Prospective randomized study comparing outcome of myocardial protection with Del-Nido Cardioplegia versus Saint Thomas Cardioplegia in adult cardiac surgical patients

Objectives: To compare the effectiveness of Del-Nido cardioplegia as myocardial protective agent with Saint Thomas cardioplegia in adult cardiac surgical patients. Methods: This prospective randomized study was conducted in cardiac surgery department of Bahawal Victoria hospital Bahawalpur, from October 2020 to March 2021. Eighty adult patients who underwent primary Isolated coronary artery bypass grafting (CABG) or isolated Valve surgery requiring cardiopulmonary bypass were randomly divided into Del Nido (DN, n=40) and Saint Thomas (ST, n=40) groups. Data regarding operative and post-operative variables such as cardiopulmonary bypass (CPB) and aortic cross clamp (AXC) times, inotropic requirements, resumption of sinus rhythm, need for electrical defibrillation, post-operative CKMB, blood requirement and ICU stay were noted. Results: CPB and AXC times were statistically insignificantly different. Resumption of Sinus rhythm was seen significantly in more patients of DN group (95%) than in ST group (72.5%) [p-value 0.05]. Less patients of DN group (5%) were candidates of electrical defibrillation than ST group (17.5%) [p-value <0.001). Post- operative CKMB values were significantly lower in DN group as compared to ST group (30.5±22.6 IU vs 50.5±50.28 IU, p value.008). Blood transfusion was significantly lower in DN group; 50% versus 80% in ST group (p-value 0.005). Ventilation time was significantly less in DN group than ST group (165.95±48.09 minutes versus 165.95±48.09 minutes respectively, p-value 0.03). While ICU stay was also less in DN group; 5.2±0.8 days versus 6.05±1.6 days in ST group (p-value 0.003). Conclusion: Del-Nido cardioplegia is a reliable and better myocardial protective agent than Saint Thomas cardioplegia in adult cardiac surgical procedures. doi: https://doi.org/10.12669/pjms.38.3.4730 How to cite this:Rizvi MFA, Yousuf SMA, Younas A, Baig MAR. Prospective randomized study comparing outcome of myocardial protection with Del-Nido Cardioplegia versus Saint Thomas Cardioplegia in adult cardiac surgical patients. Pak J Med Sci. 2022;38(3):---------. doi: https://doi.org/10.12669/pjms.38.3.4730 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Diazoxide Post-conditioning Activates the HIF-1/HRE Pathway to Induce Myocardial Protection in Hypoxic/Reoxygenated Cardiomyocytes

Background: Previous studies have shown that diazoxide can protect against myocardial ischemia-reperfusion injury (MIRI). The intranuclear hypoxia-inducible factor-1 (HIF-1)/hypoxia-response element (HRE) pathway has been shown to withstand cellular damage caused by MIRI. It remains unclear whether diazoxide post-conditioning is correlated with the HIF-1/HRE pathway in protective effect on cardiomyocytes.Methods: An isolated cardiomyocyte model of hypoxia-reoxygenation injury was established. Prior to reoxygenation, cardiomyocytes underwent post-conditioning treatment by diazoxide, and 5-hydroxydecanoate (5-HD), N-(2-mercaptopropionyl)-glycine (MPG), or dimethyloxallyl glycine (DMOG) followed by diazoxide. At the end of reoxygenation, ultrastructural morphology; mitochondrial membrane potential; interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), reactive oxygen species (ROS), and HIF-1α levels; and downstream gene mRNA and protein levels were analyzed to elucidate the protective mechanism of diazoxide post-conditioning.Results: Diazoxide post-conditioning enabled activation of the HIF-1/HRE pathway to induce myocardial protection. When the mitoKATP channel was inhibited and ROS cleared, the diazoxide effect was eliminated. DMOG was able to reverse the effect of ROS absence to restore the diazoxide effect. MitoKATP and ROS in the early reoxygenation phase were key to activation of the HIF-1/HRE pathway.Conclusion: Diazoxide post-conditioning promotes opening of the mitoKATP channel to generate a moderate ROS level that activates the HIF-1/HRE pathway and subsequently induces myocardial protection.

