Glucocorticoid administration reduces cardiac dysfunction after brain death in pigs.
BACKGROUND
Traumatic brain injury and subsequent brain death (BD) account for nearly half of all organ donors, yet only 33% of available hearts are transplanted. Alterations in multiple physiologic pathways after BD can lead to cardiac dysfunction and exclusion from transplantation. Triple hormone resuscitation with methylprednisolone, thyroid hormone and vasopressin has had inconsistent results in the effort to reduce cardiac dysfunction associated with BD, but individual analysis of these agents is limited. The hypothesis was that glucocorticoid administration alone could reduce BD-associated cardiac dysfunction.


METHODS
Crossbred pigs (25 to 35 kg) had BD induced by sub-dural balloon inflation. Hemodynamics were measured for 360 minutes after BD. Negative cerebral perfusion pressures and decreased laser Doppler cerebral blood flow confirmed BD. Animals (n = 5/treatment group) received: saline (Group 1); 30 mg/kg methylprednisolone 2 hours before BD (Group 2); or 30 mg/kg methylprednisolone 1 hour after BD (Group 3). Repeated measures analysis of variance and unpaired t-tests were used for appropriate comparisons.


RESULTS
Left ventricular (LV) pre-load recruitable stroke work (PRSW) decreased in untreated Group 1 over time (p < 0.001), whereas PRSW in animals treated with glucocorticoids, Groups 2 and 3, was not different from baseline at 360 minutes after BD. Diastolic function measured as LV -dP/dt (minimum derivative of the change in pressure over time) and tau (time constant of isovolumic relaxation) was also preserved 360 minutes after brain death by glucocorticoids in Groups 2 and 3 (p > 0.05). Oxygen delivery 360 minutes after BD was higher in Group 2 compared with Group 1 (p = 0.02) and Group 3 (p = 0.006).


CONCLUSIONS
Glucocorticoid therapy before or after BD preserved LV systolic and diastolic function. Glucocorticoids administered after brain death might increase the number of hearts available for transplant by reducing brain death-associated cardiac dysfunction.
Lyons
Jefferson M
JM
Cincinnati Children's Hospital Medical Center, Division of Cardiothoracic Surgery, Cincinnati, Ohio 45229, USA.
Pearl
Jeffrey M
JM
McLean
Kelly M
KM
Akhter
Shahab A
SA
Wagner
Connie J
CJ
Pandalai
Prakash K
PK
Duffy
Jodie Y
JY
D000818:Animals; D001926:Brain Death; D002395:Catecholamines / Q000097:blood; D003971:Diastole; D004334:Drug Administration Schedule; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D016027:Heart Transplantation; D006439:Hemodynamics / Q000187:drug effects; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D009206:Myocardium / Q000473:pathology*; D011897:Random Allocation; D013552:Swine; D013599:Systole; D014019:Tissue Donors; D016277:Ventricular Function, Left
D002395:Catecholamines; D005938:Glucocorticoids; D008775:Methylprednisolone