Mitral annular dynamics are influenced by left ventricular load and contractility in an acute animal model.

The purpose of this study was to investigate the effects of loading conditions and left ventricular (LV) contractility on mitral annular dynamics. In 10 anesthetized pigs, eight piezoelectric transducers were implanted equidistantly around the mitral annulus. High-fidelity catheters measured left ventricular pressures and the slope of the end-systolic pressure-volume relationship (Ees ) determined LV contractility. Adjustments of pre- and afterload were done by constriction of the inferior caval vein and occlusion of the descending aorta. Mitral annulus area indexed to body surface area (MAAi ), annular circularity index (ACI), and non-planarity angle (NPA) were calculated by computational analysis. MAAi was more dynamic in response to loading interventions than ACI and NPA. However, MAAi maximal cyclical reduction (-Δr) and average deformational velocity (- v ¯ $$ \overline{v} $$ ) did not change accordingly (p = 0.31 and p = 0.22). Reduced Ees was associated to attenuation in MAAi -Δr and MAAi - v ¯ $$ \overline{v} $$ (r2 = 0.744; p = 0.001 and r2 = 0.467; p = 0.029). In conclusion, increased cardiac load and reduced LV contractility may cause deterioration of mitral annular dynamics, likely impairing coaptation and increasing susceptibility to valvular incompetence.

Left ventricular venting during extracorporeal membrane oxygenation; the effects on cardiac performance in a porcine model of critical post-cardiotomy failure.

INTRODUCTION: Left ventricular distension is a major concern with postcardiotomy veno-arterial extracorporeal membrane oxygenation (VA-ECMO) supporting a critical heart failure after cardiac surgery. This porcine study evaluates the effects of left ventricular venting on cardiac function during ECMO-supported circulation and after weaning from ECMO. METHODS: Twenty anaesthetised open-chest pigs were put on cardiopulmonary bypass with aortic cross-clamping and suboptimal cardioplegic arrest for 40 min. After declamping and defibrillation, the animals were supported by VA-ECMO for 180 min either with or without additional left ventricular venting. Continuous haemodynamic evaluations were performed at baseline and at cardiac arrest, during VA-ECMO and for 120 min after weaning from circulatory support. Left ventricular perfusion and function were evaluated with microspheres, pressure-volume loops and epicardial echocardiography at baseline and after 1 and 2 h with unsupported circulation. RESULTS: In vented animals both mean aortic and left ventricular peak systolic pressure increased at the end of the ECMO-supported period compared to those not vented and remained increased also after weaning. Both at 60 min and 120 min after weaning from circulatory support, left ventricular stroke work and pressure-volume area were increased in vented compared to not vented animals. At 120 min left ventricular stroke volume was increased in vented compared to not vented animals, myocardial perfusion did not differ. The left ventricular mechanical efficiency, defined as the ratio between pressure volume area and myocardial perfusion, was increased (53.2 ± 5 vs 36.2 ± 2.1 J/mL/g, p = 0.011) in vented- compared to not vented hearts. CONCLUSION: This experimental study demonstrate that left ventricular venting during post-cardiotomy veno-arterial ECMO for 3 h attenuates deterioration of left ventricular function and haemodynamics early after weaning from circulatory support.

Effects of Add-On Left Ventricular Assist Device to Extracorporeal Membrane Oxygenation During Refractory Cardiac Arrest in a Porcine Model.

This study evaluated the effects of extracorporeal membrane oxygenation (ECMO) in combination with a percutaneous adjunctive left ventricular assist device (LVAD) in a porcine model during 60 minutes of refractory cardiac arrest (CA). Twenty-four anesthetized swine were randomly allocated into three groups given different modes of circulatory assist: group 1: ECMO 72 ml/kg/min and LVAD; group 2: ECMO 36 ml/kg/min and LVAD; and group 3: ECMO 72 ml/kg/min. During CA and extracorporeal cardiopulmonary resuscitation (ECPR), mean left ventricular pressure (mLVP) was lower in group 1 (p = 0.013) and in group 2 (p = 0.003) versus group 3. Mean aortic pressure (mAP) and coronary perfusion pressure (CPP) were higher in group 1 compared with the other groups. In group 3, mean pulmonary artery flow (mPAf) was lower versus group 1 (p = 0.003) and group 2 (p = 0.039). If the return of spontaneous circulation (ROSC) was achieved after defibrillation, up to 180 minutes of unsupported observation followed. All subjects in groups 1 and 3, and 5 subjects in group 2 had ROSC. All subjects in group 1, five in group 2 and four in group 3 had sustained cardiac function after 3 hours of spontaneous circulation. Subjects that did not achieve ROSC or maintained cardiac function post-ROSC had lower mAP (p < 0.001), CPP (p = 0.002), and mPAf (p = 0.004) during CA and ECPR. Add-on LVAD may improve hemodynamics compared with ECMO alone during refractory CA but could not substitute reduced ECMO flow. Increased mAP and CPP could be related to ROSC rate and sustained cardiac function. Increased mLVP was related to poor post-ROSC cardiac function.

Long-term follow-up after surgery for atrial fibrillation with concomitant open heart surgery. / Langtidsoppfølging etter atrieflimmeroperasjon og samtidig åpen hjertekirurgi.

BACKGROUND: Patients with atrial fibrillation and atrial flutter scheduled to undergo open heart surgery can receive ablation treatment of arrhythmogenic foci during the same intervention. Sinus rhythm is restored in the majority in the short term, but the long-term results are more uncertain. This study, which is part of the international CURE-AF trial, evaluates results after Cox-Maze IV surgery for atrial fibrillation in Norway at six-year follow-up. MATERIAL AND METHOD: Nineteen patients were included in this prospective cohort study. Atrial fibrillation had persisted for 40 months in the group with long-standing persistent atrial fibrillation (n = 12) and 6 months in the group with persistent atrial fibrillation (n = 7). Surgery for atrial fibrillation was performed according to the Cox-Maze IV procedure in the CURE-AF protocol. Follow-up in the first 12 months was strictly according to the CURE-AF protocol, thereafter conducted by the primary health service. RESULTS: Sinus rhythm was restored in 11 patients at the time of discharge and in 14 patients six months postoperatively. After 5-6 years of follow-up, all patients with long-standing persistent atrial fibrillation had experienced recurrence. Two achieved sinus rhythm after electroconversion. Six of the seven in the group with persistent atrial fibrillation had sinus rhythm after 5-6 years. INTERPRETATION: The results were good initially, with restoration of sinus rhythm in more than two thirds of the patients after 6-9 months. Five years later, a high recurrence rate was found in patients with long-standing persistent atrial fibrillation. Several recurrences had not been detected by the public health service or treatment had not been attempted.

Effect of Temporal and Spatial Smoothing on Speckle-Tracking-Derived Strain in Neonates.

Clinical application of strain in neonates requires an understanding of which image acquisition and processing parameters affect strain values. Previous studies have examined frame rate, transmitting frequency, and vendor heterogeneity. However, there is a lack of human studies on how user-regulated spatial and temporal smoothing affect strain values in 36 neonates. This study examined nine different combinations of spatial and temporal smoothing on peak systolic left ventricular longitudinal strain in 36 healthy neonates. Strain values were acquired from four-chamber echocardiographic images in the software-defined epicardial, midwall, and endocardial layers in the six standard segments and average four-chamber stain. Strain values were compared using repeated measure ANOVAs. Overall, spatial smoothing had a larger impact than temporal smoothing, and segmental strain values were more sensitive to smoothing settings than average four-chamber strain. Apicoseptal strain decreased by approximately 4% with increasing spatial smoothing, corresponding to a 13-19% proportional change (depending on wall layer). Therefore, we recommend clinicians be mindful of smoothing settings when assessing segmental strain values.

Balanced Biventricular Assist Versus Extracorporeal Membrane Oxygenation in Cardiac Arrest.

