The effect of ozone treatment on remote organ myocardial injury in an aortic ischemia-reperfusion model.

BACKGROUND: This study aims to investigate the effect of ozone on myocardial ischemia-reperfusion injury occurring after occlusion - reperfusion of infrarenal abdominal aorta in rats. METHODS: Thirty-two Wistar albino rats (weighing 200-250 g) were randomized into four equal groups. The control (sham) group underwent laparotomy and dissection of the infrarenal abdominal aorta without occlusion. Intraperitoneal ozone was applied for 10 days 1 mg/kg/day in the control+ozone group. Afterwards, control+ozone group underwent laparotomy and dissection of the infrarenal abdominal aorta without occlusion. Aortic ischemia-reperfusion and aortic ischemia-reperfusion+ozone groups underwent dissection of the infrarenal abdominal aorta, followed by achieving ischemia and reperfusion by cross-clamping the infrarenal abdominal aorta for 60 minutes and removing the cross-clamp for 60 minutes, respectively. The tissue levels of malondialdehyde and activity levels of superoxide dismutase, catalase, and myeloperoxidase were measured in the myocardial specimens. The tumor necrosis factor, interleukin-6 and troponin-I levels were measured in the plasma. A histopathological examination of the myocardial specimens was undertaken. RESULTS: Biochemical analysis showed that aortic ischemia-reperfusion significantly increased (p<0.05 vs. control) while ozone significantly decreased (p<0.05 vs. aortic ischemia-reperfusion) the myocardial tissue levels of superoxide dismutase and catalase and level of plasma troponin-I. Histologically, in the aortic ischemia-reperfusion group, myocardial disorganization, myofiber swelling and myofiber eosinophilia in the myocardial tissue samples were significantly increased compared to the control group (p<0.05 vs. control). However, histopathological changes in the aortic ischemia-reperfusion+ozone group decreased compared to the aortic ischemia-reperfusion group. CONCLUSION: The results of this experimental study indicate that ozone attenuates myocardial injury and oxidative stress that develop after infrarenal aortic ischemia-reperfusion through three markers; (i) decreased tissue superoxide dismutase and catalase levels, (ii) d ecreased p lasma t roponin-I l evels, a nd (iii) reduced histopathological changes, albeit not statistically significant.

Frequency of development of aspirin resistance in the early postoperative period and inadequate inhibition of thromboxane A2 production after coronary artery bypass surgery.

BACKGROUND: This study aims to investigate the frequency of the development of aspirin resistance, whether or not this resistance was reversible, and to evaluate the efficiency of the mechanism of incomplete inhibition of thromboxane A2 in development of aspirin resistance in the early postoperative period in patients who had undergone coronary artery bypass grafting. METHODS: Eighty patients (55 males, 25 females; mean age 63.1±9.2 years; range 51 to 75 years) who underwent coronary artery bypass grafting between February 2009 and March 2010 at our clinic were prospectively evaluated. Venous blood samples were collected from all patients and evaluated by a platelet function analyzer in the preoperative period and on postoperative days 7 and 15. Aspirin resistance diagnosis was defined as collagen-epinephrine closure time less than 186 seconds. The urine levels of 11-dehidro thromboxane B2 were also measured on postoperative day one. RESULTS: Aspirin resistance was found in 23 patients (28.75%) in the preoperative period, in 31 patients (38.75%) on the postoperative seventh day and in 25 patients (31.25%) on the postoperative 15th day. The urine levels of 11-dehidro thromboxane B2 in patients with aspirin resistance on the postoperative seventh day were significantly higher than those in patients without aspirin resistance (p<0.001). The mean aortic cross-clamping time (p=0.003) and cardiopulmonary bypass time (p=0.029) in the patients with aspirin resistance on the postoperative seventh day were significantly higher than those in patients without aspirin resistance. CONCLUSION: The results of this study suggest that aspirin resistance develops within the first seven days after coronary artery bypass grafting and is highly reversible, and that the mechanism of inadequate inhibition of thromboxane A2 by aspirin has a role in the development of aspirin resistance in the early postoperative period.

Relationship between site of myocardial infarction, left ventricular function and cytokine levels in patients undergoing coronary artery surgery.

