Blood flow and oxygenation of tumors in mice.I. Effects of breathing gases containing carbon dioxide at atmospheric pressure

Kruuv, J.; Inch, W. R.; McCredie, J. A.

doi:10.1002/1097-0142(1967)20:1<51::aid-cncr2820200108>3.0.co;2-d

Cited by 73 publications

(20 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using the C3HBA mammary carcinoma implanted subcutaneously in mice as a tumour model, Kruuv et al (1966) showed that carbogen breathing resulted in a 20% increase in TBF compared to air breathing. Allowing the mice to breathe 10% CO 2 -90% O 2 caused blood flow to increase by an average of 50% (Kruuv et al, 1966). Similarly, it was recently shown that carbogen breathing for 6 min resulted in a 50-70% increase in blood flow in RIF-1 tumours growing subcutaneously in mice (Honess and Bleehen, 1995).…”

Section: Effects Of Different O 2 -Co 2 Breathing Mixtures On Tad Andmentioning

confidence: 99%

“…A common current approach has been the breathing of hyperoxic gases, including 100% oxygen (O 2 ) and carbogen (95% O 2 and 5% CO 2 ). The rationale for the use of carbogen over 100% O 2 is based on the following putative mechanisms: (1) CO 2 blocks hyperoxia-induced vasoconstriction, (2) increased CO 2 tensions cause a rightward shift of the oxygen-haemoglobin dissociation curve and (3) CO 2 has a positive chronotropic effect (Kruuv et al, 1966). Despite these sound theoretical grounds, the inhalation of carbogen has had only moderate success as a radiosensitizer (Siemann et al, 1977;Overgaard, 1989;Rojas, 1991).…”

mentioning

confidence: 99%

See 1 more Smart Citation

The effects of hyperoxic and hypercarbic gases on tumour blood flow

et al. 1999

View full text Add to dashboard Cite

Summary Carbogen (95% O 2 and 5% CO 2 ) has been used in preference to 100% oxygen (O 2 ) as a radiosensitizer, because it is believed that CO 2 blocks O 2 -induced vasoconstriction. However, recent work suggests that both normal and tumour arterioles of dorsal flap window chambers exhibit the opposite: no vasoconstriction vs constriction for O 2 vs carbogen breathing respectively. We hypothesized that CO 2 content might cause vasoconstriction and investigated the effects of three O 2 -CO 2 breathing mixtures on tumour arteriolar diameter (TAD) and blood flow (TBF). Fischer 344 rats with R3230Ac tumours transplanted into window chambers breathed either 1%, 5%, or 10% CO 2 + O 2 . Intravital microscopy and laser Doppler flowmetry were used to measure TAD and TBF respectively. Animals breathing 1% CO 2 had increased mean arterial pressure (MAP), no change in heart rate (HR), transient reduction in TAD and no change in TBF. Rats breathing 5% CO 2 (carbogen) had transiently increased MAP, decreased HR, reduced TAD and a sustained 25% TBF decrease. Animals exposed to 10% CO 2 experienced a transient decrease in MAP, no HR change, reduced TAD and a 30-40% transient TBF decrease. The effects on MAP, HR, TAD and TBF were not CO 2 dose-dependent, suggesting that complex physiologic mechanisms are involved. Nevertheless, when ≥ 5% CO 2 was breathed, there was clear vasoconstriction and TBF reduction in this model. This suggests that the effects of hypercarbic gases on TBF are site-dependent and that use of carbogen as a radiosensitizer may be counterproductive in certain situations.

show abstract

Section: Effects Of Different O 2 -Co 2 Breathing Mixtures On Tad Andmentioning

confidence: 99%

mentioning

confidence: 99%

The effects of hyperoxic and hypercarbic gases on tumour blood flow

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Many tumours have poor vascularity and tend to be resistant to radiotherapy and chemotherapy because of factors ranging from intrinsic genetic resistance to extrinsic physiological factors (as reviewed by Vaupel et al, 1989). As some studies have shown that it is possible to enhance tumour blood flow and/or oxygenation by carbogen (95% oxygen/5% carbon dioxide) breathing in animals (Kruuv et al, 1967;Honess et al, 1995;Robinson et al, 1995) and humans (Falk et al, 1992), the effects of carbogen breathing on IF pharmacokinetics were also studied. Carbogen breathing has also been shown to increase the efficacy of radiotherapy (Rojas 1991).…”

mentioning

confidence: 99%

In vivo detection of ifosfamide by 31P-MRS in rat tumours: increased uptake and cytotoxicity induced by carbogen breathing in GH3 prolactinomas

Rodrigues

Maxwell²,

McSheehy³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

SummaryThe direct detection and monitoring of anti-cancer drugs in vivo by magnetic resonance spectroscopy (MRS) may lead to improved anti-cancer strategies. 31P-MRS has been used to detect and quantify ifosfamide (IF) in vivo in GH3 prolactinomas and N-methyl-Nnitrosourea (MNU)-induced mammary tumours in rats. The average concentration of IF in the GH3 prolactinoma over the first 2 h following a dose of 250 mg kg-' i.v. was calculated to be 0.42 ,umol g-1 wet weight, with a half-life of elimination (t,,2) of 2-4 h. Carbogen (95% oxygen/5% carbon dioxide) breathing increased the amount of IF taken up by the GH3 prolactinoma by 50% (P<0.01) to 0.68 ,umol g-1 wet weight, although t,,2 elimination rates were unchanged. IF was also detected in the liver in vivo, with a t,,c of about 1 h. Carbogen breathing did not affect the maximum peak area (Cmax) or the t,,2 in the liver. Most importantly, the carbogen-induced increase in IF uptake by the tumour caused significant growth delay at all time points in the GH3 tumour growth between day 5 and day 12 (P < 0.01) compared with IF alone. These findings show that carbogen breathing has potential for increasing the efficacy of anti-cancer drugs. Isolated GH3 cells were sensitive to the parent drug (IF) in vitro (C~50 = 1.3 ± 0.2 mM) suggesting that the GH3 cells may be either expressing P450 enzymes or are sensitive to the parent drug per se.

show abstract

“…The radiosensitivity of tumors can be improved by increasing tumor oxygen levels, which can be achieved by breathing high-oxygen-content gases [15,26,30]. Addition of CO 2 to O 2 was thought to prevent intermittent vascular closure, thereby improving perfusion, or act on tumor metabolism, resulting in a further improvement of tumor oxygenation [25,27,31,38]. For head-and-neck tumors, breathing a hyperoxic hypercapnic gas mixture like carbogen (95% O 2 , 5% CO 2 ) in combination with nicotinamide administration resulted in a significantly improved tumor response to accelerated radiotherapy (accelerated radiotherapy with carbogen and nicotinamide [ARCON]) [19,20].…”

Section: Introductionmentioning

confidence: 99%