Question 18

College Answer

Candidates often misinterpreted the question and described determinants of cardiac output. The answer should have focussed on factors affecting/contributing to normal LV function - not pathological states. Some answers showed a lack of appreciation that normal left ventricular function is afterload independent, due to compensatory reflexes. Answers needed to consider intrinsic and extrinsic factors affecting LV function - the latter (e.g. SNS, PSNS, hormones, drugs) was often left out. Answers needed to consider both systolic and diastolic function. An excellent answer included physiological phenomena such as the Treppe effect, Anrep effect and baroreceptor and chemoreceptor reflexes. Mention of normal conduction and pacing as well as blood supply limited by diastole scored additional marks.

Discussion

It is no wonder this question had such a low pass rate. What is remarkable is that 12% of the candidates somehow accidentally stumbled on the exact thing the examiners had in mind. Which would have been the only way they would have arrived there, because certainly a direct reading of the question does not betray anything of their expectations.

Judging by the college comments, what they really wanted was a discussion of the physiological influences which affect LV afterload ("appreciation that normal left ventricular function is afterload independent, due to compensatory reflexes"), LV preload ("blood supply limited by diastole") and LV contractility ("Treppe effect, Anrep effect").  These, interestingly, are also important determinants of cardiac output. However, it appears we would have to phrase the answer in a way which does not make any reference to the determinants of cardiac output. What follows is an attempt to carefully step around this issue by rewording some of the determinants. As the function of the LV mainly involves contracting and relaxing cyclically, "systolic" and "diastolic" seemed like reasonable headings.

Main influences on LV systolic function:

• Preload:
  • Increasing preload increases the force of LV contraction 
• Afterload
  • Arterial compliance
  • Inertia of the blood column
  • Ventricular outflow tract resistance 
  • Peripheral arterial resistance
• Contractility:
  • The Anrep effect: increased afterload causes an increased end-systolic volume, which increases the sarcomere stretch, and leads to an increase in the force of contraction
  • the Bowditch effect, or Treppe effect: with higher heart rates, the myocardium does not have time to expel intracellular calcium, so it accumulates, increasing the force of contraction.
  • 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.

Main influences on LV diastolic function:

• Preload:
  • Intrathoracic pressure, atrial pressure (specifically the LA-LV pressure gradient), mean systemic filling pressure, total venous blood volume and venous vascular compliance
  • Compliance of the left ventricle and the pericardial sack
• Afterload
  • ​​​​​​​High afterload results in a high end-systolic volume, which impedes diastolic filling
• Contractility
  • ​​​​​​​Active LV relaxation (lusitropy) is determined by many of the same factors that determine LV systolic contractility 
• Heart rate
  • ​​​​​​​Diastole is shorter in tachycardia; diastolic filling is time-dependent

Muir, William W., and Robert L. Hamlin. "Myocardial Contractility: Historical and Contemporary Considerations." Frontiers in Physiology 11 (2020).

Penefsky, Zia J. "The determinants of contractility in the heart." Comparative Biochemistry and Physiology Part A: Physiology 109.1 (1994): 1-22.

Abraham, T. P., and R. A. Nishimura. "Myocardial strain: can we finally measure contractility?." (2001): 731-734.

KARLINER, JOEL S., et al. "Mean velocity of fiber shortening: A simplified measure of left ventricular myocardial contractility." Circulation 44.3 (1971): 323-333.