Improved Tissue Perfusion During Pressure-Regulated Hyperthermic Regional Isolated Perfusion in Dogs

Fontijne, Wpj; Vries, Jessica de; Mook, Ph; Elstrodt, Jm; Oosterhuis, J. Wolter; Koops, H. Schraffordt; Oldhoff, J; Wildevuur, Ch. R. H.

doi:10.1016/s0022-5347(17)50144-5

Cited by 5 publications

(7 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Specifically, after treatment of mice with hypoxia three times per day, we measured an arterial pO 2 of 20 -25 mmHg, significantly below that of normoxic mice. It is important that this degree of hypoxia is similar to that observed in critically ill patients [37] and is consistent with tissue levels of oxygen, which are observed in models of endotoxemia [38], at sites of necrosis [39], as well as in murine and human peritonitis [40,41]. Although we now find an important role for hypoxia in the regulation of phagocytosis, we acknowledge the possibility that hypoxia may induce the release of mediators from the lung or other distant organs, which could themselves induce the increase in phagocytosis that is observed.…”

Section: Discussionsupporting

confidence: 72%

Hypoxia causes an increase in phagocytosis by macrophages in a HIF-1α-dependent manner

Anand

Gribar

et al. 2007

Journal of Leukocyte Biology

166

121

View full text Add to dashboard Cite

Phagocytosis is the process by which microbial pathogens are engulfed by macrophages and neutrophils and represents the first line of defense against bacterial infection. The importance of phagocytosis for bacterial clearance is of particular relevance to systemic inflammatory diseases, which are associated with the development of hypoxia, yet the precise effects of hypoxia on phagocytosis remain largely unexplored. We now hypothesize that hypoxia inhibits phagocytosis in macrophages and sought to determine the mechanisms involved. Despite our initial prediction, hypoxia significantly increased the phagocytosis rate of particles in vitro by RAW264.7 and primary peritoneal macrophages and increased phagocytosis of labeled bacteria in vivo by hypoxic mice compared with normoxic controls. In understanding the mechanisms involved, hypoxia caused no changes in RhoA-GTPase signaling but increased the phosphorylation of p38-MAPK significantly. Inhibition of p38 reversed the effects of hypoxia on phagocytosis, suggesting a role for p38 in the hypoxic regulation of phagocytosis. Hypoxia also significantly increased the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in macrophages, which was reversed after p38 inhibition, suggesting a link between p38 activation and HIF-1alpha expression. It is striking that small interfering RNA knockdown of HIF-1alpha reversed the effects of hypoxia on phagocytosis, and overexpression of HIF-1alpha caused a surprising increase in phagocytosis compared with nontransfected controls, demonstrating a specific role for HIF-1alpha in the regulation of phagocytosis. These data indicate that hypoxia enhances phagocytosis in macrophages in a HIF-1alpha-dependent manner and shed light on an important role for HIF-1alpha in host defense.

show abstract

Section: Discussionsupporting

confidence: 72%

Hypoxia causes an increase in phagocytosis by macrophages in a HIF-1α-dependent manner

Anand

Gribar

et al. 2007

Journal of Leukocyte Biology

166

121

View full text Add to dashboard Cite

show abstract

“…High flow rates lead to an increased recruitment of previously poorly perfused vessels and, if the oncotic pressure is inadequate, fluid retention will occur in the limb (Wu et al, 1993;Cross et al, 1994). In ILP, the use of high perfusion flow rates was advocated to improve oxygenation (Fontijne et al, 1984(Fontijne et al, , 1985 and to achieve optimal tissue temperatures more rapidly (Thompson et al, 1994b). However, high flow rates in human ILP could lead to a higher incidence of oedema, localized toxicity and a higher leakage of melphalan into the systemic circulation (Kroon, 1988;Omlor et al, 1990; Klaase et al, 1994b).…”

