R1 Research and Development

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Overview of Research and Development Activities


State of the Science on Spinal Cory Injury


Research Projects: Effect of Local Cooling | Effects of Weight Shifting | Handrim Technology


Development Projects: Inflammation Modeling | Low Shear, Cool Cushion | Propulsion Training Tools


 

R1 Effectiveness of local cooling on enhancing tissue tolerance

Task Leader(s): David M. Brienza, PhD
Co-Investigator: Yi-Ting Tzen, PhD



Specific Aims

  • Aim 1: To investigate the blood flow response to local skin cooling at various cooling rates in weight-bearing sacral tissues
  • Aim 2: To develop methods for selecting temperature settings to enhance tissue tolerance to loading pressure in people with various degrees of neurological impairments

Hypotheses and Rationale

The general objective of this study is to investigate the effectiveness of local cooling on enhancing tissue tolerance to loading pressure based on laser Doppler skin blood flow measurements. Two hypotheses will be tested to assess the effectiveness of cooling on enhancing tissue tolerance to loading pressure (Aim 1). The hypotheses are as follows:

  • Hypothesis 1a:
    The skin under local cooling (at fast and slow rates) has a shorter recovery time of reactive hyperemia as compared with the skin without local cooling after 60 mmHg of pressure for 20 minutes.
  • Hypothesis 1b:
    The skin under fast cooling (-4°C/min) has a shorter recovery time of reactive hyperemia as compared with the skin under slow cooling (-0.33°C /min) after 60 mmHg of pressure for 20 minutes.

Rationale for Hypotheses 1a & 1b: Within the same subject, the intensity of reactive hyperemia could be used to assess the imposed tissue stress. The recovery time of reactive hyperemia time is highly correlated with oxygen debt and metabolic wastes. This measurement will be used to assess the influences of local cooling on tissue metabolic rates. Other parameters used to characterize reactive hyperemia (i.e. total skin blood flow, half life, time to peak flow, and peak flow) will also be used to investigate benefits associated with local skin cooling. Several research groups have adopted the use of reactive hyperemia to assess the effects of pressure on skin blood flow response.
The application of local cooling to lower skin temperature to 25°C with different rates will elicit varying skin blood flow responses. With a fast cooling rate of -4°C per minute, vasoconstriction is less obvious as compared with a slower cooling rate of -0.33°C per minute. A smaller vasoconstriction indicates more blood flow supply under skin cooling. Given the metabolic rate of local cells is dependent on temperature surrounded them, if we reduce metabolic rates with cooling and, at the same time, allow more blood flow supply to the compressed skin and muscles, the ischemic tolerance of tissues would be increased. Such benefits could be applied to cushion technology by adding the cooling elements and active feedback (such as in Project D2 - Development of low-shear, cool cushion). In order to guide the development, we will examine the effects of cooling rates on skin blood flow response to loading pressure. Our finding will direct future research regarding the application of local cooling on preserving tissue viability.

To develop methods for selecting temperature settings to maximize tissue protection by using local cooling, we will test the following hypotheses:

  • Hypothesis 2a:
    Persons with SCI at T6 and above have a longer recovery time from reactive hyperemia as compared with persons with SCI at T6 and below.
  • Hypothesis 2b:
    Persons with SCI at T6 and below have a longer recovery time from reactive hyperemia as compared with healthy controls.

Rationale for Hypotheses 2a & 2b: In order to develop methods for selecting a cooling setting to accommodate an individual's impairment, a customized temperature setting and rate might be needed to maximize the protection provided by local cooling. In order to achieve Specific Aim 2, we propose to compare cooling responses in three groups. Persons with SCI at T6 and above are well known for impaired cardiovascular regulation including skin blood flow response to pressure or heating. The impairment in this population might cause a different skin blood flow response to cooling. Thus temperature and rate settings for persons with SCI should at least account for this factor.
Although persons with SCI below T6 have intact sympathetic control of the cardiovascular system, the skin blood flow response to cooling in this population might still be impaired as compared with healthy controls. In order to further examine this factor, only people with complete injury (ASIA grade A) will be recruited into the study. Based on results from this research design, we will be able to predict microvascular response to local cooling in individuals with incomplete SCI.



