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Inhaled but not intravenous milrinone prevents pulmonary endothelial dysfunction after cardiopulmonary bypass
1Research Center, and Department of Surgery, Montreal Heart Institute, 5000 Belanger Street East, Montreal, Quebec H1T 1C8, Canada. louis.perrault@icm-mhi.org
Objective:
Cardiopulmonary bypass triggers a systemic inflammatory response that alters pulmonary endothelial function, which can contribute to pulmonary hypertension. Milrinone is a type III phosphodiesterase inhibitor. The objective of this study was to compare the effects of inhaled and intravenous milrinone on the pulmonary endothelium-dependent relaxations and hemodynamic and oxygenation parameters after cardiopulmonary bypass in a porcine model.
Methods:
Five groups of Landrace swine were compared: (1) control group, no cardiopulmonary bypass; (2) bypass group, 90 minutes of normothermic bypass and 60 minutes of reperfusion; (3) inhaled milrinone group, bypass preceded by a 1.8-mg bolus of inhaled milrinone followed by a continuous milrinone nebulization; (4) intravenous milrinone group, bypass preceded by 2 mg of intravenous milrinone; and (5) inhaled NaCl group, bypass preceded by inhaled saline solution. After sacrifice, pulmonary arterial endothelium-dependent relaxations to acetylcholine and bradykinin were studied in organ chambers.
Results:
Inhaled milrinone caused less hypotension ( P < .05), a lesser decrease in peripheral vascular resistances ( P < .01), and a lower heart rate ( P < .05) than intravenous milrinone. Inhaled milrinone prevented the alterations in relaxations of pulmonary arteries to acetylcholine caused by cardiopulmonary bypass, and relaxations to bradykinin were improved in the inhaled milrinone group ( P < .05) compared with the cardiopulmonary bypass and control groups.
Conclusions:
Inhaled milrinone prevents the occurrence of the pulmonary endothelial dysfunction seen after cardiopulmonary bypass. The hemodynamic and oxygenation profiles obtained with inhaled milrinone are safer than with intravenous milrinone. These strategies might be useful in preventing pulmonary hypertension after cardiac surgery.
Insights
Inhaled milrinone effectively prevents pulmonary endothelial dysfunction after cardiopulmonary bypass, offering a safer alternative to intravenous administration for managing pulmonary hypertension.
Area of Science:
- Cardiovascular Research
- Pulmonary Medicine
- Pharmacology
Background:
- Cardiopulmonary bypass (CPB) can induce systemic inflammation, leading to pulmonary endothelial dysfunction and potentially pulmonary hypertension.
- Milrinone, a phosphodiesterase inhibitor, is explored for its therapeutic potential in mitigating CPB-induced complications.
Purpose of the Study:
- To compare the efficacy of inhaled versus intravenous milrinone in preserving pulmonary endothelium-dependent relaxations post-CPB.
- To evaluate the hemodynamic and oxygenation effects of different milrinone administration routes in a porcine model.
Main Methods:
- A porcine model was used with five groups: control, CPB only, inhaled milrinone, intravenous milrinone, and inhaled saline.
- Pulmonary arterial relaxations to acetylcholine and bradykinin were assessed post-CPB in organ chambers.
- Hemodynamic and oxygenation parameters were monitored throughout the experiment.
Main Results:
- Inhaled milrinone resulted in less hypotension and a lower heart rate compared to intravenous milrinone.
- Inhaled milrinone preserved pulmonary artery relaxations to acetylcholine, which were impaired by CPB.
- Pulmonary artery relaxations to bradykinin were enhanced with inhaled milrinone treatment.
Conclusions:
- Inhaled milrinone effectively prevents post-CPB pulmonary endothelial dysfunction.
- The hemodynamic profile of inhaled milrinone is safer than that of intravenous administration.
- This inhaled strategy shows promise for preventing pulmonary hypertension after cardiac surgery.
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