Biomedical subjects

Steven H Quarfordt

Publications and source records attributed to Steven H Quarfordt.

4 recordsLinked to original sources

PubMed2003

Effect of hepatic artery flow on bile secretory function after cold ischemia.

These studies evaluated the influence of hepatic arterial flow on biliary secretion after cold ischemia. Preparation of livers for transplantation or hepatic support impairs biliary secretion. The earliest indication of cold preservation injury during reperfusion is circulatory function. Arterial flow at this time may be critical for bile secretion. Porcine livers were isolated, maintained at 4 degrees for 2 h and connected in an extracorporeal circuit to an anesthetized normal pig. The extracorporeal livers were perfused either by both the hepatic artery and portal vein (dual) or by the portal vein alone (single). Incremental doses of sodium taurocholate were infused into the portal vein of both the dual and single perfused livers, and the bile secretion was compared. Most endogenous bile acids are lost during hepatic isolation. After supplementation, the biliary secretion of phosphatidyl choline and cholesterol was significantly better in the dual than single vessel-perfused livers; however, no difference was seen in bilirubin output. Single perfused livers were completely unable to increase biliary cholesterol in response to bile acid. The dependence of bile cholesterol secretion on arterial flow indicates the importance of this flow to the detoxification of compounds dependent on phosphatidyl choline transport during early transplantation.

Animals↗

PubMed2002

Porcine hepatic phospholipid efflux during reperfusion after cold ischemia.

BACKGROUND: Cold preservation produces hepatic injury that is difficult to assess during early reperfusion. The value of reperfusion plasma choline phospholipid in predicting subsequent organ function is documented in these studies. MATERIALS AND METHODS: Livers of female Yorkshire pigs were prepared for transplantation. After 2 h of cold ischemia the reperfusion plasma was evaluated for choline phospholipid and cholesterol. These values were correlated with bile secretion, hepatic hemodynamics, oxygen uptake, and plasma sorbitol dehydrogenase levels. RESULTS: The isolated porcine liver demonstrates a rapid efflux of choline phospholipids into plasma during early reperfusion after cold preservation. After this initial efflux no subsequent plasma increment occurred. These choline-phospholipid increments were isolated in plasma higher density (d > 1.063) lipoproteins and were not accompanied by equivalent increases in cholesterol. Neither biliary reflux nor lecithin cholesterol acyl transferase abnormalities contributed appreciably to the phospholipid increments in reperfusion plasma. Livers with the largest efflux of choline phospholipids had the most impaired circulatory and bile secretory function at 4 h of reperfusion. CONCLUSION: The immediate increase of choline phospholipids, particularly lysophosphatidylcholine, in reperfusion plasma after cold ischemia provides an index of the injury occurring during this interval and correlates with early organ function.

Animals↗

PubMed2002

Regulation of NFkappaB in hepatic ischemic preconditioning.

BACKGROUND: The second messengers tyrosine kinase (TK) and protein kinase C (PKC) have been implicated in mediating the cellular signaling cascade during hepatic ischemic preconditioning (IPC). We evaluated the role of TK and PKC on the modulation of the transcription factor nuclear factor kappa B (NFkappaB) and its inhibitor IkappaB alpha during IPC. STUDY DESIGN: Yorkshire pigs underwent routine harvest. IPC livers underwent 15 minutes of ischemia and 15 minutes of in situ perfusion before harvest, with or without pretreatment with a TK inhibitor (genistein) or a PKC inhibitor (chelerythrine). During cold storage and reperfusion, tissue extracts were analyzed for IkappaB alpha phosphorylation and NFkappaB levels and for TK and PKC activity by Western blot. RESULTS: Control pig livers demonstrated no change in the levels of TK, PKC, IkappaB alpha, or NFkappaB before cold ischemia. IPC grafts demonstrated activation of TK and PKC with increased IkappaB alpha phosphorylation and NFkappaB levels before cold ischemia. IPC grafts pretreated with genistein demonstrated inhibition of TK activation but not of PKC activation. Genistein-pretreated grafts also demonstrated inhibition of IkappaB alpha phosphorylation and a lack of NFkappaB translocation to the nucleus throughout the entire experiment. IPC grafts pretreated with chelerythrine demonstrated inhibition of PKC activation but not TK activation. Chelerythrine-pretreated grafts also demonstrated IkappaB alpha phosphorylation before cold ischemia and enhanced nuclear levels of NFkappaB. CONCLUSIONS: Data suggest that the role of TK in IPC might be mediated in part by NFkappaB, but PKC does not depend on NFkappaB for its effect. Two parallel signaling pathways might explain these data.

Alkaloids↗

PubMedDate not supplied

Donor hepatic function: a factor in postreperfusion syndrome.

Reperfusion of support livers after cold preservation produces hemodynamic instability (i.e., postreperfusion syndrome) in the recipient during both orthotopic liver transplantation and extracorporeal liver perfusion. We evaluated the effect of the normal porcine cold-preserved support liver on healthy recipient hemodynamics and in situ liver function during extracorporeal liver perfusion. Support livers were harvested from Yorkshire pigs and reperfused in an extracorporeal circuit with a healthy, anesthetized recipient pig. Correlation analyses were performed between support liver variables of function (oxygen consumption, bile flow, and biliary phospholipid and cholesterol output) and both recipient hemodynamic stability (heart rate, blood pressure, urine output, and vasopressor use) and hepatic function (bile flow and biliary phospholipid secretion). The data indicate that optimally functioning support livers are associated with improved recipient hemodynamic stability manifested by decreased recipient heart rate and vasopressor use and increased recipient urine output. Support livers exhibiting poor biliary secretory function (i.e., bile flow and phospholipid output) were associated with similarly diminished recipient liver biliary secretory function. These data indicate that the functional condition of the support liver after harvest and cold preservation may influence both recipient hemodynamic parameters and the endogenous function of the recipient liver.

Animals↗