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Atrial nitroso-redox balance and refractoriness following on-pump cardiac surgery: a randomized trial of atorvastatin.
Jayaram, R, Jones, M, Reilly, S, Crabtree, MJ, Pal, N, Goodfellow, N, Nahar, K, Simon, J, Carnicer, R, DeSilva, R, et al
Cardiovascular research. 2022;(1):184-195
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Abstract
AIMS: Systemic inflammation and increased activity of atrial NOX2-containing NADPH oxidases have been associated with the new onset of atrial fibrillation (AF) after cardiac surgery. In addition to lowering LDL-cholesterol, statins exert rapid anti-inflammatory and antioxidant effects, the clinical significance of which remains controversial. METHODS AND RESULTS We first assessed the impact of cardiac surgery and cardiopulmonary bypass (CPB) on atrial nitroso-redox balance by measuring NO synthase (NOS) and GTP cyclohydrolase-1 (GCH-1) activity, biopterin content, and superoxide production in paired samples of the right atrial appendage obtained before (PRE) and after CPB and reperfusion (POST) in 116 patients. The effect of perioperative treatment with atorvastatin (80 mg once daily) on these parameters, blood biomarkers, and the post-operative atrial effective refractory period (AERP) was then evaluated in a randomized, double-blind, placebo-controlled study in 80 patients undergoing cardiac surgery on CPB. CPB and reperfusion led to a significant increase in atrial superoxide production (74% CI 71-76%, n = 46 paired samples, P < 0.0001) and a reduction in atrial tetrahydrobiopterin (BH4) (34% CI 33-35%, n = 36 paired samples, P < 0.01), and in GCH-1 (56% CI 55-58%, n = 26 paired samples, P < 0.001) and NOS activity (58% CI 52-67%, n = 20 paired samples, P < 0.001). Perioperative atorvastatin treatment prevented the effect of CPB and reperfusion on all parameters but had no significant effect on the postoperative right AERP, troponin release, or NT-proBNP after cardiac surgery. CONCLUSION Perioperative statin therapy prevents post-reperfusion atrial nitroso-redox imbalance in patients undergoing on-pump cardiac surgery but has no significant impact on postoperative atrial refractoriness, perioperative myocardial injury, or markers of postoperative LV function. CLINICAL TRIAL REGISTRATION https://clinicaltrials.gov/ct2/show/NCT01780740.
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Effects of inorganic nitrate on ischaemia-reperfusion injury after coronary artery bypass surgery: a randomised controlled trial.
Eriksson, KE, Eidhagen, F, Liska, J, Franco-Cereceda, A, Lundberg, JO, Weitzberg, E
British journal of anaesthesia. 2021;(4):547-555
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Abstract
BACKGROUND Nitric oxide (NO) is an important signalling molecule in the cardiovascular system with protective properties in ischaemia-reperfusion injury. Inorganic nitrate, an oxidation product of endogenous NO production and a constituent in our diet, can be recycled back to bioactive NO. We investigated if preoperative administration of inorganic nitrate could reduce troponin T release and other plasma markers of injury to the heart, liver, kidney, and brain in patients undergoing cardiac surgery. METHODS This single-centre, randomised, double-blind, placebo-controlled trial included 82 patients undergoing coronary artery bypass surgery with cardiopulmonary bypass. Oral sodium nitrate (700 mg×2) or placebo (NaCl) were administered before surgery. Biomarkers of ischaemia-reperfusion injury and plasma nitrate and nitrite were collected before and up to 72 h after surgery. Troponin T release was our predefined primary endpoint and biomarkers of renal, liver, and brain injury were secondary endpoints. RESULTS Plasma concentrations of nitrate and nitrite were elevated in nitrate-treated patients compared with placebo. The 72-h release of troponin T did not differ between groups. Other plasma biomarkers of organ injury were also similar between groups. Blood loss was not a predefined outcome parameter, but perioperative bleeding was 18% less in nitrate-treated patients compared with controls. CONCLUSION Preoperative administration of inorganic nitrate did not influence troponin T release or other plasma biomarkers of organ injury in cardiac surgery. CLINICAL TRIAL REGISTRATION NCT01348971.
