High-dose adenosine versus saline-induced cardioplegic arrest in coronary artery bypass grafting: A randomized double-blind clinical feasibility trial.

BACKGROUND AND OBJECTIVE: In this clinical trial, we evaluated if a short-acting nucleoside, adenosine, as a high-dose bolus injection with blood cardioplegia induces faster arrest and provides better myocardial performance in patients after bypass surgery for coronary artery disease. METHODS: Forty-three patients scheduled for elective or urgent coronary artery bypass grafting were prospectively recruited in two-arm 1:1 randomized parallel groups to either receive 20 mg of adenosine (in 21 patients) or saline (in 22 patients) into the aortic root during the first potassium-enriched blood cardioplegia infusion. The main outcomes of the study were ventricular myocardial performance measured with cardiac index, right ventricular stroke work index, and left ventricular stroke work index at predefined time points and time to asystole after a single bolus injection of adenosine. Conventional myocardial biomarkers were compared between the two groups at predefined time points as secondary endpoints. Electrocardiographic data and other ad hoc clinical outcomes were compared between the groups. RESULTS: Compared with saline, adenosine reduced the time to asystole (68 (95% confidence interval (95% CI) = 37-100) versus 150 (95% CI = 100-210) seconds, p = 0.005). With myocardial performance, the results were inconclusive, since right ventricular stroke work index recovered better in the adenosine group (p = 0.008), but there were no significant overall differences in cardiac index and left ventricular stroke work index between the groups. Only the post-cardiopulmonary bypass cardiac index was better in the adenosine group (2.3 (95% CI = 2.2-2.5) versus 2.1 (95% CI = 1.9-2.2) L/min/m2, p = 0.016). There were no significant differences between the groups in cardiac biomarker values. CONCLUSIONS: A high dose adenosine bolus at the beginning of the first cardioplegia infusion resulted in significantly faster asystole in coronary artery bypass grafting patients but enhanced only partially the ventricular performance.EudraCT number: 2014-001382-26. https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001382-26/FI.

The Effects of Amino Acids Enriched Del Nido Cardioplegia on Myocardial Leucocyte Accumulation and Ventricular Functions in Patients Undergoing Coronary Artery Bypass Grafting Surgery.

