Lecture 4 - Catecholamimes And Muscle Chemoreceptors

Question 1

Discuss the French (2007) experiment??

Answer 1

Had 10 participants perform a 80% max task, showed anticipatory increases in NA (277%) and A (255%) pre exercise.
Yet hyperventilation is not normally recorded pre-ex.

Unfortunately didn’t measure breathing, bp or heart rate to establish the physiological effects

Question 2

Discuss the work of Banister (1972)?

Answer 2

Had 5 subjects perform bike ergo until exhaustion (with a venous catheter) and showed a dose dependent venous increase of both adrenaline and noradrenaline in all levels of exercise at 3,6 and 9 minutes.
This remained elevated for 6 mins post ex, but they didn’t measure breathing.

Question 3

How did Barcroft et al (1957) try and address if injected CA increase breathing at rest??

Answer 3

Intravenously infused NA in 4 subjects (2ug/kg - don’t know if it’s enough)

Saw an increase in Ve from 11-13l/min, PaCO2 dropped from 41-39Torr

Question 4

Discuss Heistad (1972)????

Answer 4

Provided IV infusion of NE or isoproterenol (selective Beta-agonist).

Showed, although a trivial increase, B receptor stimulation increases breathing, alpha receptor stim decreases breathing but the data was very messy.

The authors claimed the effect of NE/isop was via the the peripheral chemoreceptors as blocked by 100%o2 but where are the drugs acting!
Both CA act on both receptors so it’s messy.

Question 5

Describe the Butland (1982) study??

Answer 5

Had 8 normals at rest, and gave an IV of either NA or 3 B-blockers.

NA increased Ve by 1.7+-0.3L/min and increased VCO2 by 28mmol/min
Isoproterenol increased Ve by 1.8+-0.2L/min.
All the CA were reduced by all 3 b-blockers.

Question 6

Discuss why from Heistad’s 1972 work that catecholamines are unlikely to act on Ve via peripheral arterial chemoreceptors?

Answer 6

In this study, alpha stimulation decrease chemoreceptor blood flow, and thus should increase their sensitivity, but heistad showed alpha stimulation decreases breathing.

Question 7

Discuss some extra pieces of evidence about the site of CA action on Ve is unlikely to be the peripheral arterial chemoreceptors?

Answer 7

Eisele (1967) - no evidence of centrifugal control of peripheral chemoreceptors

Wasserman (1975) - peripheral chemoreceptors not necessary for phase 1.

Even if given directly right into carotid or vertebral arteries in humans, CA’s do not stimulate breathing so site of action may not be in the CNS. (Coles, 1956)

Question 8

Discuss Brown et al’s (1976) ablation experiment??

Answer 8

Had 8 subjects perform steady state exercise (0.5kw) with or without IV propranolol (0.2mg/kg) given 20 mins post ex.

This propranolol decreased HR by 17% over 3 min, 9% VCO2 and 9% Ve decrease during 3 minute ex.

The authors proposed this decrease was due to decreased CO and not via the breathing control system.
Question always is does propranolol do nothing or did they not give enough - HR only fell 17% so were they all blocked??

Question 9

Discuss Peterson et al (1983)??

Answer 9

Had 6 subjects exercise on a bike ergo with propranolol IV (0.2mg/kg) or saline.

Showed the B block caused a 5% decreased VO2 max and 13% decreased CO. No effect on Vo2/VCO2 or HR. No significant effect on time constants for Ve
-was enough given??

Question 10

Discuss Schneider (1995)??

Answer 10

6 subjects performed incremental cycling until exhaustion with placebo or propranolol (1.1mg/kg - a lot more than others)

Hr increased from 90-170 bpm (90% inc) In saline and 78-120 bpm (53%) with B block .
No difference in Ve / VCO2 / Vo2 in control vs b blockers.

But were all the B receptors blocked?

Question 11

What other studies could be looked at as evidence for adrenaline explaining increase in breathing?

Answer 11

Referring back to Adams (1984) and Brice (1988) , adrenaline could explain the small increase in Ve during EEL in paraplegics during exercise?

Adams showed phase breathing no different from paraplegics to control
Brice showed a linear relationship between Ve and VCo2 not different from normals

Question 12

Discuss the Schmidt et al (1988) paper?

Answer 12

Had 15 T1-T4 paraplegics at rest and during wheelchair ergo at 100%VO2 max vs 15 T5-T10 paraplegics or handicapped controls.

Showed adrenal denervation @T1-T4 abolished the venous blood CA rises with ex.
In T5-T10 a 2x increase in adrenaline is seen at rest.(x0.8 in controls)

Question 13

What literature discuss how metabolites are trapped in muscle with occlusion cuffs, which increases SBP by up to 90mmhg in man ???

Answer 13

Alan and Smirk (1937); Rowell et al (1976); fisher And white (2004

Question 14

What did Dejours (1957) state about muscle chemoreceptors and breathing?

Answer 14

Occlusion must decrease VO2 and VCO2 because gas exchange with active muscle is prevented and even at rest it does by 7%.

Question 15

Discuss the Wiley (1971) experiment??

Answer 15

Had 7 subjects perform hand grip that increased Ve from 9 to 30 L/min (participants did become hypocapnic)
- when exercise stopped, breathing declined and this decline was unchanged by arm occlusion.

Question 16

Describe the innes (1989) study?

Answer 16

Had 15 steady state cycle, cuff inflation did not sustain Ve during recovery, cuff release increased Ve by 3L/min

Question 17

Rowell (1976) had 8 subjects perform a bike ergo, what were the results?

Answer 17

Cuffs post exercise did not sustain Ve or HR but did sustain Bp.

Question 18

Discuss the Scott and Piepoli (2000) paper?

Answer 18

Had a 70% VO2 max bike ergo in 12 subjects.

Cuff did not sustain Ve post exercise (sig less ventilation during occlusion)

Question 19

What are 3 papers illustrating a decrease in breathing following post-exercise occlusion following leg ext or ergo??

Answer 19

Fordyce (1982) , Hououzi (1993) , hououzi (2001)

Question 20

Describe in detail the controversial Piepoli (1995) paper??

Answer 20

Had 11 normals perform a rhythmic hand grip.
Showed post - ex occlusion led to sustained Ve at 19L/min and SBP at 148mmhg
Vo2 declined as normal whereas VCO2 did not.

Wasserman (1967) - perhaps they were hyperventilating before occlusion was applied?

This paper doesn’t explain findings and directly contradicts all other findings including Scott and Piepoli (2000)

Question 21

Describe the Lykidis (2010) experiment??

Answer 21

Had 11 subjects and confirmed a lack of increased breathing to muscle chemoreflex activation

+2-3L/min increase in Ve during occlusion if also breathing 5% CO2
Directly contradicts Piepoli 1995

Question 22

Describe the Amann et al (2010) study ?

Answer 22

Provided fentanyl at L3-L4 decreases Ve by 8-10L/min at 1.4Kw.

If you make assumption that all afferents were blocked then the effect was very small since Ve during their 325wew work was 150L/min.

The authors claim the effect even greater as the accompanying hypercapnia could have stimulated breathing and masked a greater effect - questionable extrapolation! Since no measures in the same subjects during exercise of what +5 mmhg PaCO2 does to breathing.