Effects of FR167653 on ischemia-reperfusion injury: evaluation through preservation and transplantation in canine hearts.
BACKGROUND
Ischemia-reperfusion injury may result in the local release of proinflammatory cytokines. A newly synthesized organic compound, FR167653, has been characterized as a potent suppressant of interleukin-1beta and tumor necrosis factor-alpha. We investigated the effects of FR 167653 on ischemia-reperfusion injury of canine hearts during preservation and transplantation.


METHODS
Seventeen pairs of adult mongrel dogs were used. The donor heart was removed, stored in University of Wisconsin solution at 4 degrees C for 12 hours, and then transplanted orthotopically. Recipients were divided into the FR-treated group (FR167653 1 mg/kg/hr, 8 dogs) and the control group (9 dogs). Hemodynamic parameters, including cardiac output, left ventricular pressure (LVP), and the maximum rate of increase of LVP, were assessed after 120 minutes of reperfusion. The heart specimen was then harvested for histopathologic examination.


RESULTS
The values of LVP (mm Hg) of the FR-treated and the control groups were 120+/-10 and 79+/-9, respectively. The values of LV dp/dt (mm Hg/sec) in the FR-treated and control groups were 4944+/-414 and 2292+/-380, respectively. There were significant differences in LVP (P < .05) and the maximum rate of increase of LVP (P < .01) between the two groups. The values of cardiac output (L/min) of the FR-treated and control groups were 1.27+/-0.12 and 0.71+/-0.11 of the baseline, respectively, showing a significant difference (P < .05) between the two groups. Histopathologic findings included irregular glycogen distribution in myocardial cells of the control group, although this change was less frequent in the FR-treated group.


CONCLUSIONS
FR 167653 seems to have a protective effect on tissue subjected to ischemia-reperfusion injury during the acute phase after heart transplantation.
Koyano
T
T
Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
Takeyoshi
I
I
Takahashi
T
T
Hasegawa
Y
Y
Ishikawa
S
S
Matsumoto
K
K
Morishita
Y
Y
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D016027:Heart Transplantation; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D017725:Ventricular Pressure / Q000187:drug effects
C104334:FR 167653; D007375:Interleukin-1; D011720:Pyrazoles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha