Transmural Differences in Myocardial Function and Metabolism During Direct Left Ventricular to Coronary Artery Sourcing Sandra de Zeeuw, PhD, Cornelius.

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Transmural Differences in Myocardial Function and Metabolism During Direct Left Ventricular to Coronary Artery Sourcing Sandra de Zeeuw, PhD, Cornelius Borst, MD, PhD, Cees W.J. Verlaan, Paul F. Gründeman, MD, PhD The Annals of Thoracic Surgery Volume 80, Issue 1, Pages 153-161 (July 2005) DOI: 10.1016/j.athoracsur.2005.01.070 Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 Schematic presentation of the surgical procedure. First, a right internal thoracic artery (ITA) bypass to the distal left anterior descending (LAD) coronary artery was created to allow distal perfusion during the creation of the left ventricle-coronary artery (LV-CA) bypass. In this way the myocardial area of interest would be perfused at all times. The proximal LAD bypass had its origin in the LV lumen and consisted of a free left ITA graft (arterial conduit) with a polytetrafluoroethylene-covered stent at one end inserted through the LV wall. In this way direct left ventricular sourcing of the LAD was established. Blood flow was measured by placement of transonic flow probes (⊗) on the mid-LAD (Qmid-LAD), and on the LV-CA bypass (QLV-CA bypass). To measure myocardial contractile performance, two pairs of ultrasonic echocrystals were embedded in the subendocardium and subepicardium. For measurement of myocardial metabolism, interstitial lactate and glucose concentrations were determined using microdialysis probes (T). During the protocol, the distal ITA-LAD bypass was closed and three different blood supply conditions were compared. The Annals of Thoracic Surgery 2005 80, 153-161DOI: (10.1016/j.athoracsur.2005.01.070) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 Schematic drawing of the experimental protocol. In protocol A, three different sources of blood were compared. Condition 1: baseline, blood supply by native LAD flow (LV-CA bypass occluded); condition 2: both proximal LAD and LV-CA bypass are open; condition 3: direct left ventricular sourcing, blood supply through the LV-CA bypass, proximal LAD is clamped. In group 1, hemodynamics (H) and contractile function (F) were measured at the end of each condition (5 minutes). In group 2 hemodynamics (H) were measured at 5 minutes of each condition, while microdialysis samples (M) were collected after 10 minutes. In protocol B, after 120 minutes condition 3, the heart was stressed by infusion of three consecutive concentrations of dobutamine (Dobu; 5, 10, and 20 μg/kg/min). Hemodynamics were measured at 5 minutes of each condition, while microdialysis samples were collected after 10 minutes. (LAD = left anterior descending coronary artery; LV-CA = left ventricle-coronary artery.) The Annals of Thoracic Surgery 2005 80, 153-161DOI: (10.1016/j.athoracsur.2005.01.070) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

Fig 3 Protocol A, group 1. Mean mid-LAD flow and regional systolic shortening (SS%) in the subepicardium and subendocardium of the area perfused by the LV-CA bypass during condition 2 (hatched bars: native + LV-CA bypass) and condition 3 (closed bars: LV-CA bypass). Condition 2: both proximal LAD and LV-CA bypass were fully patent. Condition 3: blood supply solely by the LV-CA bypass. Data are presented as % of baseline (BL, condition 1 native flow, mean ± standard error of the mean). *p < 0.05 vs BL. (LAD = left anterior descending coronary artery; LV-CA = left ventricle-coronary artery.) The Annals of Thoracic Surgery 2005 80, 153-161DOI: (10.1016/j.athoracsur.2005.01.070) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

Fig 4 Protocol A, group 2. Mid-LAD flow, regional interstitial lactate (% of BL) and glucose (% of BL) concentrations in the subepicardium and subendocardium of the area perfused by the LV-CA bypass during condition 2 (hatched bars: native + LV-CA bypass) and condition 3 (closed bars: LV-CA bypass). Condition 2: both proximal LAD and LV-CA bypass were fully patent. Condition 3: blood supply solely by the LV-CA bypass (0–10 min and 11–20 min). Data are presented as % of BL (condition 1 native flow, mean ± standard error of the mean). * p < 0.05 vs BL. (BL = baseline; LAD = left anterior descending coronary artery; LV-CA = left ventricle-coronary artery.) The Annals of Thoracic Surgery 2005 80, 153-161DOI: (10.1016/j.athoracsur.2005.01.070) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

Fig 5 Protocol B, group 3. Representative recording of mid-LAD flow pattern during native blood supply (condition 1, baseline [BL]) and during direct left ventricular sourcing with a LV-CA shunt (condition 3) at rest and in stress condition. Top graphs show the left ventricular pressure ([LVP], mm Hg), middle graphs show the mid-LAD flow pattern (mL/min), and bottom graphs show mean (closed bars), systolic (open bars), and diastolic (hatched bars) mid-LAD flow (mL/min). End diastole was defined as the onset of rapid increase in LV pressure, while end systole was defined at the maximal rate of fall in left ventricular pressure (LV dP/dt min). *p < 0.05 vs BL. Note that for completeness of this figure the data in the bottom graphs are presented as mean ± standard error of the mean, which are the same values as given in Table 2. (D = diastole; LAD = left anterior descending coronary artery; LV-CA = left ventricle-coronary artery; S = systole.) The Annals of Thoracic Surgery 2005 80, 153-161DOI: (10.1016/j.athoracsur.2005.01.070) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

Fig 6 Regional interstitial lactate (% of BL) (top) and glucose (% of BL) (bottom) concentrations in the subepicardium (open circles) and subendocardium (black circles) of the area perfused by the left ventricle-coronary artery (LV-CA) bypass during an extended period of direct left ventricular sourcing. At time point 0, baseline (BL) measurements were taken (condition 1, native flow), which was followed by 150 minutes direct left ventricular sourcing (condition 3). The first 120 minutes were at rest and the remaining 30 minutes (grey area) under stress conditions induced by infusion of 3 consecutive concentrations of dobutamine (5, 10, and 20 μg/kg/min). Data were presented as % of BL (condition 1, native flow, mean ± standard error of the mean). * p < 0.05 vs BL (condition 1: native blood supply); † p < 0.05 vs 120 min LV-CA bypass (condition 3). The Annals of Thoracic Surgery 2005 80, 153-161DOI: (10.1016/j.athoracsur.2005.01.070) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions