Thermal and thermic effects of wIRA and production of a therapeutically usable field of heat

As an effect related to the transfer of heat radiation en- ergy (“thermal” effect) wIRA produces a therapeutically usable field of heat in tissue [1], [2] by
• reaching capillaries near the surface of the skin by the infrared-A radiation (primary warming)
• heat distribution by the blood (cooling of tissue areas near the surface of the skin, spreading of the heat into the depth)
• increasing capillary bloodflow near the surface of the skin with expansion of the blood flow areas accessible to the radiation and by this augmenting the second mechanism
• conduction of heat into the depth

• secondary energy release by stimulation of metabolism (increase of metabolism) caused by the increase of temperature (in accordance with the reaction velocity temperature rule a 3°C higher temperature means approximately 30% more speed of reaction and by this more energy provision and release in the tissue)
• relatively high primary depth effectiveness of wIRA.
Thermal effects of wIRA – transfer of heat energy, e.g. bringing an amount of heat (heat energy) into tissue – can lead to a temperature increase in the tissue and by this to temperature depending (“thermic”) effects (like the desired sufficient energy production in the tissue, see below). Therefore thermal effects can represent the basis of such thermic effects.
Based on its special properties, wIRA allows a high energy transfer into tissue (with relevant thermal effects) com- bined with a limited temperature increase in the tissue (limited thermic effects, ideal dosing properties). This is especially of importance concerning safety aspects, see separate section about safety aspects below.
An additional example of a temperature depending effect (thermic effect) of wIRA might be the activating of tran- sient receptor potential channels of the vanilloid (TRP-V) family depending on the increased temperature.

Non-thermal and non-thermic effects of wIRA

Non-thermal and non-thermic effects of wIRA (without a relevant transfer of heat energy and without a relevant change of temperature) are based on putting a stimulus on cells and cellular structures as a specific (direct) radi- ation effect. Reactions of the cells at infrared radiation – even partly at very small irradiances – are e.g. target oriented growth of surface extensions (plasmodia) [5], influence on the cytochrome c oxidase [9], [15], [16], target oriented growth of neurons [8], stimulation of wound repair [17], [18] as well as cell protective effects of infrared-A [19], [20], [21], [22] (including signalling pathway [20], [21]) and water-filtered infrared-A (wIRA) [23], [24], [25]. For wIRA with appropriate therapeutic ir- radiances and doses it could not only be demonstrated, that it is harmless for human skin (no induction of matrix metalloproteinase 1) [13], [24], but that it has cell protec- tive effects against the damages caused by UV radiation [23], [24], [25]. (Safety aspects of the clinical use of wIRA are discussed as well in a separate section below.) In addition, wavelengths within wIRA have been shown to influence adhesive interactions between cells and extra- cellular matrices [9], playing a regulative role in wound repair processes, and may have a positive effect on cos- metic results [26]. It is also supposed that wIRA has im- munomodulatory effects [1], [2].
Concerning both thermal and thermic as well as non- thermal and non-thermic effects of wIRA the mediation by pathways like nitric oxide in vasodilatation or by cy- tokines or neurotropines should also be taken into ac- count [27].

Energy-related aspects of wound healing and oxygen

Wound healing and infection defense (e.g. function of granulocytes including their antibacterial oxygen radical formation) represent processes with an extremely high energy demand [1], [26], [27]. Hence they depend on a sufficient supply with energy and oxygen quite decisively. On the long run energy must be provided mostly aerobi- cally (with oxygen). Oxygen plays a double role in wound healing: as an agent in the energy production and as a substrate for the oxygen radical formation of the granulocytes (respiratory burst) [1].
Wound repair and energy production therefore depend on the integrity of the following three vital factors [1], [26], [27]:
• tissue temperature
• tissue oxygen partial pressure
• tissue perfusion.
Even one single factor lying clearly in the pathological area can deter energy production and wound healing or makes them both impossible [1], [26], [27]:

• Below 28° C no wound healing is possible (too slow metabolism in accordance with the reaction velocity temperature rule) [1], [28] and the center of chronic wounds is often relatively hypothermic [1], [26], [27] – while e.g. both preoperative [1], [29] and postopera- tive [1], [26], [30] heat supply to the operation field can improve healing of acute wounds.
• Without a sufficient oxygen partial pressure no aerobic energy production (and no granulocyte function) is possible (the center of chronic wounds frequently has an oxygen partial pressure near zero [1], [26], [27], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41]), which increases markedly the risk of wound in- fections [26].
• A sufficient tissue blood flow including capillary blood flow is required for the transport of high-energy sub- strates to the tissue and for the removal of metabolic waste products [1].
The complex interaction of growth factors, cytokines, proteases and others in the context of wound healing with differences between acute and chronic wounds as well as influences of the age and the importance of the extracellular matrix – with e.g. an outweighing of inflam- mation mediators and proteases (matrix metallopro- teinases) in chronic wounds – are today already quite well-known in detail [42], [43].
wIRA augments the cellular energy provision per time considerably by increasing all three factors, where the effects of wIRA on these three factors have been proven by different study groups by means of various methods [1], [26]:
• Tissue temperature, proved in humans by means of a direct measuring of the tissue temperature with stitch probes [44], [45], [46] as well as with implanted probes (in 2 cm of tissue depth in operation wounds) [26] and thermographically [27], [47], [48] as well as in addition in animal experiments with stitch probes up to 7 cm of tissue depth [49];
e.g. wIRA can increase the temperature in 2 cm of tis- sue depth by approximately 2.7°C [26], the field of heat can reach into a depth of approximately 5(-7) cm [49].
• Oxygen partial pressure in the tissue, proved in hu- mans by means of a direct oxygen partial pressure measurement in the tissue with implanted probes in operation wounds [26] as well as by means of mea- suring of the oxygen saturation of the hemoglobin with an external white light-measuring probe [50];
e.g. wIRA can increase the oxygen partial pressure in 2 cm of tissue depth by approximately 30% [26].
• Tissue blood flow/capillary blood flow, proved in hu- mans by means of blood flow measurement with laser Doppler perfusion imaging (= scanning laser Doppler imaging) [47], [48], [51] and by means of blood flow measurement at two depths with an external laser Doppler-measuring probe [50] as well as in animal experiments by means of color microsphere technique up to 7 cm of tissue depth [49];