Section: Discussionmentioning

confidence: 99%

“…An argument against the use of high perfusion flow rates in ILP is the potential increased incidence of oedema, localized toxicity and leakage of melphalan to the systemic circulation with higher morbidity (Kroon, 1988;Omlor et al, 1990;Klaase et al, 1994b;Vrouenraets et al, 1995). However, flow rates higher than the physiological flow have been advocated to provide higher oxygenation (Fontijne et al, 1984(Fontijne et al, , 1985 or enable optimal tissue temperatures to be achieved more rapidly (Thompson et al, 1994a). We have found that high flow rates also lead to an increased recruitment of vessels and, if the oncotic pressure is inadequate, fluid retention in limbs (Wu et al, 1993;Cross et al, 1994).…”

mentioning

confidence: 99%

The effects of perfusion conditions on melphalan distribution in the isolated perfused rat hindlimb bearing a human melanoma xenograft

Smithers²,

Parsons³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Summary An isolated rat hindlimb perfusion model carrying xenografts of the human melanoma cell line MM96 was used to study the effects of perfusion conditions on melphalan distribution. Krebs-Henseleit buffer and Hartmann's solution containing 4.7% bovine serum albumin (BSA) or 2.8% dextran 40 were used as perfusates. Melphalan concentrations in perfusate, tumour nodules and normal tissues were measured using high-performance liquid chromatography (HPLC). Increasing the perfusion flow rates (from 4 to 8 ml min-') resulted in higher tissue blood flow (determined with 5'Cr-labelled microspheres) and melphalan uptake by tumour and normal tissues. The distribution of melphalan within tumour nodules and normal tissues was similar for both Krebs-Henseleit buffer and Hartmann's solution; however, tissue concentrations of melphalan were significantly higher for a perfusate containing 2.8% dextran 40 than for one containing 4.7% BSA. The melphalan concentration in the tumour was one-third of that found in the skin if the perfusate contained 4.7% BSA. In conclusion, this study has shown that a high perfusion flow enhances the delivery of melphalan into implanted tumour nodules and normal tissues, and a perfusate with low melphalan binding (no albumin) is preferred for maximum uptake of drug by the tumour.

show abstract

“…The systemic vascular resistance was expressed in absolute units whereas the regional vascular resistance was defined as a product of the mean arterial pressure/mean pump flow rate and was expressed in hybrid resistance units. Delta pressure (Δ P ) (10) was defined as the difference between the mean systemic arterial pressure and the regional arterial pressure. The double product was calculated as heart rate × mean arterial pressure.…”

Section: Methodsmentioning

confidence: 99%

Systemic Effects of Hyperthermic Isolated Lower Limb Perfusion with Carboplatin and Interferon‐β

Tominaga¹,

Nakano²,

Shibata

et al. 2001

Artificial Organs

View full text Add to dashboard Cite

The changes in systemic circulation during hyperthermic isolated lower limb perfusion with carboplatin and interferon-beta were investigated in 19 patients with malignant melanoma. The cardiac output (CO) increased significantly (p < 0.01) from 3.81 +/- 0.22 L/min before the procedure to 5.30 +/- 0.49 L/min 1 h after hyperthermic perfusion. The double product (mean arterial pressure x heart rate) also increased significantly (p < 0.01) from 5,145 +/- 372 mm Hg/min to 6,760 +/- 486 mm Hg/min. In some patients, it increased to more than twice the control value. These changes were accompanied by an increase in body temperature, presumably caused by the systemic leakage of both warmed blood and interferon-beta. Blood chemistry data demonstrated no significant changes in the liver or renal function. However, the serum CPK level increased markedly on the first postoperative day, and persisted for 1 week, thus suggesting that some muscle damage occurred during the procedure. There was no operative death or severe complications. From these data, we concluded that hyperthermic isolated limb perfusion with interferon-beta is a relatively safe therapeutic method for malignant melanoma of the extremities. However, care should be taken in patients with ischemic heart disease who may suffer a heart attack due to the rapid increase in cardiac work during the procedure.

show abstract

Improved Tissue Perfusion During Pressure-Regulated Hyperthermic Regional Isolated Perfusion in Dogs

Cited by 5 publications

References 9 publications

Hypoxia causes an increase in phagocytosis by macrophages in a HIF-1α-dependent manner

Hypoxia causes an increase in phagocytosis by macrophages in a HIF-1α-dependent manner

The effects of perfusion conditions on melphalan distribution in the isolated perfused rat hindlimb bearing a human melanoma xenograft

Systemic Effects of Hyperthermic Isolated Lower Limb Perfusion with Carboplatin and Interferon‐β

Contact Info

Product

Resources

About