Christian Arvei Moen

Left ventricular strain, rotation, and torsion as markers of acute myocardial ischemia

This study investigates how tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) describe regional myocardial deformation during controlled reductions of left anterior descending (LAD) coronary artery perfusion pressure. In eight anesthetized pigs, a shunt with constrictor was installed from the brachiocephalic artery to the LAD. Data were obtained with open shunt, followed by four degrees of stenosis (S1-S4) of increasing severity: S1, ∼15%; S2, ∼35%; S3, ∼50%; and S4, ∼60% reductions of LAD perfusion pressure. At each situation, microspheres for perfusion measurements were injected and left ventricular (LV) short- and long-axis cineloops were recorded. In the anterior wall, radial, circumferential, and longitudinal one-layer STE strain, one-layer radial TDI strain, and three-layer radial TDI and STE strain were measured. LV peak mean rotation was measured at six equidistant levels from apex to base (in 7 pigs). LV torsion was calculated from end-systolic mean rotation. With open shunt, three-layer TDI analysis showed a transmural strain gradient with no perfusion gradient. Perfusion, one-layer TDI strain, and strain in the mid- and subendocardium from three-layer TDI were reduced at S2 (P < 0.05). STE strain was not affected until S3 (P < 0.05). Peak mean rotation, increasing toward the apex, decreased at the three apical levels at S4 (P < 0.05). LV torsion did not decrease (P = 0.26). In conclusion, TDI strain detected dysfunction already with minor changes in global hemodynamics, whereas STE strain was first reduced with moderate changes. LV peak mean rotation was not reduced until severe reduction of LAD perfusion pressure, but remained increasingly counterclockwise toward the apex. LV torsion remained unaffected by ischemia.

Multidose Cold Oxygenated Blood Is Superior to a Single Dose of Bretschneider HTK-Cardioplegia in the Pig

BACKGROUND A single-dose strategy for cardioplegia is desired in minimal invasive approaches to valve surgery and aortic arch repairs. We hypothesized that a single infusion of Bretschneider HTK solution offers myocardial protection comparable to repeated cold oxygenated blood. METHODS Sixteen pigs on bypass with 60 minutes of aortic cross-clamping were randomized to a single dose of Custodiol (HTK group) or repeated oxygenated blood cardioplegia (CBC group). Left ventricular function and perfusion were evaluated by conductance catheter, echocardiography, and microspheres. Myocardial injury was assessed with serum troponin-T. RESULTS Baseline values showed no group differences. One hour after declamping cardiac index was reduced in the HTK group, 3.5 +/- 0.2 L x min(-1) x m(-2) (mean +/- standard error of the mean) compared with 4.7 +/- 0.4 L x min(-1) x m(-2) in the CBC group (p < 0.0005), decreasing to 4.0 +/- 0.2 and 3.9 +/- 0.2 L x min(-1) x m(-2) after 2 and 3 hours, respectively (p < 0.005 versus 1 hour). In the HTK group cardiac index remained low and unchanged. In the CBC group preload recruitable stroke work was 72.6 +/- 1.2 mm Hg 1 hour after declamping, decreasing to 65.2 +/- 2.5 and 60.3 +/- 3.9 mm Hg after 2 and 3 hours, respectively (p < 0.05 versus 1 hour). In the HTK group corresponding values after 1, 2, and 3 hours were low at 47.2 +/- 4.4, 48.4 +/- 4.2, and 50.7 +/- 4.3 mm Hg, respectively (p < 0.025 versus CBC for all). Subendocardial radial peak systolic strain averaged 80.5% +/- 4.8% after declamping in the CBC group versus 53.4% +/- 5.5% in the HTK group (p = 0.002). Serum troponin-T release was lower in the CBC group. CONCLUSIONS Repeated oxygenated blood cardioplegia provides better myocardial protection and preservation of left ventricular function than a single dose of HTK during the early hours after declamping.

