Biomedical subjects

D E Sawaya

Publications and source records attributed to D E Sawaya.

5 recordsLinked to original sources

PubMed2000

Both ischemic and pharmacological preconditioning decrease hepatic leukocyte/endothelial cell interactions.

BACKGROUND: Ischemic preconditioning has been shown to protect some tissues from ischemia/reperfusion (I/R) injury. Adenosine is believed to play an important role by attenuating leukocyte-endothelial cell adhesive interactions. Dipyridamole increases adenosine bioavailability. The purpose of this study was to evaluate the effects of mechanical (MPC) and pharmacological preconditioning (PPC) on leukocyte endothelial cell interaction in hepatic I/R injury. METHODS: C57BL6 mice were subjected to 30 min of ischemia to the left lobe of the liver. Groups tested at 30 min, 2, 5, 12, and 24 hr of reperfusion had 1) sham laparotomy (n = 10, 2) I/R (n = 25), 3) ischemic preconditioning with 5 min of ischemia and 10 min reperfusion before I/R (n = 25), and 4) (PPC) with dipyridamole (n = 25). Intravital microscopic examination was used to assess leukocyte/endothelial cell adhesion. Blood was drawn for leukocyte counts and liver function tests. RESULTS: A significant decrease in leukocyte rolling was observed at 30-min and 5-hr reperfusion intervals in the PPC and ischemic preconditioning groups compared with the I/R group. A significant decrease in leukocyte saltation was also observed in the PPC and MPC groups at 2, 5, and 12 hr of reperfusion when compared with the I/R group. aspartate aminotransferase was significantly decreased in the 5-hr preconditioning groups. There was not a significant decrease in the white blood cell count because of PPC or MPC vs. I/R CONCLUSIONS: Preconditioning decreases endothelial/ leukocyte interaction and reduces liver damage as measured by aspartate aminotransferase. These data prove that IPC and PPC provide some degree of hepatic protection in I/R injury.

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PubMed1999

The role of ischemic preconditioning in the recruitment of rolling and adherent leukocytes in hepatic venules after ischemia/reperfusion.

BACKGROUND: We have recently shown that hepatic ischemia/reperfusion (I/R) results in rolling and adherence of leukocytes in terminal hepatic venules (THV) followed by hepatic enzyme elevation and tissue destruction. The objective of this study was to determine the effect of ischemic preconditioning on the recruitment of leukocytes in THV after liver I/R. METHODS: Left hepatic lobe ischemia was induced for 5 min (preconditioning) in anesthetized C57B1/6 mice followed by reperfusion for 10 min and then prolonged ischemia for 30 min. The number of rolling, saltating, and adherent leukocytes in THV was measured at 0.5, 2, 5, 12, and 24 h after reperfusion using intravital video microscopy. Matching sham groups were evaluated after 30 min of ischemia. RESULTS: Hepatic I/R elicited significant increases in the number of rolling, saltating, and adherent leukocytes, with peak values observed at 30 min and 5 h after reperfusion. All of these responses were significantly attenuated in mice undergoing ischemic preconditioning. Rolling leukocytes in THV following I/R without preconditioning reached peak levels of 25.2 +/- 1.4 leuk/2 min (leukocytes/2 min) at 30 min reperfusion and 31.4 +/- 1.5 leuk/2 min at 5 h reperfusion. With ischemic preconditioning these values fell to 12.3 +/- 0.9 leuk/2 min and 14.4 +/- 1.0 leuk/2 min, respectively (P < 0.001). Similarly, adherent leukocytes in nonpreconditioned mice reached peak values of 4.8 +/- 1.3 leuk/2 min at 30 min reperfusion and 8.3 +/- 1.2 leuk/2 min at 5 h reperfusion compared with 2.0 +/- 1.5 leuk/2 min and 1.6 +/- 1.1 leuk/2 min in preconditioned mice, respectively (P < 0.001). CONCLUSION: Ischemic preconditioning attenuates the initial events leading to leukocyte-mediated hepatic destruction following I/R injury. Delineating these mechanisms may play an important role in hepatic transplantation, resection, shock, and sepsis.

