Physiology, Cardiac Output

Cellular Level

Actively metabolizing tissue requires a constant supply of blood for the delivery of nutrients and the removal of waste products. Under ideal conditions, the 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 down 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 are detrimental l cellular, tissue, organ, and eventually, global catastrophe if left uncorrected.

Organ Systems Involved

Cardiac output is dependent on the heart as well as the circulatory system- veins and arteries. CO is the product of heart rate (HR) by stroke volume (SV), the volume of blood ejected by the heart with each beat. Thus, the heart can directly alter CO. However, the arterial compliance, vasoconstriction, and arterial pressure (afterload) directly affect the volume of blood able to leave the heart (SV), and thus also affect CO.  Last, since the circulatory system is a closed-loop, CO is dependent on the volume of blood entering the heart from the veins, or venous return VR. The venous return also depends on the central venous pressure, which in turn is altered by venoconstriction. One has to recall that about 60% of the blood is stored in the capacitance vessels, and can alter the volume of blood returning to the heart. 

Function

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 and can be used to calculate cardiac output based on oxygen exchange through a capillary bed. 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.  This Fick’s principle also represents one method to measure CO.

Another method for measuring CO function is the thermodilution method using the change in temperature of blood between a port in the catheter and a thermistor. Thermodilution catheters are usually placed with the proximal (injection port) in the superior or inferior vena cava or right atrium, and the distal port where the thermistor is located is in the pulmonary arteries.

CO is dynamically altered by changes in mean arterial pressure (MAP) and total peripheral resistance (TPR) or systemic vascular resistance. This can be represented by CO = MAP/TPR.

Mechanism

Cardiac output is the product of heart rate (HR) and stroke volume (SV) and is measured in liters per minute. HR is most commonly defined as the number of times the heart beats in one minute. SV is the volume of blood ejected during ventricular contraction or for each stroke of the heart. Not all of the blood that fills the heart by the end of diastole (end-diastolic volume or EDV) can be ejected from the heart during systole. Thus the volume left in the heart at the end of systole is the end-systolic volume (ESV). Thus, the stroke volume is not equal to the end-diastolic volume but the EDV- ESV.  HR and VS are simultaneously affected by several factors. Cardiac output in humans is generally 5-6 L/min in an at-rest to more than 35 L/min in elite athletes during exercise.

HR is determined by signals from the sinoatrial node, which automatically depolarizes at an intrinsic rate of 60 to 100 times each minute. SV is the other major determinant of cardiac output and is also affected by several factors. The amount of blood ejected each beat depends on preload, contractility, and afterload. Preload represents all of the factors that contribute to passive muscle tension in the muscles at rest. [7]  Preload is proportional to the end-diastolic ventricular volume, or the amount of blood in the ventricles immediately before systole. Greater end-diastolic volumes of blood returned to the heart, increase the passive stretching of the heart muscles. This in turn results in the ventricles contracting with more force- a phenomenon called the Frank-Starling law of the heart. [8] Contractility describes the force of myocyte contraction, also referred to as inotropy. As the force of contraction increases, the heart is able to push more blood out of the heart, and thus increases the stroke volume. The final determinant of stroke volume is afterload. Afterload represents all the factors that contribute to total tension during isotonic contraction. [7] As such afterload can be related to 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 via chronotropy (timing), dromotropy (conduction speed), and lusitropy (myocardial relaxation rate). These influences also increase preload through increased venous return via receptor-mediated vasoconstriction. Additionally, contractility is improved through the Frank-Starling mechanism [8] 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.

Pathophysiology

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 chronic problems like hypertension or coronary atherosclerosis to cause noticeable symptoms. However, it is important to understand that all diseases due to cardiac dysfunction share a compromised ability of the heart’s ability to supply oxygen to the body effectively.

Clinical Significance

Cardiovascular diseases cause 1 in 6 deaths in the US in 2006, and each year about 795,000 people will have strokes. [9] Cardiac deterioration occurs in both an acute and chronic fashion.

Major modifiable risk factors include high lipid values, diabetes, overweight, and obesity. [9] Primary prevention for the general public should focus on maintenance of a body mass index (BMI) less than 25 kg/m, consuming a healthful diet, avoidance of tobacco, blood pressures of less than 140/90 mmHg, LDL cholesterol less than 130 mg/dL, HDL cholesterol greater than 35 mg/dL, and glycated hemoglobin less than 6.5%. Secondary prevention includes 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, the SV divided by the end-diastolic volume, is greater than or equal to 50%, the condition is called diastolic heart failure or heart failure with preserved ejection fraction (HFpEF). [10] Typically, in this case, the dysfunction is due to the ventricle becoming stiff, and cannot relax normally during diastole. We should note that a normal ejection fraction is 55-65%. [11] With a decline in the ejection fraction less than or equal to 40%, the condition becomes systolic heart failure or heart failure with reduced ejection fraction (HFrEF). [10] In this case, this is due to the heart not being able to contract with enough force during systole. However, there is a new classification of heart failure in the mid-range EF. [10]  Interventions for each diagnosis are variable and complex, but the goal for each is to preserve function, minimize symptoms, and prevent disease progression.

Acute failure of the heart, with reduced CO, and the ability to perfuse tissue is called shock. Four primary categories exist based on origin: cardiogenic, distributive, hypovolemic, and obstructive. [12] Therapy for each class of acute heart failure is guided by etiology, symptomology, and patient characteristics.