The influence of acute unloading on left ventricular strain and strain rate by speckle tracking echocardiography in a porcine model

Noninvasive measurements of myocardial strain and strain rate by speckle tracking echocardiography correlate to cardiac contractile state but also to load, which may weaken their value as indices of inotropy. In a porcine model, we investigated the influence of acute dynamic preload reductions on left ventricular strain and strain rate and their relation to the pressure-conductance catheter-derived preload recruitable stroke work (PRSW) and peak positive first derivative of left ventricular pressure (LV-dP/dtmax). Speckle tracking strain and strain rate in the longitudinal, circumferential, and radial directions were measured during acute dynamic reductions of end-diastolic volume during three different myocardial inotropic states. Both strain and strain rate were sensitive to unloading of the left ventricle (P < 0.001), but the load dependency for strain rate was modest compared with strain. Changes in longitudinal and circumferential strain correlated more strongly to changes in end-diastolic volume (r = -0.86 and r = -0.72) than did radial strain (r = 0.35). Longitudinal, circumferential, and radial strain significantly correlated with LV-dP/dtmax (r = -0.53, r = -0.46, and r = 0.86), whereas only radial strain correlated with PRSW (r = 0.55). Strain rate in the longitudinal, circumferential and radial direction significantly correlated with both PRSW (r = -0.64, r = -0.58, and r = 0.74) and LV-dP/dtmax (r = -0.95, r = -0.70, and r = 0.85). In conclusion, the speckle tracking echocardiography-derived strain rate is more robust to dynamic ventricular unloading than strain. Longitudinal and circumferential strain could not predict load-independent contractility. Strain rates, and especially in the radial direction, are good predictors of preload-independent inotropic markers derived from conductance catheter.

Multi-layer radial systolic strain vs. one-layer strain for confirming reperfusion from a significant non-occlusive coronary stenosis

AIMS The aim of this study was to investigate whether multi-layer radial strain and strain rate analysis is superior to one-layer strain analysis for confirming reperfusion following a non-occlusive coronary stenosis. METHODS AND RESULTS In 10 anaesthetized pigs, an extracorporeal shunt was inserted from the brachiocephalic to the left anterior descending coronary artery. Microspheres were injected and left ventricular (LV) short- and long-axis echocardiographic views were recorded with the open shunt, during the 120 min of severe stenosis and 20 min (early) and 100 min (late) after reperfusion. The anterior wall was analysed for radial one-layer and three-layer tissue Doppler imaging (TDI) strain and strain rate, in addition to radial, circumferential, and longitudinal speckle-tracking echocardiography (STE) strain. During stenosis, perfusion was reduced in the two inner wall layers (P< 0.01). All peak systolic strain and strain rate parameters were reduced, whereas post-systolic longitudinal strain and post-systolic strain in the two inner layers increased (P< 0.001). At early reperfusion, hyperaemia was evident in all layers (P< 0.01). Peak systolic TDI strain and strain rate increased in the mid- and subendocardial layer, whereas post-systolic strain decreased (P< 0.05). Peak systolic STE strain increased in the circumferential and longitudinal direction, whereas post-systolic longitudinal strain decreased (P< 0.05). At late reperfusion, strain and strain rate were unchanged while perfusion returned to baseline values in the mid- and subendocardium. CONCLUSION Both multi-layer radial TDI strain and strain rate and one-layer STE strain measurements in the circumferential and longitudinal direction can confirm reperfusion early after a non-occlusive coronary stenosis. An advantage of multi-layer analysis was not evident.

Esmolol added in repeated, cold, oxygenated blood cardioplegia improves myocardial function after cardiopulmonary bypass.

OBJECTIVE This study investigated if the β-receptor blocking agent esmolol, added to standard oxygenated blood cardioplegia, improved myocardial function after weaning from bypass. DESIGN A block-randomized, blinded study. SETTING A university laboratory. PARTICIPANTS Twenty anesthetized pigs, Norwegian Landrace. INTERVENTIONS After cardiopulmonary bypass, cardiac arrest was induced with cold (12°C), oxygenated blood cardioplegia, enriched with either esmolol or vehicle, repeated every 20 minutes. After 100 minutes the heart was reperfused and weaned. MEASUREMENTS AND MAIN RESULTS Left ventricular function was evaluated with pressure-volume loops, local myocardial function with multilayer strain and strain rate by epicardial short-axis tissue Doppler imaging. One hour after declamping, preload recruitable stroke work did not differ between groups, but increased to 72±3 mmHg in esmolol-treated animals v 57±4 mmHg (p<0.001) in controls after 3 hours. Radial peak ejection strain rate also was increased by esmolol; 6.0±1.0 s(-1)v 2.9±0.3 s(-1) (p<0.001) in subendocardium and 3.9±0.5 s(-1)v 2.3±0.2 s(-1) (p<0.005) in the midmyocardium. Cardiac index was increased, 4.0±0.2 L/min/m(2) by esmolol v 3.3±0.1 L/min/m(2) for controls (p<0.05). Isovolumetric relaxation time constant was reduced by esmolol, 23±1 ms v 26±1 ms (p<0.025). Troponin-T did not differ and was 339±48 ng/L for the esmolol group and 357±55 ng/L for the control group (p = 0.81). CONCLUSIONS Esmolol added to blood cardioplegia preserved systolic cardiac function during the first 3 hours after reperfusion in a porcine model with 100 minutes of cardioplegic arrest.

