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.
Hirota
Masanori
M
Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. mhirota@md.okayama-u.ac.jp
Ishino
Kozo
K
Tedoriya
Takeo
T
Sano
Shunji
S
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects* / Q000502:physiology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D016027:Heart Transplantation / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use; D023421:Models, Animal; D011180:Postmortem Changes; D013927:Thrombosis / Q000150:complications / Q000188:drug therapy; D010959:Tissue Plasminogen Activator / Q000494:pharmacology* / Q000627:therapeutic use; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D000925:Anticoagulants; D006493:Heparin; D010959:Tissue Plasminogen Activator