BACKGROUND: One of the main sources of ischemia/reperfusion injury (IRI) and release of free oxygen radicals (FORs) during extracorporeal circulation (ECC) during cardiac surgery is neutrophils. In this study, we investigated the potential effects of our modification of del Nido cardioplegia (mDNC) (amino acids enriched del Nido cardioplegia) on myocardial polymorphonuclear leucocyte (PMNL) accumulation. We also compared the effects of our mDND and classical del Nido cardiplegia (cDNC) on ventricular contractile functions in coronary artery bypass grafting (CABG) surgery. PATIENTS AND METHODS: Our study included 100 isolated CABG patients with similar characteristics, including age, gender, preoperative medications, diabetes, hypertension, and left ventricular ejection fraction (LVEF). The patients were divided into two groups. Amino acids supplemented del Nido cardioplegia (L-aspartate and L-glutamate at a dose of 13 milimol/L) in 50 patients (study group, G1). In the remaining 50 patients, we used a classical del Nido cardioplegic solution (cDNC) (control group, G2). Myocardial Tru-Cut biopsy from the right ventricle was taken before the institution of ECC and after weaning from ECC in all patients. Cardiac troponine-I (cTn-I), tumor necrosis factor-alpha (TNF-Alpha), Pro-Brain Natriuretic Peptide (Pro-BNP), and lactate levels were measured pre- and postoperatively. Invasive monitoring was performed to provide the left ventricular functions in both groups in the operating room and noted by a blinded anaesthesiologist. RESULTS: Five patients died post-surgery (5%) (two from SG and three from CG (P = .67), due to low cardiac output syndrome or multiorgan failure. At the postoperative period, cardiac output (CO) and stroke volume index (SVI) was higher in mDNC (mean ± SDS; 32.1 ± 7 versus 22.2 ± 6.9 mL/min/m² (P < .001). CI was significantly higher in mDNC after surgery (3.10 ± 0.76 versus 2.40 ± 0.30L/min/m² (P = .002). Ten patients (20%) in mDNC and 16 patients (32%) in cDNC required inotropic support (P < .001). The postoperative inotropic requirement was less in mDNC (6.1 ± 1.8 mg/kg versus 9.2 ± 1.9 mg/kg, P < .004). Blood gas analyses from the coronary sinus showed that myocardial acidosis was more severe in the control group [pH (0.10 ± 0.09 versus 0.054 ± 0.001; P = .34)]. Blood lactate levels were significantly high in the control group (1.01 ± 0.007 mmol/L versus 1.92 ± 0.35 mmol/L) (P = .22). No difference was found when compared with cardioplegia volume in the mDNC and cDNC groups (mDNC= 990.00 ± 385 mL in DNC = 960 ± 240 mL, P = .070). An aortic cross-clamp time in the mDNC and cDNC groups were 88.4 ± 8.9 min, and 93 ± 11 min, (P = .76), but cardiopulmonary bypass time was significantly low in mDNC (mDNC = 98.3 ± 22.5 min, DNC = 126 ± 19.5 min, P = .0020). TNF-Alpha and Pro-BNP levels in patients received mDNC were significantly low (P = .022). Postoperative cardiac enzyme levels (creatine kinase-MB and high sensitive troponin-I) were significantly low in the mDNC group (P = .0034). Myocardial biopsy results showed that myocardial PMNL accumulation was significantly high in the control group (P = .001). The amount of inotropic agent use was significantly high in the control group (P = .003). After weaning from ECC, the left ventricular stroke work index (LVSWI), cardiac index (CI), and heart rate (HR) were significantly high in the study group (P = .032; P = .002; P = .01). Postoperative blood and blood products requirements were significantly low in the mDNC group (P = .002). At pre-discharge echocardiography, the mDNC group demonstrated significantly higher ventricular ejection fraction (37.9 ± 4.3% and 29.7 ± 3.8%, respectively (P = .003). CONCLUSION: Our study findings show that glutamate-aspartate supplemented del Nido cardioplegia significantly decrease myocardial PMNL accumulation with reduced release of biochemical markers, including cardiac troponin-I, TNF-alpha, and Pro-Bnp. Our study results demonstrated that amino acids supplementation in del Nido cardioplegia has some advantages in CABG patients, including the decrease of perioperative myocardial infarction and increase significantly the left ventricular functions including ventricular SVI and CI.

Role of Zinc Supplementation on Ischemia/Reperfusion Injury in Various Organs.

Ischemia-reperfusion (I/R) injury is a serious condition which is associated with myocardial infarction, stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease, and sleep apnea and can lead to high morbidity and mortality. Salts of zinc (Zn) are commonly used by humans and have protective effects against gastric, renal, hepatic, muscle, myocardial, or neuronal ischemic injury. The present review evaluates molecular mechanisms underlying the protective effects of Zn supplement against I/R injury. Data of this review have been collected from the scientific articles published in databases such as Science Direct, Scopus, PubMed, and Scientific Information Database from 1991 to 2019. Zn supplementation increased the decreased parameters including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione (GSH), metallothionein (MT), protein sulfhydryl (P-SH), and nuclear factor-erythroid 2-related factor-2 (Nrf2) expression and decreased the increased elements such as endoplasmic reticulum (ER) stress, mitochondrial permeability transition pore (mPTP) opening, malondialdehyde (MDA), serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and microRNAs-(122 and 34a), apoptotic factors, and histopathological changes. Zn also increases phosphatidylinositol 3-kinase (PI3K)/Akt and glycogen synthase kinase-3ß (GSK-3ß) phosphorylation and preserves protein kinase C isoforms. It is suggested that Zn can be administered before elective surgeries for prevention of side effects of I/R injury.

Acute calcium channel blocker withdrawal-induced cardiac arrest.

Acute withdrawal of calcium channel blockers can lead to the so-called calcium channel blocker withdrawal phenomenon, in particular, when high dosages are used. In the case presented, inadequate drug substitution led to this phenomenon which resulted in a serious course of events. Careful monitoring the process of drug substitution with respect to equal therapeutic dosages is therefore a necessity, especially in vulnerable patients.

Our modified technique of combined antegrade-vein graft cardioplegia infusion versus conventional antegrade method in coronary artery bypass grafting. A randomized clinical trial.

