SUMMARY The Lewis lung carcinoma growing subcutaneously in the hind leg of male C57BL mice is very hypoxic, having 92% of the p 0 2 measurements ~5 mmHg as determined with a polarographic oxygen electrode. Administration of a perflubron emulsion (8 mVkg) along with carbogen breathing increased the tumor oxygen level so that 82% of the PO, readings were 6 5 mmHg. Treating tumor-bearing animals with TNP-470 (30 mgkg, s.c.) on alternate days and minocycline (10 mgkg, i.p.) daily beginning on day 4 after tumor cell implantation resulted in decreased hypoxia in the tumors on day 9 when p 0 2 measurements were made. The percent of p 0 2 readings s 5 mmHg in the tumors of the TNP-470/ minocycline-treated animals was 75%, which upon administration of the perflubron emulsion along with carbogen breathing was reduced to 45 YO. Therapeutically daily fractionated radiation (2, 3, or 4 Gy x 5 ) was used as an oxygen-dependent cytotoxic modality. The radiation response of the tumors in TNP-470/minocycline-treated animals was greater than that in the untreated tumors. The addition of carbogen breathing for 1 hr prior to and during radiation delivery further increased the radiation response so that overall there was a 2.2-fold increase in the tumor growth delay produced by the fractionated radiation in the animals treated with TNP-470/minocycline compared with untreated animals. Administration of the perflubron emulsion along with carbogen breathing prior to and during radiation delivery resulted in a 3.4-fold increase in tumor growth delay by the fractionated radiation regimens in the TNP-470/minocycline-treated animals compared with the tumor growth delay obtained with radiation alone. There was a linear relationship between decrease in the percent of pOz readings s5 mmHg and tumor growth delay at each radiation dose indicating that the diminution in tumor hypoxia produced by these treatments may be directly responsible for the increase in the effectiveness of the radiation therapy.

In non-smokers, passive heat stress increases shear stress and vasodilation, decreasing arterial stiffness. Smokers, who reportedly have arterial dysfunction, may have similar improvements in arterial stiffness with passive heat stress. Therefore, we examined the effects of an acute bout of whole-body passive heat stress on arterial stiffness in smokers vs. non-smokers. Thirteen smokers (8.8 ± 5.5 [median = 6] cigarettes per day for > 4 years) and 13 non-smokers matched for age, mass, height, and exercise habits (27 ± 8 years; 78.8 ± 15.4 kg; 177.6 ± 6.7 cm) were passively heated to 1.5 °C core temperature (T C) increase. At baseline and each 0.5 °C T C increase, peripheral (pPWV) and central pulse wave velocity (cPWV) were measured via Doppler ultrasound. No differences existed between smokers and non-smokers for any variables (all p > .05), except cPWV slightly increased from baseline (526.7 ± 81.7 cm · s(-1)) to 1.5 °C ΔT C (579.7 ± 69.8 cm · s(-1); p < 0.005), suggesting heat stress acutely increased central arterial stiffness. pPWV did not change with heating (grand mean: baseline = 691.9 ± 92.9 cm · s(-1); 1.5 °C ΔT C = 691.9 ± 79.5 cm · s(-1); p > 0.05). Changes in cPWV and pPWV during heating correlated (p < 0.05) with baseline PWV in smokers (cPWV: r = -0.59; pPWV: r = -0.62) and non-smokers (cPWV: r = -0.45; pPWV: r = -0.77). Independent of smoking status, baseline stiffness appears to mediate the magnitude of heating-induced changes in arterial stiffness.

VF is a reliable index of 24-h hydration status when healthy young males are EU or HY and voiding at a consistent 'urgency'.

Heat stress via exercise in the heat does not acutely change arterial stiffness. However, passive heating reduces U , indicating that heat stress has an independent effect on PWV.

This is the first known investigation to compare thermoregulatory responses to exercise heat stress between men with high and low body fat (BF) in a physiologically uncompensable environment while simultaneously examining the confounding influence of hydration status. Both groups demonstrated similar sweating and cutaneous vasodilatory responses when euhydrated, despite vast differences in rectal temperature. Furthermore, in contrast to low BF, individuals with high BF demonstrated similar increases in core body temperature when either euhydrated or hypohydrated.