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Safety and Effectiveness of Del Nido Cardioplegia in Comparison to Blood-Based St. Thomas Cardioplegia in Congenital Heart Surgeries: A Prospective Randomized Controlled Study.
Haranal, M, Chin, HC, Sivalingam, S, Raja, N, Mohammad Shaffie, MS, Namasiwayam, TK, Fadleen, M, Fakhri, N
World journal for pediatric & congenital heart surgery. 2020;(6):720-726
Abstract
BACKGROUND To compare the safety and effectiveness of del Nido cardioplegia with blood-based St Thomas Hospital (BSTH) cardioplegia in myocardial protection in congenital heart surgery. METHODS It is a prospective, open-labeled, randomized controlled study conducted at National Heart Institute, Kuala Lumpur from July 2018 to July 2019. All patients with simple and complex congenital heart diseases (CHD) with good left ventricular function (left ventricular ejection fraction [LVEF] >50%) were included while those with LVEF <50% were excluded. A total of 100 patients were randomized into two groups of 50 each receiving either del Nido or BSTH cardioplegia. Primary end points were the spontaneous return of activity following aortic cross-clamp release and ventricular function between two groups. Secondary end point was myocardial injury as assessed by troponin T levels. RESULTS Cardiopulmonary bypass and aortic cross-clamp time, return of spontaneous cardiac activity following the aortic cross-clamp release, the duration of mechanical ventilation, and intensive care unit stay were comparable between two groups. Statistically significant difference was seen in the amount and number of cardioplegia doses delivered (P < .001). The hemodilution was significantly less in the del Nido complex CHD group compared to BSTH cardioplegia (P = .001) but no difference in blood usage (P = .36). The myocardial injury was lesser (lower troponin T release) with del Nido compared to BSTH cardioplegia (P = .6). CONCLUSION Our study showed that both del Nido and BSTH cardioplegia are comparable in terms of myocardial protection. However, single, less frequent, and lesser volume of del Nido cardioplegia makes it more suitable for complex repair.
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Vitamin D Treatment Attenuates Heart Apoptosis After Coronary Artery Bypass Surgery: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.
Tasdighi, E, Hekmat, M, Beheshti, M, Baghaei, R, Mirhosseini, SM, Torbati, P, Pourmotahari, F, Foroughi, M
Journal of cardiovascular pharmacology and therapeutics. 2020;(4):338-345
Abstract
BACKGROUND Vitamin D plays an important role in immune system and in the regulation of inflammatory cytokines. Coronary artery bypass graft (CABG) with cardiopulmonary bypass (CPB) is associated with an extensive inflammatory response. The aim of this study is to examine the effect of vitamin D treatment on the apoptosis and inflammatory changes developed after CABG. METHODS This trial was conducted on 70 patients undergoing CABG with CPB. Patients were randomly administered either in placebo or in the group of orally consuming 150 000 IU vitamin D daily for 3 consecutive days before surgery. The right atrium sample was taken to assess caspases 2, 3, and 7 activity using immunohistochemistry method. The serum level of interleukin-10 (IL-10) and insulin-like growth factor 1 (IGF-1) were compared at intervals. RESULTS The average number of positive cells for caspases 2 and 3 were less in vitamin D group (P = .006 and P < .001, respectively). There was an increase in serum levels of IL-10 after 3 days from vitamin D treatment before surgery (vitamin D group = 4.4 ± 4.9 ng/mL and control group = 1 ± 0.5 ng/mL, P = .001). After operation, IL-10 increased in both groups, higher level in vitamin D group (P < .001). The comparison of serum IGF-1 showed significant difference after 3 days (P = .006) and remained higher in vitamin D group after CPB (P < .001). CONCLUSIONS These findings suggest the apoptosis rate after CPB can be reduced by vitamin D. Vitamin D treatment may improve the inflammatory status before and after surgery. Further studies are needed to confirm the antiapoptotic property of vitamin D and clinical implication.
