Selective hypothermia in repair of aneurysms of the descending aorta.

Since 1991, we have used a simple, single-clamp technique with open distal anastomosis to repair aneurysms of the descending aorta. To enhance the results of the single-clamp technique in a recent high-risk patient, we used selective hypothermia, cooling primarily the tissues and organs supplied by the aorta and tributaries distal to the left subclavian artery. This preliminary report describes the technique and gives the rationale for its use.

The development and magnitude of thermotolerance during chronic hyperthermia in murine bone marrow granulocyte-macrophage progenitors: I.

Murine bone marrow granulocyte-macrophage progenitors (CFU-GM) are capable of developing thermotolerance during exposure to temperatures < 42.5 degrees C. Bone marrow from the tibia and femora was heated to 40-42 degrees C (i.e. chronic hyperthermia), and challenged immediately with 15 min at 44 degrees C at regular intervals during treatment (step-up heating). CFU-GM were heated and cultured in McCoy's 5A medium + 15% FBS (fetal bovine serum) and lung-conditioned medium (source of colony stimulating factor) in semisolid agar. The kinetics of thermotolerance development and decay, and the magnitude of the thermotolerance during chronic heating with temperatures of 40-41.5 degrees C were similar. Survival increased rapidly to a maxima by approximately 120 min of hyperthermia (temperatures of 40-41.5 degrees C) and thereafter decreased with a slope similar to the controls. Normalization for cell killing by chronic hyperthermia that occurred during "step-up' heating permitted analysis of thermotolerance in the surviving cells. The surviving fraction after 15 min at 44 degrees C, during incubation at 40, 41 and 41.5 degrees C increased from 0.13 to maxima of 0.56 +/- 0.04, 0.71 +/- 0.03 and 0.82 +/- 0.03 respectively, by 150 min and did not decrease for up to 480 min during chronic hyperthermia. The surviving fraction after 15 min at 44 degrees C during incubation at 42 degrees C increased more slowly than during incubations at 40-41.5 degrees C. The survival of thermotolerant cells after exposure to 15 min at 44 degrees C during 42 degrees C chronic hyperthermia was maximal at 0.87 +/- 0.08 by 120 min and then decreased after approximately 150 min of exposure to 42 degrees C. The thermotolerance ratios (TTR's) were 4.0, 5.4, 6.7 and 6.9 for temperatures of 40, 41, 41.5 and 42 degrees C respectively. The results suggest that chronic hyperthermia temperatures (i.e. 40-42 degrees C) induce rapid thermotolerance development in CFU-GM during the thermal exposure and protect this normal marrow progenitor during whole body hyperthermia or ex vivo purging of leukaemic cells.

Intrinsic thermal response, thermotolerance development and stepdown heating in murine bone marrow progenitor cells.

Thermal response, thermotolerance development and stepdown heating (SDH) in the murine bone marrow granulocyte-macrophage (CFU-GM) progenitors were determined in vitro. Marrow was removed from femora and tibia, heated in McCoy's 5A medium plus 15% FBS and cultured in soft agar in the presence of three different sources of colony stimulating factor. D0's (+/- SE) for survival curves of CFU-GM heated in vitro were 147 +/- 13, 71 +/- 9, 37 +/- 2, 19 +/- 0.7, 11 +/- 1, and 4.3 +/- 0.3 min, for temperatures of 41.8, 42, 42.3, 42.5, 43 and 44 degrees C, respectively. Arrhenius analysis showed inactivation enthalpies of 812 +/- 9 KJoules/mole (193 +/- 2 Kcal/mole) above, and 2142 +/- 157 KJoules/mole (509 +/- 37 Kcal/mole) below, an inflection at 42.5 degrees C. Thermotolerance development was evident during prolonged hyperthermia exposure at temperatures below 42.5 degrees C (chronic hyperthermia) as a change in the slope of the survival curves after approximately 110 min of heating. Thermotolerance development at 37 degrees C after exposure to temperatures of 43 degrees C or greater (acute hyperthermia) was assessed by fractionated heat treatments consisting of an initial heat treatment (15 min at 44 degrees C) followed by incubation at 37 degrees C and challenge with 15 min or 25 min at 44 degrees C. Maximum thermotolerance occurred after 210 and 330 min at 37 degrees C, respectively. The half-time for maximum thermotolerance development was 36 min. Depending on the amount of heat damage and the maximum amount of thermotolerance development, the decay of thermotolerance was complete after approximately 48-72 h at 37 degrees C. An exposure of 10 min at 44 degrees C before incubation at 40 or 41 degrees C (stepdown heating) reduced the slope of the 40 or 41 degrees C survival curves by inhibiting thermotolerance development that would have otherwise occurred. D0's were 100 +/- 19 and 45 +/- 5 min for 40 and 41 degrees C incubation preceded by 10 min at 44 degrees C, respectively. These studies indicate that whole-body or regional hyperthermia protocols designed either to treat solid tumours or to purge leukemic stem cells from marrow ex vivo should avoid inadvertent temperature elevations to large volumes of marrow. Although, marrow progenitors are capable of thermotolerance development during exposure to temperatures up to 42.3 degrees C, results suggest that conditions of stepdown heating may prevent thermotolerance development.

