skin blood flow and sweating in health and disease

Skin blood flow and sweating in health and disease

Craig Crandall, Ph.D.

Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas,

and

Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas.

Semenza et al. Am J Prev Med 1999

Semenza et al. N Engl J Med. 1996

Heat stress

Cutaneous vasodilation

Decreases systemic vascular

resistance

Increases cardiac output

Maintenance of blood pressure

Heart FailureBlood pressure = TPR * CO

Of the “excess” death identified in the cohort from the 1995 Chicago heat wave, 39% had a prior “heart condition”Semenza et al. N Engl J Med. 1996

Normothermia Heat stress

E.F. (%) 30 2 -

Age (yrs) 51 4 -

MAP (mmHg) 90 3 85 4

HR (bpm) 70 4 87 5*

Tsk ( C) 34.1 0.1 38.0 0.2*

Normothermia Heat stress

64 1 -

51 4 -

87 2 82 2

58 4 80 4*

34.1 0.1 38.0 0.2*

Heart Failure (N=14)NYHA Class II and III

Controls (N=14)

Cui, Arbab-Zadah, Prasad, Durand, Levine, Crandall. Circulation (2005)

Increase in core temperature (ºC)

0.0 0.2 0.4 0.6 0.8 1.0 1.2

Sw

eat r

ate

(mg/

cm2 /

min

)

0.0

0.2

0.4

0.6

0.8

1.0

Cui, Arbab-Zadah, Prasad, Durand, Levine, Crandall Circulation (2005)

CutaneousVasculature

Central NervousSystem

Vasodilation

Vasoconstriction

Internal Temp

Skin Temp

SweatGland

Sudomotor

Congestive Heart Failure

Cui, Arbab-Zadah, Prasad, Durand, Levine, Crandall Circulation (in press)

Summary

Impaired thermoregulation in subjects with CHF is primarily due to reduced cutaneous vasodilation since sweating responses are normal during the heat stress.

Possible mechanisms ???

“We had a new recruit die here at ----------- last week due to a heat-induced

arrhythmia.  His core temp was 106 F.  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 reg 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.”

Whole-body heat stress

Laser Scanner

SweatCapsule

Local Heater &Laser Probe Graft

Markings forScanner

Normotherm. Heat Stress

GraftGraft

0

1000

500

Sw

eat R

ate

(mg/

cm2 /

min

)

Control Graft

0.0

0.2

0.4

0.6

0.8

*

Normothermia Cold Stress Heat Stress

Cut

aneo

us V

ascu

lar

Con

duct

ance

(uni

ts/m

mH

g)

0.0

0.3

0.6

0.9

1.2

1.5

*

Grafted Skin

Normothermia Cold Stress Heat Stress

Cut

aneo

us V

ascu

lar

Con

duct

ance

(uni

ts/m

mH

g)

0.0

0.3

0.6

0.9

1.2

1.5

*

*Normal Skin

ACh Administration

SNP Administration Cutaneous

Vasculature

ACh Co-transmitters

EDHFNO VIP, etc.PGsEndothelium

Sympathetic Cholinergic Nerve

Dry Nitrogen Gas

Sweat Capsule Humidit

y Sensor

Laser Doppler Probe

Acetylcholine (ACh)(10-7 M to 1 M) Skin

10 mm

*

*

**

* P<0.05

Control EC50 = -3.34 ± 0.46 EC50 = -2.61 ± 0.44

P<0.01†

†

CV

C fr

om B

asel

ine

(au/

mm

Hg)

log [ACh]

-7 -6 -5 -4 -3 -2 -1-0.25

0.00

0.25

0.50

0.75

1.00

1.25

1.50

1.75

2.00

▼Graft

Cutaneous vascular conductance (CVC) response to exogenous acetylcholine (ACh)

log [SNP]

-8 -7 -6 -5 -4 -3 -2-0.25

0.00

0.25

0.50

0.75

1.00

1.25

1.50

1.75

2.00

2.25

Cutaneous vascular conductance (CVC) response to exogenous sodium nitroprusside (SNP)

