min-1, mean ± SD, p = 0.02). In parallel, diastole significantly lengthened without pacing (EP: 241 ± 35, DK+EP: 234 ± 38, DK-EP: 459 ± 220 ms, p = 0.04). Aortic flow was decreased in the presence of DK (EP: 40.6 ± 21.7, DK+EP: 32.8 ± 17.9 ml/min) and even further in the absence of pacing (DK-EP: 22.8 ± 24.6 ml/min). However, stroke volume (EP: 0.31 ± 0.16, DK+EP: 0.26 ± 0.14 ml) and peak isovolumic left ventricular pressure (EP: 109 ± 19, DK+EP: 92 ± 20, mmHg) were only moderately reduced. DP/dtmax remained essentially unchanged after DK (EP: 1355 ± 545, DK+EP: 1390 ± 830 mmHg/s), but decreased without pacing (DK-EP: 890 ± 500 mmHg/s). DP/dtmin, as a measure of early relaxation, had a tendency to decrease after DK with and without pacing (EP: -1245 ± 625, DK+EP: -1055 ± 410, DK-EP: -725 ± 340 mmHg/s), while the left ventricular end-diastolic pressure remained unchanged after DK and significantly decreased without pacing (EP: 10 ± 7, DK+EP: 9 ± 6, DK-EP: 5 ± 5 mmHg, p = 0.03). Coronary blood flow (CBF) decreased from 204 ± 29 to 156 ± 21 ml/min/100 g with DK and remained almost constant without pacing (148 ± 33 ml/min/100 g). The relation between subendocardial and subepicardial flow (colored microspheres) decreased slightly with DK (EP: 1.46 ± 0.39, DK+EP: 1.40 ± 0.28, DK?EP: 1.36 ± 0.41). The myocardial oxygen consumption (MVO2) decreased with DK and further without pacing (EP: 9.8 ± 3.0, DK+EP: 8.7 ± 3.0, DK-EP: 6.2 ± 3.8 ml/min/100 g). Conclusions: DK effectively reduced HR and prolonged diastole. The drug has no major negative inotropic effect, reduces MVO2 and permits, in parallel, CBF to fall. In consequence, this novel bradycardic agent could prevent tachycardia in the experimental setting or could prevent unwanted, postoperative tachycardia. In addition, it could be an effective approach to induce bradycardia for off-pump coronary operations without compromising left ventricular function. J Clin Basic Cardiol 2000; 3: 191-6.