Mechanical assist devices in refractory cardiac arrest are increasingly employed. We compared the hemodynamics and organ perfusion during cardiac arrest with either veno-arterial extracorporeal membrane oxygenation (ECMO) or biventricular assisted circulation combining left- and right-sided impeller devices (BiPella) in an acute experimental setting. Twenty pigs were randomized in two equal groups receiving circulatory support either by ECMO or by BiPella during 40 minutes of ventricular fibrillation (VF) followed by three attempts of cardioversion, and if successful, 60 minute observation with spontaneous, unsupported circulation. Hemodynamic variables were continuously recorded. Tissue perfusion was evaluated by fluorescent microsphere injections. Cardiac function was visualized by intracardiac echocardiography. During VF device output, carotid flow, kidney perfusion, mean aortic pressure (AOPmean), and mean left ventricular pressure (LVPmean) were all significantly higher in the ECMO group, and serum-lactate values were lower compared with the BiPella group. No difference in myocardial or cerebral perfusion was observed between groups. In 15 animals with sustained cardiac function for 60 minutes after return of spontaneous circulation, left ventricular subendocardial blood flow rate averaged 0.59 ± 0.05 ml/min/gm during VF compared with 0.31 ± 0.07 ml/min/gm in five animals with circulatory collapse (p = 0.005). Corresponding values for the midmyocardium was 0.91 ± 0.06 vs. 0.65 ± 0.15 ml/min/gm (p = 0.085). Both BiPella and ECMO could sustain vital organ function. ECMO provided a more optimal systemic circulatory support related to near physiologic output. Myocardial tissue perfusion and sustained cardiac function were related to coronary perfusion pressure during VF, irrespective of mode of circulatory support.

Myocardial perfusion and cardiac dimensions during extracorporeal membrane oxygenation-supported circulation in a porcine model of critical post-cardiotomy failure.

INTRODUCTION: Venoarterial extracorporeal membrane oxygenation is widely used as mechanical circulatory support for severe heart failure. A major concern with this treatment modality is left ventricular distension due to inability to overcome the afterload created by the extracorporeal membrane oxygenation circuit. The present porcine study evaluates coronary circulation, myocardial perfusion and ventricular distension during venoarterial extracorporeal membrane oxygenation. METHODS: Ten anesthetized open-chest pigs were cannulated and put on cardiopulmonary bypass. Heart failure was achieved by 90 minutes of aortic cross-clamping with insufficient cardioplegic protection. After declamping, the animals were supported by venoarterial extracorporeal membrane oxygenation for 3 hours. Continuous haemodynamic measurements were performed at baseline, during cardiopulmonary bypass/aortic cross-clamping and during venoarterial extracorporeal membrane oxygenation. Fluorescent microsphere injections at baseline and after 1, 2 and 3 hours on venoarterial extracorporeal membrane oxygenation evaluated myocardial perfusion. Left ventricular function and distension were assessed by epicardial echocardiography. RESULTS: The myocardial injury caused by 90 minutes of ischaemia resulted in a poorly contracting myocardium, necessitating venoarterial extracorporeal membrane oxygenation in all animals. The circulatory support maintained the mean arterial blood pressure within a satisfactory range. A hyperaemic left anterior descending coronary artery flow while on extracorporeal membrane oxygenation was observed compared to baseline. Myocardial tissue perfusion measured by microspheres was low, especially in the subendocardium. Echocardiography revealed myocardial tissue oedema, a virtually empty left ventricle, and a left ventricular output that remained negligible throughout the extracorporeal membrane oxygenation run. CONCLUSION: Coronary artery blood flow is maintained during venoarterial extracorporeal membrane oxygenation after cardiopulmonary bypass and cardioplegic arrest despite severely affected performance of the left ventricle. Myocardial perfusion decreases, however, presumably due to rapid development of myocardial tissue oedema.

Left ventricular dysfunction after two hours of polarizing or depolarizing cardioplegic arrest in a porcine model.

