This chapter is relevant to Section G2(ii) of the 2017 CICM Primary Syllabus, which asks the exam candidate to "define the components and determinants of cardiac output". This wishful phrase would be perhaps better directed to the scientific community, who have struggled with this concept for the better part of the last two hundred years. "Significant differences exist among textbook definitions for the terms preload and afterload, leading to confusion and frustration among students and faculty alike", understates a clearly enraged James Norton in a 2001 editorial which reads best if it were read aloud through gritted teeth. It's not as if we have not had enough time to achieve scientific consensus on this matter. The situation is of course made more frustrating by the observation that the clinical application of these concepts clearly does not suffer greatly from a lack of valid scientific definitions. Any unwashed rube can crack a vial of inotrope and augment "contractility" without knowing what "contractility" really is, or how to properly measure it, or why it is so difficult to conceptualise.
Unfortunately, the aforementioned rube will ultimately be called upon to deifne these concepts at least once in their life, if they plan to complete this training program. This topic has real exam relevance. Multiple questions have asked for definitions and interpretations of these parameters with various levels of detail expected. Weirdly, afterload seems to be the favourite, in case the time-poor candidate is so poor that they only have time to study one determinant of cardiac output to the exclusion of the others.
What, then, is the take-home message for the CICM exam candidate?
- Pick a definition
- Make it a definition from a past paper answer
- If there are none, pick a definition from the official textbooks
- Have a faint awareness that there are other possible definitions
The obsessive author, indulging his ugliest demons, pursued these definitions and determinants to the point where their discussion grew beyond what any single page could reasonably contain. Preload, contractility and afterload are therefore discussed in detail, separately, elsewhere. For the casual reader, what follows is a pointform summary, ready for rapid revision.
- Preload can be defined as:
- Myocardial sarcomere length just prior to contraction, for which the best approximation is end-diastolic volume
- Tension on the myocardial sarcomeres just prior to contraction, for which the best approximation is end-diastolic pressure
- The determinants of preload, if we choose to define it as a a volume, are:
- Pressure filling the ventricle:
- Intrathoracic pressure,
- Atrial pressure
- Atrial contractility and rhythm
- Atrioventricular valve competence
- Ventricular end-systolic volume
- Ventricular compliance
- Right atrial pressure
- Mean systemic filling pressure
- Total venous blood volume
- Venous vascular compliance
- Cardiac output, insofar as it supplies the total blood volume
- Compliance of the ventricle:
- Pericardial compliance:
- Compliance of the pericardial walls
- Compliance of the pericardial contents
- Ventricular wall compliance:
- Duration of ventricular diastole
- Wall thickness
- Relaxation (lusitropic) properties of the muscle
- End-systolic volume of the ventricle (i.e. afterload)
- Afterload can be defined as the resistance to ventricular ejection - the "load" that the heart must eject blood against. It consists of two main sets of determinant factors:
- Myocardial wall stress, which represents intracardiac factors
- Input impedance, which represents extracardiac factors
- Wall stress is described by the Law of Laplace ( P × r / T)
and therefore depends on:
- P, the ventricular transmural pressure, which is the difference between the intrathoracic pressure and the ventricular cavity pressure.
- Increased transmural pressure (negative intrathoracic pressure) increases afterload
- Decreased transmural pressure (eg. positive pressure ventilation) decreases afterload
- r, the radius of the ventricle
- Increased LV diameter increases wall stress at any LV pressure
- T, the thickness of the ventricular wall
- A thicker wall decreases wall stress by distributing it among a larger number of working sarcomeres
- Input impedance describes ventricular cavity pressure during systole and receives contributions from:
- Arterial compliance
- Aortic compliance influences the resistance to early ventricular systole (a stiff aorta increases afterload)
- Peripheral compliance influences the speed of reflected pulse pressure waves (stiff peripheral vessels increase afterload)
- Inertia of the blood column
- Ventricular outflow tract resistance (increases afterload in HOCM and AS)
- Arterial resistance
- Length of the arterial tree (the longer the vessels, the greater the resistance)
- Blood viscosity (the higher the viscosity, the greater the resistance)
- Vessel radius (the smaller the radius, the greater the resistance)
- Contractility is the change in peak isometric force (isovolumic pressure) at a given initial fibre length (end diastolic volume).
- Physiological determinants of contractility include:
- Increasing preload increases the force of contraction
- The rate of increase in force of contraction per any given change in preload increases with higher contractility
- This is expressed as a change in the slope of the end-systolic pressure volume relationship (ESPVR)
- Afterload (the Anrep effect):
- The increased afterload causes an increased end-systolic volume
- This increases the sarcomere stretch
- That leads to an increase in the force of contraction
- Heart rate (the Bowditch effect):
- With higher hear rates, the myocardium does not have time to expel intracellular calcium, so it accumulates, increasing the force of contraction.
- Contractility is also dependent on:
- Myocyte intracellular calcium concentration
- Catecholamines: increase the intracellular calcium concentration by a cAMP-mediated mechanism, acting on slow voltage-gated calcium channels
- ATP availability (eg. ischaemia): as calcium sequestration in the sarcolemma is an ATP-dependent process
- Extracellular calcium- availability of which is necessary for contraction
- Temperature: hypothermia decreases contractility, which is linked to the temperature dependence of myosin ATPase and the decreased affinity of catecholamine receptors for their ligands.
- Measures of contractility include:
- ESPVR, which describes the maximal pressure that can be developed by the ventricle at any given LV volume. The ESPVR slope increases with increased contractility.
- dP/dT (or ΔP/ΔT), change in pressure per unit time. Specifically, in this setting, it is the maximum rate of change in left ventricular pressure during the period of isovolumetric contraction. This parameter is dependent on preload, but is minimally affected by normal afterload.