Cardiovascular and renal effects of milrinone in beta-adrenoreceptor blocked and non-blocked anaesthetized dogs.
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.
Department of Cardiovascular Pharmacology, Sterling Research Group, Rensselaer, NY 12144.
K C
KC
Lee
P C
PC
Canniff
D W
DW
Hamel
E D
ED
Pagani
A M
AM
Ezrin
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001784:Blood Gas Analysis; D004285:Dogs; D004298:Dopamine / Q000494:pharmacology; D004573:Electrolytes / Q000652:urine; D005260:Female; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D020105:Milrinone; D011728:Pyridones / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D004573:Electrolytes; D011728:Pyridones; D008353:Mannitol; D020105:Milrinone; D007545:Isoproterenol; D004298:Dopamine