CARDIAC OUTPUT

CARDIAC OUTPUT

The cardiac output (CO) is defined as the total blood flow delivered by the heart, representing the amount of blood pumped by each ventricle separately per minute. It is the total flow available to perfuse all body tissues. For the left ventricle, it is the product of heart rate and volume ejected per stroke, or cycle, into the aorta. 

Cardiac output = Heart rate * Stroke volume.= 70 bpm * 70 ml = 4900 ml/min

At rest, the cardiac output is approximately 5 L/min in a 70-kg human, with normal values in healthy adults ranging from 4.5 to 6 liters/min (about 10% lower in females).

The cardiac index is the cardiac output normalized to body surface area, expressed in liters per minute per square meter (L/min/m2). The normal adult cardiac index at rest is about 3.0 L/min/sq. metre, with values between 2.4 and 3.5 L/min/sq.metre being typical, slightly higher in males and considerably higher in children.

Factors Affecting Cardiac Output

Cardiac output is a product of two primary factors: heart rate (HR) and stroke volume (SV). These are strictly cardiac factors, though modulated by neural and humoral mechanisms. In the intact organism, changes in one feature almost invariably alter the others.

The four main factors controlling cardiac output are heart rate, myocardial contractility, preload, and afterload. Preload and afterload serve as "coupling factors" as they depend on the characteristics of both the heart and the vascular system.

1. Heart Rate (HR)

    ◦ Control: The heart rate is primarily controlled by the cardiac nerves; sympathetic stimulation increases it (positive chronotropic effect), while the vagus nerve (parasympathetic) has the opposite effect (negative chronotropic effect).

    ◦ Impact on CO and SV: An increase in heart rate typically reduces the duration of diastole, which can diminish ventricular filling and thus reduce preload. However, a rise in heart rate also increases the net rate of calcium (Ca$^{2+}$) influx into myocardial cells, which enhances myocardial contractility.

    ◦ If heart rate alone is increased (e.g., by an artificial pacemaker), the stroke volume may decrease proportionately due to reduced ventricular refilling time.

    ◦ The relationship between cardiac output and heart rate can be complex; over a wide range of heart rates, a change in heart rate may have little influence on cardiac output.

    ◦ Changes in heart rate also alter preload, afterload, and contractility.

2. Stroke Volume (SV)

    ◦ Stroke volume is the volume of blood ejected from the ventricle on each beat. It is calculated as the end-diastolic volume minus the end-systolic volume. The strength, speed, and extent of ventricular muscle contraction determine the stroke volume.

    ◦ Preload:

        ▪ Refers to the load on the heart that determines the length of cardiac muscle cells prior to contraction, typically represented by end-diastolic volume (EDV) or pressure.

        ▪ An increase in preload (e.g., from increased venous return) leads to an increase in stroke volume, based on the Frank-Starling relationship. This is reflected as an increased width of the pressure-volume loop to the right (higher end-diastolic volume).

        ▪ In the intact circulation, central venous pressure (CVP) constitutes the preload of the heart.

    ◦ Afterload:

        ▪ Refers to the load the heart experiences as it ejects blood into its outflow tracts. For the left ventricle, this is primarily the aortic pressure.

        ▪ An increase in afterload means the ventricle must eject blood against a higher pressure, resulting in a decrease in stroke volume (a narrower pressure-volume loop width) and an increase in end-systolic volume. Increased afterload will decrease the velocity with which the left ventricle can contract or shorten.

    ◦ Contractility (Inotropism):

        ▪ The intrinsic ability of cardiac muscle to develop force at a given muscle length. It is directly related to the intracellular Ca$^{2+}$ concentration.

        ▪ Positive inotropic agents (e.g., $\beta$-adrenergic agonists like norepinephrine/epinephrine, digitalis, insulin, cardiotonic steroids) increase myocardial contractility. This causes the ventricle to develop greater tension, increasing stroke volume (by decreasing end-systolic volume). Increased contractility shifts the cardiac function curve upward.

        ▪ Negative inotropic agents (e.g., L-type Ca$^{2+}$ channel blockers like propranolol) decrease contractility.

        ▪ Contractility represents the heart's performance at a given preload and afterload, depending on the state of excitation-contraction coupling processes within the cells.

Interplay of Factors: Preload and afterload are influenced by the vascular system's characteristics (e.g., venomotor tone, peripheral resistance) and the heart's behavior (e.g., heart rate, stroke volume). Physiologically, multiple changes usually occur simultaneously, making the regulation of cardiac output a complex interplay.

Methods of Recording Cardiac Output

Several methods are used to measure cardiac output:

1. Fick Principle

    ◦ This method is based on the law of conservation of mass. It states that the amount of a substance taken up or released by an organ per unit time is equal to the product of blood flow through that organ and the arteriovenous concentration difference of the substance.

    ◦ Calculation (Oxygen): Cardiac Output (Q) = Oxygen Consumption (VO2) / ({O2pulmonary\ vein} - [O2_{pulmonary\ artery}).