BACKGROUND: To determine the efficacy of antegrade cardioplegia supplemented with venous graft perfusion in patients scheduled for coronary artery bypass grafting (CABG). METHODS: 223 consecutive patients scheduled for isolated CABG were randomized to receive either continuous crystalloid cardioplegia via vein grafts on completion of each distal anastomosis plus intermittent blood cardioplegia through aortic root (group 1, n = 110) or antegrade blood cardioplegia alone (group 2, n = 113). Two groups were similar in terms of preoperative patients' and procedural characteristics. The primary end-points were low output syndrome (LOS) variables. RESULTS: The inotrope and intra-aortic balloon pump demand during weaning were significantly higher in the control group (31.8% vs. 20%, p = 0.043 and 7.9% vs. 1.8%, p = 0.034 respectively). Postoperative level of potassium and arterial base excess (BE), stood in the normal range in both groups, despite significant inter-group differences. Peak serum level of myocardial injury biomarkers (CK, CK-MB, and cTnI) at 12 h following operation, though markedly greater in the group 2, did not reach the cut-off point of myocardial necrosis. Postoperative arrhythmia was more commonly encountered in the control group (p = 0.045). The duration of ventilation and hospital stay were considerably longer in the group 2. In a subgroup with LVEF<30%, the length of ICU stay was more prolonged in the control group, as well (p = 0.0145). The significant differences among groups regarding LOS parameters were more remarkable in the two high-risk subgroups (LVEF<30%, left main coronary stenosis). CONCLUSIONS: Given the better postoperative cardiac performance, we recommend this method to all CABG candidates, particularly in higher-risk patients.

A dose-response study of glutamate supplementation in isolated, perfused rat hearts undergoing ischaemia and cold cardioplegia.

OBJECTIVES: Several studies have reported superior post-cardioplegic recovery after glutamate supplementation. The optimum dose of glutamate supplementation is unknown. The purpose of this study was to find the optimal protective concentration of glutamate supplementation in a model of ischaemia/cardioplegia and reperfusion. METHODS: Isolated rat hearts (n = 77) were perfused with the Krebs-Henseleit buffer. After stabilization, the hearts were subjected to 25 min of normothermic ischaemia followed by a single 3-min infusion of cold (4-6 °C) St. Thomas' Hospital II cardioplegia and 87 min of cardioplegic ischaemic arrest and 60 min of reperfusion. Sodium-l-glutamate was added to the perfusate (control group had zero glutamate) in increasing concentrations (0.01, 0.1, 1, 10, 20, 30 and 100 mM) and given throughout perfusion. Corresponding concentrations were added to the cardioplegic solution. A balloon in the left ventricle inserted via the left atrium measured left ventricular pressures isometrically. Left ventricular developed pressure was calculated. Myocardial exchange of glucose and lactate was measured prior to ischaemia and during reperfusion. Myocardial content of glycogen and glutamate was measured at the end of reperfusion. RESULTS: During reperfusion left ventricular developed pressure increased (P < 0.0001) in groups supplemented with 0.1, 1.0, 10, 20 and 30 mM glutamate, whereas left ventricular end-diastolic pressure was attenuated (P = 0.008) when compared with the controls. No additional benefit on the continuous data left ventricular developed pressure and left ventricular end-diastolic pressure was observed with glutamate concentrations above 1 mM. Onset of LV pressure rise during the period of ischaemia was delayed by 100 mM of glutamate (P = 0.02). Myocardial content of glutamate was increased in a dose-related manner in Groups 10, 20, 30 and 100 compared with the control hearts (P < 0.0001). Glycogen was increased in the hearts supplemented with 100 mM of glutamate (P = 0.02). CONCLUSIONS: Even low concentrations of l-glutamate improved postischaemic and post-cardioplegic heart function and 1 mM seems to be optimal.

Intralipid Restoration of Myocardial Contractions Following Bupivacaine-Induced Asystole: Concentration- and Time-Dependence In Vitro.

