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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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Oral glutamine reduces myocardial damage after coronary revascularization under cardiopulmonary bypass. A randomized clinical trial.
Chávez-Tostado, M, Carrillo-Llamas, F, Martínez-Gutiérrez, PE, Alvarado-Ramírez, A, López-Taylor, JG, Vásquez-Jiménez, JC, Fuentes-Orozco, C, Rendón-Félix, J, Irusteta-Jiménez, L, Calil-Romero, VC, et al
Nutricion hospitalaria. 2017;(2):277-283
Abstract
BACKGROUND Glutamine is the most abundant free amino acid in the body. It modulates immune cell function and is an important energy substrate for cells in critically ill patients. Reduction of injury cardiac markers had been observed in patients receiving intravenous glutamine and in a pilot study with oral glutamine. The aim of this study was to analyze the effect of preoperative oral supplementation of glutamine on postoperative serum levels of cardiac injury markers. METHODS A randomized clinical trial was performed in 28 Mexican patients with ischemic heart disease who underwent cardiopulmonary bypass with extracorporeal circulation. Patients were randomly assigned to receive oral glutamine (0.5 g/kg/day) or maltodextrin 3 days before surgery. Cardiac injury markers as troponin-I, creatine phosphokinase, and creatine phosphokinase-Mb were measured at 1, 12, and 24 hours postoperatively. RESULTS At 12 and 24 hours serum markers levels were significantly lower in the glutamine group compared with controls (p = 0.01 and p = 0.001, respectively) (p = 0.004 and p < 0.001, respectively). Overall, complications were significantly lower in the glutamine group (p = 0.01, RR = 0.54, 95% CI 0.31-0.93). Mortality was observed with 2 cases of multiple organ failure in control group and 1 case of pulmonary embolism in glutamine group (p = 0.50). CONCLUSION Preoperative oral glutamine standardized at a dose of 0.5 g/kg/day in our study group showed a significant reduction in postoperative myocardial damage. Lower cardiac injury markers levels, morbidity and mortality were observed in patients receiving glutamine.
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Pharmacological prevention of the deleterious effects of cardiopulmonary bypass.
Hassantash, SA, Omrani, GR, Givtaj, N, Afrakhteh, M
Asian cardiovascular & thoracic annals. 2007;(3):218-24
Abstract
Indomethacin is a known immune modulator that inhibits cyclooxygenase. Studies indicate that ketoconazole, a selective lipoxygenase and thromboxane A(2) synthetase inhibitor, can prevent activation of the inflammatory cascade by inhibition of proinflammatory mediators. This study was designed to determine if ketoconazole or indomethacin could reduce the adverse effects of extracorporeal circulation. As a double-blind prospective study, 76 patients were randomized into 3 groups according to preoperative medication: indomethacin, ketoconazole, and placebo groups, with 25, 26, and 25 patients, respectively. Four types of parameters were evaluated preoperatively and up to 24 hr after cardiac surgery in all patients: inflammatory (complement C3 and C4, C-reactive protein, immunoglobulins); hematologic; coagulation; and physiologic (blood loss, fluid and blood components received, weight gain, and duration of ventilation). Statistical analyses showed similar patient profiles in each group. Complement C4 decreased in all groups postoperatively, but significantly less in the indomethacin group ( p < 0.01). Ketoconazole reduced postoperative bleeding ( p < 0.0001) as well as the incidence of re-operation for bleeding ( p = 0.05). It was concluded that indomethacin decreases complement (specifically C4) consumption during cardiopulmonary bypass, and ketoconazole may reduce postoperative bleeding by limiting coagulation abnormalities in cardiac surgery patients.
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Normothermic beating heart surgery with assistance of miniaturized bypass systems: the effects on intraoperative hemodynamics and inflammatory response.
Rex, S, Brose, S, Metzelder, S, de Rossi, L, Schroth, S, Autschbach, R, Rossaint, R, Buhre, W
Anesthesia and analgesia. 2006;(2):352-62
Abstract
The use of miniaturized cardiopulmonary bypass (CPB) circuits and avoidance of cardioplegic arrest are attempts to reduce the inflammatory response to cardiac surgery. We studied the effects of beating heart surgery (BHS) with assistance of simplified bypass systems (SBS) on global hemodynamics, myocardial function and the inflammatory response to CPB. We hypothesized that the use of SBS was associated with less hemodynamic instability after CPB resulting from attenuation of the inflammatory response when compared with surgery performed with a conventional CPB (cCPB) circuit. Forty-five patients undergoing coronary artery bypass grafting were prospectively studied. Fifteen patients were randomized to the use of a cCPB circuit, cold crystalloid cardioplegia, and moderate hypothermia. Two groups of 15 patients underwent BHS during normothermia with assistance of two different SBS consisting of only blood pump and oxygenator. Hemodynamic variables were assessed with transpulmonary thermodilution and transesophageal echocardiography. Plasma levels of proinflammatory and antiinflammatory mediators were measured perioperatively. After CPB, variables of global hemodynamics and systolic ventricular function did not differ among groups. Left ventricular diastolic function was impaired after CPB equally in all groups (P < 0.01 versus pre-CPB). At the end of surgery, there was more need for vasopressor (norepinephrine) support in both SBS groups than in the cCPB group (P < 0.01). After CPB, the release of interleukin (IL)-6 did not differ significantly among groups, whereas plasma levels of IL-10 were higher in the cCPB group (P < 0.01 versus SBS). The extent of myocardial necrosis (Troponin T) was comparable in all groups. We conclude that in our study, miniaturizing bypass systems and avoidance of cardioplegic arrest were not effective in improving hemodynamic performance and in attenuating the proinflammatory immune response after CPB.
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5.
Prostaglandin E1 attenuates impairment of cellular immunity after cardiopulmonary bypass.
Sano, T, Masuda, M, Morita, S, Yasui, H
The Japanese journal of thoracic and cardiovascular surgery : official publication of the Japanese Association for Thoracic Surgery = Nihon Kyobu Geka Gakkai zasshi. 2006;(4):149-54
Abstract
OBJECTIVE It is well documented that cardiopulmonary bypass (CPB) severely impairs cellular immunity. The objective of this study was to investigate the effect of prostaglandin E1 (PGE1) on cellular immunity after CPB. METHODS Patients who underwent elective cardiac surgery were randomly divided into the PGE1 group (n=12) and the control group (n=12). In the PGE1 group, PGE1 was administered at 20 ng/kg/min from just after the induction of anesthesia to the end of surgery. Peripheral blood mononuclear cells (PBMCs) were taken before anesthesia and on postoperative days 1, 3 and 7 (POD 1, POD 3 and POD 7). Proliferation responses of T cells to phytohemagglutinin (PHA) and pure protein derivative (PPD) antigen were measured as indicators of cellular immunity. RESULTS PGE1 significantly attenuated the impairment of both PHA and PPD response after cardiac surgery on POD 1 (PHA response, 30 +/- 21% vs. 53 +/- 32%, control vs. PGE, p=0.048; PPD response, 18 +/- 21% vs. 39 +/- 27%, control vs. PGE, p=0.046). The reduced glutathione content of PBMCs in the control group was significantly decreased on POD 1. CONCLUSION PGE1 attenuated the impairment of cellular immunity after cardiac surgery with CPB by reducing oxidative stress on PBMCs.