The limited stores of ATP in skeletal muscles can fuel approximately 5 to 10 seconds of high-intensity work (Figure 18-1). ATP must be continuously resynthesized from adenosine diphosphate (ADP) to allow exercise to continue.^70,¹¹⁴ Muscle fibers contain three metabolic pathways for producing ATP: the creatine phosphate system, rapid glycolysis, and aerobic oxidation.^26,^103,¹⁰⁸

FIGURE 18-1 Energy sources in relation to duration of contraction. Muscular metabolism available from the various substrates participating in supplying energy during the first 2 minutes of an attempted maximal contraction. The relative contribution of each substrate at any moment is indicated. The intensity of metabolic activity over the 2-minute period is adjusted to the change of the isometric tension produced during a sustained voluntary maximal contraction.

(Redrawn from DeLateur BJ: Therapeutic exercise to develop strength and endurance. In: Kottke FJ, Stillwell GK, Lehmann JF, editors: Krusen’s handbook of physical medicine and rehabilitation, Philadelphia, 1982, Saunders, with permission.)

Creatine Phosphate System

When limited stores of ATP are nearly depleted during high-intensity exercise (5 to 10 seconds), the creatine phosphate system transfers a high-energy phosphate from creatine phosphate to rephosphorylate ATP from ADP:

Because it involves a single reaction, this system can provide ATP at a very rapid rate. Because there is a limited supply of creatine phosphate in the muscle, however, the amount of ATP that can be produced is also limited.

There is enough creatine phosphate stored in skeletal muscle for approximately 25 seconds of high-intensity work (see Figure 18-1). The ATP–creatine phosphate system lasts for about 30 seconds (5 seconds for the stored ATP and 25 seconds for creatine phosphate). This provides energy for activities such as sprinting and weightlifting. The creatine phosphate system is considered an anaerobic system, because oxygen is not required.^26,^103,¹⁰⁸

Rapid Glycolysis (Lactic Acid System)

Glycolysis uses carbohydrates primarily in the form of muscle glycogen as a fuel source. When glycolysis is rapid, the pathways that normally use oxygen to make energy are circumvented in favor of other, faster yet less efficient paths that do not require oxygen. As a result, only a small amount of ATP is produced anaerobically, and lactic acid is produced as a by-product of the reaction.

For many years, lactic acid was considered to be the waste product caused by inadequate oxygen supply. Lactic acid limited physical activity by building up in muscles and leading to fatigue and diminished performance. Since the early 1980s, there has been a fundamental change in thought, and evidence now shows that a limited oxygen supply is not required for lactic acid production. Lactate is produced and used continuously under fully aerobic conditions. This is referred to as the cell-to-cell lactate shuttle in which lactate serves as a metabolic intermediate tying together glycolysis (as an end product) and oxidative metabolism.

Once lactic acid is formed, there are two possible venues it can take. The first involves conversion into pyruvic acid and subsequently into energy (ATP) under aerobic conditions (see “Aerobic Oxidation System” section below). The second involves hepatic gluconeogenesis using lactate to produce glucose, which is known as the Cori cycle.

Anaerobic oxidation starts as soon as high-intensity exercise begins and dominates for approximately 1½ to 2 minutes (see Figure 18-1). It would fuel activities such as middle-distance sprints (400-, 600-, and 800-m runs) or events requiring sudden bursts of energy such as weightlifting.

Although glycolysis is considered an anaerobic pathway, it can readily participate in the aerobic metabolism when oxygen is available and is considered the first step in the aerobic metabolism of carbohydrates.^26,^103,¹⁰⁸

Aerobic Oxidation System

The final metabolic pathway for ATP production combines two complex metabolic processes: the Krebs cycle and the electron transport chain. The aerobic oxydation system resides in the mitochondria. It is capable of using carbohydrates, fat, and small amounts of protein to produce energy (ATP) during exercise, through a process called oxidative phosphorylation. During exercise, this pathway uses oxygen to completely metabolize the carbohydrates to produce energy (ATP), leaving only carbon dioxide and water as byproducts. The aerobic oxidation system is complex and requires 2 to 3 minutes to adjust to a change in exercise intensity (see Figure 18-1). It has an almost unlimited ability to regenerate ATP, however, limited only by the amount of fuel and oxygen that is available to the cell. Maximal oxygen consumption, also known as O_2max, is a measure of the power of the aerobic energy system, and is generally regarded as the best indicator of aerobic fitness.^26,^103,¹⁰⁸