BACKGROUND: The concentration- and time-response relationships of lipid emulsion (LE; Intralipid) on the recovery of myocardial contractility following bupivacaine (BPV)-induced asystole are poorly defined. METHODS: After achieving asystole by 500-µM BPV, varied concentrations of LE were applied to determine the recovery of stimulated contractile responses and contractions in the cardiac tissues of guinea pigs at a 1.2-Hz stimulation rate. These experiments were performed with LE in either a recirculating (2%-16%) or washout (nonrecirculating) condition (0.05%-12%) for 60 minutes. The effect of LE itself (0.05%-12%) was examined. Oxfenicine was used to evaluate the metabolic action of LE to reverse asystole. BPV concentrations in solution and myocardial tissues were measured. RESULTS: In the recirculation condition, partial recovery of contractile forces was observed for 60 minutes at 4%, 8%, and 12% LE. A contracture followed after exposure to 16% LE in some asystolic muscles. In the washout experiments, following asystole, LE (0.05%-12%) had no effect on the recovery time of the first and regular contractile responses. LE (0.1%-8%) restored contractility to baseline levels after 45 minutes; partial recovery was shown with lower (0.05%) and higher (12%) concentrations. Oxfenicine did not alter the recovery of contractile forces. Contractile depression was observed with 12% LE alone. Concentration-related reduction of tissue BPV concentration by LE was observed in both circulating conditions. CONCLUSIONS: LE induced time- and concentration-dependent recovery of stimulated myocardial contractions from BPV-induced asystole. The lipid uptake effect, along with other undefined mechanisms of LE, seems to contribute to the recovery of contractile function; however, the LE effect on myocardial metabolism is less likely involved at this concentration (500 µM) of BPV.

Danshen-Enhanced Cardioprotective Effect of Cardioplegia on Ischemia Reperfusion Injury in a Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Model.

Myocardial ischemia-reperfusion (I/R) injury is unavoidable during cardioplegic arrest and open-heart surgery. Danshen is one of the most popular traditional herbal medicines in China, which has entered the Food and Drug Administration-approved phase III clinical trial. This study was aimed to develop a human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) model to mimic I/R injury and evaluate the cardioprotective effect of regular cardioplegic solution with Danshen. hiPSC-CMs were cultured with the crystalloid cardioplegic solution (Thomas group) and Thomas solution with 2 or 10 µg/mL Danshen (Thomas plus Danshen groups). The cells under normoxic culture condition served as baseline group. Then, the cells were placed in a modular incubator chamber. After 45 min hypoxia and 3 h reoxygenation, hiPSC-CMs subjected to hypoxia/reoxygenation resulted in a sharp increase of reactive oxygen species (ROS) content in Thomas group versus baseline group. Compared with the Thomas group, ROS accumulation was significant suppressed in Thomas plus Danshen groups, which might result from elevating the content of glutathione and enhanced activities of superoxide dismutase and glutathione peroxidase. The enhanced L-type Ca2+ current in hiPSC-CMs after I/R injury was also significantly decreased by Danshen, and meanwhile intracellular Ca2+ level was reduced and calcium overload was suppressed. Thomas plus Danshen groups also presented less irregular transients and lower apoptosis rates. As a result, Danshen could improve antioxidant and calcium handling in cardiomyocytes during I/R and lead to reduced arrhythmia events and apoptosis rates. hiPSC-CMs model offered a platform for the future translational study of the cardioplegia.

DHA-supplemented diet increases the survival of rats following asphyxia-induced cardiac arrest and cardiopulmonary bypass resuscitation.

Accumulating evidence illustrates the beneficial effects of dietary docosahexaenoic acid (DHA) on cardiovascular diseases. However, its effects on cardiac arrest (CA) remain controversial in epidemiological studies and have not been reported in controlled animal studies. Here, we examined whether dietary DHA can improve survival, the most important endpoint in CA. Male Sprague-Dawley rats were randomized into two groups and received either a control diet or a DHA-supplemented diet for 7-8 weeks. Rats were then subjected to 20 min asphyxia-induced cardiac arrest followed by 30 min cardiopulmonary bypass resuscitation. Rat survival was monitored for additional 3.5 h following resuscitation. In the control group, 1 of 9 rats survived for 4 h, whereas 6 of 9 rats survived in the DHA-treated group. Surviving rats in the DHA-treated group displayed moderately improved hemodynamics compared to rats in the control group 1 h after the start of resuscitation. Rats in the control group showed no sign of brain function whereas rats in the DHA-treated group had recurrent seizures and spontaneous respiration, suggesting dietary DHA also protects the brain. Overall, our study shows that dietary DHA significantly improves rat survival following 20 min of severe CA.