Del Nido versus HTK cardioplegia for myocardial protection during adult complex valve surgery: a retrospective study

Background Histidine-tryptophan-ketoglutarate (HTK) and del Nido (DN) cardioplegia are intracellular-type and extracellular-type solution respectively, both can provide a long period of myocardial protection with single-dose infusion, but studies comparing the two are rare for adult cardiac surgery. This study aims to evaluate whether DN is suitable for cardioplegia in complex and high-risk valve surgery with long-term cardiac ischemia when compared with HTK. Methods The perioperative records of adult patients infused with DN/HTK as a cardioplegic solution who underwent complex valve surgery with an expected myocardial ischaemic duration longer than 90 min between Oct 2018 and Oct 2019 were analysed retrospectively. Results Of the 160 patients who received DN/HTK and underwent complex valve surgery, we propensity matched 73 pairs. Both groups achieved satisfactory cardiac arrest effects, and no significant difference was found in their cTnI and CK-MB levels within 12 to 72 h postoperatively. The DN group had a higher rate of return to spontaneous rhythm (0.88 v 0.52, P < 0.001), a lower frequency of postoperative severe arrythmias (12% v 26%, P = 0.036), a higher postoperative stroke volume (65 v 59 ml, P = 0.011) and a higher cardiac output (6.0 v 4.9 L/min, P = 0.007) as evaluated by echocardiography, fewer transfusions and shorter ICU stays (both P < 0.05). The two groups had similar inotrope usage and similar incidences of low cardiac output, morbidities and mortality. Subgroup analysis showed that when the aortic clamping time was greater than 120 min, the advantages of DN were weakened. Conclusions DN can be safely applied to complex valve surgery, and it has a similar myocardial protection effect as HTK. Further prospective studies are required to verify these retrospective findings. Trial registration retrospectively registered.

Mediation of the Cardioprotective Effects of Mannitol Discovered, with Refutation of Common Protein Kinases

The osmodiuretic agent Mannitol exerts cardioprotection against ischemia and reperfusion (I/R) injury when applied as a pre- and/or postconditioning stimulus. Previously, we demonstrated that these properties are mediated via the activation of mitochondrial ATP-sensitive potassium (mKATP) channels. However, considering Mannitol remains in the extracellular compartment, the question arises as to which receptor and intracellular signaling cascades are involved in myocardial protection by the osmodiuretic substance. Protein kinase B (Akt) and G (PKG), as part of the reperfusion injury salvage kinase (RISK) and/or endothelial nitric oxide (eNOS)/PKG pathway, are two well-investigated intracellular targets conferring myocardial protection upstream of mitochondrial potassium channels. Adenosine receptor subtypes have been shown to trigger different cardioprotective pathways, for example, the reperfusion injury. Further, Mannitol induces an increased activation of the adenosine 1 receptor (A1R) in renal cells conferring its nephroprotective properties. Therefore, we investigated whether (1) Akt and PKG are possible signaling targets involved in Mannitol-induced conditioning upstream of the mKATP channel and/or whether (2) cardioprotection by Mannitol is mediated via activation of the A1R. All experiments were performed on male Wistar rats in vitro employing the Langendorff isolated heart perfusion technique with infarct size determination as the primary endpoint. To unravel possible protein kinase activation, Mannitol was applied in combination with the Akt (MK2206) or PKG (KT5823) inhibitor. In further groups, an A1R blocker (DPCPX) was given with or without Mannitol. Preconditioning with Mannitol (Man) significantly reduced the infarct size compared to the control group. Co-administration of the A1R blocker DPXPC fully abolished myocardial protection of Mannitol. Interestingly and in contrast to the initial hypothesis, neither administration of the Akt nor the PKG blocker had any impact on the cardioprotective properties of Mannitol-induced preconditioning. These results are quite unexpected and show that the protein kinases Akt and PKG—as possible targets of known protective signaling cascades—are not involved in Mannitol-induced preconditioning. However, the cardioprotective effects of Mannitol are mediated via the A1R.

Effects of Transcutaneous Electrical Nerve Stimulation on Myocardial Protection in Patients Undergoing Aortic Valve Replacement: A Randomized Clinical Trial

BackgroundTranscutaneous electrical nerve stimulation (TENS) has been found to have cardioprotective effects. However, its effects on adult cardiac surgery patients remain unclear. We investigated the effects of TENS on myocardial protection in patients undergoing aortic valve replacement surgery using cardiopulmonary bypass.MethodsThirty patients were randomized to receive TENS or sham in three different anesthetic states – pre-anesthesia, sevoflurane, or propofol (each n = 5). TENS was applied at the upper arm for 30 min. Sham treatment was provided without nerve stimulation. The primary outcome was the difference in myocardial infarct size following ischemia-reperfusion injury in rat hearts perfused with pre- and post-TENS dialysate from the patients using Langendorff perfusion system.ResultsThere were no differences in myocardial infarct size between pre- and post-treatment in any group (41.4 ± 4.3% vs. 36.7 ± 5.3%, 39.8 ± 7.3% vs. 27.8 ± 12.0%, and 41.6 ± 2.2% vs. 37.8 ± 7.6%; p = 0.080, 0.152, and 0.353 in the pre-anesthesia, sevoflurane, and propofol groups, respectively).ConclusionsTENS did not have a cardioprotective effect in patients undergoing aortic valve replacement surgery.Trial registrationThis study was registered at clinicaltrials.gov (NCT03859115, on March 1, 2019).