BACKGROUND: The purpose of this study was to examine the relationship between left ventricular (LV) function, cytokine levels and site of myocardial infarction (MI) in patients undergoing coronary artery bypass grafting (CABG). METHODS: Sixty patients undergoing CABG were divided into three groups (n = 20) according to their history of site of myocardial infarction (MI): no previous MI, anterior MI and posterior/inferior MI. In the pre-operative period, detailed analysis of LV function was done by transthoracic echocardiography. The levels of adrenomedullin, interleukin-1-beta, interleukin-6, tumour necrosis factor-alpha (TNF-α) and angiotensin-II in both peripheral blood samples and pericardial fluid were also measured. RESULTS: Echocardiographic analyses showed that the anterior MI group had significantly worse LV function than both the group with no previous MI and the posterior/inferior MI group (p < 0.05 for LV end-systolic diameter, fractional shortening, LV end-systolic volume, LV end-systolic volume index and ejection fraction). In the anterior MI group, both plasma and pericardial fluid levels of adrenomedullin and and pericardial fluid levels of interleukin-6 and interleukin- 1-beta were significantly higher than those in the group with no previous MI (p < 0.05), and pericardial fluid levels of adrenomedullin, interleukin-6 and interleukin-1-beta were significantly higher than those in the posterior/inferior MI group (p < 0.05). CONCLUSIONS: The results of this study indicate that (1) patients with an anterior MI had worse LV function than patients with no previous MI and those with a posterior/inferior MI, and (2) cytokine levels in the plasma and pericardial fluid in patients with anterior MI were increased compared to patients with no previous MI.

Addition of N-acetyl cysteine to carvedilol decreases the incidence of acute renal injury after cardiac surgery.

BACKGROUND: Oxidative stress and inflammation during cardiac surgery may be associated with acute renal injury (ARI). N-acetyl cysteine (NAC) and carvedilol have antioxidant and anti-inflammatory properties. HYPOTHESIS: A combination of carvedilol and NAC should decrease the incidence of ARI more than metoprolol or carvedilol. METHODS: Patients undergoing cardiac surgery were randomized to metoprolol, carvedilol, or carvedilol plus NAC. End points were occurrence of ARI and change in preoperative to postoperative peak creatinine levels. RESULTS: ARI incidence was lower in the carvedilol plus NAC group compared with the metoprolol (21.0% vs 42.1%; P = 0.002) or carvedilol (21.0% vs 38.6%; P = 0.006) groups, but was similar between the metoprolol and carvedilol groups (P = 0.62). Preoperative and postoperative day 1 creatinine levels were similar among the metoprolol (1.02 [0.9-1.2] and 1.2 [0.92-1.45]) the carvedilol (1.0 [0.88-1.08] and 1.2 [0.9-1.5]) and the carvedilol plus NAC groups (1.06 [0.9-1.18] and 1.1 [1.0-1.21] mg/dL; all P values >0.05). Postoperative day 3, day 5, and peak creatinine levels were lower in the carvedilol plus NAC group (1.11 [1.0-1.23], 1.14 [1.0-1.25] and 1.15 [1.0-1.25]) as compared with the metoprolol (1.4 [1.3-1.49], 1.3 [1.0-1.54] and 1.3 [1.0-1.54]) or carvedilol groups (1.2 [1.0-1.52], 1.25 [1.0-1.52] and 1.25 [1.0-1.55] mg/dL; all P values <0.05), but were similar between the metoprolol and carvedilol groups (all P values >0.05). CONCLUSIONS: Combined carvedilol and NAC decreased ARI incidence as compared with carvedilol or metoprolol. No difference was detected between carvedilol and metoprolol.

Oxidative status, inflammation, and postoperative atrial fibrillation with metoprolol vs carvedilol or carvedilol plus N-acetyl cysteine treatment.