Novel cardioprotection strategies for the aged heart: evidence from pre-clinical studies.

The incidence of cardiovascular disease is rising as the population ages. This has led to an increase in the need to perform cardiac surgery in older patients. However, aged hearts are particularly susceptible to reperfusion injury following periods of myocardial ischaemia that occur during cardiac surgery. Indeed, older adults experience myocardial dysfunction and reduced survival post-surgery compared to younger people and certain groups, including older women and frail older adults, are at particular risk. This highlights the need to design cardioprotective strategies specifically for the ageing heart. Cardioprotection during surgery is often accomplished by perfusing the heart with chemical arresting agents, known as cardioplegic solutions. New protective strategies have been developed and tested in animal models, where cardioplegic solutions have been modified by changing their temperature, chemical components and/or the frequency of delivery. In addition, drugs designed to activate cardioprotective mechanisms or to inhibit mechanisms involved in injury have been added to improve the efficacy of these solutions. However, most experimental studies have developed and optimized cardioplegic solutions in hearts from younger male animals. This review discusses pre-clinical models used to optimize cardioplegic solutions, with an emphasis on the few studies that have used hearts from older animals. Pharmacologic agents that have been shown to enhance the benefits of cardioplegia in younger hearts and could, in theory, protect vulnerable older hearts are also considered. We emphasize the need to conduct studies in frail older animals of both sexes to facilitate translation of laboratory-based observations to the clinic.

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.

Pilot Trial of Intravenous Lipid Emulsion Treatment for Severe Nifedipine-Induced Shock.

Animal studies and human case reports show promise in using lipid rescue to treat refractory calcium channel antagonist toxicity. However, the majority of research and clinical experience has focused on non-dihydropyridine agents. Thus, we sought to investigate the value of lipid emulsion (ILE) therapy for dihydropyridine-induced shock. This IACUC-approved study utilized seven swine that were sedated with alpha-chloralose, mechanically ventilated, and instrumented for drug delivery and hemodynamic measures. After stabilization and basal measures, nifedipine (0.01875 mg/kg/min) was infused until imminent cardiac arrest (seizure, end tidal CO2 < 10 mmHg, bradydysrhythmia, or pulseless electrical activity). Animals then received a 7 mL/kg bolus of 20% lipid emulsion via central catheter. Lipid circulation was visually confirmed by the presence of fat in peripheral arterial blood. Hemodynamics were continuously monitored until 10 min after lipid bolus. Surviving animals were euthanized. Pre- and post-lipid treatment parameters were analyzed using the Wilxocon signed rank test (p <0.05 significant). Nifedipine toxicity was characterized by vasodilatory hypotension, impaired vascular contractility, and tachycardia with terminal bradycardia. The median time to imminent cardiac arrest from start of nifedipine infusion was 218 min. Lipid treatment did not improve hemodynamics or restore circulation in any animal. There was no benefit from lipid rescue in this model of nifedipine toxicity. Further study of ILE for dihydropyridine toxicity is warranted but initial animal model results are not promising.

Cardiopulmonary Bypass Strategy for a Cyanotic Child With Hemoglobin SC Disease.

Hemoglobin SC (HbSC) disease is a hemoglobinopathy that may produce sickling under conditions of hypoxemia, dehydration, and acidosis. We present a case of HbSC disease and tricuspid atresia, type IB. We describe management by cardiopulmonary bypass CPB using exchange transfusion at initiation of bypass and fractionation of collected blood, allowing platelet and plasma apheresis, as an option for patients unable to undergo this procedure off pump.

Adding Emulsified Isoflurane to Cardioplegia Solution Produces Cardiac Protection in a Dog Cardiopulmonary Bypass Model.