INTRODUCTION: This experimental study compares myocardial function after prolonged arrest by St. Thomas' Hospital polarizing cardioplegic solution (esmolol, adenosine, Mg2+) with depolarizing (hyperkalaemic) St. Thomas' Hospital No 2, both administered as cold oxygenated blood cardioplegia. METHODS: Twenty anaesthetized pigs on tepid (34°C) cardiopulmonary bypass (CPB) were randomised to cardioplegic arrest for 120 min with antegrade, repeated, cold, oxygenated, polarizing (STH-POL) or depolarizing (STH-2) blood cardioplegia every 20 min. Cardiac function was evaluated at Baseline and 60, 150 and 240 min after weaning from CPB, using a pressure-conductance catheter and epicardial echocardiography. Regional tissue blood flow, cleaved caspase-3 activity and levels of malondialdehyde were evaluated in myocardial tissue samples. RESULTS: Preload recruitable stroke work (PRSW) was increased after polarizing compared to depolarizing cardioplegia 150 min after declamping (73.0±3.2 vs. 64.3±2.4 mmHg, p=0.047). Myocardial tissue blood flow rate was high in both groups compared to the Baseline levels and decreased significantly in the STH-POL group only, from 60 min to 150 min after declamping (p<0.005). Blood flow was significantly reduced in the STH-POL compared to the STH-2 group 240 min after declamping (p<0.05). Left ventricular mechanical efficiency, the ratio between total pressure-volume area and blood flow rate, gradually decreased after STH-2 cardioplegia and was significantly reduced compared to STH-POL cardioplegia after 150 and 240 min (p<0.05 for both). CONCLUSION: Myocardial protection for two hours of polarizing cardioplegic arrest with STH-POL in oxygenated blood is non-inferior compared to STH-2 blood cardioplegia. STH-POL cardioplegia alleviates the mismatch between myocardial function and perfusion after weaning from CPB.

Left Versus Biventricular Assist Devices in Cardiac Arrest.

Maintaining adequate organ perfusion during cardiac arrest remains a challenge, and various assist techniques have been evaluated. We assessed whether a right ventricular impeller assist device (RVAD) in adjunct to a left ventricular impeller assist device (LVAD) is beneficial. Twenty anesthetized pigs were randomized to maximized circulatory support by percutaneously implanted left- or biventricular assist device(s) during 30 minutes of electrically induced ventricular fibrillation followed by three attempts of cardioversion. Continuous hemodynamic variables were recorded. Cardiac output and myocardial, cerebral, renal, and ileum mucosa tissue perfusion were measured with fluorescent microspheres, and repeated blood gas analyses were obtained. With biventricular support, an increased LVAD output was found compared with left ventricular (LV) support; 3.2 ± 0.2 (SEM) vs. 2.0 ± 0. 2 L/minute just after start of ventricular fibrillation, 3.2 ± 0.1 vs. 2.0 ± 0.1 L/minute after 15 minutes, and 3.0 ± 0.1 vs. 2.1 ± 0.1 L/minute after 30 minutes of cardiac arrest (pg < 0.001). Biventricular support also increased aortic and LV pressure, in addition to end-tidal CO2. Tissue blood flow rates were increased for most organs with biventricular support. Blood gas analyses showed improved oxygenation and lower s-lactate values. However, myocardial perfusion was degraded with biventricular support and return of spontaneous circulation less frequent (5/10 vs. 10/10; p = 0.033). Biventricular support was associated with high intraventricular pressure and decreased myocardial perfusion pressure, correlating significantly with flow rates in the LV wall. A transmural flow gradient was observed for both support modes, with better maintained subepicardial than midmyocardial and subendocardial perfusion.

Myocardial energy metabolism and ultrastructure with polarizing and depolarizing cardioplegia in a porcine model.