Radial deformation by tissue Doppler imaging in multiple myocardial layers

OBJECTIVES Measuring strain in multiple myocardial layers using 2-dimensional tissue Doppler imaging may provide valuable diagnostic information about non-transmural disease. However, its feasibility in humans has not been demonstrated previously, and optimal machine settings not defined. DESIGN From parasternal short axis, zoomed tissue Doppler imaging of the left ventricular inferior wall was obtained in 23 young, healthy humans. Images were recorded with six different machine settings. Velocity, strain rate and strain were measured in two and three layers across the wall. RESULT For two-layer-measurements, all subendocardial values were significantly higher than the subepicardial ones (p<0.003 for all data sets). Minimal radial and maximal lateral averaging resulted in largest strain differences: 106.4+/-32.6% (mean+/-SD) subendocardially versus 54.2+/-20.1% subepicardially. By similar settings in three layers, strain was 105.7+/-34.5% subendocardially, 81.2+/-26.9% midmyocardially and 48.3+/-26.9% subepicardially (p <0.05). CONCLUSION We have demonstrated that it is feasible to measure radial velocity, strain rate and strain in up to three individual layers in young healthy humans, and the diagnostic potentials should be tested on patient groups.

Is strain by Speckle Tracking Echocardiography dependent on user controlled spatial and temporal smoothing? An experimental porcine study

BackgroundSpeckle Tracking Echocardiography (STE) strain analysis relies on both spatial and temporal smoothing. The user is often allowed to adjust these smoothing parameters during analysis. This experimental study investigates how different degrees of user controllable spatial and temporal smoothing affect global and regional STE strain values in recordings obtained from normal and ischemic myocardium.MethodsIn seven anesthetized pigs, left ventricular short- and long-axis B-mode cineloops were recorded before and after left anterior descending coronary artery occlusion. Peak- and postsystolic global STE strain in the radial, circumferential and longitudinal direction as well as corresponding regional strain in the anterior and posterior walls were measured. During post-processing, strain values were obtained with three different degrees of both spatial and temporal smoothing (minimum, factory default and maximum), resulting in nine different combinations.ResultsAll parameters for global and regional longitudinal strain were unaffected by adjustments of spatial and temporal smoothing in both normal and ischemic myocardium. Radial and circumferential strain depended on smoothing to a variable extent, radial strain being most affected. However, in both directions the different combinations of smoothing did only result in relatively small changes in the strain values. Overall, the maximal strain difference was found in normal myocardium for peak systolic radial strain of the posterior wall where strain was 22.0 ± 2.2% with minimal spatial and maximal temporal smoothing and 30.9 ± 2.6% with maximal spatial and minimal temporal smoothing (P < 0.05).ConclusionsLongitudinal strain was unaffected by different degrees of user controlled smoothing. Radial and circumferential strain depended on the degree of smoothing. However, in most cases these changes were small and would not lead to altered conclusions in a clinical setting. Furthermore, smoothing did not affect strain variance. For all strain parameters, variance remained within the corresponding interobserver variance.

Reperfusion Therapy with Low-Dose Insulin or Insulin-Like Growth Factor 2; Myocardial Function and Infarct Size in a Porcine Model of Ischaemia and Reperfusion

In an open‐chest porcine model, we examined whether myocardial pharmacological conditioning at the time of reperfusion with low‐dose insulin or insulin‐like growth factor 2 (IGF2), not affecting serum glucose levels, could reduce infarct size and improve functional recovery. Two groups of anaesthetized pigs with either 60 or 40 min. of left anterior descending artery occlusion (total n = 42) were randomized to receive either 0.9% saline, insulin or IGF2 infusion for 15 min., starting 5 min. before a 180‐min. reperfusion period. Repeated fluorescent microsphere injections were used to confirm ischaemia and reperfusion. Area at risk and infarct size was determined with Evans blue and triphenyltetrazolium chloride staining. Local myocardial function was evaluated with multi‐layer radial tissue Doppler strain and speckle‐tracking strain from epicardial echocardiography. Western blotting and TUNEL staining were performed to explore apoptosis. Infarct size did not differ between treatment groups and was 56.7 ± 6.8%, 49.7 ± 9.6%, 56.2 ± 8.0% of area at risk for control, insulin and IGF2 group, respectively, in the 60‐min. occlusion series. Corresponding values were 45.6 ± 6.0%, 48.4 ± 7.2% and 34.1 ± 5.8% after 40‐min. occlusion. Global and local cardiac function did not differ between treatment groups. No differences related to treatment could be found in myocardial tissue cleaved caspase‐3 content or the degree of TUNEL staining. Reperfusion therapy with low‐dose insulin or with IGF2 neither reduced infarct size nor improved function in reperfused myocardium in this in vivo porcine model.