This study investigated whether caridoplegia solution with Emulsified Isoflurane (EI) could improve cardiaoprotection in a dog CPB model of great similarity to clinical settings. Adult dogs were randomly assigned to receive one of the following cardioplegia solutions: St. Thomas with EI (group ST+EI), St. Thomas with 30% Intralipid (group ST+EL) and St. Thomas alone (group ST). The aorta was cross-clamped for two hours followed by reperfusion for another two hours, during which cardiac output was measured and dosages of positive inotropic agent to maintain normal hemodynamics were recorded. Serum level of cardiac troponin I (cTnI) and CK-MB were measured. Deletion of cardiac mitochondrial DNA was examined at the end of reperfusion. Compared with ST, ST+EI decreased the requirement of dopamine support while animals receiving ST+EI had a significantly larger cardiac output. ST+EI reduced post-CPB release of cTnI and CK-MB. Mitochondrial DNA loss was observed in only one of the tested animals from group ST+EI while it was seen in all the tested animals from group ST+EL and ST. Addition of emulsified isoflurane into cardioplegia solution protects against myocardial ischemia reperfusion injury. This protective effect might be mediated by preserving mitochondrial ultrastructure and DNA integrity.

[Protective Effect of Shenfu Injection on Postresuscitation Lung Injury in a Porcine Model of As- physia-induced Cardiac Arrest].

Objective To observe the protective effect of Shenfu Injection ( SFI) on post-resusci- tation lung injury in a porcine model of asphyxia-induced cardiac arrest. Methods Thirty-four anaesthe- tized Wuzhi Mountain inbred miniature piglets of both sexes were subjected to asphyxia by intubation clip- ping, followed by standard cardiopulmonary resuscitation. Eighteen successfully resuscitated pigs [with recovery of return of spontaneous circulation ( ROSC) ] were divided into the SFI group and the normal saline (NS) group according to random digit table, 9 in each group. SFI at 0. 24 mg/min was intravenously pumped to piglets in the SFI group immediately from ROSC to 6 h after resuscitation, while NS at 0. 24 mg/min was intravenously pumped to piglets in the NS group immediately from ROSC to 6 h after resusci- tation. Oxygen metabolism, respiratory mechanics indices including oxygenation index (ΟI) , respiration index ( RI) , oxygen delivery ( DO2), oxygen consumption ( VO2), oxygen extraction ratio (Ο2 ER), PaCO2, lactic acid (LAC) were detected using blood gas analyzer at basic state, immediately after ROSC, 15 and 30 min, 1, 2, 4, and 6 h after ROSC. Dynamic lung compliance (Cdyn) , airway resistance (Raw), external vascular lung water index (EVLWI) , pulmonary vascular permeability index (PVPI) were monitored at each aforesaid time point. Activities of Na+-K +-ATPase and Ca² +-ATPase, contents of SOD and MDA, concentrations of TNF-α, IFN-γ, and IL-4 were determined using ELISA.IFN-γ/IL-4 ratio was calculated. Cell apoptosis was detected using TUNEL and apoptotic index (Al) calculated. Protein concentrations of Bcl-2 and Bax were detected using immunohistochemical assay, and Bax/Bcl-2 ratio calculated. Caspase-3 protein was quantitatively detected using Western blot. Results The survival rate was 88. 9% (8/9) in the SFI group and 66. 7% (6/9) in the NS group at 6 h after ROSC. The mean survival time was (5. 77 ±0. 71) h in the SFI group, longer than that in the NS group [ (4. 77 ±0. 59) h, P >0. 05]. Compared with the basic state, 01 and Cdyn obviously decreased immediately after ROSC (P <0. 05) ; RI, DO2, VΟ2, O2ER, Raw, EVLWI, PVPI, PaCO2, and LAC obviously increased immediately after ROSC (P<0. 05). All indices were recovered as time went by. Compared with the NS group, ΟI, Cdyn, DO2, VΟ2, and Ο2 ER at each time points after ROSC were significantly higher in the SFI group than in the NS group (P <0. 05, P <0. 01); RI, Raw, EVLWI, PVPI, PaCO2, and LAC were significantly lower in the SFI group than in the NS group (P <0. 05, P <0. 01 ). Compared with the NS group, activities of Na'-K '-AT- Pase and Ca² +-ATPase, contents of SOD, level of IFN-γ, IFN-γ/IL-4 ratio, concentrations of Bcl-2 in- creased more; MDA, TNF-α, IL-4 level, Al, Bax/Bcl-2 ratio, Caspase-3 protein level decreased more (P <0. 05, P <0. 01). Conclusion SFI could improve cell energy metabolism, enhance antioxidant ca- pacity of cells, reduce the release of inflammatory mediators, regulate the Thl/Th2 balance, and attenu- ate cell apoptosis of lung tissue, thereby protecting post-resuscitation lung injury.