All the energy-producing pathways are active during most types of exercise, but different exercise types place greater demands on different pathways. The contribution of the anaerobic pathways (creatine phosphate system and glycolysis) to exercise energy metabolism is inversely related to the duration and intensity of the activity. The shorter and more intense the activity, the greater the contribution of anaerobic energy production, whereas the longer the activity and the lower the intensity, the greater the contribution of aerobic energy production. In general, carbohydrates are used as the primary fuel at the onset of exercise and during high-intensity work. But during prolonged exercise of low to moderate intensity (longer than 30 minutes), a gradual shift from carbohydrate toward an increasing reliance on fat as a substrate occurs. The greatest amount of fat use occurs at about 60% of maximal aerobic capacity (O_2max).^26,^103,¹⁰⁸

Cardiovascular Exercise

Cardiorespiratory Physiology

The cardiorespiratory system consists of the heart, lungs, and blood vessels. The purpose of this system is the delivery of oxygen and nutrients to the cells, as well as the removal of metabolic waste products to maintain the internal equilibrium.^70,^103,¹⁰⁸

Cardiac Function

Effects of Arm Versus Leg Exercise

Pulmonary Ventilation

Pulmonary ventilation (e) is the volume of air exchanged per minute, and generally is approximately 6 L/min at rest in an average sedentary adult man. However, at maximal exercise, e increases 15- to 25-fold over resting values. During mild to moderate exercise, e increases primarily by increasing tidal volume, but during vigorous activity it increases by increasing the respiratory rate.^48,¹⁰¹

Increases in e are generally directly proportional to an increase in oxygen consumption (O₂) and carbon dioxide that is produced (CO₂). At a critical exercise intensity (usually 47% to 64% of the O_2max in healthy untrained individuals and 70% to 90% O_2max in highly trained individuals), however, e increases disproportionately relative to the O₂ (paralleling an abrupt increase in serum lactate and CO₂). This is called the anaerobic (ventilatory) threshold.^48,^101,¹⁰⁸

The Anaerobic Threshold

The anaerobic threshold signifies the onset of metabolic acidosis during exercise, and traditionally has been determined by serial measurements of blood lactate. It can be noninvasively determined by assessment of expired gases during exercise testing, specifically e and carbon dioxide production (CO₂). The anaerobic threshold signifies the peak work rate or oxygen consumption at which the energy demands exceed the circulatory ability to sustain aerobic metabolism.^48,^101,¹⁰⁸

Maximal Oxygen Consumption

The most widely recognized measure of cardiopulmonary fitness is the aerobic capacity, or O_2max. This variable is defined physiologically as the highest rate of oxygen transport and use that can be achieved at maximal physical exertion.

The resting oxygen consumption of an individual (250 mL/min) divided by body weight (70 kg) gives the resting energy requirement, 1 MET (about 3.5 mL/kg per minute). Multiples of this value are used to quantify levels of energy expenditure. For example, running a 6-mph pace requires 10 times the resting energy expenditure, giving an aerobic cost of 10 METs, or 35 mL/kg per minute. Because there is little variation in HR_max and maximal systemic arteriovenous oxygen difference with physical training, O_2max virtually defines the pumping capacity of the heart. When expressed as milliliters of oxygen per kilogram of body weight per minute (mL/kg per minute) or in METs, it is considered the best index of physical work capacity or cardiorespiratory fitness.^48,^101,¹⁰⁸

Oxygen Pulse

The oxygen pulse (mL/beat) is the ratio of O₂ (mL/min) to HR (beats/min), when both measures are obtained simultaneously. Oxygen pulse increases with increasing work effort. A low value during exercise indicates an excessive HR for workload and can be an indicator of heart disease.²⁹

Respiratory Quotient and Respiratory Exchange Ratio

The respiratory quotient (RQ) is the ratio of CO₂ produced by cellular metabolism to O₂ used by tissues. It quantifies the relative amounts of carbohydrate and fatty acids being oxidized for energy. An RQ of 0.7 implies dependence on free fatty acids. An RQ of 1.0 indicates dependence on carbohydrate. The RQ does not exceed 1.0.