Carvedilol-enriched cold oxygenated blood cardioplegia improves left ventricular diastolic function after weaning from cardiopulmonary bypass

OBJECTIVES To investigate whether adding carvedilol, a nonselective β- and selective α1-receptor blocking agent with antioxidant properties, to oxygenated blood cardioplegia improves myocardial function after weaning from bypass. DESIGN A randomized controlled study. SETTING A university laboratory. PARTICIPANTS Twenty anesthetized pigs, Norwegian Landrace. INTERVENTIONS On cardiopulmonary bypass, cardiac arrest was induced with cold (12°C), oxygenated blood cardioplegia, enriched with carvedilol or vehicle, and repeated every 20 minutes. After 100 minutes, the heart was reperfused and weaned. MEASUREMENTS AND MAIN RESULTS Left ventricular function was evaluated with pressure-volume loops, local myocardial systolic strain, and strain rate from Speckle tracking analysis and multilayer short-axis tissue Doppler Imaging. In the carvedilol group, the load-independent logarithmic end-diastolic pressure volume relationship, β, decreased from 1 to 3 hours of reperfusion and was low, 0.028±0.004 v 0.042±0.007 (p<0.05) in controls at 3 hours, demonstrating improved left ventricular compliance. The diastolic relaxation constant τ was decreased, 28.9±0.6 ms v 34.6±1.3 ms (pg<0.035), and dP/dtmin was more negative,-1,462±145 mmHg/s v-1,105±105 mmHg/s (pg = 0.024), for carvedilol v control group. The systolic variables, preload recruitable stroke work and end-systolic pressure-volume relationship, did not differ between groups, neither did left ventricular systolic strain and strain rate. Myocardial oxidative stress, measured as tissue levels of malondialdehyde, was reduced by carvedilol, 0.19±0.01 compared to 0.24±0.01 nmol/mg (p = 0.004) in controls. CONCLUSIONS Carvedilol added to blood cardioplegia improved diastolic cardiac function and reduced oxidative stress during the first 3 hours after reperfusion in a porcine model, with 100 minutes of cardioplegic arrest.

Intracoronary insulin administered at reperfusion in a porcine model of acute coronary syndrome

Background: Experimental studies have demonstrated that insulin elicits cardioprotection in coronary occlusion-reperfusion models. We studied the effects of intracoronary insulin on regional cardiac function in a porcine model with reperfusion after a critical coronary artery stenosis. Methods: In 20 anaesthetized pigs with an extracorporeal shunt from the brachiocephalic to the left anterior descending coronary artery, a fixed stenosis was applied, obtaining 50% reduction of shunt flow for 60 min. Intracoronary insulin 1 1U/kg or 0.9% saline was infused for 15 min, starting 5 min prior to initiation of 180 min of reperfusion. Microsphere injections confirmed ischaemia and reperfusion. Epicardial echocardiographic multilayer radial tissue Doppler strain and strain rate and one-layer speckle-tracking strain evaluated myocardial function. Apoptosis was evaluated by cleaved caspase-3 activity. Area at risk and infarct size were determined with Evans Blue and triphenyltetrazolium chloride staining. Results: In both groups, the area at risk constituted approximately 26% of the left ventricular mass. Minor areas of infarction were predominantly seen subendocardially, where tissue blood flow rate was severely reduced during stenosis. After 180 min of reperfusion, recovery of speckle-tracking circumferential strain averaged 57.5 ± 11.4% of baseline values in insulin treated animals compared to 22.3 ± 8.7% in controls (p = 0.025). Multilayer radial strain and strain rate did not differ between groups. Cleaved caspase-3 activity was most prominent in the subepicardial layer in the saline-treated group. Conclusions: Intracoronary insulin at the onset of reperfusion alleviated regional myocardial dysfunction in acute ischaemia-reperfusion and was associated with a reduction of apoptosis.