Enhanced vasodilatory responses to milrinone in catecholamine-precontracted small pulmonary arteries.
Beta-adrenergic agonists (e.g., epinephrine [E] and norepinephrine [NE]) and phosphodiesterase-III inhibitors (e.g., milrinone) are often used in combination to augment ventricular function in the perioperative period. In the myocardium, milrinone acts synergistically with beta-adrenergic agonists to increase contractility. However, the potential interaction between catecholamines with combined alpha- and beta-adrenergic activity and milrinone in the pulmonary circulation has not been determined. We evaluated the vasodilatory effects of milrinone and nitroglycerine on large elastic and small muscular porcine pulmonary vascular rings precontracted with catecholamines with beta-adrenergic agonist activity (E and NE), the alpha-adrenergic agonist phenylephrine, and a nonadrenergic agonist, the thromboxane analog U46619. In small pulmonary arteries, the vasorelaxation with milrinone was significantly enhanced in rings precontracted with E or NE compared with those precontracted with phenylephrine or U46619. However, in large pulmonary arteries, the vasorelaxation with milrinone was similar in all vessel rings and was not influenced by the agonist used to induce precontraction. In marked contrast, the vasorelaxant responses to nitroglycerine were not altered by the specific agonist used for precontraction in either small or large pulmonary vascular rings. Thus, the pulmonary vascular effects of milrinone are enhanced when combined with drugs with beta-adrenoreceptor agonist activity. The vasodilatory interactions exhibited by phosphodiesterase-III inhibitors and the catecholamines NE and E suggest that their combined use might be beneficial in circumstances in which ventricular dysfunction and increased pulmonary vascular resistance occur.


CONCLUSIONS
This study demonstrated that milrinone had enhanced vasodilator effects when combined with drugs with beta-adrenoreceptor agonist activity in small pulmonary artery segments removed from pigs.
Jhaveri
Rajiv
R
Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
Kim
Soonyul
S
White
A Ron
AR
Burke
Sean
S
Berkowitz
Dan E
DE
Nyhan
Daniel
D
D000818:Animals; D002395:Catecholamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D020105:Milrinone / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D002395:Catecholamines; D020105:Milrinone