Physiology, Cardiac Output

Article Author:
Jordan King
Article Editor:
David Lowery
5/7/2019 8:49:47 AM
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Physiology, Cardiac Output


Cardiac output (CO) is the amount of blood pumped by the heart minute, or in other words, cardiac output is the amount of work performed by the heart in response to the body’s need for oxygen. Two ways to increase oxygen delivery are through alterations of local blood flow and adjustment of cardiac output by modulating heart rate (HR) and stroke volume (SV). Because every tissue in the body relies on the heart for nourishment, any cardiovascular dysfunction has the potential to result in significant morbidity and mortality. Heart disease affects nearly 30 million Americans annually and is the number one cause of death in the United States. The degree of functional impairment can be assessed by a variety of methods which guides diagnosis, prognosis, and treatment. Almost every clinician will come across heart disease in the course of their practice and should be familiar with the basics of cardiac function.[1][2][3][4][5]


Actively metabolizing tissue requires a constant supply of blood for delivery of nutrients and removal of waste products. Under ideal conditions, blood supply to the tissue is matched to the rate of oxygen consumption to allow biochemical processes to proceed at optimal speeds. Situations resulting in insufficient blood supply slow or completely halt vital reactions. More specifically, subprime perfusion causes cells to shift to anaerobic metabolic pathways leading to the generation of lactic acid and other bioactive compounds. Effects of toxic metabolite accumulation include reduced cellular pH, enzyme denaturation, and altered membrane potentials. These changes could spell cellular, tissue, organ, and eventually, global catastrophe if left uncorrected.

Organ Systems Involved

Cardiac output provides the nourishment for all the tissues and organs in the body. It is frequently considered from a cardio-centric approach since all blood that circulates to tissues must pass through the heart. However, this limited perspective obfuscates the importance of local capillary bed function in ensuring adequate organ perfusion. In situations where total body oxygen requirements are unchanged, global catastrophe will not increase. Instead, blood is preferentially distributed to the organs placed under stress by rerouting supply from tissues at rest. This is accomplished through local vasodilation and concomitant vasoconstriction elsewhere. Consider skeletal muscles and the gastrointestinal (GI) system both during light exercise and following a large meal. While walking, skeletal muscles perform relatively more work than the GI system. Following a large meal, the opposite is true. Blood supply is reorganized to reflect these differences in metabolic need. However, once total body oxygen requirements increase, it will not be enough to redistribute supply. The heart meets these demands by pumping blood more rapidly which can be observed as an increase in absolute cardiac output.[6][7]

The heart and brain as the target organ of blood supply are unique. Cerebral tissue receives a relatively constant supply of blood regardless of total oxygen requirements. The heart varies in that its source of supply is not as cut and dry as other organs. Myocardial and pericardial layers are supplied by vessels called coronary arteries that arise from the aorta, just distal to the aortic valve. Perfusion is complicated because these small vessels are temporarily collapsed by the high pressures generated during ventricular systole. At rest, when metabolic requirements of cardiac tissue are low, diastole and associated cardiac perfusion account for roughly two-thirds of the cardiac cycle. At accelerated heart rates, time spent in diastole relative to systole decreases, leaving less time for perfusion. This paradoxical reduction in blood supply during times of increased myocardial oxygen demand predisposes the heart to inadequate perfusion, also known as ischemia. Clinically, this is observed as angina.


The amount of blood pumped by the heart is closely matched to global metabolic needs. Changes in cardiac output from baseline are directly proportionate to changes in total body oxygen needs. During times of physiologic stress, cardiac output will increase to ensure adequate tissue perfusion. Fick’s principle illustrates this notion in equation form: CO = VO2/ (a – v O2 difference) where VO2 represents oxygen use by tissue and a-V O2 is the difference in oxygen content of arterial and venous blood. Regulation of cardiac output is subject to a complex mechanism involving the autonomic nervous system, endocrine, and paracrine signaling pathways.[8]


Cardiac output is the product of heart rate (HR) and stroke volume (SV). HR is most commonly defined as the number of times the heart beats in one minute. SV is the amount of blood ejected during ventricular contraction. Each component is the composite of a variety of factors that can be modulated based on need. Values of cardiac output in humans are dependent on body size and activity level. Commonly reported numbers in healthy subjects range from 4 L/min in an at-rest person with a small body habitus to more than 35 L/min in elite athletes during exercise.