The respiratory exchange ratio (RER) reflects pulmonary exchange of CO₂ and O₂ at rest and during exercise. The RER also ranges between 0.7 and 1.0 during rest, and can also reflect substrate preference. During strenuous exercise, however, the RER can exceed 1.0 because of increasing metabolic activity not matched by O₂ and additional CO₂ derived from bicarbonate buffering of lactic acid. The terms RQ and RER are often used interchangeably, but their distinction is important.²⁹

Effects of Exercise Training

Cardiovascular System

The effects of regular exercise on cardiovascular activity can be grouped into changes that occur at rest, during submaximal exercise, and during maximal work (Box 18-1).^103,¹⁰⁸ Regular exercise can also affect a number of physiologic parameters (Box 18-2).

BOX 18-1 Effects of Regular Exercise on Cardiovascular Activity

Changes at Rest

• Heart rate decreases, probably secondary to decreased sympathetic tone, increased parasympathetic tone, and a decreased intrinsic firing rate of the sinoatrial node.

• Stroke volume increases secondary to increased myocardial contractility.

• Cardiac output is unchanged at rest.

• Oxygen consumption does not change at rest.^103,¹⁰⁸

Changes at Maximal Work

• Maximal heart rate does not change with exercise training.

• Stroke volume increases because of increased contractility and/or increased heart size.

• Maximal cardiac output increases because of increased stroke volume.

• Maximal oxygen consumption (

O_2max) increases primarily because of increased stroke volume.

• Ability of the local mitochondria to use oxygen is improved.^103,¹⁰⁸ (Because measured avO₂ difference represents whole-body avO₂ difference, there is generally little change in the measured avO₂ difference.)

^∗ Submaximal work is defined as a workload during which a steady state is achieved.

BOX 18-2 Physiologic Changes After a Regular Exercise Program

Blood Pressure

• In normotensive individuals, regular exercise does not appear to have a significant impact on resting or exercising blood pressure. In hypertensive individuals, there can be a modest reduction in resting blood pressure as a result of regular exercise.^103,¹⁰⁸

Blood Volume Changes

• Total blood volume increases because of an increased number of red blood cells and expansion of the plasma volume.^103,¹⁰⁸

Blood Lipids

• Total cholesterol can be decreased in individuals with hypercholesterolemia.

• High-density lipoprotein cholesterol increases with exercise training.

• Low-density lipoprotein cholesterol can remain the same or decrease with regular exercise.

• Triglycerides can decrease in those with elevated triglycerides initially. This change is facilitated by weight loss.^103,¹⁰⁸

Body Composition

• Total body weight usually decreases with regular exercise.

• Fat-free weight does not normally change.

• Percent body fat declines.^103,¹⁰⁸

Biochemical Changes

• Stored muscle glycogen increases.

• The percentage of fast- and slow-twitch fibers does not change, but the cross-sectional area occupied by these fibers may change because of selective hypertrophy of either fast- or slow-twitch fibers.^103,¹⁰⁸

Energy System Changes

• Specificity of training refers to the fact that the changes that occur are specific to the muscles and energy systems that are being used.

• Chronic anaerobic training using the ATP–creatine phosphate system results in improved capacity and power of this system because of enhancement of enzyme activity and increases in the amount of ATP and creatine phosphate in the muscle.

• Anaerobic glycolysis is improved if the training program uses this system, resulting in increased stores of muscle glycogen and improved ability of enzymes in the system.

• Regular aerobic training improves

O_2max. It increases muscle glycogen and triglyceride stores, as well as the rate at which carbohydrates and fat are metabolized.^103,¹⁰⁸

ATP, Adenosine triphosphate; O_2max, maximal oxygen consumption.

