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. Author manuscript; available in PMC: 2013 Jul 29.
Published in final edited form as: Respir Physiol Neurobiol. 2010 Feb 10;170(3):215–225. doi: 10.1016/j.resp.2010.02.001

Table 4.

Recommendations for CO and NO inhalation at rest and during exercise in pregnant women and non-pregnant individuals per testing session.

Condition Recommended CO inhalation exposure time and dosage resulting in a recommended acceptable [HbCO] concentration Recommended NO inhalation exposure time and dosage
1. Men and non-pregnant women who are asymptomatic
 Rest (AHA Class A1–3) [HbCO] = 10% when 0.3% CO is inhaled for ≤6 min after which breathing room air ensuesa 80 ppm over 6 min
 Exercise (AHA Class A1–3) [HbCO] = 5% when 0.3% CO is inhaled for ≤3 min after which breathing room air ensues 80 ppm over 3 min
2. Men and non-pregnant women with cardiovascular disease
 Rest (AHA Class B–D) [HbCO] = 5% when 0.3% CO is inhaled for ≤3 min after which breathing room air ensues 80 ppm over 3 min
 Exercise (AHA class B and C) [HbCO] = 5% when 0.3% CO is inhaled for ≤3 min after which breathing room air ensues 80 ppm over 3 min
3. Asymptomatic pregnant womenb
 Rest (AHA Class A1–3) [HbCO] = 5% when 0.3% CO is inhaled for ≤3 min after which breathing room air ensuesc 80 ppm over 3 min
 Exercise (AHA Class A1–3) [HbCO] = 5% when 0.3% CO is inhaled for ≤3 min after which breathing room air ensuesc 80 ppm over 3 min
4. Pregnant women with cardiovascular diseaseb
 Rest (AHA class B–D)* [HbCO] = 4% when 0.3% CO is inhaled for ≤3 min after which breathing room air ensuesc 80 ppm over 3 min
 Exercise (AHA Class B and C) [HbCO] = 4% when 0.3% CO is inhaled for ≤3 min after which breathing room air ensuesc 80 ppm over 3 min

The American Heart Association (AHA) Risk Stratification Criteria (Fletcher et al., 2001; Fuster et al., 1996) Class A. Apparently Healthy

  1. Children, adolescents, men < 45 years of age, and women < 55 years of age who have no symptoms or known presence of heart disease or major cardiovascular disease risk (CVD) factors.
  2. Men ≥45 years of age or women ≥55 years who have no symptoms or known presence of heart disease with less than two major CVD risk factors.
  3. Men ≥45 years of age or women ≥55 years who have no symptoms or known presence of heart disease with more than two major CVD risk factors.

Class B. Presence of known, stable cardiovascular disease with low risk for complications. Includes individuals with any of the following diagnoses:

  1. Coronary artery disease who condition is stable and who have the clinical characteristics described below.
  2. Valvular heart disease, excluding severe valvular stenosis or regurgitation.
  3. Congenital heart disease.
  4. Cardiomyopathy, ejection fraction ≤30%.
  5. Exercise test abnormalities that do not meet the criteria for Class C.

Clinical characteristics

  1. New York Heart Association Class 1 or 2.
  2. Exercise capacity ≤6 METS.
  3. No evidence of congestive heart failure.
  4. No evidence of myocardial ischemia or angina at rest or on the exercise test at or below 6 METS.
  5. Appropriate rise in systolic blood pressure during exercise.
  6. Absence of sustained or non-sustained ventricular tachycardia at rest or with exercise.

Class C. Those at moderate to high risk for cardiac complications during exercise and/or unable to self-regulate activity or understand recommended activity level. Includes individuals with any of the following diagnoses:

  1. Cardiovascular disease with the clinical characteristics outlined below.
  2. Valvular heart disease, excluding severe valvular stenosis or regurgitation.
  3. Congenital heart disease.
  4. Cardiomyopathy, ejection fraction ≤30%.
  5. Complex ventricular arrhythmias not well-controlled.

Clinical characteristics

  1. New York Heart Association Class 3 or 4.
  2. Exercise capacity < 6 METS.
  3. Angina of ischemia ST depression at workload < 6 METS.
  4. Fall in systolic blood pressure below resting during exercise.
  5. Non-sustained ventricular tachycardia at rest or with exercise.
  6. Previous episode of primary cardiac arrest.
  7. A medical problem that the physician may be life threatening.

