HARD QUIZ REGULATION OF CARDIAC OUTPUT

Cardiac Output Regulation

• Cardiac output (CO) is the volume of blood pumped by the heart per minute.
• CO = Stroke volume (SV) x Heart rate (HR)
• Factors impacting preload, afterload, and inotropy affect CO
• Preload is the initial stretching of the cardiomyocyte sarcomere before contraction. It's relative to end-diastolic volume (EDV).
• Afterload is the force (tension) a cardiomyocyte needs to shorten against a load, primarily the pressure in the aorta for ejection.
• Inotropy is the intrinsic ability of cardiac muscle to develop force, independent of preload changes.

Learning Objectives

• Describe how changes in heart rate and stroke volume affect cardiac output.
• Define ventricular preload, afterload, and inotropy.
• Detail factors affecting preload, such as central venous pressure, blood volume, ventricular compliance, atrial inotropy, heart rate, inflow/outflow resistance, and afterload.
• Describe how changes in preload affect cardiomyocyte contractile force.
• Identify clinical conditions impacting afterload.
• Explain Frank-Starling relationships and their effect on stroke volume (SV).
• Depict ventricular pressure-volume loops demonstrating effects of preload, afterload, and inotropy on end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF).
• Outline mechanisms for sympathetic and catecholamine regulation of cardiac muscle excitation-contraction coupling.
• Show interdependent effects of preload, afterload, and inotropy on LVESV and LVEDV using pressure-volume loops.

Frank-Starling Relationship

• Increased ventricular filling (preload) increases stroke volume.
• The relationship between stroke volume and preload is called the Frank-Starling relationship or Starling's Law of the heart.
• Length-dependent activation is a key mechanism within this relationship.

Length-Dependent Activation

• Changes in the sarcomere's TN-C affinity for calcium relate to stretching.
• Sarcomere stretching increases calcium binding to TN-C, which leads to increased muscle active tension during contraction.
• Modification of actin-myosin filament overlap increases active binding sites between actin and myosin.
• Stretching from 1.6 to 2.2 μ increases available binding sites.

Factors Affecting Preload

• Factors increasing preload: Increased venous return, total blood volume, increased venous pressure, increased ventricular compliance.
• Factors decreasing preload: Decreased venous return, decreased total blood volume, decreased venous pressure, decreased ventricular compliance.

Afterload

• Afterload is the pressure the ventricle must overcome to eject blood into the aorta.
• Increased afterload results in higher ESV and decreased SV and ejection fraction
• Increased afterload may be due to hypertension or outflow tract obstructions.
• Decreased afterload may be a result from lowering pressure in the aorta, or reducing resistance of outflow tract.

Inotropy

• Inotropy is the intrinsic ability of cardiac muscle to generate force, unaffected by preload changes.
• Increased inotropy raises stroke volume by increasing contractile force and the velocity of fiber shortening.
• Decreased inotropy reduces stroke volume (SV).

Regulation of Inotropy

• Sympathetic adrenergic nerves and circulating catecholamines increase inotropy in both atria and ventricles.
• Parasympathetic nerves primarily affect the atria and not the ventricles.
• Heart rate (Bowditch effect) and afterload (Anrep effect – weaker) indirectly impact inotropy.

Physiological Considerations

• Sympathetic stimulation leads to increased intracellular cAMP.
• This triggers activation of protein kinase A (PKA), affecting calcium handling within the cardiomyocytes.
• Opening of DHP channels and ryanodine receptors boosts intracellular calcium levels.
• Inotropy increase results in increased force of contraction and raising ejection velocity. This further decreases end-systolic volume.
• Preload, afterload, and inotropy all have an interdependent relationship

Summary of Preload, Afterload & Inotropy on Cardiac Function

• Increased preload (LVEDP) increases stroke volume (SV) along a given Starling curve.
• Decreased preload (LVEDP) decreases SV along a given Starling curve.
• Increased afterload or decreased inotropy decreases SV and increases preload.
• Decreased afterload or increased inotropy increases SV and decreases preload.

Effects of Heart Rate on Pressure and Volume

• Increased heart rate (HR) decreases end-diastolic volume (EDV).
• Increased HR increases end-systolic volume (ESV).
• Increased HR reduces stroke volume (SV).
• Increased HR lowers ejection fraction (EF).
• Decreased HR increases EDV.
• Decreased HR decreases ESV.
• Decreased HR raises SV.
• Decreased HR raises the ejection fraction (EF).

Regulation of Atrial Function

• Atria respond to preload, afterload, and inotropic interventions similarly to ventricles.
• Increased atrial volume (preload) raises atrial contraction force.
• Sympathetic stimulation increases atrial inotropism.
• Vagal stimulation reduces atrial inotropy.

Questions and Answers

• (Q1): A sudden decrease in venous return to the heart*

• Correct Answer is (C)

• (Q2): Reducing afterload in heart failure*

• Correct Answer is (A)

• (Q3): Increasing inotropy leads to a secondary decrease in preload*

• Correct Answer is (B)

• (Q4): Sympathetic activation increases inotropy*

• Correct Answer is (D)