Decellularization reduces the immune response to aortic valve allografts in the rat

ObjectivesCryopreserved valve allografts used in congenital cardiac surgery are associated with a significant cellular and humoral immune response. This might be reduced by removal of antigenic cellular elements (decellularization). The aim of this study was to determine the immunologic effect of decellularization in a rat allograft valve model.MethodsBrown Norway and Lewis rat aortic valves were decellularized with a series of hypotonic and hypertonic buffers, protease inhibitors, gentle detergents (Triton X-100), and phosphate-buffered saline. Valves were implanted into Lewis rats in syngeneic and allogeneic combinations. Cellular (CD3 and CD8) infiltrates were assessed with morphometric analysis, and the humoral response was assessed with flow cytometry.ResultsMorphometric analysis identified a significant reduction in CD3+ cell infiltrates (cells per square millimeter of leaflet tissue) in decellularized allografts compared with that seen in nondecellularized allografts at 1 (79 ± 29 vs 3310 ± 223, P < .001), 2 (26 ± 11 vs 109 ± 20, P = .004), and 4 weeks (283 ± 122 vs 984 ± 145, P < .001). Anti-CD8 staining confirmed the majority of infiltrates were cytotoxic T cells. Flow cytometric mean channel fluorescence intensity identified a negative shift (abrogated antibody formation) for decellularized allografts compared with nondecellularized allografts at 2 (19 ± 1 vs 27 ± 3, P = .033), 4 (35 ± 2 vs 133 ± 29, P = .001), and 16 weeks (28 ± 2 vs 166 ± 54, P = .017).ConclusionsDecellularization significantly reduces the cellular and humoral immune response to allograft tissue. This could prolong the durability of valve allografts and might prevent immunologic sensitization of allograft recipients

β3-Adrenoceptor Antagonist SR59230A Attenuates the Imbalance of Systemic and Myocardial Oxygen Transport Induced by Dopamine in Newborn Lambs

Background In neonates, the increase in O 2 -delivery (DO 2 ) by dopamine is offset by a greater increase in O 2 -consumption (VO 2 ). This has been attributed to β 3 -adrenergic receptors in neonatal brown fat tissue. β 3 receptors in the heart have negative inotropic properties. We evaluated the effects of SR59230A, a β 3 -antagonist, on the balance of systemic and myocardial O 2 -transport in newborn lambs treated with dopamine. Methods Lambs (2-5 days old, n = 12) were anesthetized and mechanically ventilated. Heart rate (HR) and rectal temperature were monitored. VO 2 was measured by respiratory mass spectrometry and cardiac output (CO) by a pulmonary artery transonic flowmeter. Arterial, jugular bulb venous and coronary sinus blood gases and lactate were measured to calculate DO 2 , O 2 extraction ratio (ERO 2 ), myocardial O 2 and lactate extraction ratios (mERO 2 , mERlac). After baseline measurements, lambs were randomized to receive SR59230A at 5 mg/kg iv (SRG) or placebo. Both groups received incremental doses of a dopamine infusion (0-5-10-15-20 mcg/kg/min) every 15 min. Measurements were repeated at the end of each dose. Results After SR59230A infusion, CO and HR trended to decrease ( P = 0.06), but no significant changes occurred in other parameters. Over the incremental doses of dopamine, temperature increased in both groups ( P 0.1). DO 2 trended to a small increase ( P = 0.08). VO 2 increased in both groups ( P < 0.0001) but to a lesser degree in SRG ( P < 0.0001). As a result, ERO 2 increased in both groups ( P < 0.0001), but to a lesser degree in SRG ( P < 0.0001). mERO 2 was lower in SRG ( P = 0.01) with a faster increase ( P < 0.0001). mERlac was higher in SRG ( P = 0.06) with a faster decrease ( P = 0.04). Conclusion Although SR59230A tends to induce an initial drop in CO, it significantly attenuates the rise in VO 2 and hence the imbalance of systemic and myocardial O 2 transport induced by dopamine at higher doses. Studies are warranted to examine the effect of SR59230A in cases of cardiac dysfunction and increased VO 2 , observed after cardiac surgery