Detraining

The changes induced by regular exercise training generally are lost after 4 to 8 weeks of detraining. If training is re-established, the rate at which the training effects occur does not appear to be faster.^103,¹⁰⁸

Exercise Prescriptions

Exercise prescriptions are designed to enhance physical fitness, promote health by reducing risk factors for chronic disease, and ensure safety during exercise participation. The fundamental objective of the prescription is to bring about a change in personal health behavior to include habitual physical activity. The optimal exercise prescription for an individual is determined from an objective evaluation of that individual’s response to exercise, including observations of HR, blood pressure, rating of perceived exertion (RPE) to exercise, electrocardiogram when appropriate, and O_2max measured directly or estimated during a graded exercise test. The exercise prescription should be developed with careful consideration of the individual’s health status, medications, risk factor profile, behavioral characteristics, personal goals, and exercise preferences.^45,^108,¹²¹

Components of an Exercise Prescription

• Mode is the particular form or type of exercise. The selection of mode should be based on the desired outcomes, focusing on exercises that are most likely to sustain participation and enjoyment.

• Intensity is the relative physiologic difficulty of the exercise. Intensity and duration of exercise interact and are inversely related.

• Duration or time is the length of an exercise session.

• Frequency refers to the number of exercise sessions per day and per week.

• Progression (overload) is the increase in activity during exercise training, which, over time, stimulates adaptation.^45,^103,^108,¹²¹

These five essential components apply when developing an exercise prescription for persons of all ages and fitness levels. Each component of fitness (e.g., cardiorespiratory endurance, muscular strength and endurance, and flexibility) has its own specific exercise prescription associated with it. The following section reviews the ACSM guidelines for each component of fitness.

Exercise Prescription for Cardiorespiratory Endurance

Cardiorespiratory endurance is the ability to take in, deliver, and use oxygen. It is dependent on the function of the cardiorespiratory system (heart and lungs) and the cellular metabolic capacities. The degree of improvement that can be expected in cardiorespiratory fitness is directly related to the frequency, intensity, duration, and mode of exercise. O_2max can increase between 5% and 30% with training. It has become apparent recently, however, that the level of physical activity necessary to achieve the majority of health benefits is less than that needed to attain a high level of cardiorespiratory fitness.^45,^108,¹²¹

ACSM Recommendations for Cardiorespiratory Endurance Training

Mode

• The best improvements in cardiorespiratory endurance occur when large muscle groups are engaged in rhythmic aerobic activity.

• Various activities can be incorporated into an exercise program to increase enjoyment and improve compliance.

• Appropriate activities include walking, jogging, cycling, rowing, stair climbing, aerobic dance (“aerobics”), water exercise, and cross-country skiing.^45,^108,¹²¹

Intensity

• ACSM recommendations describe minimum exercise intensity as exercise of at least moderate intensity (i.e., 40% to 60% of

O_2max that noticeably increases HR and breathing).

• A combination of moderate and vigorous exercise (≥60% of

O_2max that results in substantial increases in HR and breathing) is ideal for the attainment of improvements in health and fitness in most adults.^45,^108,¹²¹

Calculating Intensity

Because of limitations in using O₂ calculations for prescribing intensity, the most common methods of setting the intensity of exercise to improve or maintain cardiorespiratory fitness use HR and RPE.^45,^100,¹⁰⁸

Heart Rate Methods

Heart rate is used as a guide to set exercise intensity, because of the relatively linear relationship between HR and percentage of O_2max. It is best to measure HR_max during a progressive exercise test whenever possible, because HR_max declines with age. HR_max can be estimated by using the following equation: HR_max = 220 – age. This estimation has significant variance, with a standard deviation of 10 beats/min.^45,^100,^108,¹²¹

Maximal heart rate method

One of the oldest methods of setting the target HR range uses a straight percentage of the HR_max. Using 70% to 85% of an individual’s HR_max approximates 55% to 75% of O_2max and provides the stimulus needed to improve or maintain cardiorespiratory fitness.^45,^100,^108,¹²¹ For example, if the HR_max is 180 beats/min, then the target HR (70% to 85% of HR_max) would range from 126 to 153 beats/min. (See also Chapter 33.)