Response of murine bone marrow granulocyte-macrophage colony-forming units to hyperthermia in situ.

A detailed understanding of how bone marrow stem cell progenitors are affected by heat is prerequisite to predicting how whole-body or regional hyperthermia protocols may affect bone marrow function. This investigation reports the reproductive integrity of murine tibial bone marrow granulocyte-macrophage colony-forming units (CFU-GM) after in situ hyperthermia. Heat was applied by water bath immersion of the leg of male BALB/c mice anesthetized with 90 mg/kg pentobarbital given subcutaneously. Tibial and rectal temperatures were monitored in representative animals by microthermocouples (tip diameter approximately 100 microns). By approximately 3 min after immersion of the limb, marrow temperature was within 0.3 degree C of water bath temperature (O'Hara et al., Int. J. Hyperthermia 5, 589-601, 1989) and was within 0.1 degree C by 5 min after immersion. The CFU-GM were cultured in "lung-conditioned" McCoy's 5A medium supplemented with 15% fetal calf serum and 0.3% Bacto agar. In situ heating of tibial marrow to exposure temperatures of 42, 42.5, 43, 44, and 45 degrees C gave D0's (+/- 95% CI) of 91 +/- 44, 44 +/- 27, 27 +/- 2.2, 16 +/- 6, and 7 +/- 4 min, respectively. Heating to 41.5 degrees C for up to 180 min did not result in cytotoxicity. Development of thermotolerance after approximately 100 min of heating was apparent by the presence of a "resistant tail" of the 42 degrees C survival curve. A plot of D0 vs water bath temperature was bimodal with an inflection point at approximately 42.5 degrees C. The inactivation enthalpy for temperatures above 42.5 degrees C was 586 kJ/mol (140 kcal/mol) and for temperatures below 42.5 degrees C was estimated to be 1205 kJ/mol (288 kcal/mol). These results show that CFU-GM can be heated predictably in situ, can be inactivated with thermal exposures as low as 42 degrees C, and are capable of developing thermotolerance. These findings underscore the necessity to understand stem cell inactivation by hyperthermia in situ prior to widespread implementation of clinical hyperthermia protocols where bone marrow may be included in the treatment field.

Digital radiography of the chest by self-scanning linear diode arrays.

Diode array digital radiography DADR is a method of radiographic imaging that combines the advantages of computer technology with self-scanning linear diode arrays. These digital images are superior to those obtained by film in recording and displaying information in the lightest and the darkest areas of the film, resulting in a balanced image of the entire thorax without compromising detail, and at reduced radiation dose. This is a direct result of the wide dynamic range, high contrast sensitivity, fiber optic coupling, small diode size, short exposure time, and rejection of scattered x-rays of the system coupled with digital post-processing enhancement of the image displayed at 1024 X 1024 pixels.