        ▪ Measurements Needed: The whole-body oxygen consumption, oxygen content of systemic arterial blood (which is essentially identical to pulmonary vein blood), and mixed venous blood (from the pulmonary artery).

    ◦ The Fick method is considered a standard against which other methods are checked. An indirect Fick method using CO2 excretion also exists.

2. Indicator Dilution Technique

    ◦ Also based on the law of conservation of mass.

    ◦ A known quantity of an indicator substance (e.g., dye or isotope that remains within the circulation) is injected rapidly into a central vein or the right side of the heart. The concentration of the indicator is then continuously monitored downstream (e.g., in an artery) over time.

    ◦ Dye Dilution Method: Uses a substance like Evans blue dye. The cardiac output is calculated from the amount of dye injected and the mean concentration of the dye during its first circulation within a given time.

    ◦ Thermodilution: A popular technique where cold saline is injected into the right atrium, and a thermistor in the pulmonary artery records temperature changes. The greater the cardiac output, the greater the dilution of the injected substance.

3. Ventricular Dimensions and Volumes (Angiography and Echocardiography)

    ◦ Ejection Fraction (EF): The fraction of the end-diastolic volume ejected in each stroke volume. It is calculated as (Stroke Volume / End-Diastolic Volume) and is normally about 0.55 (55%). EF is a measure of cardiac function and an index of contractility.

    ◦ Gated Radionuclide Imaging: Uses $\gamma$-emitting isotopes (e.g., technetium Tc 99m) to image cardiac chambers, providing relative ventricular volumes and allowing estimation of ejection fraction from the difference between end-diastolic and end-systolic volumes.

    ◦ Echocardiography: A non-invasive method that can visualize the movement of ventricular walls and valves.

Clinical Conditions in Which Cardiac Output is Changed

Cardiac output changes significantly in various physiological and pathological conditions:

1. Increased Cardiac Output

    ◦ Exercise: Cardiac output increases substantially, often 4- to 5-fold during severe exercise, by increasing both heart rate and stroke volume. Physical training enhances the body's capacity to deliver oxygen.

    ◦ Hyperthyroidism: Characterized by increased heart rate, myocardial contractility, and reduced systemic vascular resistance, leading to a higher cardiac output.

    ◦ Pregnancy: Associated with about a 40% increase in cardiac output due to positive chronotropic and inotropic effects.

    ◦ Sympathetic Stimulation: Generally enhances heart rate and contractility, which can lead to increased cardiac output.

2. Decreased Cardiac Output

    ◦ Heart Failure: A general term for conditions where the heart cannot provide adequate blood flow to tissues.

        ▪ Myocardial Dysfunction: Leads to poor cardiac performance and decreased effective circulating volume. This can paradoxically cause the kidneys to retain NaCl and water, leading to increased extracellular fluid (ECF) volume and edema (e.g., pulmonary and peripheral edema).

        ▪ Impaired Contractility: The cardiac function curve shifts downward and to the right. The residual volume of blood in the ventricles after systole can become much greater than the stroke volume.

        ▪ Patients with severe congestive heart failure often have very small arterial pulse pressures.

    ◦ Hemorrhage: Acute blood loss significantly reduces cardiac output.

    ◦ Aortic Stenosis: Narrowing of the aortic valve increases the afterload, forcing the left ventricle to generate much higher pressures to eject blood. This often results in a reduced stroke volume.

    ◦ Mitral Stenosis: Narrowing of the mitral valve impedes left ventricular filling, leading to a reduced end-diastolic volume, a smaller pressure-volume loop, and a reduced stroke volume.

    ◦ Aortic Regurgitation: The incompetent aortic valve allows blood to flow backward into the left ventricle during diastole, significantly increasing end-diastolic volume (preload). While the total stroke volume ejected might be larger (due to both forward and regurgitant flow), the net forward stroke volume may be reduced depending on severity. This can lead to increased arterial pulse pressures due to the large stroke volume ejected.

    ◦ Mitral Regurgitation: The incompetent mitral valve allows blood to flow backward into the left atrium during ventricular systole. This reduces the effective forward stroke volume. The left ventricle may compensate by increasing its end-diastolic volume.

    ◦ Profound Bradycardia: Excessively slow heart rates (e.g., in sick sinus syndrome or complete atrioventricular block) can lead to inadequate ventricular filling, causing a substantial decrease in cardiac output. Artificial pacemakers may be required to maintain adequate cardiac output.

    ◦ Excessively High Tachycardia: Heart rates above approximately 200 beats/min can also decrease cardiac output, as the reduction in filling time becomes too severe.

    ◦ Hypovolemia: A decrease in blood volume (e.g., from severe diarrhea or hemorrhage) directly reduces cardiac output.

    ◦ Hypothyroidism: Leads to sluggish cardiac activity, a slow heart rate, and diminished cardiac output.

    ◦ Beta-Blockers (e.g., Propranolol): Drugs like propranolol can reduce cardiac output by inhibiting $\beta_1$ receptors in the sinoatrial node (reducing heart rate) and in ventricular muscle (decreasing contractility).