Expected Findings and Deliverables

Local cooling has a great potential to complement current technology used to prevent pressure ulcers in persons with SCI. We anticipate that the proposed research will provide objective evidence supporting that the application of local cooling preserves tissue viability of the weight-bearing soft tissues. Our approach will used to guide the selection of temperature and rate settings to accommodate people with various degrees of neurological impairment. Such findings will facilitate the development of commercial cushions with cooling capacity for the prevention of pressure ulcers in persons with SCI.



Project Update

2012

This project was completed in 2011. Publication of results has continued. Publication of the results of the impact of local cooling in individuals with SCI has been submitted. Another publication looking at the relationship of sensation and autonomic function to reactive hyperemia in people with and without SCI is in preparation.

2011

During the reporting period, we have completed the test on 8 subjects (4 in above T6 SCI, and 4 in below T6 SCI) in the study. All subjects reported that the protocols are acceptable without inducing any discomfort or pain during the experiment. And no adverse events occurred with the implementation of the protocol.
We've analyzed the skin blood flow data collected with fast, slow cooling and without cooling by applying both the short-time Fourier transform and the exponential curve-fitting technique. We found that the reactive hyperemia was reduced with both fast and slow cooling applications. Although this was not observed in subjects with SCI, spectral density data showed that the signal attributed to the metabolic control mechanisms increased significantly without cooling and with slow cooling. Our results suggested that local skin cooling is beneficial to ischemic tissue by decreasing the metabolic demand regardless of the cooling rate in people with different levels of neurological deficits. Findings from this study suggest that cooling the skin may increase tissue tolerance to pressure. The result was reported in Yi-Ting Tzen's Ph.D. dissertation: Effectiveness of local cooling on enhancing tissue ischemia tolerance in people with spinal cord injury (published in Electronic Dissertation Database, University of Pittsburgh). The results were also submitted in an extended abstract to NPUAP biennial conference. The abstract was accepted as honorable mention of the new investigator award and for presentation in a platform session: Tzen YT, Brienza DM, Karg PE, Loughlin PJ, Geyer MJ. Effectiveness of local cooling on enhancing tissue ischemia tolerance in people with spinal cord injury. A manuscript of the results were also submitted to Journal of Applied Physiology, and it is currently in the process of peer review. One main limitation of this study was that we did not reach our proposed sample size in the below T6 group. The inclusion criteria had been changed to obtain more subjects and at the same time to maintain the ability to examine our original hypotheses. However, the majority of the people with injury level below T6 preserved mobility and activity which excluded them from this study as non-wheelchair users. The study maintained its goal of including the wheelchair users only so the results would be more reflective of the population of SCI affected by pressure ulcers.
We also analyzed the relationship of sensation and autonomic function to reactive hyperemia in people with and without SCI. We used the normalized peak skin blood flow and perfusion area of the 33 subjects that had reactive hyperemic response at least in pressure only test condition, and we performed the regression analysis to test the predictors of this response. We found that in pressure only test condition, there were no predictors. However with fast cooling, autonomic function and sensation predict the normalized peak SBF and the perfusion area. With slow cooling, only autonomic function predicts the normalized peak SBF and the perfusion area. Our results suggested that the existence of autonomic function decreases the reactive hyperemic response with both cooling interventions, while the existence of sensation increases the response with fast cooling. The reasons for these differences were not clear and further investigation of both neurological functions might assist in understanding the changes of vascular control after injury and pressure ulcer risk. The results were submitted in an extended abstract to ASIA/iSCoS conference. The abstract was accepted for presentation in a platform session: Tzen YT, Brienza DM, Karg PE. Effects of sensation and autonomic function on reactive hyperemia following pressure with and without cooling in people with spinal cord injury. A manuscript of the results will be submitted to a peer-reviewed journal.