Heart rate reserve method

The HR reserve (HRR) method is also known as the Karvonen method. In this method the target range is calculated as follows: subtract standing resting HR (HR_rest) from HR_max to obtain HRR. Calculate 50% and 85% of the HRR. Add each of these values to the HR_rest to obtain the target range. Therefore the target range is as follows:

The small but systematic differences between the two HR methods occur because the percentage HR_max is 55% to 75% of O_2max, whereas the percentage HRR_max is 60% to 80% of O_2max. Either method can be used to approximate the range of exercise intensities known to increase or maintain cardiorespiratory fitness or O_2max.^45,^108,¹²¹

Rating of Perceived Exertion

The RPE is a subjective grading of how hard individuals feel they are exercising. Use of RPE is considered an adjunct to monitoring HR. It has proven to be a valuable aid in prescribing exercise for individuals who have difficulty with HR palpation, and in cases where the HR response to exercise may have been altered because of a change in medication. The most commonly used scale of perceived exertion is the Borg Scale (see Table 18-1). The average RPE range associated with physiologic adaptation to exercise is 13 to 16 (“somewhat hard” to “hard”) on the Borg Scale category. One should suit the RPE to the individual on a specific mode of exercise, and not expect an exact matching of the RPE to a percentage HR_max or percentage HRR. It should be used only as a guideline in setting the exercise intensity.^45,^94,^100,^108,¹²¹

The appropriate exercise intensity is one that is safe and compatible with a long-term active lifestyle for that individual and achieves the desired outcome given the time constraints of the exercise session. The ACSM recommends an intensity that will elicit an RPE within a range of 12 to 16 on the original 6 to 20 Borg Scale (Table 18-1).

Table 18-1 Borg Scale of Perceived Exertion ⁹⁴

Level	Perceived Exertion
6	—
7	Very, very light
8
9	Fairly light
10
11
12
13	Somewhat hard
14
15	Hard
16
17	Very hard
18
19	Very, very hard
20

Duration

• Duration can be measured by duration of physical activity or by the total caloric expenditure.

• A dose-response relationship exists between the number of calories used during activity and the health and fitness benefits.

• Physical activity may be continuous or intermittently accumulated during a day through one or more sessions of activity lasting greater than 10 minutes.

• ACSM recommends the following quantity of physical activity for most healthy adults: 1000 kcal/wk (or approximately 150 min/wk or 30 min/day).

• For most adults, larger quantities of exercise (i.e., ≥2000 kcal/wk or ≥250 min/wk or 50 to 60 min/day) results in greater health benefits.^45,^100,^108,¹²¹

Frequency

• As above, activity can be continuous or intermittent and accumulated over the course of a day through more than one session of activity lasting greater than 10 minutes.

• The ACSM recommends exercise 3 to 5 days a week.

• Less conditioned people can benefit from lower intensity, shorter duration exercise performed at higher frequencies per day and/or per week.^45,^108,¹²¹

Progression

• The rate of progression depends on health and fitness status, individual goals, and compliance rates.

• Frequency, intensity and/or duration can be increased to provide overload.

• The ACSM notes a 5- to 10-minute increase every 1 to 2 weeks over the first 4 to 6weeks of an exercise is reasonable for a healthy adult.^45,^108,¹²¹

Medical Clearance

Exercise training might not be appropriate for everyone. Patients whose adaptive reserves are severely limited by disease processes might not be able to adapt to or benefit from exercise. In this small subpopulation of people with severe or unstable cardiac, respiratory, metabolic, systemic, or musculoskeletal disease, exercise programming can be fatal, injurious, or simply not beneficial, depending on the clinical status and condition of the individual.^46,¹²¹

The recommended level of screening before beginning or increasing an exercise program depends on the risk for the individual and the intensity of the planned physical activity. For individuals planning to engage in low- to moderate-intensity activities, the Physical Activities Readiness Questionnaire (PAR-Q) (Box 18-4) should be considered the minimal level of screening. The PAR-Q was designed to identify the small number of adults for whom physical activity might be inappropriate or those who should receive medical advice concerning the most suitable type of activity.^46,^108,¹²¹

BOX 18-4 Physical Activity Readiness Questionnaire ^∗

• Has your doctor ever said that you have a heart condition and that you should only do physical activity recommended by a doctor?

• Do you feel pain in your chest when you do physical activity?

• In the past month, have you had chest pain when you were not doing physical activity?

