Effect of Inspired Oxygen on Portal and Hepatic Oxygenation: Effective Arterialization of Portal Blood by Hyperoxia

Abstract

Because hypoxia may compromise the survival of intraportally transplanted pancreatic islets, we have measured portal blood flow and both portal and hepatic oxygenation in normal and diabetic rats breathing graded inspired oxygen concentrations. Portal blood flow and hepatic tissue oxygenation were measured using a transonic flowmeter and near infrared spectroscopy while gas analysis was carried out on portal venous blood samples. The effects of breathing 13%, 21%, 50%, or 100% oxygen were compared in animals with steptozotocin-induced diabetes and in controls. In diabetic rats breathing 21% oxygen, portal blood flow was significantly lower than in controls (7.2 ± 0.7 vs. 9.1 ± 0.8 ml/min, p < 0.05). In both groups, breathing 100% oxygen significantly increased portal flow (to 8.4 ± 1.0 and 12.2 ± 0.7 ml/min, respectively). This effect was not secondary to hepatic arterial vasoconstriction because it was not prevented by hepatic artery ligation. In controls, breathing 100% oxygen increased portal pO 2 from 5.0 ± 0.9 to 14.4 ± 1.4 kPa (p < 0.05) and portal venous oxygen saturation (PSaO 2 ) from 53.9 ± 12.1% to 92.9 ± 1.4% (p < 0.05), a value not significantly different from peripheral (arterial) saturation. Similarly, in diabetic animals pO 2 rose from 5.6 ± 0.3 to 11.7 ± 0.4 kPa (p < 0.01) and SO 2 from 55.5 ± 5.2% to 88.5 ± 0.6% (p < 0.05). Hepatic oxyhemoglobin rose and deoxyhemoglobin fell reciprocally as a function of the inspired oxygen concentration. Improved hepatic oxygenation observed in animals breathing oxygen-enriched gas mixtures results from an increase in splanchnic blood flow coupled with a marked increase in portal oxygen saturation. This effective arterialization of portal blood may have important consequences for the success of intraportal transplantation of pancreatic islets.Key words: Experimental transplantation; Islets; Hyperoxia; Portal oxygenation INTRODUCTIONever, the mechanism underlying this effect was not clear. We would not expect that increasing the concenPancreatic islet transplantation potentially offers an tration of oxygen in inspired air would have a significant effective cure for insulin-dependent (type I) diabetes effect on arterial hemoglobin saturation, but hypothemellitus. Shapiro and Lakey have recently reported insusized that hyperoxia might nevertheless exert selective lin independence in 43 consecutive patients transplanted effects on splanchnic blood flow. We therefore studied using a steroid-free immunosuppressive regimen (22,24).the effect of the concentration of inspired oxygen on However, they have had to use an average of two transportal blood oxygenation and flow as well as on hepatic plants per recipient, suggesting that an insufficient numtissue oxygenation. Because oxygen tensions in islets ber of islets survive transplantation. Consistent with this transplanted into various sites, including the liver, are concept, we have previously estimated that only ϳ50% lower in diabetic than in control rats (3) we included islets survive intraportal transplantation in ...

Noninvasive quantification of oxygen saturation in the portal and hepatic veins in healthy mice and those with colorectal liver metastases using QSM MRI

“…Although there is little in the literature concerning ShvO 2 in preclinical experiments, the values measured here are broadly in line with similar experiments in rats (~60% during normoxia) . Similarly, previous reports in the literature of the response of portal venous blood in rats to hyperoxia describe an increase from ~53% under normoxia to ~93% under hyperoxia in healthy control animals . It is therefore encouraging that this normoxic SpvO 2 value is comparable to the measurement made here.…”

“…11,13 Similarly, previous reports in the literature of the response of portal venous blood in rats to hyperoxia describe an increase from ~53% under normoxia to ~93% under hyperoxia in healthy control animals. 29 It is therefore encouraging that this normoxic SpvO 2 value is comparable to the measurement made here. Indeed, while the increase under induced hyperoxia was greater than we observed, this could be due to differences between experimental protocols, the efficiency of oxygen delivery, or differences between species.…”

Postnatal Hyperoxia Exposure Differentially Affects Hepatocytes and Liver Haemopoietic Cells in Newborn Rats

“…Direct analyses of tissue oxygen partial pressure were not performed in the present study but increased levels of oxygen and hemoglobin oxygen saturation have already been demonstrated in previous analogous experimental protocols [29]–[31]. Moreover, hyperoxic breathing has been reported to increase portal pO 2 and portal venous oxygen saturation [32]. Liver was excised from each rat, washed in phosphate-buffered saline (PBS) and cut into two blocks which have been fixed in 10% phosphate-buffered formalin or frozen at −80°C.…”

Non-invasive measurement of hepatic venous oxygen saturation (ShvO2) with quantitative susceptibility mapping in normal mouse liver and livers bearing colorectal metastases

“…Previous reports in the literature of the response of portal venous blood in rats to hyperoxia describe an increase from ~53% under normoxia to ~93% under hyperoxia in healthy control animals [22] . It is highly encouraging that this nomoxic SpvO2 value is comparable with the measurement made in our experiment.…”