Propofol cardioplegia: A single-center, placebo-controlled, randomized controlled trial.

OBJECTIVES: Cardiac surgery with cardiopulmonary bypass and cardioplegic arrest is an effective treatment for coronary artery and aortic valve diseases. However, the myocardium sustains reperfusion injury after ischemic cardioplegic arrest. Our objective was to assess the benefits of supplementing cardioplegia solution with the general anesthetic propofol in patients undergoing either coronary artery bypass grafting (CABG) or aortic valve replacement (AVR). METHODS: A single-center, double-blind randomized controlled trial was carried out to compare cardioplegia solution supplemented with propofol (concentration 6 µg/mL) versus intralipid (placebo). The primary outcome was cardiac troponin T release over the first 48 hours after surgery. RESULTS: We recruited 101 participants (51 in the propofol group, 50 in the intralipid group); 61 underwent CABG and 40 underwent AVR. All participants were followed to 3 months. Cardiac troponin T release was on average 15% lower with propofol supplementation (geometric mean ratio, 0.85; 95% confidence interval [CI], 0.73-1.01; P = .051). There were no differences for CABG participants but propofol-supplemented participants undergoing AVR had poorer postoperative renal function (geometric mean ratio, 1.071; 95% CI, 1.019-1.125; P = .007), with a trend toward longer intensive care stay (median, 89.5 vs 47.0 hours; hazard ratio, 0.58; 95% CI, 0.31-1.09; P = .09) and fewer with perfect health (based on the EQ-5D health utility index) at 3 months (odds ratio, 0.26; 95% CI, 0.06-1.05; P = .058) compared with the intralipid group. Safety profiles were similar. There were no deaths. CONCLUSIONS: Propofol supplementation in cardioplegia appears to be cardioprotective. Its influence on early clinical outcomes may differ between CABG and AVR surgery. A larger, multicenter study is needed to confirm or refute these suggestions.

Custodiol-N, the novel cardioplegic solution reduces ischemia/reperfusion injury after cardiopulmonary bypass.

BACKGROUNDS: On the basis of Custodiol preservation and cardioplegic solution a novel cardioplegic solution was developed to improve the postischemic cardiac and endothelial function. In this study, we investigated whether its reduced cytotoxicity and its ability to reduce reactive oxygen species generation during hypoxic condition have beneficial effects in a clinically relevant canine model of CPB. METHODS: 12 dogs underwent cardiopulmonary bypass with 60 minutes of hypothermic cardiac arrest. Dogs were divided into 2 groups: Custodiol (n = 6) and Custodiol-N (n = 6) (addition of L-arginin, N-α-acetyl-L-histidine and iron-chelators: deferoxamine and LK-614). Left ventricular hemodynamic variables were measured by a combined pressure-volume conductance catheter at baseline and after 60 minutes of reperfusion. Coronary blood flow, myocardial ATP content, plasma nitrate/nitrite and plasma myeloperoxidase levels were also determined. RESULTS: The use of Custodiol-N cardioplegic solution improved coronary blood flow (58 ± 7 ml/min vs. 26 ± 3 ml/min) and effectively prevented cardiac dysfunction after cardiac arrest. In addition, the myocardial ATP content (12,8 ± 1,0 µmol/g dry weight vs. 9,5 ± 1,5 µmol/g dry weight) and plasma nitrite (1,1 ± 0,3 ng/ml vs. 0,5 ± 0,2 ng/ml) were significantly higher after application of the new cardioplegic solution. Furthermore, plasma myeloperoxidase level (3,4 ± 0,4 ng/ml vs. 4,3 ± 2,2 ng/ml) significantly decreased in Custodiol-N group. CONCLUSIONS: The new HTK cardioplegic solution (Custodiol-N) improved myocardial and endothelial function after cardiopulmonary bypass with hypothermic cardiac arrest. The observed protective effects imply that the Custodiol-N could be the next generation cardioplegic solution in the protection against ischemia-reperfusion injury in cardiac surgery.

Outcomes of isolated reoperative coronary artery bypass grafting in elderly patients.

