Research article

BMC Neurology

, 12:81

Open Access This content is freely available online to anyone, anywhere at any time.

The effects of levosimendan on brain metabolism during initial recovery from global transient ischaemia/hypoxia

  • Anna B RoehlAffiliated withDepartment of Anaesthesiology, RWTH Aachen University Hospital Email author 
  • , Norbert ZorembaAffiliated withDepartment of Anaesthesiology, RWTH Aachen University Hospital Email author 
  • , Markus KippAffiliated withDepartment of Neuroanatomy, RWTH Aachen
  • , Johannes SchieferAffiliated withDepartment of Neurology, RWTH Aachen University Hospital
  • , Andreas GoetzenichAffiliated withDepartment of Anaesthesiology, RWTH Aachen University Hospital
  • , Christian BleilevensAffiliated withDepartment of Anaesthesiology, RWTH Aachen University Hospital
  • , Nikolaus Kuehn-VeltenAffiliated withMLHB, Medical Laboratory Bremen
  • , Rene TolbaAffiliated withDepartment of Experimental Animal Science, RWTH Aachen University Hospital
  • , Rolf RossaintAffiliated withDepartment of Anaesthesiology, RWTH Aachen University Hospital
    • , Marc HeinAffiliated withDepartment of Anaesthesiology, RWTH Aachen University Hospital

Abstract

Backround

Neuroprotective strategies after cardiopulmonary resuscitation are currently the focus of experimental and clinical research. Levosimendan has been proposed as a promising drug candidate because of its cardioprotective properties, improved haemodynamic effects in vivo and reduced traumatic brain injury in vitro. The effects of levosimendan on brain metabolism during and after ischaemia/hypoxia are unknown.

Methods

Transient cerebral ischaemia/hypoxia was induced in 30 male Wistar rats by bilateral common carotid artery clamping for 15 min and concomitant ventilation with 6% O2 during general anaesthesia with urethane. After 10 min of global ischaemia/hypoxia, the rats were treated with an i.v. bolus of 24 μg kg-1 levosimendan followed by a continuous infusion of 0.2 μg kg-1 min-1. The changes in the energy-related metabolites lactate, the lactate/pyruvate ratio, glucose and glutamate were monitored by microdialysis. In addition, the effects on global haemodynamics, cerebral perfusion and autoregulation, oedema and expression of proinflammatory genes in the neocortex were assessed.

Results

Levosimendan reduced blood pressure during initial reperfusion (72 ± 14 vs. 109 ± 2 mmHg, p = 0.03) and delayed flow maximum by 5 minutes (p = 0.002). Whereas no effects on time course of lactate, glucose, pyruvate and glutamate concentrations in the dialysate could be observed, the lactate/pyruvate ratio during initial reperfusion (144 ± 31 vs. 77 ± 8, p = 0.017) and the glutamate release during 90 minutes of reperfusion (75 ± 19 vs. 24 ± 28 μmol·L-1) were higher in the levosimendan group. The increased expression of IL-6, IL-1ß TNFα and ICAM-1, extend of cerebral edema and cerebral autoregulation was not influenced by levosimendan.

Conclusion

Although levosimendan has neuroprotective actions in vitro and on the spinal cord in vivo and has been shown to cross the blood–brain barrier, the present results showed that levosimendan did not reduce the initial neuronal injury after transient ischaemia/hypoxia.

Keywords

Levosimendan Cerebral ischaemia Hypoxia Microdialysis