Alpha-2 agonist attenuates ischemic injury in spinal cord neurons.

BACKGROUND: Paraplegia secondary to spinal cord ischemia-reperfusion injury remains a devastating complication of thoracoabdominal aortic intervention. The complex interactions between injured neurons and activated leukocytes have limited the understanding of neuron-specific injury. We hypothesize that spinal cord neuron cell cultures subjected to oxygen-glucose deprivation (OGD) would simulate ischemia-reperfusion injury, which could be attenuated by specific alpha-2a agonism in an Akt-dependent fashion. MATERIALS AND METHODS: Spinal cords from perinatal mice were harvested, and neurons cultured in vitro for 7-10 d. Cells were pretreated with 1 µM dexmedetomidine (Dex) and subjected to OGD in an anoxic chamber. Viability was determined by MTT assay. Deoxyuridine-triphosphate nick-end labeling staining and lactate dehydrogenase (LDH) assay were used for apoptosis and necrosis identification, respectively. Western blot was used for protein analysis. RESULTS: Vehicle control cells were only 59% viable after 1 h of OGD. Pretreatment with Dex significantly preserves neuronal viability with 88% viable (P < 0.05). Dex significantly decreased apoptotic cells compared with that of vehicle control cells by 50% (P < 0.05). Necrosis was not significantly different between treatment groups. Mechanistically, Dex treatment significantly increased phosphorylated Akt (P < 0.05), but protective effects of Dex were eliminated by an alpha-2a antagonist or Akt inhibitor (P < 0.05). CONCLUSIONS: Using a novel spinal cord neuron cell culture, OGD mimics neuronal metabolic derangement responsible for paraplegia after aortic surgery. Dex preserves neuronal viability and decreases apoptosis in an Akt-dependent fashion. Dex demonstrates clinical promise for reducing the risk of paraplegia after high-risk aortic surgery.

Implantable cardioverter-defibrillator shocks in patients with a left ventricular assist device.

BACKGROUND: Left ventricular assist device (LVAD) use is becoming increasingly common for patients with end-stage heart failure. However, the rate of implantable cardioverter-defibrillator (ICD) shocks and the effect of these shocks on outcomes in patients with LVADs remain unknown. METHODS: Medical records were reviewed from patients with both an ICD and a LVAD from September 2000 to February 2009. The association between ICD shocks and survival while receiving device support was assessed using Cox proportional hazards modeling. RESULTS: Thirty-three of 61 patients with a LVAD also had an ICD and form the basis of this report. The mean duration of LVAD support was 238 days. One or more ICD shocks were delivered to 14 patients (42%) with 8 (24%) receiving appropriate shocks for ventricular arrhythmias and 6 (18%) receiving inappropriate shocks. No patients received both appropriate and inappropriate shocks. When compared with receiving no ICD shock, receiving any ICD shock or an appropriate ICD shock were both associated with an increase in the risk of death (hazard ratio [HR] 4.5, 95% confidence interval [CI] 1.2 to 17.3, p = 0.027, and HR 5.3, 95% CI 1.3 to 22.6, p = 0.023, respectively); receipt of an inappropriate shock showed a non-significant trend for an increased risk of death (HR 3.2, 95% CI 0.7 to 16.1, p = 0.151). CONCLUSIONS: ICD shocks are common after implantation of LVADs, with nearly equal numbers of appropriate and inappropriate shocks. ICD shocks are associated with higher mortality. Larger studies are needed for assessing the independent relationship of ICDs to a variety of clinical outcomes in patients with LVADs.