Cardioplegia between Evolution and Revolution: From Depolarized to Polarized Cardiac Arrest in Adult Cardiac Surgery

Despite current advances in perioperative care, intraoperative myocardial protection during cardiac surgery has not kept the same pace. High potassium cardioplegic solutions were introduced in the 1950s, and in the early 1960s they were soon recognized as harmful. Since that time, surgeons have minimized many of the adverse effects by lowering the temperature of the heart, lowering K+ concentration, reducing contact K+ time, changing the vehicle from a crystalloid solution to whole-blood, adding many pharmacological protectants and modifying reperfusion conditions. Despite these attempts, high potassium remains a suboptimalway to arrest the heart. We briefly review the historical advances and failures of finding alternatives to high potassium, the drawbacks of a prolonged depolarized membrane, altered Ca2+ intracellular circuits and heterogeneity in atrial-ventricular K+ repolarization during reanimation. Many of these untoward effects may be alleviated by a polarized membrane, and we will discuss the basic science and clinical experience from a number of institutions trialling different alternatives, and our institution with a non-depolarizing adenosine, lidocaine and magnesium (ALM) cardioplegia. The future of polarized arrest is an exciting one and may play an important role in treating the next generation of patients who are older, and sicker with multiple comorbidities and require more complex operations with prolonged cross-clamping times.

Del Nido vs St Thomas II Cardioplegia in Adult cardiac surgery: A prospective randomized trial of short-term outcomes

Aim/Objective: To assess short term clinical outcomes based on peri-operative troponin T levels (before start of surgery, 2 hours and 12 hours after coming of CPB) of adult patients undergoing cardiac surgery using the del Nido cardioplegia technique compared with st thomas conventional blood cardioplegia Material and method: This was a prospective randomized study with a sample size of 100, which included patients with valvular heart disease requiring single valve replacement in our center from February 2019 to march 2020. Simple randomization technique was used for dividing into two groups of 50 patients each and were given del-nido or st Thomas II cardioplegia accordingly. Perioperative TROPONIN levels, TEE ejection fraction, post-operative inotrope requirement was analyzed. Results: Total of 100 Patients were enrolled in the studie. Mean troponin T immediate post CPB was 559.76 in del nido and 531.14 in blood showing no significance (P 0.146) and 24hrs post-surgery where 290.08 and 231.6 respectively with no significant (0.089) difference. Other parameters like coming of pump need for defibrillation(p-0.629), change in EF measured pre and post CPB (p-0.678) did not show any signifance. Conclusion: Myocardial protection in open cardiac surgery is still evolving. Del-nido cardioplegia is a viable alternative to st thomas cardioplegia which has proven to be statically equivalent in myocardial protection in adult population also. Further studies are required to look into the long-term outcome of use of del nido and to expand the use of del-nido cardioplegia in other adult open cardiac surgeries.

An infant with suspected missed diagnosis of Williams syndrome failed weaning off CPB after surgical correction of pulmonary stenosis: a case report and literature review

Williams syndrome (WS) is a rare congenital developmental disorder caused by the deletion of between 26 and 28 genes on chromosome 7q11.23. For patients with WS, in view of the particularity of the supravalvular aortic stenosis, choosing appropriate arterial cannula, maintaining higher perfusion pressure as well as strengthening myocardial protection during cardiopulmonary bypass (CPB) is essential to the clinical outcome. Here, we report a child with pulmonary artery valvular stenosis who failed to wean off CPB because of malignant arrhythmias and cardiac insufficiency after surgical correction of pulmonary valvular stenosis. With the assistance of extracorporeal membrane oxygenation (ECMO), emergency cardiac catheterization revealed supravalvular aortic stenosis (SVAS), which suggests a suspected missed diagnosis of WS. Finally, under the support of ECMO, the cardiac function gradually returned to normal, and the child was discharged 23 days after surgery.