The effects of body mass index on outcomes for patients undergoing surgical aortic valve replacement

Abstract Background Most of the studies of obesity and postoperative outcome have looked predominantly at coronary artery bypass grafting with fewer focused on valvular disease. The purpose of this study was to compare the outcomes of patients undergoing aortic valve replacement stratified by body mass index (BMI, kg/m^2). Methods The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry captured 4780 aortic valve replacements in Alberta, Canada from January 2004 to December 2018. All recipients were stratified by BMI into five groups (BMI:  = 35). Log-rank test and Cox regression were used to examine the crude and adjusted survival differences. Results Intra-operative clamp time and pump time were similar among the five groups. Significant statistical differences between groups existed for the incidence of isolated AVR, AVR and CABG, hemorrhage, septic infection, and deep sternal infection (p < 0.05). While there was no significant statistical difference in the mortality rate across the BMI groups, the underweight AVR patients (BMI < 20) were associated with increased hazard ratio (1.519; 95% confidence interval: 1.028–2.245) with regards to all-cause mortality at the longest follow-up compared with normal weight patients. Conclusion Overweight and obese patients should be considered as readily for AVR as normal BMI patients

sj-tiff-1-sjs-10.1177_14574969221124468 – Supplemental material for Does sex impact outcomes after mitral valve surgery? A systematic review and meta-analysis

Supplemental material, sj-tiff-1-sjs-10.1177_14574969221124468 for Does sex impact outcomes after mitral valve surgery? A systematic review and meta-analysis by Ryaan EL-Andari, Sabin J. Bozso, Nicholas M. Fialka, Jimmy J.H. Kang and Jeevan Nagendran in Scandinavian Journal of Surgery</p

sj-tiff-2-sjs-10.1177_14574969221124468 – Supplemental material for Does sex impact outcomes after mitral valve surgery? A systematic review and meta-analysis

Supplemental material, sj-tiff-2-sjs-10.1177_14574969221124468 for Does sex impact outcomes after mitral valve surgery? A systematic review and meta-analysis by Ryaan EL-Andari, Sabin J. Bozso, Nicholas M. Fialka, Jimmy J.H. Kang and Jeevan Nagendran in Scandinavian Journal of Surgery</p

AMPK-dependent inhibitory phosphorylation of ACC is not essential for maintaining myocardial fatty acid oxidation

Rationale: The energy sensor AMP-activated protein kinases (AMPK) is thought to play an important role in regulating myocardial fatty acid oxidation (FAO) via its phosphorylation and inactivation of acetyl coenzyme A carboxylase (ACC). However, studies supporting this have not directly assessed whether the maintenance of FAO rates and subsequent cardiac function requires AMPK-dependent inhibitory phosphorylation of ACC. Objective: To determine whether preventing AMPK-mediated inactivation of ACC influences myocardial FAO or function. Methods and Results: A double knock-in (DKI) mouse (ACC-DKI) model was generated in which the AMPK phosphorylation sites Ser79 on ACC1 and Ser221 (Ser212 mouse) on ACC2 were mutated to prevent AMPK-dependent inhibitory phosphorylation of ACC. Hearts from ACC-DKI mice displayed a complete loss of ACC phosphorylation at the AMPK phosphorylation sites. Despite the inability of AMPK to regulate ACC activity, hearts from ACC-DKI mice displayed normal basal AMPK activation and cardiac function at both standard and elevated workloads. In agreement with the inability of AMPK in hearts from ACC-DKI mice to phosphorylate and inhibit ACC, there was a significant increase in cardiac malonyl-CoA content compared with wild-type mice. However, cardiac FAO rates were comparable between wild-type and ACC-DKI mice at baseline, during elevated workloads, and after a more stressful condition of myocardial ischemia that is known to robustly activate AMPK. Conclusions: Our findings show AMPK-dependent inactivation of ACC is not essential for the control of myocardial FAO and subsequent cardiac function during a variety of conditions involving AMPK-independent and AMPK-dependent metabolic adaptations