2010

During the reporting period, we have modified our inclusion criteria to recruit people with incomplete spinal cord injury. The majority of people contacting us had incomplete spinal cord injury, and we were only able to recruit 3 people based on our original criteria. After waiting for four months, we decided to change our inclusion criteria to recruit people with spinal cord injury and are not ambulatory. We sent out our new research flyer to several facilities and were able to recruit another 14 subjects with SCI. During the reporting period, we have completed the test on 18 subjects (4 in neurologically intact control group, 10 in above T6 SCI, and 4 in below T6 SCI) in the study. All subjects reported that the protocols are acceptable without inducing any discomfort or pain during the experiment. And no adverse events occurred with the implementation of the protocol.

We've analyzed the skin blood flow data with the short-time Fourier transform (STFT) in the pilot study, and the results were submitted to a peer-reviewed journal. The manuscript was accepted: Tzen YT, Brienza DM, Karg P, Loughlin P. Effects of local cooling on sacral skin perfusion response to pressure: implications for pressure ulcer prevention. Journal of Tissue Viability. The manuscript reported that our study agreed with previous studies that skin temperatures naturally increase when in close contact with other materials for a prolonged period of time. The results also showed that the skin perfusion response after pressure relief was significantly attenuated under the local cooling application. This indicated that local cooling influenced the skin vasomotion under prolonged pressure. STFT showed that such influence might be due to reduced metabolic vasodilator substances accumulation at the skin or increased smooth muscle tone with skin local coolng. Our results denoted that local cooling had a protective effect on the skin under prolonged pressure in human subjects.

We've also analyzed the skin blood flow data collected with fast, slow cooling and without cooling by applying the same analytic methods. The results were submitted in an extended abstract to RESNA 2010. The abstract was accepted as the winner of the student scientific paper competition and for presentation in a platform session: Tzen Y, Brienza DM, Karg PE, Loughlin PJ, Geyer MJ. Effectiveness of local fast and slow cooling on pressure induced reactive hyperemia (RH) in adult human participants. The abstract reported our skin perfusion results collected from neurologically intact adults with fast, slow cooling and without cooling. Reactive hyperemia was used as an outcome measure tool and STFT was used to characterize the underlying mechanisms. Our results showed that both fast and slow cooling provided a protective effect on ischemic tissue by decreasing the metabolic demand and suppressing the smooth muscle activity. Our results also suggested that fast cooling might be more beneficial than slow cooling since fast cooling reduced the severity of adverse effects of tissue ischemia.

We've analyzed the reactive hyperemic response by using the exponential curve-fitting technique. We are able to objectively select the parameters of the reactive hyperemic response, and this analytical method will be used to characterize the reactive hyperemia after pressure relieve in all data collected in this study. This method will be documented in the next manuscript of this study.
 

2009

Instrumentation modifications and IRB approval have been obtained for the second phase of the study to recruit people with spinal cord injury. The modified instrument has been used on ten subjects (neurologically intact control group) in the study. It is able to control the skin temperature at two different cooling rates: fast cooling (-4°C/min) and slow cooling (-.33°C/min). All ten subjects reported that the protocols are acceptable without inducing any discomfort or pain during the experiment. And no adverse events occurred with the implementation of the protocol. We performed analysis of the skin perfusion data on all ten subjects from the pilot study, and the results were submitted in an extended abstract to the Science 2008 Conference (University of Pittsburgh annual celebration on Science and Technology). The abstract was accepted for poster presentation: Tzen Y, Jan YK, Porach EA, Karg PE, Brienza DM. Effects of local cooling on sacral skin perfusion response to pressure: implications for pressure ulcer prevention. We also submitted the results in an extended abstract to the National Pressure Ulcer Advisory Panel (NPUAP) Biennial Conference, and the abstract was accepted for poster presentation as well. The abstract reported that our study agreed with previous studies that skin temperatures naturally increase when in close contact with other materials for a prolonged period of time. The results also showed that the skin perfusion response after pressure relief was significantly attenuated under the local cooling application. This indicated that local cooling influenced the skin vasomotion under prolonged pressure. Such influence might be due to reduced metabolic vasodilator substances accumulation at the skin. Our results denoted that local cooling had a protective effect on the skin under prolonged pressure in human subjects.
We’ve incorporate short-time Fourier transform to further analyze the skin perfusion we collected in the pilot study. The results were submitted in an extended abstract to RESNA 2009. The abstract was accepted for presentation in a platform session: Tzen Y, Loughlin PJ, Brienza DM. Analyzing the mechanisms of local cooling on pressure induced reactive hyperemia by applying short-time Fourier transform (STFT). The abstract reported on the technique of analyzing the blood flow signal using the spectrogram (magnitude-square STFT). Both wideband and narrowband spectrograms were computed, and from which normalized post-occlusion energy density spectra were calculated and compared for pressure application with and without cooling. The results suggested that the spectrogram allowed us to compare the differences between cooling and non-cooling within the four target frequency bands of physiological responses. And this may direct further investigation on distinguishing different physiological response of the skin under local cooling using STFT.

2008

Configuration of the test instrumentation, IRB approval and a pilot study on ten young healthy adults have been completed. The developed integrated system worked well to control pressure and temperature and no adverse events occurred. Results of the pilot study have been reported in three extended abstracts, a Masters thesis, and a draft peer-reviewed manuscript. The pilot study and analysis revealed the need for modification to our instrumentation. We have completed instrument modification and started screening subjects with SCI. The system successfully controls skin temperature at the two different cooling rates that will be evaluated in the second phase of testing. Based on the analysis of the pilot data, an attenuated reactive hyperemic response was found after local cooling application. This indicates that local cooling provides a protective effect to the skin under localized pressure. Further experiments using slow and fast cooling rates will determine the cooling rate that is most beneficial for enhancing tissue tolerance under localized pressure in individuals with SCI.



Publications

Tzen Y, Jan YK, Brienza DM. Development of a system to study the effect of local cooling on skin blood flow response to interface pressure. The Rehabilitation Engineering and Assistive Technology Society of North America (RESNA) Annual Conference, Washington, DC, 2008.

Tzen Y. Effects of local cooling on skin perfusion response to pressure: implications to pressure ulcer prevention. MS Thesis, published in University of Pittsburgh Electronic Dissertation Database, 2008.

Tzen Y, Jan YK, Porach EA, Karg PE, Brienza DM. Effects of local cooling on sacral skin perfusion response to pressure: implications for pressure ulcer prevention. National Pressure Ulcer Advisory Panel (NPUAP) Biannual Conference, Washington, DC, 2009.

Tzen Y, Loughlin PJ, Brienza DM. Analyzing the mechanisms of local cooling on pressure induced reactive hyperemia by applying short-time Fourier transform (STFT). The Rehabilitation Engineering and Assistive Technology Society of North America (RESNA) Annual Conference, New Orleans, LA, 2009.

Tzen YT, Brienza DM, Karg P, Loughlin P. Effects of Local Cooling on Sacral Skin Perfusion Response to Pressure: Implications for Pressure Ulcer Prevention. Journal of Tissue Viability, 2010.19(3), 86-97.

Tzen Y, Brienza DM, Karg PE, Loughlin PJ, Geyer MJ. (2011). Effectiveness of Local Cooling on Enhancing Tissue Ischemia Tolerance in People with Spinal Cord Injury. Proceedings of the NPUAP Biennial Conference. Las Vegas, NV.

Tzen Y, Brienza DM, Karg PE. (2011). Effects of Sensation and Autonomic Function on Reactive Hyperemia Following Pressure With and Without Cooling in People with Spinal Cord Injury. Topics in Spinal Cord Injury Rehabilitation, 16.1, 42.

Matthew Johnson, Ana Allegretti, PhD, David Brienza, PhD, Patricia Karg, MSE(2011)
Preliminary Data on Occurrence Rates of Pressure Ulcers in Spinal Cord Injury Patients Across Care Settings

Tzen, YT.; Brienza, DM.; Lachenbruch C.; Karg, PE. (2012). Relative contribution of pressure, temperature and shear force on ischemia induced skin blood flow response. Proceedings of the European Pressure Ulcer Advisory Panel (EPUAP) Focus Meeting. Tel Aviv, Israel.

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This work is funded by the National Institute on Disability and Rehabilitation Research (NIDRR),
Rehabilitation Engineering Research Center (RERC) on Spinal Cord Injury, Grant #H133E070024
The ideas and opinions expressed herein are those of the authors and not necessarily reflective of the NIDRR.

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Last Updated: 07.10.2012 | 15:45

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