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Updated: Apr 19, 2026
Brain Death Induction in Mice Using Intra-Arterial Blood Pressure Monitoring and Ventilation via Tracheostomy
Published on: April 17, 2020
Short- and long-term effects of brain death on post-transplant graft function in a rodent model
Shiliang Li1, Sevil Korkmaz2, Sivakkanan Loganathan2
1Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany lishiliangcom@hotmail.com.
Insights
Brain death (BD) impairs donor heart function, but short-term BD effects are reversible after transplantation. Long-term BD increases susceptibility to ischemia/reperfusion injury, impacting graft outcomes.
Area of Science:
- Cardiology
- Transplantation Immunology
- Physiology
Background:
- Heart transplantation is a vital treatment for end-stage heart failure.
- Donors after brain death (BD) are the primary source for cardiac grafts.
- Brain death can cause hemodynamic instability and cardiac dysfunction, potentially affecting post-transplant graft function.
Purpose of the Study:
- To investigate the impact of short-term (1-hour) and long-term (5-hour) brain death on cardiac function.
- To evaluate the subsequent graft function after heterotopic heart transplantation in a rat model.
Main Methods:
- Brain death was induced in Lewis rats using a balloon catheter; sham-operated rats served as controls.
- Cardiac function was assessed using left ventricular (LV) pressure-volume analysis.
- Hearts were preserved, stored, and heterotopically transplanted, with graft function evaluated post-transplant.
Main Results:
- Brain death significantly reduced LV contractility and relaxation compared to controls.
- Graft function was impaired in the 5-hour BD group but not in the 1-hour BD group post-transplantation.
- Short-term BD-induced cardiac dysfunction was reversible, while long-term BD exacerbated injury.
Conclusions:
- A validated rat model using pressure-volume analysis effectively studied brain death's effects on cardiac function.
- Short-term brain death leads to reversible cardiac dysfunction, while prolonged brain death compromises graft viability.
- These findings highlight the critical time window of donor brain death in heart transplantation outcomes.
Objectives:
Heart transplantation has become the most effective treatment for end-stage heart failure. Donors after brain death (BD) are currently the only reliable source for cardiac transplants. However, haemodynamic instability and cardiac dysfunction have been demonstrated in brain-dead donors and this could therefore also affect post-transplant graft function. We studied the effects of BD on cardiac function and its short-term (1 h) or long-term (5 h) impacts on graft function.
Methods:
In Lewis rats, BD was induced by inflation of a subdurally placed balloon catheter (n = 7). Sham-operated rats served as controls (n = 9). We continuously assessed cardiac function by left ventricular (LV) pressure-volume analysis. Then, 1 or 5 h after BD or sham operation, hearts were perfused with a cold preservation solution (Custodiol), then explanted, stored at 4°C in Custodiol and heterotopically transplanted. We evaluated graft function 1.5 h after transplantation.
Results:
BD was associated with decreased left ventricular contractility (ejection fraction: 37 ± 6 vs 57 ± 5%; maximum rate of rise of LV pressure dP/dtmax: 4770 ± 197 vs 7604 ± 348 mmHg/s; dP/dtmax-end-diastolic volume: 60 ± 7 vs 74 ± 2 mmHg/s; slope Emax of the end-systolic pressure-volume relationship: 2.4 ± 0.1 vs 4.4 ± 0.3 mmHg/µl; preload recruitable stroke work: 47 ± 9 vs 78 ± 3 mmHg; P <0.05) and relaxation (maximum rate of fall of left ventricular pressure dP/dtmin: -6638 ± 722 vs -11 285 ± 539 mmHg/s; time constant of left ventricular pressure decay Tau: 12.6 ± 0.7 vs 10.5 ± 0.4 ms; end-diastolic pressure-volume relationship: 0.22 ± 0.05 vs 0.09 ± 0.03 mmHg/µl, P <0.05) 45 min after its initiation and for the rest of 5 h compared with controls. Moreover, after transplantation, graft systolic and diastolic functions were impaired in the 5-h brain-dead group, while they were identical in the 1-h brain-dead group compared with the corresponding controls.
Conclusions:
We established a well-characterized in vivo rat model to examine the influence of BD on cardiac function using a miniaturized technology for pressure-volume analysis. These results demonstrate that impaired donor cardiac function after short-term BD is reversible after transplantation and long-term BD renders hearts more susceptible to ischaemia/reperfusion injury.
