Adverse Effects of Nicotine and Interleukin-1

1
Adverse Effects of Nicotine and Interleukin-1ß on
Autoresuscitation after Apnea in Piglets
Implications for Sudden Infant Death Syndrome

• Author - J. F Frøen et al
• Presented by Carmen L. Trinidad

2
Objective

• The affects of nicotine and IL-1ß on induced
  apnea to better understand the relationship
  between maternal smoking and infant death syndrome

3
What is Sudden Infant Death Syndrome?

• SIDS - also called crib or cot death
• Unexplained sudden death, during sleep of an
  apparently healthy infant
• In the U.S, SIDS is the leading cause of death in
  infants between 1 - 12 months of age
• Rate of 1 of every 1,000 live births

4
Risk Factors

• Infants with low birth weights lt 3.5 lbs
• Inadequate prenatal care
• Mothers (non-smoker) who do not breast feed
• Sleeping position
• Insufficient exchange of oxygen - Apnea
• Prenatal, Postnatal, Passive smoking

5
Smoking- Major risk factor

• Case control studies have shown clear,
  dose-related associations between maternal
  smoking and infant death
• Strongest relationship found when mother smoked
  during pregnancy Postnatally
• Exposure to environmental tobacco smoke increases
  risk of having night cough respiratory
  infections

6
Smoking- Major risk factor

• SIDS victims have a slight infection triggered
  immune system before their death
• Release cytokines
• a large group of molecules involved in signaling
  between cells during immune responses
• interleukin 1ß (IL-1ß) - may depress respiration

7
Apnea

• Apneas - associated with SIDS in infants
• brief suspension of breathing occurring
  repeatedly during sleep
• Postnatal exposure to tobacco and infections
  adversely affect ability to cope with an apneic
  episode

8
Purpose of Investigation

• Investigate the acute effects of nicotine and
  IL-1ß on apnea by laryngeal reflex stimulation
  and the subsequent autoresuscitation

9
Methods

• 30 - 1 week old piglets were sedated with
  butyrophenone azaperone
• Catheter was inserted into immediate subglottic
  space in left femoral artery
• Heart rate monitored
• Blood pressure recorded
• Airflow monitored

10
Methods

• Blood samples tested for analysis of glucose,
  blood gas, hematology
• Piglets were allowed 30 min. stabilization before
  recording of baseline values

11
Method

• 1) Immediate infusion of IL-1ß intravenously
• 2) Slow infusion of nicotine intravenously-5min.
  Later
• 3) Both IL-1ß and nicotine (NIC)
• 4) Placebo by infusion of .9 NaCl (CTR)

12
Inducing Apnea

• 15 min. later apnea was induced by insufflation
  of .1ml .9 NaCl acidified with HCl through
  tracheal catheter
• Apnea induced 5 times with 5 min intervals
• apnea - defined as no airflow for gt5 seconds
• end of apnea - defined as the start of a
  respiratory movement producing airflow gt5 seconds

13
Results Pretreatment with nicotine

• Caused more spontaneous apneas
• repeated spontaneous apneas caused an inability
  to increase respiratory rate

14
Addition of IL-1ß

• Prolonged apneas
• inability to hyperventilate

15
Addition of IL-1ß NIC

• More spontaneous apneas
• Apneas were prolonged
• Inability to hyperventilate normally after apnea
• decrease in respiratory rate

16
Insufflation of acidified saline (CTR)-Placebo

• Insufflation of saline produced apneas
• followed by decrease in heart rate
• fall in blood pressure
• swallowing
• occasional coughs
• finally autoresuscitation with gasping

17

• Before During
• BP HR BP

• After
• HR BP HR

18
Table 1 Results

• Heart rate of piglets was higher after the apnea
  attack
• Heart rate was lowest during the apnea attack
• Results for the blood pressure were similar to
  that of the heart rate

19
Fig. 1. Change in respiratory rate (in percent)
after end of induced apnea versus baseline
values.
20
Change in Respiratory Rate

• The control group had a significantly higher
  respiratory rate than that of the Nicotine and
  IL-1ß groups

21
Spontaneous Apneas 5min. before and after
22
Spontaneous Apneas Results

• The amount and duration of the spontaneous apneas
  were higher in the IL-1ß groups comparing to the
  control, nicotine and IL-1ß groups alone

23
Oxygen saturation at start of Apnea, and end of
apnea
24
Oxygen Saturation Results

• The oxygen saturation of the experimental groups
  were below that of the control group

25
Characteristics which enhance, produce, prolong
apneas

• interfere with normal autoresuscitation after
  apnea
• vomiting
• low gestational age
• overheating
• hypoxia
• infection - release of interleukines

26
Conclusions

• Apnea by laryngeal reflex plays an important role
  in apnea associated with SIDS
• Nicotine combined with IL-1ß has an adverse
  effect on apnea and autorescscitation

27
References

• Frøen J.F et al. 2000. Adverse Effects of
  Nicotine and Interleukin-1ß on Autoresuscitation
  after Apnea in Piglets Implications for Sudden
  Infant Death Syndrome. Pediatrics 105 52
• Haslam R. 2000. Smoking and Sleep position are
  only pieces of the puzzle resulting in the sudden
  infant death syndrome. Pediatric Research 48
  715.
• Schoendorf K, Kiely J. 1996. Relationship of
  sudden infant death syndrome to maternal smoking
  during and after pregnancy. Pediatrics 90
  905-908.
• Wisborg K, et al. 2000. A prospective study of
  smoking during pregnancy and SIDS. Arch Dis
  Child 83 203-206.