Thorac Cardiovasc Surg 2012; 60 - V232
DOI: 10.1055/s-0031-1297622

Dimethylsulfoxide-preconditioning ameliorates pulmonary ischemia-reperfusion injury in rats

SP Sommer 1, 2, S Sommer 1, B Sinha 2, 3, I Aleksic 1, M Leistner 1, C Schimmer 1, B Wurdak 1, RG Leyh 1
  • 1Universitätsklinikum Würzburg, Klinik für Herz-, Thorax- und thorakale Gefäßchirurgie, Würzburg, Germany
  • 2Universitätsklinikum Würzburg, Interdisziplinäres Zentrum für Klinische Forschung, Würzburg, Germany
  • 3Universität Würzburg, Institut für Hygiene und Mikrobiologie, Würzburg, Germany

Objectives: Ischemia-Reperfusion (IR) highly contributes to mortality after pulmonary transplantation. Dimethylsulfoxide (DMSO) has been reported to ameliorate IR injury in organs. This study analyzes the impact of DMSO-preconditioning on IR-induced pulmonary mitochondrial dysfunction, tissue degradation and inflammation.

Methods: Rats received mechanical ventilation. IR was induced by 30min. pulmonary clamping followed by 60min. reperfusion. Animals were subjected to control, sham and study groups (IR30/60, DMSO-IR30/60), receiving DMSO (12.5µl) or PBS i.v. before ischemia. Wet/dry weight ratios, mitochondrial respiratory chain complex activities (I-V, II-V, III-V), Cytochrome C (Cyt C) content, MMP9-activation were analyzed.

Results: Tissue water content in controls was 81%, in shams 81%, in IR 30/60 87% and in DMSO-IR30/60 85% (sham vs. IR30/60 P< .01). Mitochondrial function (State3-respiration) was impaired in IR30–60 animals, DMSO protected mitochondrial function when compared to IR30/60 (I-V, P>.05; II-V, P< .01; III-V, P< .05;).

Control

Sham

IR30/60

DMSO-IR30/60

I-V

3.12±0.90

2.69±0.86

1.63±0.30

2.32±0.27

II-V

3.15±0.44

3.25±0.69

1.42±0.35

2.93±0.57

III-V

6.52±1.45

6.25±1.27

3.89±0.94

5.89±0.75

[Respiratory chain function [dO2/dt]]

Significant Cyt C loss was evident in IR30/60 (P< .01), DMSO insignificantly preserved from Cyt C loss (3.5±1.9 vs. 4.1±1.3, P>.05). IR-induced activation of MMP9 (P< .001) was significantly inhibited by DMSO (P< .01).

Fig.1: Tissue MMP9-activity

DMSO showed a strong trend to ameliorate IR-induced MPO-accumulation in lung tissue (0.02±0.01 vs. 0.01±0.01; P>.05).

Conclusions: DMSO ameliorates IR associated mitochondrial dysfunction in combination with reduced inflammation and tissue damage; the underlying mechanism might result from radical-scavenging. DMSO appears to be a promising pharmacological agent to protect graft function during pulmonary IR. Physiologic studies in a large-animal model have to demonstrate improved graft-function after DMSO.