The suppression of proinflammatory cytokines improves heart function from non-heart-beating donors following transplantation in a canine model.
We evaluated the effectiveness of a suppressant of the production of proinflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha on a canine heart transplantation model with non-heart-beating donors (NHBDs).Adult mongrel dogs were divided into 3 groups of 5: a control group; FR-1 in which donors were given FR167653, a potent suppressant of IL-1beta and TNF-alpha production; and FR-2 in which both donors and recipients were given FR167653. After measuring the baseline hemodynamic parameters, including cardiac output (CO), left ventricular pressure (LVP), and maximum and minimum rates of increase in LVP (+/- LVdp/dt), FR167653 was administered continuously for 30 minutes before ischemia in the FR-1 and FR-2 groups. Cardiac arrest was obtained by rapid exsanguination from the abdominal aorta and inferior vena cava. The organ was left in the cadaver for 30 minutes. The coronary vascular beds were washed out with 4 degrees C Celsior solution, and then the donor heart was preserved in 4 degrees C Celsior solution for 4 hours. The donor heart was transplanted orthotopically with cardiopulmonary bypass (CPB). FR167653 was administered intravenously from 15 minutes before aortic-cross clamping until the end of the experiment in the FR-2 group. The recipient was weaned from CPB 1 hour after reperfusion. We compared the hemodynamic parameters at 3 hours after reperfusion with the preoperative values in donor animals with the right atrial pressure at 10 mmHg and a 5 microg/kg/min dopamine infusion. Histopathological analysis was also performed.There were no significant differences in the recovery rates of the hemodynamic parameters between the control and FR-1 groups and between the FR-1 and FR-2 groups. However, the recovery rates of CO and -LVdp/dt in the FR-2 group were significantly (P < 0.05) higher than those in the control group. Histopathological analysis showed that myofilaments were better preserved in the FR-2 group compared with the control group.The administration of a suppressant of proinflammatory cytokines before both ischemia and reperfusion effectively preserves donor heart function after transplantation with NHBDs.
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Gunma, Japan.
Shigeru
S
Ohki
Kiyohiro
K
Oshima
Hirofumi
H
Tsutsumi
Norimasa
N
Koike
Koshi
K
Matsumoto
Izumi
I
Takeyoshi
D000465:Algorithms; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D004195:Disease Models, Animal; D004285:Dogs; D006321:Heart / Q000187:drug effects; D016027:Heart Transplantation / Q000379:methods*; D006439:Hemodynamics / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000096:biosynthesis*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009926:Organ Preservation / Q000379:methods; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
C104334:FR 167653; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D011720:Pyrazoles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha