Improvement of liver preservation by the calcium channel blocker nisoldipine. An experimental study applying intravital microscopy to transplanted rat livers.
It has been shown recently that inclusion of the calcium channel blocker nisoldipine to University of Wisconsin (UW) solution significantly improves survival after rat liver transplantation. To further elucidate the mechanisms involved, rat livers were stored for 1 h in UW solution with or without the addition of 1.4 microM nisoldipine (Miles, West Haven, Conn., USA). The liver grafts were investigated in vivo 90 min after transplantation by intravital fluorescence microscopy. Sinusoidal perfusion was reduced in all sublobular regions of the liver in the UW group (e.g. portal area: 76.7 +/- 2.1%) and in the nisoldipine group (85.8 +/- 1.5%). Diameters of liver sinusoids were comparably reduced in the UW and nisoldipine groups indicating that nisoldipine did not cause vasodilatation. Adhesion of leukocytes, however, rose significantly after liver transplantation particularly in periportal regions (25.8 +/- 2.5%) compared to controls (17.1 +/- 2.8%; P < 0.05). Adhesion of leukocytes was reduced when nisoldipine was included in UW solution (13.3 +/- 1.7%; P < 0.05). Administration of latex particles, which were given in additional experimental groups, demonstrated an impressive increase in phagocytic activity of Kupffer cells after liver transplantation in periportal and pericentral areas (161 +/- 14% and 184 +/- 19% of controls). Phagocytosis was significantly reduced by nisoldipine in the periportal region (101 +/- 10%; P < 0.01). Thus, the beneficial effect of nisoldipine was most pronounced in periportal regions, where the majority of Kupffer cells are located and leukocyte adhesion was at a maximum.
Marzi
I
I
Chirurgische Universitätsklinik, Homburg/Saar, Germany.
Walcher
F
F
Bühren
V
V
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005978:Glutathione; D007328:Insulin; D008102:Liver Circulation / Q000187:drug effects; D016031:Liver Transplantation / Q000473:pathology* / Q000502:physiology*; D008833:Microcirculation / Q000187:drug effects; D008853:Microscopy / Q000379:methods; D023421:Models, Animal; D015737:Nisoldipine / Q000494:pharmacology*; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D011887:Raffinose; D051381:Rats; D011917:Rats, Inbred Lew
D002121:Calcium Channel Blockers; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D015737:Nisoldipine; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose