hypothesis driven research 20 years of burn related
play

Hypothesis-Driven Research (20+ years of burn-related research) Craig Crandall PhD Thermal and Vascular Physiology Laboratory Institute for Exercise and Environmental Medicine; University of Texas Southwestern Medical Center Dallas Brown

0 downloads 6 Views 5,04 MB Size Report
  1. Hypothesis-Driven Research (20+ years of burn-related research) Craig Crandall PhD Thermal and Vascular Physiology Laboratory Institute for Exercise and Environmental Medicine; University of Texas Southwestern Medical Center Dallas

  2. Brown Recluse

  3. 11/28/95

  4. 12/6/95

  5. 12/11/95

  6. Epidermis HEALTHY SKIN Dermis Subcutaneous Tissue Muscle THIRD DEGREE BURN SPLIT-THICKNESS SKIN GRAFT

  7. Curiosity How do humans “thermoregulate”?

  8. Question: What are the implications of such an injury and subsequent grafting on skin blood flow and sweating? Identify a hypothesis and design an experiment to test that hypothesis.

  9. ECG 30 Graft Skin Blood Flow (au) 28 26 24 22 20 18 16 14 Control Skin Blood Flow (au) 16 15 14 13 12 11 10 9 8 15 seconds

  10. Laser doppler scanner-grafted skin 1.75 P < 0.05 Graft Photo Image Graft 1.50 ∆ CVC (au/mm Hg) 1.25 HEAT STRESS 1.00 NORMOTHERMIA 0.75 0.50 0.25 Flux Image 0.00 Control Graft 0 500 1000

  11. Increases in cutaneous vascular conductance during whole-body heating at control and grafted sites across differing durations post- graft surgery. 1.50 Control P<0.01 Graft 1.25 ∆ CVC (au/mm Hg) 1.00 0.75 0.50 0.25 0.00 5-9 Months 26-38 Months 50-86 Months

  12. 2.0 ∆ SR from Baseline (mg/cm 2 /min) 1.8 P < 0.05 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 Control Graft

  13. Increase in sweat rate (SR) to whole-body heating 2.5 Control P<0.01 Graft 2.0 ∆ SR (mg/cm 2 /min) 1.5 1.0 0.5 0.0 2-3 Years 4-8 Years 5-9 Months 26-38 Months 50-86 Months J Burn Care Res 2009

  14. Question: Where are the deficits resulting in impaired increases in skin blood flow and sweating in grafted skin? Identify a hypothesis and design an experiment to test that hypothesis.

  15. Dose response curves to exogenous acetylcholine (ACh) in normal and grafted skin 1.8 ∆ CVC from Baseline (au/mmHg) Control 1.6 Graft 1.4 1.2 1.0 0.8 0.6 0.4 0.2 EC 50 :P=0.003 0.0 1x10 -7 1x10 -6 1x10 -5 1x10 -4 1x10 -3 1x10 -2 1x10 -1 [ACh] J Burn Care Res 2007

  16. Dose response curves to exogenous sodium nitroprusside (SNP) in normal and grafted skin 1.8 ∆ CVC from Baseline (au/mmHg) Control 1.6 Graft 1.4 1.2 1.0 0.8 0.6 0.4 0.2 EC 50 :P=0.33 0.0 5x10 -8 5x10 -7 5x10 -6 5x10 -5 5x10 -4 5x10 -3 5x10 -2 [SNP] J Burn Care Res 2007

  17. Increases in sweat rate (SR) to exogenous acetylecholine (ACh) from normal and grafted skin 1.4 ∆ SR from Baseline (mg/cm 2 /min) Control 1.2 Graft 1.0 0.8 0.6 0.4 0.2 0.0 -0.2 1x10 -7 1x10 -6 1x10 -5 1x10 -4 1x10 -3 1x10 -2 1x10 -1 [ACh] J Burn Care Res 2007

  18. “We had a new recruit die here last week due to a heat- induced arrhythmia. His core temp was 106 ° F (~41 ° C). He died standing in the chow line- and had done very minimal exertion that day (2 mi walk several hours earlier). The guy had burn injuries at age 11- he had skin grafts covering 30% of his trunk- to include one axilla. Our Army medical fitness regulations make no mention of skin grafting/burns as a disqualifier and we are seeking additional knowledge to see if we need to change the regulation. Since so many of our soldiers have recently acquired burn injuries and are subjected to tremendous thermal stress we think that this is a very important question.”

  19. So what’s next? Identify a hypothesis and design an experiment to test that hypothesis.

  20. Groups • 17-40% BSA grafted; BSA grafted: 30±7%. 40±13 years. • >40% BSA grafted; BSA grafted: 54±11%. 34±11 years • Non-grafted controls. 32±10 years

  21. Skin grafts impair temperature regulation. (40 °C and 30% RH) Ganio, Schlader, Pearson, Lucas, Gagnon, Rivas, Kowalske, Crandall, 2015

  22. Question: Can impaired thermoregulatory responses be modified? Identify a hypothesis and design an experiment to test that hypothesis.

  23. Pre-heat Heat acclimation: 90 min of exercise (@ Post-heat acclimation 45% VO 2 max) in 40°C, 30% RH for 7 acclimation evaluation consecutive days evaluation Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7

  24. 2 way ANOVA Group: P<0.001 Acclimation: P<0.001 Interaction: P=0.073 2.5 Pre-Acclimation Post-Acclimation Temperature (Deg C) 2.0 Increase in Internal 1.5 1.0 0.5 0.0 Control 17-40% >40% Subject Groups

  25. Pre-Heat Acclimation Post-Heat Acclimation

  26. Schlader et al. J Appl Phyisol 2015

  27. Donor Sites Question: What questions come to mind regarding donor sites? Identify a hypothesis and design an experiment to test that hypothesis.

  28. Donor Sites 400 Uninjured 1.5 Donor Cutaneous Blood Flow (PU) 300 P=0.26 Local Sweat Rate (mg/cm^2/min) 1.0 200 P=0.78 0.5 100 0 0.0 Pre-Exercise Post-Exercise Uninjured Donor

  29. Serendipitous Findings Maximal Aerobic Capacity

  30. J Burn Care Res 2015 ACSM age and sex normative scale: ~75% of burn survivors had a VO 2max in the lowest 20 th percentile. American Heart Association Normative Scale: 88% of burn survivors had a VO 2max below the age-adjusted normative values 80% of burn survivors had a VO 2max in the lowest quartile of the Aspenes database (4631 subjects)

  31. Question: Why are burned individuals generally unfit (consider the variables that influence aerobic capacity)? Identify a hypothesis and design an experiment to test that hypothesis.

  32. Cardiovascular Deconditioning 4000 Actual age-related decrease in VO 2max in uninjured individuals 3000 VO 2max (ml/min) 2000 1000 20 30 40 50 60 70 Age (years)

  33. 1 day hospitalization per 1% BSA burned

  34. Cardiovascular Deconditioning 4000 Actual age-related decrease in VO 2max in uninjured individuals 3000 VO 2max (ml/min) 2000 1000 20 30 40 50 60 70 Age (years)

  35. Cardiovascular Deconditioning 4000 Actual age-related decrease in VO 2max in uninjured individuals 3000 VO 2max (ml/min) 2000 1000 20 30 40 50 60 70 Age (years)

  36. 10+ years post-injury

  37. Question: Are these “adverse” responses modifiable? Identify a hypothesis and design an experiment to test that hypothesis.

  38. Pre- and post-6 months exercise training Assessments Steady state followed by maximal oxygen uptake evaluation (X 2) Assessments of vascular function (FMD, nitro, PWV) Quality of life surveys Functional capacity assessments Cardiac structure/function (MRI and/or echo) Body composition (DEXA) Muscle biopsy (citrate synthase & cytochrome C oxidase activity) Blood volume assessment Pulmonary function testing

  39. 6 month Endurance Exercise Training Pre-exercise training Group: P= 0.008 Post-exercise training Pre/Post: P<0.001 Group x Pre/Post: 0.51

  40. GM068865-12; ~$3.5 million W81XWH-15-1-0647; ~$2.0 million

  41. US Army Standards of Medical Fitness, AR 40-501 2-28-(1) Prior burn injury (to include donor sites) involving a total body surface area of 2-28-(2) Prior burn injury involving less than 40 percent total body surface area, which results in a loss or degradation of thermoregulatory function does not meet the standard Where’s the data to support these guidelines?

  42. Psycho-social

  43. 2.0 R=0.59; P<0.01 70 kg; 175 cm; 1.8 m 2 ; 33% graft = 1.2 m 2 for heat dissipation. 1.6 Delta Tcore (°C) 1.2 0.8 0.4 108 kg; 195 cm; 2.4 m 2 BSA … so he has ~1.6 m 2 BSA ungrafted skin available to dissipate heat 0.0 10 20 30 40 50 60 70 80 Body Surface Area Grafted (%)

  44. 2.0 R=0.71; P<0.01 1.6 Delta Tcore (°C) 1.2 0.8 0.4 0.0 0.4 0.8 1.2 1.6 2.0 Body Surface Area Available for Heat Dissipation (m 2 )

