Systemic Inflammatory Response Syndrome After Contentious-Flow Left Ventricular Assist Device Implantation and Change in Platelet Mitochondrial Membrane Potential

Abstract

Background: The objective of this study was to investigate the change of platelet function and platelet mitochondrial membrane potential in contentious-flow left ventricular assist device (CF-LVAD)-implanted heart failure (HF) patients with or without systemic inflammatory response syndrome (SIRS).

Methods and results: We recruited 31 CF-LVAD patients (16 SIRS and 15 non-SIRS) and 11 healthy volunteers as control. Pre- and post-implantation blood samples were collected. We used PFA-100 to test platelet functionality. Mitochondrial potential-sensitive dye was used to detect platelet dysfunction (mitochondrial membrane potential; ΔΨm) via flow cytometry. The percentage of depolarized-ΔΨm platelets was found to be a preexisting condition in all HF patients before CF-LVAD implantation compared with control subjects (10.3 ± 6.3% vs 2.8 ± 2.2%; P < .001). As evident from the PFA-100 test, the HF patients who developed SIRS after CF-LVAD implantation had significantly more qualitative platelet defects and thrombocytopathies compared with baseline. After implantation, the depolarized platelets in the SIRS patients increased by 2-fold compared with baseline (18.2 ± 8.4% vs 9.0 ± 6.6%; P < .01); whereas no change was noticed in the non-SIRS patients (10.9 ± 6.2% vs 11.7 ± 5.8%; P = .75).

Conclusions: We identified that platelet function and mitochondrial damage were enhanced in CF-LVAD patients with SIRS. Our findings suggest that depolarization of mitochondrial membrane potential is associated with SIRS after CF-LVAD implantation surgery.

Keywords: Heart failure; left ventricular assist device; platelet mitochondrial dysfunction; systemic inflammatory response syndrome.

Figure 1

Laboratory hematology and blood chemistry tests of the Non-SIRS and SIRS groups of the HF patients before (Pre-OP) and after one week (POD-1W) of CF-LVAD implantation. Data are expressed as mean±SD. The dotted lines in each line diagram indicating the normal high and normal low values of each parameter measured.

Figure 2

Parameters of whole blood hemostasis test of the Non-SIRS and SIRS groups of HF patients before (Pre-OP) and after one week (POD-1W) of CF-LVAD implantation. Data are expressed as mean±SD. The dotted lines in each line diagram indicating the normal high and normal low values of each parameter measured.

Figure 3

The change in % depolarized ΔΨ_m platelets among the Non-SIRS and SIRS groups before and after CF-LVAD implantation. (A) FSC versus SSC dot plot. The gate indicates position of platelets. (B) The distribution histograms show the change in TMRE fluorescence in the control, Non-SIRS and SIRS groups. (C) Scatter plot representing the differences in % depolarized ΔΨ_m platelets between the healthy controls and the HF patients at the baseline. *p<0.05 is considered significant in Student’s t-test. (D) Box-whisker plot shows the differences in % depolarized ΔΨ_m platelets before and after CF-LVAD implantation in the Non-SIRS and SIRS groups. The lines across each box plot represent the median value. The lines that extend from the top and the bottom of each box represent the lowest and highest observations still inside the lower and upper limit of confidence. *p<0.05 is considered significant in Mann–Whitney U-test.

Figure 4

The change in % depolarized ΔΨ_m platelets associated with different adverse events after CF LVAD implantation among the SIRS group. The lines across each box plot represent the median value. The lines that extend from the top and the bottom of each box represent the lowest and highest observations still inside the lower and upper limit of confidence. *p<0.05 is considered significant in Mann–Whitney U-test.

Figure 5

Relationship between mitochondrial dysfunction and platelet function tests in both the SIRS (A,B) and Non-SIRS groups (C,D).