Cardiovascular Integration Notes (PDF)

Donal S. O'Leary, Ph.D. Cardiovascular Physiology INTEGRATION OF CARDIOVASCULAR SYSTEM Learning Objectives: 1. Describe a cardiovascular responses to dynamic exercise 2. Differentiate the responses in normal individuals from those seen in cardiac patients or world clas...

Donal S. O'Leary, Ph.D. Cardiovascular Physiology INTEGRATION OF CARDIOVASCULAR SYSTEM Learning Objectives: 1. Describe a cardiovascular responses to dynamic exercise 2. Differentiate the responses in normal individuals from those seen in cardiac patients or world class athletes. 3. Understand factors controlling oxygen consumption 4. Understand compensatory responses to hyperthermia Lecture Outline: 1. Cardiovascular responses to dynamic exercise a. Cardiac patient b. Olympic athlete 2. Mechanisms mediating changes in autonomic activity during exercise a. Central Command b. Baroreflex c. Skeletal muscle afferents 3. Dynamic exercise vs. isometric exercise 4. Hyperthermia – competition between skin and muscle 5. The normal cardiovascular responses to graded dynamic exercise. 1 Donal S. O'Leary, Ph.D. Cardiovascular Physiology Oxygen Consumption = Blood Flow x (a-v)O2 Oxygen consumption is equal to the blood flow times the arterio-venous O2 difference (Extraction). Normally only about 25% of the O2 is used by most tissues (although this varies widely from very, very little in skin during heat stress when skin blood flow is very high, to over 75% in the coronary circulation even at “rest”). Mixed venous O2 content is about 75% of arterial content. Thus, we can increase O2 consumption by increasing blood flow and/or by increasing extraction of the O2 that is delivered – OR BOTH. In most vascular beds O2 consumption is increased by both increasing extraction and increasing flow. However, in the cardiac muscle, even at “Rest” extraction is already near maximal, so the only effective way to increase O2 consumption is to increase blood flow. 2 Donal S. O'Leary, Ph.D. Cardiovascular Physiology The typical responses to graded dynamic exercise in three groups of individuals, normally active subjects (NA), endurance trained athletes (ATH), and patients with mitral stenosis (MS) are shown below. Note that cardiac output and heart rate increase in proportion to the increase in workload (here indicated by the oxygen uptake). Also note that splanchnic and renal blood flow decrease and plasma norepinephrine (an index of sympathetic activity) increases as workload increases. ATH 40 30 Cardiac Output NA 20 (l min-1) 10 MS 0 200 ATH 150 Stroke Volume NA 100 (ml) 50 MS 0 200 MS NA ATH 150 Heart Rate SNA 100 NE (beats min-1) 50 0 18 MS NA ATH Arteriovenous 14 Oxygen Difference 10 (ml 100 ml-1 min-1) 6 0 200 MS NA ATH 3.6 Splanchnic 150 3.4 and Renal Log Predicted Blood Flow 100 3.2 NE Concentration (% change) (ng ml-1) 50 3.0 MS NA ATH 0 2.8 SR 1 2 3 4 5 6 Oxygen Uptake (l min-1) 3 Donal S. O'Leary, Ph.D. Cardiovascular Physiology The distribution of cardiac output at rest and during maximal exercise in the three groups. Note that relative to NA or ATH, in MS a larger fraction of the increase in muscle blood flow comes at the expense of flow to the inactive areas. Maximal Exercise (ATH) 40 35 30 Maximal Exercise (NA) 25 Blood Flow 20 (l/min) Muscle 15 Maximal Heart Exercise (MS) Other 10 Skin Rest Brain 5 Kidneys Liver & GI 0 4 Donal S. O'Leary, Ph.D. Cardiovascular Physiology Mechanisms mediating cardiovascular responses to exercise: The mechanisms mediating the cardiovascular responses to exercise are not completely understood. Currently it is thought that response to exercise occur via three different but interdependent mechanisms. CENTRAL COMMAND: Central command refers to the volition or will to exercise. Activation of central command increases heart rate predominately via reduction in parasympathetic activity. Central command appears to have little control over sympathetic activity. ARTERIAL BAROREFLEX: For many years it was thought that since arterial blood pressure increases during exercise the arterial baroreflex must be "shut off" during exercise otherwise this reflex should oppose any rise in blood pressure. Rather, recent studies have shown that instead of being turned off during exercise, the arterial baroreflex is reset to a higher level. Thus, rather than oppose the rise in arterial pressure, the baroreflex may in fact reinforce the rise in pressure during exercise. The 5 Donal S. O'Leary, Ph.D. Cardiovascular Physiology mechanisms mediating the resetting of the arterial baroreflex are not known. One hypothesis is that activation of central command causes baroreflex resetting. SKELETAL MUSCLE METABOREFLEX and MECHANOREFLEX: When oxygen delivery to active skeletal muscle is insufficient for the metabolic demands, metabolites (i.e. K+, lactate, H+, CO2, etc.) accumulate within the muscle and stimulate group