OBJECTIVES: This study investigated whether the novel St. Thomas' Hospital polarizing cardioplegic solution (STH-POL) with esmolol/adenosine/magnesium offers improved myocardial protection by reducing demands for high-energy phosphates during cardiac arrest compared to the depolarizing St. Thomas' Hospital cardioplegic solution No 2 (STH-2). METHODS: Twenty anaesthetised pigs on tepid cardiopulmonary bypass were randomized to cardiac arrest for 60 min with antegrade freshly mixed, repeated, cold, oxygenated STH-POL or STH-2 blood cardioplegia every 20 min. Haemodynamic variables were continuously recorded. Left ventricular biopsies, snap-frozen in liquid nitrogen or fixed in glutaraldehyde, were obtained at Baseline, 58 min after cross-clamp and 20 and 180 min after weaning from bypass. Adenine nucleotides were evaluated by high-performance liquid chromatography, myocardial ultrastructure with morphometry. RESULTS: With STH-POL myocardial creatine phosphate was increased compared to STH-2 at 58 min of cross-clamp [59.9 ± 6.4 (SEM) vs 44.5 ± 7.4 nmol/mg protein; P < 0.025], and at 20 min after reperfusion (61.0 ± 6.7 vs 49.0 ± 5.5 nmol/mg protein; P < 0.05), ATP levels were increased at 20 min of reperfusion with STH-POL (35.4 ± 1.1 vs 32.4 ± 1.2 nmol/mg protein; P < 0.05). Mitochondrial surface-to-volume ratio was decreased with polarizing compared to depolarizing cardioplegia 20 min after reperfusion (6.74 ± 0.14 vs 7.46 ± 0.13 µm 2 /µm 3 ; P = 0.047). None of these differences were present at 180 min of reperfusion. From 150 min of reperfusion and onwards, cardiac index was increased with STH-POL; 4.8 ± 0.2 compared to 4.0 ± 0.2 l/min/m 2 ( P = 0.011) for STH-2 at 180 min. CONCLUSIONS: Polarizing STH-POL cardioplegia improved energy status compared to standard STH-2 depolarizing blood cardioplegia during cardioplegic arrest and early after reperfusion.

Outcome After Rewarming From Accidental Hypothermia by Use of Extracorporeal Circulation.

BACKGROUND: Accidental hypothermia with arrested circulation remains a condition associated with high mortality. In our institution, extracorporeal circulation (ECC) rewarming has been the cornerstone in treating such patients since 1987. We here explore characteristics and outcomes of this treatment, to identify significant merits and challenges from 3 decades of experience in ECC rewarming. METHODS: Sixty-nine patients rewarmed by ECC during the period from December 1987 to December 2015 were analyzed. One patient was excluded from the analyses because of combined traumatic cerebral injury. The analysis was focused on patient characteristics, treatment procedures, and outcomes were focused. Survivors were evaluated according to the cerebral performance categories scale. Simple statistics with nonparametric tests and χ2 tests were used. Median value and range are reported. RESULTS: Median age was 30 years (minimum 1.5, maximum 76), and the cause of accidental hypothermia was cold exposure (27.9%), avalanche (5.9%), and immersion/submersion accidents (66.2%). Eighteen patients survived (26.5%). The survival rate did not improve during the years. Survivors had lower serum potassium (p = 0.002), higher pH (p = 0.03), lower core temperature (p = 0.02), and shorter cardiopulmonary resuscitation time (p = 0.001), but ranges were wide. Although suspected primary hypoxia and hypothermia were associated with lower survival, we observed a 10.5% survival of these victims. Sixteen survivors had good outcome (cerebral performance category 1 or 2), whereas 2 patients with suspected primary hypoxia survived with severe cerebral disability (cerebral performance category 3). CONCLUSIONS: Despite extended experience with ECC rewarming, improved handling strategies, and intensive care, no overall improvement in survival was observed. Good outcome was observed even among patients with a dismal prognosis.

Carvedilol-Enriched Cold Oxygenated Blood Cardioplegia Improves Left Ventricular Diastolic Function After Weaning From Cardiopulmonary Bypass.

OBJECTIVES: To investigate whether adding carvedilol, a nonselective ß- 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, ß, 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.

Does Roller Pump-Induced Pulsatile CPB Perfusion Affect Microvascular Fluid Shifts and Tissue Perfusion?