OBJECTIVE: Primary coronary artery bypass grafting (CABG) is performed routinely in elderly patients with good results. However, the risk profile and outcomes of reoperative CABG in elderly patients are not well defined. Our purpose was to study the risk profile and hospital outcomes of isolated reoperative CABG in elderly patients (75 years and older) compared to isolated primary CABG in the same age group. METHODS: Between January 1990 and December 2010, 3483 elderly patients (age ≥ 75 years) underwent isolated CABG at our institution. Of these, 129 (3.7%) underwent reoperative CABG. Data were prospectively collected in a computerized database. Independent predictors of hospital mortality were determined by multivariable logistic regression. RESULTS: Hospital mortality was 3.2% and 8.5% (p < 0.001) in elderly patients in the primary group and reoperative group, respectively. Perioperative myocardial infarction (MI) occurred in 2.9% and 8.5% (p < 0.001), and low cardiac output syndrome (LCOS) occurred in 6.2% and 20.9% (p < 0.001) of patients in the primary group and reoperative group, respectively. The prevalence of perioperative MI was threefold higher in elderly patients undergoing reoperative CABG with antegrade cardioplegia alone (11.5%) compared to combined antegrade/retrograde cardioplegia (3.9%). Additionally, mortality was higher in elderly patients undergoing reoperative surgery with use of antegrade cardioplegia alone (12.8% vs. 2%, p = 0.03). Combined use of antegrade and retrograde cardioplegia was independently protective from mortality in the reoperative group (OR = 0.10; p = 0.03). CONCLUSION: Elderly patients undergoing reoperative CABG have an approximately threefold increase in the risk of mortality compared to elderly patients undergoing primary CABG. The higher risk of mortality is primarily driven by a higher rate of perioperative MI and LCOS. Combined use of antegrade and retrograde cardioplegia was associated with lower perioperative MI and lower mortality.

Initial large-dose administration of modified St. Thomas' solution.

BACKGROUND: We introduced an initial large dose of modified St. Thomas' Hospital cardioplegic solution with the aim of providing both myocardial protection as well as a smooth intraoperative process. METHODS: In 90 cases of isolated aortic valve replacement, we used the modified technique of cardioplegia in 45 (group S) and conventional administration of glucose-insulin-potassium solution in 45 (group G). The patients were selected at random. In group S, we added 4 mEq of potassium to the original St. Thomas' Hospital solution and administered 30 mL·kg(-1) as an initial dose. The temperature was decreased to 2. RESULTS: The mean of reperfusion time after declamping in group S was significantly shorter (16.7 ± 6.4 vs. 21.5 ± 10.0 min; p = 0.007). The average of postoperative maximum creatine kinase-MB was significantly lower in group S (25.6 ± 9.5 vs. 40.6 ± 37.2 IU·L(-1); p = 0.014). On multivariate analysis, use of the modified cardioplegia and aortic crossclamp time were significantly associated with creatine kinase-MB level and reperfusion time after declamping. CONCLUSIONS: This modified technique was an acceptable option that provided a bloodless operative field and avoided multiple cardioplegic administrations.

Retrograde cardioplegia revisited: open technique for long aortic cross clamping.

BACKGROUND: The efficacy of retrograde cardioplegia for myocardial protection is still controversial. In our institution, we exclusively use intermittent administration of tepid, undiluted blood supplemented with potassium and magnesium for the cases with aortic insufficiency, requiring aortotomy, or undergoing mitral valve repair. In using this retrograde technique, we make a point of cannulating a retrograde perfusion catheter under direct vision following right atriotomy. The purpose of this retrospective study is to evaluate the clinical outcome of using this technique. METHODS: This study comprises 49 patients who underwent elective valve surgery using direct-vision retrograde cardioplegia exclusively, requiring more than 3h aortic cross-clamping. Their clinical outcome was reviewed retrospectively. RESULTS: There was no hospital mortality in this study. No patient was noted to have evidence of mediastinitis, myocardial infarction, or cerebral complications in the postoperative period. The case requiring the longest aortic cross-clamping time (380 min) survived the operation without the use of intra-aortic balloon pumping or percutaneous cardiopulmonary support, and the postoperative course was uneventful. CONCLUSIONS: Our result suggests that direct-vision retrograde cardioplegia is a safe and effective method of cardioplegia delivery, and provides a longer period of myocardial protection than previously thought.