  45. 2.0 Control subjects 1.6 Delta Tcore (°C) 1.2 0.8 0.4 0.0 0.4 0.8 1.2 1.6 2.0 Body Surface Area Available for Heat Dissipation (m 2 )

  46. ‡ different from pre-HA (main effect; P=0.05)

  47. * * *

  48. 24 °C (75 °F), 20% humidity 39 °C (102 °F), 20% humidity 2.5 2.5 Elevation in Core Temperature (°C) Elevation in Core Temperature (°C) 2.0 0% burn injury 2.0 0% burn injury 20% burn injury 20% burn injury * 40% burn injury 40% burn injury 60% burn injury 60% burn injury * 1.5 1.5 * * 1.0 1.0 0.5 0.5 * P<0.01 from 0% burn 0.0 0.0 0 10 20 30 40 50 60 0 10 20 30 40 50 60 Time of Exercise (min) Time of Exercise (min)

  49. Individuals with significant skin grafts are generally more sedentary. Distribution of maximal oxygen uptake in 34 skin graft patients 20 76% in the lowest Number of Subjects in Each Category two categories 15 10 5 0 10 20 30 40 50 60 70 80 90 Percentile Ranking for Maximal Oxygen Uptake Percentile rankings for age and sex adjusted maximum oxygen uptake Ganio, Pearson, Schlader, Brothers, Lucas, Rivas, Kowalske, Crandall, 2014

Recommend Documents


research agenda perspective from academia
RESEARCH AGENDA: PERSPECTIVE FROM

RESEARCH AGENDA: PERSPECTIVE FROM ACADEMIA (Hypothesis Driven) Eugene O.

integrative cardiovascular physiology a
Integrative cardiovascular physiology:

Integrative cardiovascular physiology: a primer to hypothesis driven research

burn wounds
Burn wounds Burns are one of the most

Burn wounds Burns are one of the most common and devastating forms of trauma

chapter 6 hypothesis testing what is hypothesis testing
Chapter 6 Hypothesis Testing What is

Chapter 6 Hypothesis Testing What is Hypothesis Testing? the use of

chapter 6 hypothesis testing what is hypothesis testing
Chapter 6 Hypothesis Testing What is

Chapter 6 Hypothesis Testing What is Hypothesis Testing? the use of

computations related to the riemann hypothesis
Computations related to the Riemann

Computations related to the Riemann Hypothesis William F. Galway Department

three years of emsb in indonesia a j ourney in
Three Years of EMSB in Indonesia: A J

Three Years of EMSB in Indonesia: A J ourney in Standardizing and Escalating

hypothesis testing for a proportion
Hypothesis Testing for a Proportion

Hypothesis Testing for a Proportion August 21, 2019 August 21, 2019 1 / 64

slow burn contagion
Slow-burn contagion Eli Remolona

Slow-burn contagion Eli Remolona Professor of Finance Research Seminar

crash and burn learning from failure
Crash and Burn: Learning from Failure

Crash and Burn: Learning from Failure SOA 2020 June 17, 2020 Crash and Burn

neonicotinoid insecticides for ornamentals
Neonicotinoid Insecticides for

Neonicotinoid Insecticides for Ornamentals The Good, Bad and Ugly Catharine

10 4 2016
10/4/2016 Challenges of Geriatric

10/4/2016 Challenges of Geriatric Patients Nurse Practitioners of Oregon 39

animal movements such as locomotion eating copulation and
Animal movements , such as

Animal movements , such as locomotion, eating, copulation, and

1
1 People with dementia have trouble

1 People with dementia have trouble sleeping Poor sleep can contribute to

in vitro skin sensitisation photo dpra
In vitro Skin Sensitisation, Photo-DPRA

In vitro Skin Sensitisation, Photo-DPRA Dr. Rahul Date A Global Contract

closing the gap
Closing the Gap: Treatment of Tobacco

Closing the Gap: Treatment of Tobacco Dependence Disclosure of Relevant

panbc conferenc e
PANBC Conferenc e Nov 5, 2016

SMOKING CESSATION PANBC Conferenc e Nov 5, 2016 Steve Petrar

clearing the air vaping nicotine and cannabis
Clearing The Air Vaping , Nicotine and

Clearing The Air Vaping , Nicotine and Cannabis Presented by: David Fialko,

nervous system function of the nervous system
Nervous System Function of the

Nervous System Function of the Nervous System Receive sensory information,

underwriting with prescription histories across the
Underwriting with Prescription

Underwriting with Prescription Histories Across the Mental Health Continuum

brain toniq
Brain ToniQ Highly popular in America

Brain ToniQ Highly popular in America and new for other markets organic

sleepless in portland
Sleepless in Portland ~ Insomnia

Sleepless in Portland ~ Insomnia ~ A Naturopathic Approach