BACKGROUND: Pulsatile versus nonpulsatile cardiopulmonary bypass (CPB) perfusion remains debated. Beneficial effects on tissue perfusion, inflammation, and microvascular fluid exchange have been linked to pulsatile perfusion by some investigators and denied by others. This study evaluated fluid extravasation and tissue perfusion during nonpulsatile or pulsatile roller pump-induced CPB perfusion. METHODS: Fourteen pigs underwent roller pump-induced pulsatile (n = 7) or nonpulsatile CPB perfusion (n = 7) for 90 minutes. Fluid input/losses, colloid osmotic pressures (plasma/interstitium), hematocrit, serum electrolytes, serum proteins, tissue perfusion, and total tissue water content were measured, and plasma volume and fluid extravasation were calculated. RESULTS: Fluid additions/losses, plasma volume, and fluid extravasation changed similarly in both groups during CPB with no between-group differences. Neither was between-group differences observed for tissue perfusion and total tissue water content, with one exception. Total tissue water content of the right (3.92 ± 0.26 versus 4.32 ± 0.28 g/g dry weight) and left ventricle (4.02 ± 0.25 versus 4.33 ± 0.24 g/g dry weight) was lowered in the pulsatile group. CONCLUSIONS: No important differences were found between pulsatile and nonpulsatile CPB perfusion for microvascular fluid balance and tissue perfusion.

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.

Myocardial function after polarizing versus depolarizing cardiac arrest with blood cardioplegia in a porcine model of cardiopulmonary bypass.

OBJECTIVES: Potassium-based depolarizing St Thomas' Hospital cardioplegic solution No 2 administered as intermittent, oxygenated blood is considered as a gold standard for myocardial protection during cardiac surgery. However, the alternative concept of polarizing arrest may have beneficial protective effects. We hypothesize that polarized arrest with esmolol/adenosine/magnesium (St Thomas' Hospital Polarizing cardioplegic solution) in cold, intermittent oxygenated blood offers comparable myocardial protection in a clinically relevant animal model. METHODS: Twenty anaesthetized young pigs, 42 ± 2 (standard deviation) kg on standardized tepid cardiopulmonary bypass (CPB) were randomized (10 per group) to depolarizing or polarizing cardiac arrest for 60 min with cardioplegia administered in the aortic root every 20 min as freshly mixed cold, intermittent, oxygenated blood. Global and local baseline and postoperative cardiac function 60, 120 and 180 min after myocardial reperfusion was evaluated with pressure-conductance catheter and strain by Tissue Doppler Imaging. Regional tissue blood flow, cleaved caspase-3 activity, GRK2 phosphorylation and mitochondrial function and ultrastructure were evaluated in myocardial tissue samples. RESULTS: Left ventricular function and general haemodynamics did not differ between groups before CPB. Cardiac asystole was obtained and maintained during aortic cross-clamping. Compared with baseline, heart rate was increased and left ventricular end-systolic and end-diastolic pressures decreased in both groups after weaning. Cardiac index, systolic pressure and radial peak systolic strain did not differ between groups. Contractility, evaluated as dP/dtmax, gradually increased from 120 to 180 min after declamping in animals with polarizing cardioplegia and was significantly higher, 1871 ± 160 (standard error) mmHg/s, compared with standard potassium-based cardioplegic arrest, 1351 ± 70 mmHg/s, after 180 min of reperfusion (P = 0.008). Radial peak ejection strain rate increased and the load-independent variable preload recruitable stroke work was increased with polarizing cardioplegia after 180 min, 64 ± 3 vs 54 ± 2 mmHg (P = 0.018), indicating better preserved left ventricular contractility with polarizing cardioplegia. Phosphorylation of GRK2 in myocardial tissue did not differ between groups. Fractional cytoplasmic volume in myocytes was reduced in hearts arrested with polarizing cardioplegia, indicating reduction of cytoplasmic oedema. CONCLUSIONS: Polarizing oxygenated blood cardioplegia with esmolol/adenosine/magnesium offers comparable myocardial protection and improves contractility compared with the standard potassium-based depolarizing blood cardioplegia.

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

OBJECTIVE: This study investigated if the ß-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.