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Zero-balance ultrafiltration of the priming blood modifies the priming components and improves the clinical outcome in infants undergoing cardiopulmonary bypass: A randomized controlled trial.
Gholampour Dehaki, M, Niknam, S, Bakhshandeh, H, Azarfarin, R
Artificial organs. 2020;(3):288-295
Abstract
Cardiopulmonary bypass (CPB) requirement in infants presents a unique challenge because of the large prime volume-to-blood volume ratio. Packed red blood cells (PRBCs) tend to deteriorate with long-term storage owing to their unphysiological composition and osmolality. Given that blood priming is inevitable in neonates, it is suggested that the metabolic load and osmolality are diminished before CPB initiation. We conducted the present study to test the hypothesis that the zero-balance ultrafiltration (Z-BUF) of the priming blood with 0.45% saline might be sufficient for modifying the metabolic load and osmolality and, thus, achieving a physiological state. Sixty infants with a weight below 10 kg undergoing CPB were randomly assigned either to a control group or to a Z-BUF group and the Z-BUF of the priming blood was performed in the latter group. Electrolytes and osmolality were measured in the priming blood. The bleeding volume, the blood transfusion rate, the length of mechanical ventilation, the length of stay in the intensive care unit (ICU), the body temperature, and renal biomarkers were compared between the 2 groups. The osmolality and the levels of potassium, sodium, glucose, chloride, and lactate in the priming blood were significantly decreased after Z-BUF (P < .01). The Z-BUF group showed significant reductions in postoperative blood loss; postoperative blood transfusion; time to extubation; the length of stay in the ICU; the levels of lactate, sodium, and blood urea nitrogen at 24 hours postoperatively and the body temperature at 18 hours postoperatively (P < .05). However, no statistically significant differences were found between the 2 groups regarding the body temperature and the levels of serum creatinine and blood urea nitrogen after admission to the ICU. The results of the present study demonstrated that the Z-BUF of the priming blood could be a useful strategy in infants undergoing CPB insofar as it significantly modified the composition of the priming blood and improved the clinical outcome among our patients.
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Dextran- Versus Crystalloid-Based Prime in Cardiac Surgery: A Prospective Randomized Pilot Study.
Barbu, M, Kolsrud, O, Ricksten, SE, Dellgren, G, Zetterberg, H, Blennow, K, Björk, K, Thorén, A, Hansson, C, Jeppsson, A
The Annals of thoracic surgery. 2020;(5):1541-1547
Abstract
BACKGROUND The optimum priming fluid for the cardiopulmonary bypass (CPB) circuit is still debated. We compared a new hyperoncotic priming solution containing dextran 40, which has an electrolyte composition that mimics extracellular fluid, with a standard crystalloid-based prime. METHODS Eighty cardiac surgery patients were included in this double-blind, randomized, single-center study. Patients were randomized to either a dextran-based prime or a crystalloid prime containing Ringer's acetate and mannitol. The primary end point was colloid oncotic pressure in serum during CPB. Secondary end points included fluid balance, bleeding and transfusion requirements, pulmonary function, hemolysis, systemic inflammation, and markers of renal, hepatic, myocardial, and brain injury. Blood samples were collected before, during, and after CPB. RESULTS Colloid oncotic pressure was higher in the dextran group than in the crystalloid prime group during CPB (18.8 ± 2.9 versus 16.4 ± 2.9 mm Hg; P < .001) and 10 minutes after CPB (19.2 ± 2.7 versus 16.8 ± 2.9 mm Hg; P < .001). Patients in the dextran group required less intravenous fluid during CPB (1090 ± 499 versus 1437 ± 543 mL; P = .004) and net fluid balance was less positive 12 hours after surgery (1431 ± 741 versus 1901 ± 922 mL; P = .014). Plasma-free hemoglobin was significantly lower in the dextran group 2 hours after CPB (0.18 ± 0.11 versus 0.41 ± 0.33; P = .001). There were no significant differences in bleeding, transfusion requirements, organ function, systemic inflammation, or brain and myocardial injury markers between groups at any time point. CONCLUSIONS Our results suggest that a hyperoncotic dextran-based priming solution preserves intraoperative colloid oncotic pressure compared with crystalloid prime. Larger studies with clinically valid end points are necessary to evaluate hyperoncotic prime solutions further.
