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Updated: May 23, 2026
In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model
Published on: October 27, 2020
Effects of milrinone on left ventricular cardiac function during cooling in an intact animal model
1Department of Physiology & Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Introduction:
Due to adverse effects of β-receptor agonists reported when applied during hypothermia, left ventricular (LV) cardiac effects of milrinone, a PDE3 inhibitor which mode of action is deprived the sarcolemmal β-receptor-G protein-PKA system, was tested during cooling to 15 °C.
Methods:
Sprague Dawley rats were instrumented to measure left ventricular (LV) pressure-volume changes using a Millar pressure-volume conductance catheter. Core temperature was reduced from 37 to 15 °C (60 min) using internal and external heat exchangers. Milrinone, or saline placebo, was given as continuous i.v. infusions for 30 min at 37 °C and during cooling.
Results:
In normothermic controls continuous milrinone infusion for 90 min elevated cardiac output (CO) and stroke volume (SV) significantly. Significant differences in cardiac functional variables between the milrinone group and the saline control group during cooling to 15 °C were found: Compared to saline treated animals throughout cooling from 33 to 15 °CSV was significantly elevated in milrinone animals, the index of LV isovolumic relaxation, Tau, was significantly better preserved, and both HR and CO were significantly higher from 33 to 24 °C. Likewise, during cooling between 33 and 28 °C also LVdP/dt(max) was significantly higher in the milrinone group.
Conclusions:
Milrinone preserved LV systolic and diastolic function at a significantly higher level than in saline controls during cooling to 15 °C. In essential contrast to our previous results when using β-receptor agonists during hypothermia, the present experiment demonstrates the positive inotropic effects of milrinone on LV cardiac function during cooling to 15 °C.
Insights
Milrinone, a PDE3 inhibitor, improved left ventricular (LV) function during hypothermia. Unlike beta-receptor agonists, milrinone enhanced cardiac output and preserved LV systolic and diastolic function during cooling to 15°C.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Beta-receptor agonists have adverse effects during hypothermia.
- Milrinone, a PDE3 inhibitor, acts independently of the beta-receptor pathway.
- Investigating milrinone's cardiac effects during profound cooling is crucial.
Purpose of the Study:
- To evaluate the left ventricular (LV) cardiac effects of milrinone during hypothermia.
- To compare milrinone's effects with beta-receptor agonists during cooling.
- To determine if milrinone preserves cardiac function during severe temperature reduction.
Main Methods:
- Sprague Dawley rats were used to measure LV pressure-volume changes.
- Core body temperature was reduced from 37°C to 15°C over 60 minutes.
- Milrinone or saline placebo was administered via continuous intravenous infusion.
Main Results:
- Milrinone significantly increased cardiac output (CO) and stroke volume (SV) in normothermic controls.
- During cooling to 15°C, milrinone preserved LV systolic and diastolic function compared to saline.
- Milrinone significantly improved LV isovolumic relaxation (Tau), heart rate (HR), and CO at higher temperatures during cooling.
Conclusions:
- Milrinone effectively preserves LV systolic and diastolic function during profound hypothermia (cooling to 15°C).
- Milrinone demonstrates positive inotropic effects on LV function during cooling, contrasting with adverse effects of beta-receptor agonists.
- Milrinone represents a potential therapeutic option for maintaining cardiac function during hypothermia.