e.g. wIRA can increase superficial blood flow to approxi- mately 8 times the amount [47], the field of increased blood flow can reach into a depth of approximately 5(-7) cm [49].
In contrast to this, hyperbaric oxygenation (HBO) [34], [35], [36] primarily increases only one factor, the oxygen partial pressure in the tissue.
The clinically beneficial effect of wIRA on problem wounds and wound infections – including the effects to decrease pain, inflammation, and hypersecretion and to have im- munomodulatory effects – can be explained by the im- provement in both the energy provision per time (increase of the metabolic rate) and the oxygen supply (e.g. for the function of granulocytes) as well as by non-thermal and non-thermic cellular effects [1], [13].
Due to its penetration properties, wIRA allows a multiple energy transfer into subcutaneous tissue (2-3 cm) without irritating or overheating the skin like unfiltered heat radi- ation [1], [2], [26]. As many postoperative wound healing impairments and infections originate primarily in the subcutaneous layer, wIRA has advantages for local warming in acute wound healing compared to other sources such as heating bandage systems or hot packs, whose heat is absorbed in the epidermal layers and may cause burning of the skin [26], [52].
Taking the holistic point of view of quantum physics [53] into account, water-filtered infrared-A can be described as flow of photons (quanta) both with non-thermal and non-thermic as well as with thermal and thermic effects [13]. From the point of view of modern physics with its probabilistic approach [53], [54], regarding the interaction of elements within a system (with an irreversibility of time and a sequence of events and small influences leading to divergent ways and results (butterfly phenomenon)), many systems in the world, especially biological systems, are unstable thermodynamic systems, capable to build up and represent complex structures and being far away from a stable (unstructured) point (chaos) [13]. Energy delivery to the system can maintain such an unstable thermodynamic system [13], [54]. In this sense an ad- equate infrared irradiation with appropriate irradiances can help maintain such a desired unstable thermodyna- mic system: on the macroscopic level predominantly with thermal (transfer of energy) and thermic effects (clinically with increased tissue temperature, perfusion and tissue oxygen partial pressure as energy-related important variables [26]) and on the microscopic/molecular level both with non-thermal and non-thermic as well as with thermal and thermic effects on cells and cell structures [13].

Principles of clinical applications of wIRA

wIRA can always be taken into consideration when a depth effective heat application is desired/indicated clinically (with good tolerance to high power density and with a high energy flow into the tissue). wIRA can always be taken into account when pathogenetically at least one factor which can be influenced positively by the thermal and thermic as well as by non-thermal and non-thermic effects of wIRA is impaired or suboptimal [1].

Advantages of wIRA

• Decrease of pain, inflammation, and hypersecretion and positive immunomodulatory effects [1]. All four effects are clinically important. Especially the pain re- duction (or the pruritus reduction in morphea [55], [56]), seen in a variety of indications, e.g. in verrucae [2], herpes, wounds [1], [26], [27], [57], [58], [59], scleroderma [60], and observed in different study groups, with its positive consequences for the patients (less pain, remarkably less need for analgesics, less side-effects of analgesics) should be emphasized as an important clinical effect of wIRA.
• contact-free, easily used procedure
• “clean” procedure (compared to e.g. fango)
• without expenditure of material
• usable for a single body region (single radiator)
• gentle concerning blood circulation (compared with full bath)
• no need for a fixing at the body (compared with a “warm pack”)
• usable at all sorts of positionings
• offers freedom of movement
• possible combination of “heat and motion” [61]
• ideal dosing properties (dosing primarily by variation of the distance from the radiator)
• continuously rising temperature without heat shock and overheating of the superficial skin layers
• subjectively pleasant (even on wounds), therefore un- problematic use also with children
• good effects in the depth
• long lasting heat depot
• relatively low technical expenditure
• low time expenditure for staff
• easy feasibility
• limited time expenditure for the patient
Altogether, wIRA is:
• fundamentally better than “red light” (unfiltered in- frared), because a considerably higher irradiance is possible with more warming in the depth and less heating of the surface and
• also a better alternative to “wet warm packs” and other heating methods.
Beside the possibility that wIRA radiators are used in hospitals or in offices of physicians or surgeons, wIRA radiators can be used – under the supervision of the re- sponsible physician – directly at home or similarly in a nursing home: especially when for a longer period of time a wound shall be irradiated once or twice daily and the patient itself or his family or an ambulatory nursing care service takes care to use the radiator appropriately, a wIRA radiator can be provided on loan [1].