HR is determined by the speed of signal propagation through the electrical conducting system. Signals begin in the sinoatrial node which fires at an intrinsic rate of 60 to 100 times each minute following unique alterations in ion conductance across the cell membrane. Chronotropy describes the rate of spontaneous discharge and can be altered by a variety of influences. Once at threshold, an action potential (AP) is generated and is conducted through the atria to the atrioventricular (AV) node. Propagation of the signal through the AV node is relatively slow and represents another locus of control, termed dromotropy. From here, the AP is passed to the bundle of His and then the right and left bundle branches. Next, the signal reaches the Purkinje fibers and eventually arrives at the ventricular myocytes, producing a contraction. Lastly, the pathway returns to its resting state before the next impulse arrives. The final relaxation and repolarization of electrical conducting cells and myocytes are called lusitropy.

SV, the other major determinant of cardiac output, can also be manipulated when required. The amount of blood ejected each beat depends on preload, contractility, and afterload. Preload is synonymous with end-diastolic ventricular volume, or the amount of blood in the ventricles immediately before systole. Higher preload volumes mean the ventricles must eject more blood. Contractility describes the force of myocyte contraction, also referred to as inotropy. As the force of contraction increases so does the stroke volume. The final determinant of stroke volume is afterload. Afterload is the amount of systemic resistance the ventricles must overcome to eject blood into the vasculature. Afterload is proportionate to systemic blood pressures and is inversely related to stroke volume, unlike preload and contractility.

Cardiac output can be increased by a variety of signaling methods including enhancement of sympathetic tone, catecholamine secretion, and circulation of thyroid hormone. These mechanisms increase HR by exerting positive effects at chronotropic, dromotropic, and lusitropic control points. These influences also increase preload through receptor-mediated vasoconstriction. Additionally, contractility is improved through the Frank-Starling mechanism and also by direct catecholamine stimulation. The opposite effects on HR and SV occur when the parasympathetic tone is strengthened in response to decreased oxygen requirements.


Impairment of cardiac function can arise through a variety of pathophysiologic mechanisms. Common etiologies include hypertension, coronary disease, congenital problems, myocardial ischemia and infarction, congestive heart failure, shock, arrhythmias, genetic diseases, structural abnormalities, pericardial effusions, emboli, tamponade, and many others. Depending on the temporal course, not all of these ailments present with clinically apparent effects. It may take decades for a chronic problem like hypertension or coronary atherosclerosis to cause noticeable symptoms. However, it is important to understand that all cardiotropic diseases share the common quality of compromising the heart’s ability to supply oxygen to the body effectively.

Clinical Significance

Diseases of the heart are the number one cause of death in the United States, killing more than 600,000 people annually and accounting for one out of every four American deaths. Cardiac deterioration occurs in both acute and chronic fashion.

Major modifiable risk factors attributed to the development of chronic cardiac pathology include body weight, tobacco use, serum glucose and lipid levels, and blood pressure. Primary prevention for the general public should focus on maintenance of a body mass index (BMI) less than 25 kg/m^2, consuming a healthful diet, avoidance of tobacco, systolic pressures of less than 140 mmHg and diastolic pressures less than 90 mmHg, LDL cholesterol less than 130 mg/dL, HDL cholesterol greater than 35 mg/dL, and glycated hemoglobin less than 6.5%. Secondary prevention of chronic disease focuses on correcting deviations from these goals. Tools include aids for smoking cessation, hypoglycemic agents, antihypertensives, lipid-altering therapies, weight loss, and dietary modification. Once the decline in cardiac function becomes evident, assessment by echocardiogram is warranted. When ejection fraction is reduced below 50%, the condition is called diastolic heart failure. With the further decline in the function below 40%, the condition becomes systolic heart failure. Interventions for each diagnosis is variable and complex, but the goal for each is to preserve function, minimize symptoms, and prevent disease progression.

Acute failure of the heart to perfuse tissue is called shock. Three primary categories exist based on origin: cardiogenic, distributive, and hypovolemic. Cardiogenic shock denotes the heart as the reason for poor blood supply. Most often, it arises secondary to an underlying chronic disease. Over time the heart becomes unable to pump blood forward, and fluid accumulates behind the location. In left-sided heart failure, fluid accumulates in the lungs making it hard to breathe. In right-sided heart failure, fluid accumulates in the venous system and liver. Hepatomegaly, lower extremity edema, and jugular venous distension are the result. Distributive shock represents an inability to retain blood within the vasculature. It is most often seen in cases of sepsis. Disseminated pathogens release cytokines that cause a precipitous decline in systemic vascular resistance leading to massive tissue extravasation. Low intravascular volume causes hypovolemic shock. Although similar to distributive shock, systemic vascular resistance is elevated. Most often, hypovolemic shock is observed in states of severe dehydration or hemorrhage. Therapy for each class of acute heart failure is guided by etiology, symptomology, and patient characteristics.


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