Erythropoietin during porcine aortic balloon occlusion-induced ischemia/reperfusion injury.
BACKGROUND
Aortic occlusion causes ischemia/reperfusion injury, kidney and spinal cord being the most vulnerable organs. Erythropoietin improved ischemia/reperfusion injury in rodents, which, however, better tolerate ischemia/reperfusion than larger species. Therefore, we investigated whether erythropoietin attenuates porcine aortic occlusion ischemia/reperfusion injury.


METHODS
Before occluding the aorta for 45 mins by inflating intravascular balloons, we randomly infused either erythropoietin (n = 8; 300 IU/kg each over 30 mins before and during the first 4 hrs of reperfusion) or vehicle (n = 6). During aortic occlusion, mean arterial pressure was maintained at 80% to 120% of baseline by esmolol, nitroglycerine, and adenosine 5'-triphosphate. During reperfusion, noradrenaline was titrated to keep mean arterial pressure >80% of baseline. Kidney perfusion and function were assessed by fractional Na-excretion, p-aminohippuric acid and creatinine clearance, spinal cord function by lower extremity reflexes and motor evoked potentials. Blood isoprostane levels as well as blood and tissue catalase and superoxide dismutase activities allowed evaluation of oxidative stress. After 8 hrs of reperfusion, kidney and spinal cord specimens were taken for histology (hematoxylin-eosin, Nissl staining) and immunohistochemistry (TUNEL assay for apoptosis).


RESULTS
Parameters of oxidative stress and antioxidative activity were comparable. Erythropoietin reduced the noradrenaline requirements to achieve the hemodynamic targets and may improve kidney function despite similar organ blood flow, histology, and TUNEL staining. Neuronal damage and apoptosis was attenuated in the thoracic spinal cord segments without improvement of its function.


CONCLUSIONS
During porcine aortic occlusion-induced ischemia/reperfusion erythropoietin improved kidney function and spinal cord integrity. The lacking effect on spinal cord function was most likely the result of the pronounced neuronal damage associated with the longlasting ischemia.
Simon
Florian
F
Abteilung Thorax- und Gefäbetachirurgie, Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Ulm, Germany.
Scheuerle
Angelika
A
Calzia
Enrico
E
Bassi
Gabriele
G
Oter
Sükrü
S
Duy
Cuong Nguyen
CN
Kick
Jochen
J
Brückner
Uwe B
UB
Radermacher
Peter
P
Schelzig
Hubert
H
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D021721:Balloon Occlusion / Q000009:adverse effects*; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D019054:Evoked Potentials, Motor / Q000187:drug effects*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007677:Kidney Function Tests; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000517:prevention & control; D013552:Swine
D004921:Erythropoietin