Related Experiment Video
Updated: Jun 12, 2026
Pre-clinical Model of Cardiac Donation after Circulatory Death
Published on: August 2, 2019
Post-mortem tissue-type plasminogen activator preserves graft function of hearts harvested from non-pre-treated
Masanori Hirota1, Kozo Ishino, Takeo Tedoriya
1Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. mhirota@md.okayama-u.ac.jp
Background:
Intracoronary microthrombi may cause primary graft failure of hearts harvested from non-pre-treated non-heart-beating donors (NHBDs). We examined the extent of functional recovery to compare the protective effects of post-mortem tissue-type plasminogen activator (t-PA) and heparin pre-treatment.
Methods:
Heparin pre-treatment was systemically administered before hypoxic cardiac arrest in 6 mongrel dogs (Group A). No pre-treatments, including heparin, were administered in 8 dogs (Group B). After 60 minutes of ischemia, intracoronary microthrombi were flushed by retrograde blood cardioplegia with t-PA. After 120 minutes of controlled reperfusion, pre-load was increased for ejection against an after-load of 80 mm Hg. Pressure-volume loops were recorded to obtain the end-systolic pressure-volume relationship (ESPVR) and end-diastolic pressure-volume relationship (EDPVR). Stroke volume at a given pre-load was calculated from averaged ESPVR, EDPVR, and after-load identical to the averaged baseline value. The Frank-Starling relationship was obtained, and cardiac status was classified using the Forrester hemodynamic sub-set.
Results:
There were no significant differences between Group A and Group B in post-resuscitated end-systolic elastance (3.1 +/- 0.7 vs 3.0 +/- 0.8 mm Hg/ml), time constant of isovolumic relaxation (40 +/- 7 vs 40 +/- 6 msec), LV max +dP/dt (1133 +/- 131 vs 1090 +/- 105 mm Hg/s), and LV max -dP/dt (732 +/- 131 vs 752 +/- 122 mm Hg/s). The post-resuscitated cardiac index was decreased to about 50%, and cardiac status was classified as Forrester III or IV sub-set.
Conclusions:
Post-mortem t-PA preserves graft function of hearts harvested from non-pre-treated NHBDs. This pharmaceutical intervention may be an alternative to heparin pre-treatment, which could increase the number of cardiac allografts harvested from potential non-pre-treated NHBDs.
