Post-mortem tissue-type plasminogen activator preserves graft function of hearts harvested from non-pre-treated non-heart-beating donors

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.