Esmolol and landiolol, selective beta1-adrenoreceptor antagonists, provide neuroprotection against spinal cord ischemia and reperfusion in rats.
BACKGROUND
Paraplegia is a devastating and unpredictable complication occasionally resulting from surgery of the thoracic and thoracoabdominal aorta. Because ultrashort-acting selective beta(1)-adrenoreceptor antagonists provide neuroprotective effects after brain ischemia, we hypothesized that they would also ameliorate spinal cord injury after transient ischemia and reperfusion in rats.


METHODS
Male Sprague-Dawley rats were randomly assigned to one of the following 4 groups: saline (received IV infusion of 0.9% saline at a rate of 0.5 mL/h, n = 8), esmolol (esmolol 200 microg/kg/min, n = 8), landiolol (landiolol 50 microg/kg/min), or sham surgical (n = 6). Infusion of saline or drugs was initiated 30 minutes before spinal cord ischemia and continued for the subsequent 24-hour reperfusion. Spinal cord ischemia was induced by intraaortic balloon occlusion combined with proximal arterial hypotension for 10 minutes. The spinal cord was then reperfused for 24 hours. Ischemic injury was assessed in terms of the motor deficit index score of the hindlimb and the number of viable motor nerve cells in the anterior spinal cord at 24 hours after reperfusion.


RESULTS
The motor deficit index scores were significantly lower in the esmolol and landiolol groups compared with the saline group (P < 0.05). Histopathologic evaluation of the spinal cord showed less damage in the esmolol and landiolol groups than in the saline group (P < 0.05).


CONCLUSIONS
These data show that ultrashort-acting selective beta(1)-adrenoreceptor antagonists can reduce neurological injury in a rat model of spinal cord ischemia-reperfusion.
Umehara
Shino
S
Akita University Graduate School of Medicine, Akita City, Akita 010-8543, Japan. tgoyagi@doc.med.akita-u.ac.jp
Goyagi
Toru
T
Nishikawa
Toshiaki
T
Tobe
Yoshitsugu
Y
Masaki
Yoko
Y
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001784:Blood Gas Analysis; D006439:Hemodynamics / Q000502:physiology; D006614:Hindlimb / Q000503:physiopathology; D008297:Male; D009025:Morpholines / Q000627:therapeutic use*; D009043:Motor Activity / Q000502:physiology; D009046:Motor Neurons / Q000473:pathology; D009069:Movement Disorders / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D018696:Neuroprotective Agents; D011412:Propanolamines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology; D020760:Spinal Cord Ischemia / Q000188:drug therapy* / Q000473:pathology; D014508:Urea / Q000031:analogs & derivatives* / Q000627:therapeutic use
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D009025:Morpholines; D018696:Neuroprotective Agents; D011412:Propanolamines; C077049:landiolol; D014508:Urea; C036604:esmolol