**Background:** Brain death (BD) triggers a cascade of pathophysiological events including loss of neuro-hormonal control, hemodynamic instability, and inflammation, which compromise organ quality for transplantation. Up to 20% of potential donors are lost due to cardiac arrest from inadequate management. Clinical guidelines suggest volume expansion, vasopressin, thyroid hormone, and corticosteroid replacement, but evidence from controlled studies is limited. This study aimed to evaluate the effects of a progressive, optimized maintenance strategy (crystalloid, vasopressin, levothyroxine, methylprednisolone, and norepinephrine) on clinical, laboratory, and histological outcomes in a rabbit BD model.
**Methods:** Twenty male New Zealand rabbits (3.0–4.0 kg) were randomized into four groups (n=5 each): Group A (control, no BD), Group B (BD + crystalloid boluses up to 40 mL/kg), Group C (BD + crystalloid + norepinephrine 0.05–2 mcg/kg/min), and Group D (BD + crystalloid + vasopressin 0.04 U/h + methylprednisolone 15 mg/kg + levothyroxine 4 mg/kg + norepinephrine as needed). BD was induced by rapid inflation of a Fogarty catheter with 3 mL air via craniotomy, confirmed by hypertensive peak, absent corneal reflex, and fixed mydriasis. Animals were monitored for 4 hours; vital signs (MAP, HR, SpO2, temperature) and blood samples (sodium, glucose, lactate, CPK, potassium, hemoglobin, TGO, TGP, amylase) were collected at baseline and end. Organs (kidney, heart, liver) were harvested for histology (H&E staining, digital whole-slide imaging). A blinded pathologist quantified renal tubular cell size, cardiac vessel size (congestion), and hepatic steatosis. Statistical analysis used one-way ANOVA with post-hoc Scheffe or Kruskal-Wallis tests (p<0.05).
**Key Results:** One rabbit in Group B died from cardiac arrest at 3 hours. Group D showed significantly higher MAP than Group B (p=0.008) and required fewer fluid infusions (p=0.032) and lower volume (p=0.014) compared to Groups B and C. Group B required 3 times more fluid volume (p=0.006) and 3.4 times more infusions (p=0.007) than Group A; Group C required 2.3 times more volume (p=0.042) and 3.6 times more infusions (p=0.004). Group D did not require norepinephrine. Sodium levels were elevated in Group B vs. Groups C and D (p=0.021). Glucose variation was higher in Group C vs. others (p=0.026). Lactate, potassium, hemoglobin, TGO, TGP, CPK, and amylase showed no significant differences. Histologically, renal tubular cell size was smaller in Group D vs. Groups B (p=0.003) and C (p<0.001), and similar to Group A (p=0.088). Cardiac vessel size (congestion) was smaller in Group A vs. Groups B (p=0.003) and C (p=0.036), but Group D was similar to Group A (p=0.106). Hepatic steatosis area was lowest in Group D (562.6 µm²) among intervention groups, closest to Group A (208.0 µm²), though pairwise comparisons were not significant. No differences were found in other histological parameters.
**Clinical Implications:** The optimized strategy (vasopressin, levothyroxine, methylprednisolone, and norepinephrine) improved hemodynamic stability, reduced fluid requirements, and prevented hypernatremia and hyperglycemia in this rabbit BD model. Histological signs of early ischemia (renal tubular cell swelling, cardiac congestion, hepatic steatosis) were attenuated, suggesting better organ preservation. These findings support the use of combined hormone therapy and targeted hemodynamic management in potential organ donors to reduce donor loss and improve graft quality. Limitations include small sample size, short observation period (4 hours), and lack of diuresis measurement. Further studies with longer follow-up and larger samples are needed to confirm clinical applicability.