Tipping the scales of understanding: An engineering approach to design and implement whole-body cardiac electrophysiology experimental models

Abstract

The study of cardiac electrophysiology is built on experimental models that span all scales, from ion channels to whole-body preparations. Novel discoveries made at each scale have contributed to our fundamental understanding of human cardiac electrophysiology, which informs clinicians as they detect, diagnose, and treat complex cardiac pathologies. This expert review describes an engineering approach to developing experimental models that is applicable across scales. The review also outlines how we applied the approach to create a set of multiscale whole-body experimental models of cardiac electrophysiology, models that are driving new insights into the response of the myocardium to acute ischemia. Specifically, we propose that researchers must address three critical requirements to develop an effective experimental model: 1) how the experimental model replicates and maintains human physiological conditions, 2) how the interventions possible with the experimental model capture human pathophysiology, and 3) what signals need to be measured, at which levels of resolution and fidelity, and what are the resulting requirements of the measurement system and the access to the organs of interest. We will discuss these requirements in the context of two examples of whole-body experimental models, a closed chest in situ model of cardiac ischemia and an isolated-heart, torso-tank preparation, both of which we have developed over decades and used to gather valuable insights from hundreds of experiments.

Keywords: acute myocardial ischemia (AMI); cardiac electrophysiology; electrocardiographic imaging (ECGI); experimental models; isolated heart; torso tank.

FIGURE 1

Experimental approaches to controlling coronary blood flow. Panel (A) shows the hydraulic occlusion device placed around the left anterior descending coronary artery and controlled via an external calibrated hydraulic pump. Also, note the intramural and epicardial electrical recording arrays, including samples of recorded signals. Panel (B) shows an alternative approach of a controlled-flow blood pump connecting a carotid artery to the left anterior descending coronary artery to control blood flow downstream of the cannulation.

FIGURE 2

Electrical recording arrays used to measure cardiac bioelectric potentials in the experimental models. (A) A plunge needle electrode (B) a 247-lead electrode sock suspended over a plaster model during fabrication, and (C) A strip of torso electrodes containing 12 disposable electrodes.

FIGURE 3

The complete in situ closed torso experimental model of ischemia including the generated geometries and electrode locations.

FIGURE 4

Schematic example of the torso tank preparation that includes an isolated heart, suspended in the human shaped torso tank and perfused by a secondary animal. Recording arrays shown are the pericardiac cage array (blue) surrounding the isolated heart and torso tank array (brown). Reprinted from Bergquist et al. (2021) Copyright 2021, with permission from Elsevier.

FIGURE 5

Example data recorded simultaneously from the pericardiac cage array and torso tank of a normal sinus heart beat. Note the significant changes in signal amplitude between the pericardial cage and torso recordings.