Effects of Mechanical Dyssynchrony on Coronary Flow: Insights From a Computational Model of Coupled Coronary Perfusion With Systemic Circulation

Abstract

Mechanical dyssynchrony affects left ventricular (LV) mechanics and coronary perfusion. Due to the confounding effects of their bi-directional interactions, the mechanisms behind these changes are difficult to isolate from experimental and clinical studies alone. Here, we develop and calibrate a closed-loop computational model that couples the systemic circulation, LV mechanics, and coronary perfusion. The model is applied to simulate the impact of mechanical dyssynchrony on coronary flow in the left anterior descending artery (LAD) and left circumflex artery (LCX) territories caused by regional alterations in perfusion pressure and intramyocardial pressure (IMP). We also investigate the effects of regional coronary flow alterations on regional LV contractility in mechanical dyssynchrony based on prescribed contractility-flow relationships without considering autoregulation. The model predicts that LCX and LAD flows are reduced by 7.2%, and increased by 17.1%, respectively, in mechanical dyssynchrony with a systolic dyssynchrony index of 10% when the LAD's IMP is synchronous with the arterial pressure. The LAD flow is reduced by 11.6% only when its IMP is delayed with respect to the arterial pressure by 0.07 s. When contractility is sensitive to coronary flow, mechanical dyssynchrony can affect global LV mechanics, IMPs and contractility that in turn, further affect the coronary flow in a feedback loop that results in a substantial reduction of dP _LV /dt, indicative of ischemia. Taken together, these findings imply that regional IMPs play a significant role in affecting regional coronary flows in mechanical dyssynchrony and the changes in regional coronary flow may produce ischemia when contractility is sensitive to the changes in coronary flow.

Keywords: bi-directional interactions; coronary perfusion; ischemia; mechanical dyssynchrony; systemic circulation.

Figure 1

(A) Schematic of the cardiac-coronary modeling framework: the LV and the coronary tree (LAD and LCX) are connected to a closed-loop lumped model with their pressures (P), volumes (V), flow rate (Q), compliances (C), and resistances (R) where ao, art, ven, and mv denote the aorta, peripheral arteries, peripheral veins, and mitral valves, respectively; (B) A representation of the model to separate the LV into LAD and LCX compartments with their pressures (P), volumes (V), maximal chamber elastances (E_es), and time-varying elastances (e); (C) Time-varying elastance function in the LAD and LCX, e_LAD and e_LCX in mechanical dyssynchrony. Note, the LAD and LCX networks are graphically depicted by the 3D coronary tree in the lower left figure.

Figure 2

(A) Single bifurcation three-vessel network; (B) Electrical non-linear analog of a single vessel.

Figure 3

The prescribed contractility-coronary flow relationship in both the ischemic and non-ischemic myocardial regimes. The parameter “k” represents the slope of this relationship in the ischemic regime and “n” denotes normal condition.

Figure 4

A representative simulation is compared with data from the control group. Experimentally (Exp.) and numerically (Num.) predicted waveforms of (A) LV pressure; (B) LV volume; (C) IMP and its three components (Num. only); (D) q_LAD; (E) q_LCX; and (F) arterial pressure (Num. only). “S” and “D” denote systole and diastole, respectively.

Figure 5

A representative simulation of the control case (Δt = 0) and isolated mechanical dyssynchrony case (t ≠ 0 with SDI = 10%). Comparison of (A) LV pressure; (B) LV volume; (C) IMP and its three components at the LAD and the LCX for only in isolated mechanical dyssynchrony; (D) q_LAD; (E) q_LCX; and (F) arterial pressure. Dotted and dash lines denote a control and an isolated dyssynchrony with both systole (S) and diastole (D).

Figure 6

Effects of SDI on total coronary flow, mean arterial and LV pressures, and IMP_LAD and IMP_LCX over three swine. (A) Percentage difference of the quantities with respect to the control simulation for different SDI. (B) Percentage difference of the quantities with respect to the control simulation for different $\Delta \overline{t}$ with SDI = 10%.

Figure 7

A comparison between the simulations for the control case, the isolated mechanical dyssynchrony case, and the mechanical dyssynchrony (SDI = 10%) + ischemia case for k = 0.34 and 10k = 3.40 mmHg/ml² for the following variables: (A) Coronary flow in the LAD and LCX with k; (B) Arterial Pressure, LV pressure waveforms and IMPs with k; (C) Coronary flow in the LAD and LCX with 10k; (D) Arterial Pressure, LV pressure waveforms and IMPs with 10k; and (E) Percentage differences over three swine using different slopes (k) in the contractility-flow relationship in ischemic region of LCX in terms of flow, dP_LV/dt and mean arterial and LV pressures between the isolated mechanical dyssynchrony and mechanical dyssynchrony + ischemia cases.