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Zero-Balance Ultrafiltration of Priming Blood Attenuates Procalcitonin and Improves the Respiratory Function in Infants After Cardiopulmonary Bypass: A Randomized Controlled Trial.
Gholampour Dehaki, M, Niknam, S, Azarfarin, R, Bakhshandeh, H, Mahdavi, M
Artificial organs. 2019;(2):167-172
Abstract
Blood priming is needed for cardiopulmonary bypass (CPB) in neonates and infants to avoid exceeding hemodilution; however, transfusion-related inflammation affects post-CPB outcomes in infant open-heart surgery. Procalcitonin, a newly detected inflammatory moderator and a sensitive parameter for predicting pulmonary dysfunction secondary to CPB, rises after CPB. We hypothesized that the hemofiltration of priming blood before CPB might decrease inflammatory mediators in the blood and post-CPB inflammatory replications, thereby improving the respiratory function after CPB in infants. Sixty infants with a weight below 10 kg were divided randomly into two equal groups of CPB with the zero-balance ultrafiltration (Z-BUF) of priming blood and CPB without it. The procalcitonin level was measured before anesthesia, after admission to the intensive care unit (ICU), and 24 h afterward. The respiratory index and pulmonary compliance were measured after anesthesia, at the end of CPB, and 2 h after admission to the ICU. Additionally, time to extubation was recorded. The Z-BUF of priming blood maintained electrolytes within a physiologic level, and procalcitonin had a slighter rise in the Z-BUF Group at 24 h after admission to the ICU (P = 0.05). The respiratory index was decreased in the Z-BUF Group, but the difference with the control group did not reach statistical significance (P > 0.05). The change in pulmonary compliance was significantly increased in the cyanotic patients in the intervention group, but there was no significant difference between the two groups. The time to extubation and the ICU stay were shorter in the Z-BUF Group (P < 0.05). A positive correlation was found between the peak procalcitonin concentration and the time to extubation directly and pulmonary compliance reversely. These results suggest that the Z-BUF of priming blood may have some beneficial clinical effects such as improved respiratory function and attenuated procalcitonin.
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Nitric oxide provides myocardial protection when added to the cardiopulmonary bypass circuit during cardiac surgery: Randomized trial.
Kamenshchikov, NO, Mandel, IA, Podoksenov, YK, Svirko, YS, Lomivorotov, VV, Mikheev, SL, Kozlov, BN, Shipulin, VM, Nenakhova, AA, Anfinogenova, YJ
The Journal of thoracic and cardiovascular surgery. 2019;(6):2328-2336.e1
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Abstract
OBJECTIVES The aim of this pilot study was to elucidate the effects of exogenous nitric oxide (NO) supply to the extracorporeal circulation circuit for cardioprotection against ischemia-reperfusion injury during coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS A total of 60 patients with coronary artery disease scheduled for CABG with CPB were enrolled in a prospective randomized study. Patients were allocated randomly to receive treatment according to standard or modified CPB protocol where 40-ppm NO was added to the CPB circuit during cardiac surgery. The primary endpoint was the measurement of cardiac troponin I (cTnI). The secondary end points consisted in the measurements of creatine kinase-muscle/brain fraction (CK-MB) and vasoactive inotropic score (VIS). RESULTS NO delivered into the CPB circuit had a cardioprotective effect. The level of cTnI was significantly lower in NO-treated group compared with the control group 6 hours after surgery: 1.79 ± 0.39 ng/mL versus 2.41 ± 0.55 ng/mL, respectively (P = .001). The CK-MB value was significantly lower in NO-treated group compared with the control group 24 hours after surgery: 47.69 ± 8.08 U/L versus 62.25 ± 9.78 U/L, respectively (P = .001); and the VIS was significantly lower in the NO-treated group 6 hours after the intervention. CONCLUSIONS NO supply to the CPB circuit during CABG exerted a cardioprotective effect and was associated with lower levels of VIS and cardiospecific blood markers cTnI and CK-MB.