III and IV afferents within the muscle. Activation of these afferents induces a reflex increase in arterial pressure and heart rate - termed the muscle metaboreflex. This is likely the cause of the large increases in arterial pressure often seen in patients with peripheral vascular disease which limits the increase in muscle blood flow during exercise. Some of these afferents are also mechanosensitive and are stimulated with muscle contraction (note - these are not the muscle spindles or golgi tendon organs - activation of these receptors have little cardiovascular effect). Activation of these mechanoreceptors will also increase heart rate and arterial pressure. Current evidence indicates that the muscle metaboreflex has little control over parasympathetic activity but exerts its effects principally via activation of the sympathetic nervous system. Activation of the muscle metaboreflex can also increase vasopressin release. MECHANISMS OF THE CARDIOVASCULAR RESPONSES DURING GRADED EXERCISE At the initiation of exercise, parasympathetic tone rapidly decreases causing an increase in heart rate, thus increasing cardiac output. This decrease in parasympathetic tone is thought to be mediated via the activation of central command. Sympathetic activity may increases a little likely due to activation of muscle mechanoreceptors. As workload progresses, parasympathetic activity wanes (likely via further activation of central command and/or via arterial baroreflex resetting) and sympathetic activity to the heart and periphery increases (likely due to arterial baroreflex resetting, muscle mechanoactivation and possibly via activation of the muscle metaboreflex). At maximal exercise parasympathetic tone is virtually abolished and sympathetic activity is very high. 6 Donal S. O'Leary, Ph.D. Cardiovascular Physiology The responses to exercise in one subject with dysautonomia are shown below. This patient has little if any control over sympathetic activity to the periphery. Note the large decrease in arterial pressure as workload increases. This underscores the necessity of peripheral vasoconstriction during exercise. EXERCISE SITTING START STOP 0W 50 W 100 W 150 Blood Pressure (mmHg) 100 50 0 150 Heart Rate (bpm) 25 EXERCISE SUPINE START STOP SQUAT 10 W 30 W 50 W 70 W 90 W 150 Blood Pressure (mmHg) 100 50 0 150 Heart Rate (bpm) 25 10 s During whole body dynamic exercise sympathetic activity increases to inactive beds (kidney, gut, skin etc.) and also likely to the active skeletal muscle itself. Why vasoconstrict the active muscle? Skeletal muscle should be viewed as a "sleeping giant" capable of such tremendous vasodilation that it can literally outstrip cardiac pumping capacity. For example, recent evidence indicates that maximal muscle blood flow is much higher than previously estimated (textbooks commonly state that maximal muscle blood flow is ~ 800ml/min/kg muscle). In reality, maximal muscle blood flow approaches 3000 ml/min/kg muscle. Thus, if the average person maximally exercised 1/2 of their muscle mass (about 15 kg), then muscle blood flow theoretically would increase to 45 liters/min (3000ml/min/kg muscle times 15 kg muscle = 45 liters/min). The average maximal cardiac output is only ~ 25 liters/min. Thus, without vasoconstriction of active skeletal muscle during whole body exercise, vasodilation of muscle would far outstrip cardiac pumping capacity and arterial pressure would plummet. 7 Donal S. O'Leary, Ph.D. Cardiovascular Physiology ISOTONIC ISOMETRIC (Running or Swimming) (Weight Lifting) 160 Mean Aortic Pressure 140 (mmHg) 120 100 0 300 600 900 -2 0 1 2 3 Work (kg m min-1) Minutes Effects of dynamic exercise vs. static exercise on arterial pressure are shown above. How might the roles of central command, arterial baroreflex and muscle metabo/mechanoreflexes differ in the two settings? 8 Donal S. O'Leary, Ph.D. Cardiovascular Physiology HYPERTHERMIA The normal responses to hyperthermia in humans. During peak hyperthermia, the majority of the cardiac output is directed to skin both via an increase in cardiac output and redistribution of blood flow towards skin. The vasodilation in most skin occurs mainly via activation of sympathetic active vasodilator nerves (neurotransmitter is unknown). Control Heating Skin Temp., ºC 40.5 ºC 40.0 39.1 ºC TBody TBlood 35.0 36.7 ºC 24 13.0 Cardiac Output, l/m 13.0  6.6 l/min 4 6.4 Splanchnic Blood Flow, l/m 1.5  0.6 l/min 0.9 Renal Blood Flow, l/m 0.9 1.3  0.4 l/min 0.9 0.9 Muscle Blood Flow, ml/100 ml min (2.8)  0.2 l/min (2.1) Total  7.8 l/min 100 Arterial Mean Pressure, mmHg 86 80 Right Atrial Mean Pressure, mmHg 5.4 0.5 0 110 Stroke Volume, ml 108 100 1.4 Central Blood Volume, l 1.2 30 50 70  min TSkin Question - why is exercise more difficult in a hot environment? Hint - think about the ability of the heart to pump blood and competition between skin and skeletal muscle. 9