Glibenclamide Serves as a Potent Vasopressor to Treat Vasoplegia After Cardiopulmonary Bypass and Reperfusion in a Porcine Model

Abstract

The hemodynamic stabilization of patients after complex cardiac surgery is a daily challenge. The use of high doses of catecholamines is common but has potential adverse effects. Glibenclamide, a K_ATP blocker, seems to attenuate vasoplegia in different animal models of septic shock. Therefore, the aim of this study was to investigate the impact of Glibenclamide on the vasoplegic syndrome after cardiopulmonary bypass in a porcine model. In this experimental study, 20 landrace pigs were randomized into two groups and examined: In the control group, standard medical therapy, including norepinephrine, was used, and in the study group standard medical therapy plus additional Glibenclamide was administered. Following general anesthesia, prolonged cardiopulmonary bypass and aortic cross-clamping was performed. In the study group, Glibenclamide was administered 45 min after weaning from cardiopulmonary bypass. The dosage used was 10 mg/kg as a bolus, followed by a continuous infusion of 10 mg/kg/h. Hemodynamic and laboratory measurements were performed. Glibenclamide had a relevant effect on circulatory parameters. With increasing vascular resistance and blood pressure, norepinephrine was able to be reduced. While the heart rate dropped to physiological levels, the cardiac index decreased as well. The results lead to the conclusion that Glibenclamide was able to break through vasoplegic syndrome and could therefore serve as a potent drug to stabilize patients after cardiac surgery.

Keywords: Glibenclamide; cardiopulmonary bypass; reperfusion.

Figure 1

SVRI: Continuous monitoring of the systemic vascular resistance index during post-CPB observation. Values are expressed as mean ± SEM. * (p < 0.05) represents significant differences between the study and control groups at the respective time steps (Mann–Whitney U test). The dashed line displays the timeframe of significance. The reference line at 45 min signals the start of Glibenclamide application.

Figure 2

Norepinephrine: Continuous application of norepinephrine during post-CPB observation. Values are expressed as mean ± SEM. * (p < 0.05) represents significant differences between the study and control groups at the respective time steps (Mann–Whitney U test). The dashed line displays the timeframe of significance. The reference line at 45 min signals the start of Glibenclamide application.

Figure 3

Heartrate: Continuous monitoring of the heart rate during post-CPB observation. Values are expressed as mean ± SEM. * (p < 0.05) represents significant differences between the study and control groups at the respective time stamps (Independent samples t-test). The dashed line displays the time frame of significance. The reference line at 45 min signals the start of Glibenclamide application.

Figure 4

MAP: Continuous monitoring of the mean arterial pressure during post-CPB observation. Values are expressed as mean ± SEM. * (p < 0.05) represents significant differences between the study and control groups at the respective time steps (Mann–Whitney U Test). The dashed line displays the timeframe of significance. The reference line at 45 min signals the start of Glibenclamide application.

Figure 5

CI: Continuous monitoring of the pulse contour cardiac index during post-CPB observation. Values are expressed as mean ± SEM. * (p < 0.05) represents significant differences between the study and control groups at the respective time steps (Mann–Whitney U test). The dashed line displays the timeframe of significance. The reference line at 45 min signals the start of Glibenclamide application.

Figure 6

Lactate: Concentration of serum-lactate during whole experiment. Pre-CPB is before surgery, End of CPB is at the end of cardiopulmonary bypass, Post CPB 1/2 is just before the application of Glibenclamide in the study group, and Post CPB 2/2 represents the end of the experiment. Values are expressed as boxplots, continuing the median as a horizontal line inside the box. The first and third quantiles are the edges of the box. Whiskers have a distance of about 1.5 interquartile range to the edges. Outliers are plotted as dots. * (p < 0.05) represents significant differences between the Glibenclamide and control group at the respective time steps (Mann–Whitney U test).

Figure 7

Experimental protocol of the study.