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Impact of Cardiopulmonary Bypass Flow on Renal Oxygenation in Patients Undergoing Cardiac Operations.
Lannemyr, L, Bragadottir, G, Hjärpe, A, Redfors, B, Ricksten, SE
The Annals of thoracic surgery. 2019;(2):505-511
Abstract
BACKGROUND Cardiac surgery with cardiopulmonary bypass (CPB) is associated with acute kidney injury, and the risk increases with low oxygen delivery during CPB. We hypothesized that renal oxygenation could be improved at higher than normal CPB flow rates. METHODS After ethical approval and informed consent, 17 patients with normal serum creatinine undergoing normothermic CPB were included and received pulmonary artery and renal vein catheters after anesthesia induction for measurements of systemic and renal variables. Renal oxygen extraction, a direct measure of the renal oxygen delivery/renal oxygen consumption ratio, and renal filtration fraction were measured, the latter by renal extraction of 51chromium-ethylenediaminetetraacetic acid. After start of CPB and aortic cross-clamp, the pump flow rate was randomly varied between 2.4, 2.7, and 3.0 L · min-1 · m-2, and measurements were made after 10 minutes at each flow rate. RESULTS Renal oxygen extraction increased by 30% at a flow rate of 2.4 L · min-1 · m-2 versus pre-CPB (p < 0.05). At a flow rate of 2.7 and 3.0 L · min-1 · m-2, Renal oxygen extraction was 12% (p < 0.05) and 23% (p < 0.01) lower, respectively, compared with 2.4 L · min-1 · m-2. This corresponds to a 14% and 30% improvement, respectively, of the renal oxygen supply/demand relationship. Filtration fraction was not affected by changes in flow rate, indicating that the glomerular filtration rate increased in proportion to the increase in renal perfusion. CONCLUSIONS The impaired renal oxygenation seen during CPB is ameliorated by an increase in CPB flow rate. Thus, one way to protect the kidneys during CPB could be to use a higher flow rate than the one traditionally used.
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The use of mannitol in cardiopulmonary bypass prime solution-Prospective randomized double-blind clinical trial.
Ljunggren, M, Sköld, A, Dardashti, A, Hyllén, S
Acta anaesthesiologica Scandinavica. 2019;(10):1298-1305
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BACKGROUND The optimal prime solution for the cardiopulmonary bypass (CPB) circuit in adult cardiac surgery has not yet been defined. Mannitol is widely used in the priming solution for CPB despite the fact that there is no clear consensus on the role of mannitol in cardiac surgery. The aim of this study was to investigate the effect of mannitol in the CPB prime solution. METHODS This prospective, randomized, double-blind study included 40 patients with normal cardiac and renal functions, who underwent coronary artery bypass grafting. One group received a prime based on Ringer's acetate (n = 20), and the other a prime consisting of Ringer's acetate with 200 mL mannitol (n = 20). Changes in osmolality, acid-base status, electrolytes, and renal-related parameters were monitored. RESULTS No significant differences were found in osmolality between the Ringer's acetate group and the mannitol group at any time. The mannitol group showed a pronounced decrease in sodium, from 138.7 ± 2.8 mmol/L at anaesthesia onset, to 133.9 ± 2.6 mmol/L after the start of CPB (P < .001). No differences were seen in the renal parameters between the groups, apart from a short-term effect of mannitol on peroperative urine production (P = .003). CONCLUSION We observed no effects on osmolality of a prime solution containing mannitol compared to Ringer's acetate-based prime in patients with normal cardiac and renal function. The use of mannitol in the prime resulted in a short-term, significant decrease in sodium level.