The evolution of beta-adrenergic dysfunction during the induction of canine cobalt cardiomyopathy

This study was designed to investigate the changes in the beta adrenergic system during the induction of cobalt cardiomyopathy in dogs. Cobalt sulphate, at a dose of 5 mg X kg-1 X day-1 was administered intravenously with a low protein, low thiamine diet to 13 dogs. The percentage change of the left ventricular minor axis with systole by echocardiogram (% delta D) and dP/dtmax were used to monitor left ventricular function. Noradrenaline (NA) was measured in 24 h urine samples. Left ventricular (LV) free wall biopsies were assayed for noradrenaline (LV-NA), cyclic AMP, cyclic GMP and dopamine beta hydroxylase (LV-DBH). Lymphocytes were assayed for beta-receptor density. All dogs were studied at baseline and seven were studied after a midpoint cumulative dose of 60 to 90 mg X kg-1 of cobalt; the remaining six dogs were studied when they were in heart failure and had received more than 110 mg X kg-1. During the induction of heart failure the heart rate rose from 112 +/- 6 (means +/- SE) at baseline to 154 +/- 9 at the midpoint and 153 +/- 9 (both P less than 0.05) at the final measurement while the % delta D fell from 35 +/- 2% to 31 +/- 3% and 23 +/- 2% (P less than 0.05) and dP/dt fell from 333 +/- 40 kPa X s-1 at baseline to 254 +/- 46 kPa X s-1 (P less than 0.05) and 207 +/- 33 kPa X s-1 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)