• Do you lose your balance because of dizziness or do you ever lose consciousness?

• Do you have a bone or joint problem that could be made worse by a change in your physical activity?

• Is your doctor currently prescribing drugs (e.g., water pills) for your blood pressure or heart condition?

• Do you know of any other reason why you should not do physical activity?

^∗ A “yes” answer to any of the questions indicates the necessity of a physician’s referral for a preexercise evaluation before the person begins or increases physical activity.^46, ¹²¹

Preexercise Evaluation

A preexercise evaluation by a physician is more comprehensive and should include a patient history and a determination of whether the patient needs an exercise stress test.

Identification of Those Who Need an Exercise Stress Test

Indications for an exercise stress test according to the American College of Cardiology and American Heart Association are as follows ¹¹⁴:

• To evaluate patients for suspected coronary artery disease (typical and atypical angina pectoris)

• To evaluate patients with known coronary artery disease after myocardial infarction or intervention

• To evaluate patients with suspected or confirmed pulmonary limitations

• To evaluate healthy, asymptomatic individuals in the following categories:

• Individuals in high-risk occupations such as pilot, firefighter, law enforcement officer, and mass transit operator

• Men older than 40 years and women older than 50 years who are sedentary and plan to start vigorous exercise

• Individuals with multiple cardiac risk factors or concurrent chronic diseases

• To evaluate exercise capacity in patients with valvular heart disease (except severe aortic stenosis)

• Individuals with cardiac rhythm disorders for the following reasons:

• To evaluate response to treatment of exercise-induced arrhythmia

• To evaluate response of rate-adaptive pacemaker setting.

The ACSM guidelines are summarized in Box 18-5 and Tables 18-2 and 18-3.^78,¹²¹ Contraindications to exercise testing are listed in Box 18-6.

BOX 18-5 Major Symptoms or Signs Suggestive of Cardiopulmonary Disease ^78, ¹²¹

From Kenny W, Humphrey R, Bryant C: ACSM’s guidelines for exercise testing and prescription, ed 5, Philadelphia, 1995, Williams & Wilkins, 1995, with permission of Williams & Wilkins.

• Pain and discomfort (or other anginal equivalent) in the chest, neck, jaw, arms, or other areas that may be ischemic in nature

• Shortness of breath at rest or with mild exertion

• Dizziness or syncope

• Orthopnea or paroxysmal nocturnal dyspnea

• Ankle edema

• Palpitations or tachycardia

• Intermittent claudication

• Known heart murmur

• Unusual fatigue or shortness of breath with usual activities

Table 18-2 American College of Sports Medicine Recommendations for Medical Examination and Exercise Testing Before Participation and for Physician Supervision of Exercise Tests

Table 18.3 Coronary Artery Disease Risk Factor Thresholds for Use With ACSM Risk Stratification

Risk Factors	Defining Criteria
Positive
Family history	Myocardial infarction, coronary revascularization, or sudden death before 55 years of age in father or other male first-degree relative (i.e., brother or son) or before 65 years of age in mother or other female first-degree relative(i.e., sister or daughter)
Cigarette smoking	Current cigarette smoker or those who quit within the previous 6 months
Hypertension	Systolic blood pressure of ≥140 mm Hg or diastolic ≥90 mm Hg, confirmed by measurements on at least two separate occasions, or on antihypertensive medication
Hypercholesterolemia	Total serum cholesterol of >200 mg dL (5.2 mmoL/L) or high-density lipoprotein cholesterol of <35 mg/dL (0.9 mmoL/L) or on lipid-lowering medication. If low-density lipoprotein cholesterol is available, use >130 mg/dL (3.4 mmoL/L) rather than total cholesterol of >200 mg/dL
Impaired fasting glucose	Fasting blood glucose of ≥110 mg/dL (6.1 mmoL/L) confirmed by measurements on at least two separate occasions
Obesity∗	Body mass index of ≥30 kg · m^–2, or waist girth of >100cm
Sedentary lifestyle	Persons not participating in a regular exercise program or meeting the minimal physical activity recommendations in the U.S. Suregeon General’s report
Negative
High serum HDL cholesterol^†	>60 mg/dL (1.6 mmoL/L)