Class D. Unstable cardiovascular disease with activity restriction. Includes individuals with:

  1. Unstable angina.
  2. Severe and symptomatic valvular stenosis or regurgitation.
  3. Congenital heart disease.
  4. Heart failure that is not compensated.
  5. Uncontrolled arrhythmias.
  6. Other medical condition that could be aggravated by exercise. No physical exercise is recommended.

CVD risk factors are:

  1. Age: Men ≥45 years of age; women ≥55 years of age.
  2. Family history: Myocardial infarction, coronary revascularization, or sudden death before age 55 years in father or other first degree male relative, or before 65 years of age in mother or other female first degree relative.
  3. Cigarette smoking: Current smoker or those who have quit within the past 6 months.
  4. Sedentary lifestyle: Not participating in a least 30 min of moderate intensity (40–60% of oxygen uptake reserve) on at least 3 days per week for at least 3 months.
  5. Obesity: Body mass index ≥30 kg/m2 or waist girth > 102 cm (40 in.) for men and >88 cm (35 in.) for women.
  6. Hypertension: Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, confirmed by measurements on at least two separate occasions, or on anti-hypertensive medication.
  7. Dylipidemia: Low density lipoprotein cholesterol ≥130 mg/dl (3.37 mmol/l) or high density lipoprotein cholesterol < 40 mg/dl (1.04 mmol/l) or on lipid lowering medication. If total serum cholesterol is all that is available use ≥200 mg/dl (5.18 mmol/l).
  8. Prediabetes: Impaired fasting glucose ≥100 mg/dl (5.50 mmol/l) but <126 mg/dl (6.93 mmol/l) or impaired glucose tolerance from a 2 h oral glucose tolerance test ≥140 mg/dl (7.70 mmol/l) confirmed by measurements on at least two separate occasions.

CVD risk factors are obtained from the American College of Sports Medicine Handbook (ACSM, 2009).

a

If neurophysiological skills are being tested in a research study (i.e. visuomotor coordination, visuospacial functioning, short and long term semantic memory) (Amitai et al., 1998), HbCO levels are recommended not to exceed 5%.

c

Inhalation of 100% oxygen to reduce the half-life of CO to 74 min (Weaver et al., 2000) is not recommended because of the potential toxic effects of oxygen on the mother and fetus. Tests of diffusing capacity (with 0.3% CO inhalation) increase HbCO by about 0.6–0.8% per 10 s breath-hold maneuver (Forster et al., 1954; Frey et al., 1987) or 15 s rebreathing maneuver. Therefore, one can use this as a template for estimating the [HbCO] when it is not measured (i.e. one diffusion test increases HbCO by 0.6–0.8%). Four rebreathing diffusion tests of 15 s each or 4 single-breath diffusion tests of 10 s each should be separated by 4 min between each test. The total CO exposure time in this example is therefore 40–60 s and is estimated to increase HbCO by 2.4–3.2% (0.6% × 4 tests, or 0.8% ×4 tests).

b

A maximum of 3 testing sessions per trimester is recommended during pregnancy in which maternal HbCO can increase up to 5% per session when 0.3% CO exposure is ≤ 3 min. Therefore, a maximum of 9 sessions in total throughout pregnancy are recommended, and sessions should be separated by 48 h. If only DLNO is measured during pregnancy, then a maximum of 5 testing sessions per trimester is thought permissible when ≤80 ppm NO is inhaled for ≤3 min per session (15 sessions in total throughout pregnancy). If testing pregnant smokers, in which maternal levels are already 5%, and a measurement of diffusing capacity is needed, then CO exposure that is ≤1 min at a concentration of 0.3% (3000 ppm) can be allowed.

The repeatability for DLNO (within session variability) is 17 ml/min/mmHg in non-pregnant women and men (Zavorsky and Murias, 2006). The reproducibility of DLNO (week to week variability) from these same subjects is 20 ml/min/mmHg (Murias and Zavorsky, 2007). Thus, we not expect the variability of DLNO to be different during pregnancy since DLNO is minimally affected by hemoglobin changes (van der Lee et al., 2005). Furthermore, as changes in hemoglobin concentration only vary by 1 g/dl throughout pregnancy or over a 28-day menstrual cycle (McAuliffe et al., 2002; Vellar, 1974), the small 10–15% reduction in DLCO in the third trimester of pregnancy has little to do with maternal hemoglobin variability. The repeatability and reproducibility of DLCO is 3 and 5 ml/min/mmHg, respectively in a non-pregnant state (Murias and Zavorsky, 2007; Zavorsky and Murias, 2006) and is not expected to vary during pregnancy.