Cardiovascular and renal effects of milrinone in beta-adrenoreceptor blocked and non-blocked anaesthetized dogs

Abstract

The cardiovascular effects of the low Km cAMP phosphodiesterase inhibitor milrinone (0.01-0.3 mg/kg, i.v.) were characterized in anaesthetized dogs with or without beta-adrenoreceptor blockade (nadolol, 1 mg/kg, i.v.). Heart rate was increased by milrinone at greater than or equal to 0.1 mg/kg in non-blocked dogs (61 +/- 5 beats/min [mean +/- SEM, max. change] or 40.5 +/- 6.0%) and at greater than or equal to 0.03 mg/kg in beta-blocked dogs (33 +/- 5 beats/min or 26 +/- 4%). Mean arterial pressure was decreased at greater than or equal to 0.03 mg/kg in non-blocked dogs (-34 +/- 6mmHg or -27 +/- 5%) and at greater than or equal to 0.1 mg/kg in beta-blocked dogs (-17 +/- 4 mmHg or -15 +/- 3%). These changes were or tended to be greater in non-blocked than beta-blocked dogs. The maximum rate of rise in left ventricular pressure was increased at all doses in non-blocked (3747 +/- 388 mmHg/sec or 131 +/- 14%) and beta-blocked dogs (2517 +/- 445 mmHg/sec or 131 +/- 25%), with the absolute but not percent increase being greater in non-blocked than beta-blocked dogs. Left ventricular end diastolic pressure (LVEDP) was or tended to be reduced at greater than or equal to 0.03 mg/kg in beta-blocked dogs (-3 +/- 1 mmHg or -64 +/- 20%) and at 0.01-0.1 mg/kg in non-blocked dogs (-1.4 +/- 0.9 mmHg or -50 +/- 29%). The absolute, but not percent, decrease in LVEDP at 0.03 mg/kg was greater in beta-blocked than non-blocked dogs (-2.2 +/- 0.8 mmHg or 32 +/- 10% vs. 0.0 +/- 0.7 mmHg or 0 +/- 8%). Cardiac output (CO) was or tended to be similarly increased at 0.01-0.03 mg/kg in beta-blocked (0.2 +/- 0.1/min or 15 +/- 5%) and non-blocked dogs (1.2 +/- 0.7 1/min or 40 +/- 16%). In conclusion, beta-blockade attenuated the hypotensive and chronotropic effects, but did not eliminate the positive inotropism, the reduction in cardiac preload or the increase in CO induced by milrinone in anaesthetized dogs.