Thresholds for thermal damage to normal tissues: an update

Abstract

The purpose of this review is to summarise a literature survey on thermal thresholds for tissue damage. This review covers published literature for the consecutive years from 2002-2009. The first review on this subject was published in 2003. It included an extensive discussion of how to use thermal dosimetric principles to normalise all time-temperature data histories to a common format. This review utilises those same principles to address sensitivity of a variety of tissues, but with particular emphasis on brain and testis. The review includes new data on tissues that were not included in the original review. Several important observations have come from this review. First, a large proportion of the papers examined for this review were discarded because time-temperature history at the site of thermal damage assessment was not recorded. It is strongly recommended that future research on this subject include such data. Second, very little data is available examining chronic consequences of thermal exposure. On a related point, the time of assessment of damage after exposure is critically important for assessing whether damage is transient or permanent. Additionally, virtually no data are available for repeated thermal exposures which may occur in certain recreational or occupational activities. For purposes of regulatory guidelines, both acute and lasting effects of thermal damage should be considered.

Figures

Fig 1

Changes in regional blood brain barrier permeability vs. CEM43 after hyperthermia treatment in rats. (A) Fold increase in BBB permeability immediately after whole body heating with a warming pad by Kiyatkin et al. [4]. (B) Increase in BBB permeability immediately following heating in an incubator to CEM43=1.3 min by Sharma [5] and 24 h following heating on a warming pad to CEM43=0.1–0.7 min by Noor et al. [6]. In (B), some of the data was offset along the x-axis to show all the data points clearly. All data bound by the dashed lines refer to CEM43=1.3 min.

Fig 2

Change in cerebral blood flow vs. CEM43. Measurements were made either during or immediately after whole body hyperthermia treatment in rats, humans, and rabbits [, –9].

Fig 3

Heat-induced cell death in the rat brain. (A) Cell death in several brain regions at multiple assessment times after whole body hyperthermia treatment in rats at CEM43=5.9 min [10]. (B) Fold increase in cell death in several brain regions in rats compared to unheated animals, 10 hours after whole body hyperthermia treatment to CEM43=15 min [11].

Fig 4

Changes in neuronal excitability in two regions of hippocampus following whole body hyperthermia in rats (immediately and 30 min after heating). Data are shown as percent change with respect to baseline measurements (data connected by lines where assessed at both time points). Two different CEM43 are plotted for the mature rats. (A) P1 Amplitude, (B) P1 Onset Latency [15].

Fig 5

Heat-induced neurotransmitter concentration changes in the rat brain. (A) glutamate, (B) glycine, and (C) GABA levels are shown in relation to CEM43 in various rat brain regions immediately following whole body hyperthermia [5].

Fig 6

Changes in rat brain metabolism immediately after whole body hyperthermia. (A) Metabolic changes were assessed by lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) activity and RNA content at CEM43=1.07 min in three rat brain regions [20], and (B) metabolic changes vs. CEM43, as assessed by extracellular brain lactate, pyruvate, glutamate, and glycerol concentrations vs. CEM43 [8].

Fig 7

Probability of brain lesion induction and blood brain barrier disruption vs. CEM43 in (A) rabbits and rhesus monkeys and (B) pigs [–36]. In (A), some of the data were offset along the y-axis to show all the data points above CEM43=100 min.

Fig 8

Decrease in testes weight compared to control. (A) % Decrease in weight of tested vs. assessment time at several thermal doses. (B) Changes in testicular weight assessed at various times, grouped by CEM43. Human data are included for comparative purposes, but human data was reported as a measure of % decrease in volumetric measures. This chart highlights the differences in thermal sensitivity between mouse, rat, and human testes (blue symbols) [–41].

Fig 9

Fold increase in cell damage parameters after various heat treatments in mice. (A) Long-term effects, which illustrate that cell damage increases with thermal dose and that the effects occur in two phases: an early and a late phase. (B) Acute cell damage during the first two days.

Fig 10

Indications of sperm function after heating in mice and humans. (A) Early effects of heating on sperm characteristics. (B) Late effects of heating on sperm characteristics. Dashed lines: mouse data with a thermal dose of CEM43=7.5 min [44]. Solid lines: human data with a thermal dose of CEM43=180 min [40].

Fig 11

Thresholds of thermal damage in eye in rabbits and humans assessed immediately after heating. In rabbits, CEM43>21.3 min [73] started causing thermal damage in cornea while thermal lesion in retina was induced at CEM43=926 min [75]. In humans, heat treatment at CEM43=0.015–34.5 min was not sufficient to cause damage to eyelids [76].