Animals↗

PubMed1999

Are all successful renal transplants really successful?

We previously described a small group of renal transplant recipients considered to have successful allografts statistically, but who did not benefit clinically. These were patients in whom the grafts survived greater than 6 months but less than 3 years. This expanded study evaluates 179 consecutive renal transplant recipients divided into three groups. Group 1 (n = 18), group 2 (n = 41), and group 3 (n = 120) have patients with graft survival less than 6 months, between 6 months and 3 years, and greater than 3 years, respectively. Mean age, cause of renal failure, HLA match, and immunosuppressive regimen were not statistically different in any group. The number of acute rejection episodes, number of hospitalizations, and number and seriousness of complications were significantly greater in group 2 patients compared with the other groups. Patients in group 2 experienced five times the number of acute rejections (P < 0.0001), three times the number of hospitalizations (P < 0.0001), and two times the number of complications (P < 0.0001) compared with group 3 patients. In conclusion, those transplant recipients whose grafts survived longer than 6 months but less than 3 years were the most unfortunate. They experienced repeated and serious complications and spent many days in the hospital at great expense. A study with more sensitive methods of detecting presensitization might impact on graft performance in the future.

Adult↗

PubMed1999

P-selectin contributes to the initial recruitment of rolling and adherent leukocytes in hepatic venules after ischemia/reperfusion.

We have recently reported that hepatic ischemia/reperfusion (I/R) is associated with a biphasic increase in the expression of P-selectin in the liver microvasculature, with peak expression levels observed at 20 min and 5 h after reperfusion. This I/R-induced upregulation of P-selectin expression is accompanied by leukocyte-endothelial cell adhesion in terminal hepatic venules (THV). The objective of this study was to determine whether the early expression of P-selectin contributes to the initial recruitment of rolling and adherent leukocytes in THV after liver I/R. Left hepatic lobe ischemia was induced for 30 min in anesthetized C57B1/6 and P-selectin knockout (KO) mice. The number of rolling, saltating, and adherent leukocytes in THV was measured at 0, 15, 30, 60, and 120 min after reperfusion using intravital video microscopy. Hepatic I/R elicited significant increases in the number of rolling, saltating, and adherent leukocytes, with peak values observed at 30 min after reperfusion. All of these responses were absent in P-selectin KO mice and in C57B1/6 mice treated with a blocking antibody to P-selectin. Our findings suggest that P-selectin is the primary determinant of leukocyte-endothelial cell adhesion observed in hepatic venules in the initial period after I/R. Hence, this adhesion molecule may represent a target for therapeutic intervention in liver transplantation and other conditions associated with hepatic I/R.

Animals↗

PubMed1994

Prior exercise suppresses the plasma tumor necrosis factor response to bacterial lipopolysaccharide.

This study was initiated to determine the effect of physical exercise on the in vivo tumor necrosis factor-alpha (TNF) response to Escherichia coli lipopolysaccharide (LPS). Rats familiarized with treadmill running and surgically implanted with vascular catheters were either not exercised or exercised to near exhaustion (mean run time of 102 +/- 13 min) before intravenous LPS challenge (1 mg/kg; lethality of dose is 10-20% in 24 h). Compared with time-matched nonexercised control rats, exercised rats had increased heart rates, plasma lactate, and plasma corticosterone and decreased plasma glucose at the conclusion of exercise. In response to LPS, both groups became hypotensive, exhibited transient hyperglycemia, and sustained hyperlactacidemia. By 30 min post-LPS, plasma corticosterone levels were similar in the two groups. Nonexercised rats exhibited a normal plasma TNF response to LPS with the peak value (10,400 +/- 2,000 U/ml) occurring 90 min after LPS challenge. In contrast, the TNF response in rats exercised before LPS administration was blunted to 17% of the nonexercised group, with the peak occurring at an earlier time after LPS. Addition of recombinant murine TNF to postexercise plasma was fully expressed. The TNF response remained attenuated when LPS was administered up to 6 h after completion of exercise, but it returned to normal in rats allowed to recover for 24 h. The results demonstrate that exercise, perhaps as a stress modality, markedly suppresses the systemic TNF response that is normally observed in response to LPS challenge.

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