Department of Thoracic and Cardiovascular Surgery, Stanford University School of Medicine, Stanford, CA.

Department of Cardiovascular Physiology and Biophysics, Palo Alto Medical Foundation Research Institute, Palo Alto, CA.

Department of Biomedical Engineering, Texas A&M University, College Station, TX.

Alterations in Transmural Borderzone Strains during

Acute Mid-Circumflex OcclusionFiliberto Rodriguez, Frank Langer,

Katherine B. Harrington, Allen Cheng, George T. Daughters, John C. Criscione,

Neil B. Ingels Jr., D. Craig Miller

Non-ischemic infarct borderzone expansion may be important in the progression of ischemic cardiomyopathy.

Alterations in myocyte strain patterns:– Trigger production of reactive oxygen species– Stimulate myocyte apoptosis – Activate matrix metalloproteinases (MMPs)

Introduction

Characterize the abrupt alterations in transmural systolic strains during

acute ischemia that underlie LV borderzone remodeling, with emphasis

on fiber-sheet mechanics.

Purpose

How does the LV wall thicken > 40%,when fibers shorten only 15% and thicken

only 8%?

Understanding Wall Thickening

Streeter DD et al, Circ Res 1969; 24:339-47

Epi Endo

Transmural Fiber HelicesEpicardial Counter-Spiral Fiber

Circumferential Midwall Fiber

Endocardial Spiral Fiber

Spotnitz HM et al, J Mol Cell Cardiol 1973;6:317-31

Transmural Fiber Rearrangement

< 0

Sheet shear, thickening, and extension allow systolic wall thickening of > 40%

Costa KD et al, Am J Physiol 1999;276:H595-H607

Radial Wall-Thickening

Xn Xs

XnXs

Sheet shear(Esn < 0)

Sheet extension(Ess > 0)

Sheet thickening(Enn > 0)

Transmural Sheet Model

Fiber and sheet strains are altered in the borderzone between acutely ischemic

and non-ischemic myocardium.

Hypothesis

9 SheepLeft ThoracotomyCPBGlobal LV Marker Array

circumferential

longitudinal

radial

endocardium

epicardium

Video Recording

3-D reconstruction

LAO View RAO View

LVP

dP/dtECG

RAOLAO

Acute Mid-Circumflex Occlusion

Quantitative Microstructural Measurements

Cardiac coordinate system

longitudinal (X2)

circumferential (X1)

radial (X3)

Quantitative Microstructural Measurements

Cardiac coordinate system

Fiber-sheet coordinate system

fiber (Xf)

sheet (Xs)

normal (Xn)

-

- fiber angle sheet angle

longitudinal (X2)

circumferential (X1)

radial (X3)

Quantitative Microstructural Measurements

3-D Model of Wall Thickening Mechanics

Results

Baseline Ischemia p HR (b/min) 101 ± 15 101 ± 16 0.37

dP/dtmax (mmHg/s) 2310 ± 691 1600 ± 541 0.0005 EDV (mL) 213 ± 50 229 ± 46 0.02 ESV (mL) 156 ± 51 181 ± 49 0.0006

EDP (mmHg) 20 ± 4 24 ± 6 0.05 ESP (mmHg) 72 ± 7 56 ± 8 0.00003

LVPmax (mmHg) 104 ± 10 86 ± 13 0.0001

Hemodynamics

Defining the functional borderzone

Systolic Fractional Area Shortening

Annular

Basal

Equatorial

Apical

Antero-septal

Antero-lateral

Postero-lateral

Postero-septal

Antero-septal

Antero-lateral

Postero-lateral

Postero-septal

14 ± 3p=0.10

13 ± 5*p=0.02

28 ± 4p=0.14

20 ± 7*p=0.05

11 ± 4*p<0.01

14 ± 6*p<0.01

22 ± 6p=0.32

23 ± 4*p=0.03

18 ± 8p=0.24

13 ± 5p=0.20

IschemiaAntero-septal

Antero-lateral

Postero-lateral

Postero-septal

15 ± 5 17 ± 2

27 ± 7 23 ± 7 20 ± 5 21 ± 7

27 ± 8 23 ± 7 20 ± 5 23 ± 4

21 ± 5 20 ± 6 16 ± 7 20 ± 3

Baseline

17 ± 5†p=0.06

17 ± 7*p<0.01

30 ± 6*p<0.01

12 ± 4*p<0.01

Annular

Basal

Equatorial

Apical

Systolic Fractional Area Shortening

Altered Borderzone Cardiac Strains

circumferential

Increased circumferential-radial shear:Subepicardium 0.04±0.04 vs. 0.11±0.05, p=0.002Midwall 0.03±0.04 vs. 0.07±0.04, p=0.0004

ED

ES

radial

endo epi endo epi

circumferential

radial

IschemiaBaseline

Altered Borderzone Fiber-Sheet Strains

fiber

sheet

fiber

sheet

ED

ES

Decreased subendocardial fiber shortening: -0.06±0.06 vs. 0.00±0.07, p=0.02Increased subendocardial fiber-sheet shear: 0.07±0.01 vs. 0.11±0.04, p=0.04

IschemiaBaseline

Summary

Increased subepicardial and midwall circumferential-radial shear.

Acute ischemia altered transmural borderzone:

Cardiac Strains

Reduced end-systolic subendocardial fiber shortening.Increased subendocardial fiber-sheet shear.

Fiber-Sheet Strains

Implications

the perturbations we observed in the non-ischemic borderzone may be responsible for progression of ischemic cardiomyopathy.

Are remodeling processes triggered by these fiber and sheet strain alterations?

Assuming cardiac microstructure is optimally designed for normal strain patterns,