Control

EC50 = -3.94 ± 0.45 EC50 = -4.43 ± 1.08▼ Graft *

* P<0.05

CV

C f

rom

Bas

elin

e (a

u/m

mH

g)

log [ACh]

-7 -6 -5 -4 -3 -2 -1-0.2

0.0

0.2

0.4

0.6

0.8

1.0 Control▼ Graft

SR

from

Bas

elin

e (m

g/cm

2 /m

in)

Sweat rate (SR) response to exogenous acetylcholine (ACh) administration

*

*

* P<0.05

• Cutaneous vasodilation to whole-body heating is absent in grafted skin

• ACh mediated vasodilation (endothelial dependent) is inhibited in grafted skin

• Nitric oxide mediated vasodilation (endothelial independent) is attenuated at the highest dose in grafted skin

• No sweating suggests abnormal or absence of functional sweat glands

Summary of Findings

• Juvenile (i.e. 6-9 months post-surgery) split thickness skin grafts have an attenuated capability of contributing to thermoregulation

• Increased risk of heat related injury

• It is unknown whether there is a restoration of cutaneous vasodilation and sweat function with graft maturity?

Implications

31 year old man with a 10 year history of drug abuse was found disoriented and combative. Blood pressure: 115/76 mmHg; heart rate: 197 bpm; respiratory rate: 72/min; temperature 107.2 F (41.8 C). Urine specimen tested positive for cocaine metabolite and negative for ethanol and other central nervous stimulants. Patient died. Human Pathology, 22:1141-1145, 1991.

38 year old known cocaine user was transported to emergency room by the police after acting bizarrely and barking like a dog. The patient was agitated, diaphoretic, incoherent, and unresponsive to pain. Urine specimen tested positive for cocaine and cocaine metabolites and nicotine. Blood pressure: 120/69 mmHg; heart rate: 150 bpm; respiration: 40/min; temperature 41.1 C (106 F). Patient died seven days after admission. Western J. Med. 150:210-212, 1989.

14 patients with rhabdomyolysis after cocaine use had an average temperature of 103.7 F (range 99 – 106 F). The average temperature for the 5 patients that died was 105.4 F (40.8 C). Acta Neurol. Scand. 92: 161-165, 1995.

Lidocaine Cocaine P-value

Blood pressure(mmHg)

85(3)

93(3)

0.001

Heart rate(bpm)

64(4)

74(5)

0.01

Esoph. Temp.(C)

36.75(0.08)

36.79(0.10)

0.2

CVC(% max)

9(2)

7(2)

0.09

Pre-heat stress (~30 min post-drug)

Mean ±(SEM)

Crandall, Vongpatanasin, Victor Ann Int Med 2002

(2 mg/kg) (2 mg/kg)

Crandall, Vongpatanasin, Victor Ann Int Med 2002

Crandall, Vongpatanasin, Victor Ann Int Med 2002

37.0 37.2 37.4 37.6 37.80.0

0.3

0.6

0.9

LidocaineCocaine

0

20

40

60

80

LidocaineCocaine

37.0 37.2 37.4 37.6 37.8Esophageal Temperature Esophageal Temperature

Cut

aneo

us V

ascu

lar

Con

duct

ance

Sw

eat R

ate

(mg/

cm2 /

min

)

4.0 Neutral

4.5

5.0 Warm

5.5

6.0 Hot

6.5

7.0 Very hot

7.5

8.0 Unbearably hot

Toner, Drolet, Pandolf Percept Motor Skills 1986

Crandall, Vongpatanasin, Victor Ann Int Med 2002

Summary

Intranasal cocaine significantly impairs thermoregulation as evidenced by a delay in the onset of cutaneous vasodilation and sweating. Moreover, cocaine impairs the perception of heating such that the individual does not recognize they are as hot when compared to the placebo trial.

Contributors

Scott Davis, Ph.D.David Keller, Ph.D.David Low, Ph.D.Marilee Brown, R.N.Rebecca MacDougal, M.D.Obiora Chukwumah, MBBSJohn Hunt, M.D.Gary Purdue, M.D.Karen Kowalske, M.D.

Normothermia Peak heat stress

Ski

n bl

ood

flow

(un

it)

0

20

40

60

80

100

120

140CHF Control

*

*

#