BACKGROUND: Atrial fibrillation is associated with inflammation and oxidative stress. HYPOTHESIS: Carvedilol and N-acetyl cysteine (NAC) combination decreases inflammation, oxidative stress, and postoperative atrial fibrillation (POAF) rates more than metoprolol or carvedilol. METHODS: Preoperative and postoperative total oxidative stress (TOS), total antioxidant capacity (TAC), and white blood cells (WBC) were measured in metoprolol, carvedilol, or carvedilol plus NAC groups, and association with POAF was evaluated. RESULTS: Preoperative TAC, TOS, and WBC levels were similar among the groups. Postoperative TAC levels were lower in the metoprolol group compared with the carvedilol group (1.0 vs 1.4) or the carvedilol plus NAC group (1.0 vs 1.9) and were also lower in the carvedilol group compared with the carvedilol plus NAC group (all P < 0.0001). Postoperative TOS levels were higher in the metoprolol group as compared with the carvedilol (29.6 vs 24.2; P < 0.0001) or the carvedilol plus NAC groups (P < 0.0001), and were also higher in the carvedilol group as compared with the carvedilol plus NAC group (24.2 vs 19.3; P < 0.0001). Postoperative WBC counts were lower in the carvedilol plus NAC group compared with the metoprolol group (12.9 vs 14.8; P = 0.004), were similar between the carvedilol and the metoprolol groups (13 vs 14.8) and between the carvedilol plus NAC group and the carvedilol group (both P > 0.05). Postoperative TAC, TOS, and WBC were associated with POAF. CONCLUSIONS: Carvedilol plus NAC reduced oxidative stress and inflammation compared with metoprolol and decreased oxidative stress compared with carvedilol. Postoperative TAC, TOS, and WBC were associated with POAF.

Ozone therapy as an adjunct to vancomycin enhances bacterial elimination in methicillin resistant Staphylococcus aureus mediastinitis.

BACKGROUND: We aimed to investigate the influence of intraperitoneal ozone therapy on bacterial elimination and mediastinal inflammation in experimental Staphylococcus aureus mediastinitis. MATERIALS AND METHODS: Forty Wistar-Albino rats were randomized into five groups (eight per group) as follows: uncontaminated group, untreated contaminated group, ozone group, vancomycin group, and vancomycin + ozone group. Uncontaminated group underwent upper median sternotomy. The remaining four groups were inoculated with 0.5 mL 10(8) colony-forming units/mL methicillin-resistant Staphylococcus aureus in the mediastinal and sternal layers. Untreated contaminated group had no treatment. Rats in the vancomycin group received intramuscular vancomycin (40 mg/kg/d), and ozone was administered intraperitoneally (70 µg/mL, 1 mg/kg/d) in the ozone group for the treatment of mediastinitis. Vancomycin + ozone group rats were treated by the combination of both methods. At the end of 10 d, quantitative bacterial cultures and sternal tissue samples were obtained for determination of bacterial counts and histologic degree of inflammation. RESULTS: Both the vancomycin and the ozone treatments caused significant reduction of bacterial counts in quantitative bacterial cultures. Combination of vancomycin and ozone treatments resulted in further reduction of bacterial counts in mediastinum and sternum. Histologic examination of tissue samples revealed significant reduction in severity of mediastinitis related inflammation in vancomycin and vancomycin + ozone groups compared with untreated contaminated group. CONCLUSIONS: Ozone therapy as an adjunct to vancomycin leads to enhanced bacterial elimination in infected sternal and mediastinal tissues in experimental methicillin-resistant Staphylococcus aureus mediastinitis. The benefit of adjuvant ozone therapy is suggested to be related to its bactericidal effect.

Metoprolol vs. carvedilol or carvedilol plus N-acetyl cysteine on post-operative atrial fibrillation: a randomized, double-blind, placebo-controlled study.

AIMS: Carvedilol and N-acetyl cysteine (NAC) have antioxidant and anti-inflammatory properties. Aim was to evaluate the efficacy of metoprolol, carvedilol, and carvedilol plus NAC on the prevention of post-operative atrial fibrillation (POAF). METHODS AND RESULTS: Patients undergoing cardiac surgery (n = 311) were randomized to metoprolol, carvedilol, or carvedilol plus NAC. Baseline characteristics were similar. The incidence of POAF was lower in the carvedilol plus NAC group compared with the metoprolol group (P < 0.0001) or the carvedilol group (P = 0.03). There was a borderline significance for lower POAF rates in the carvedilol group compared with the metoprolol group (P = 0.06). Duration of hospitalization was lower in the carvedilol plus NAC group compared to the metoprolol group (P = 0.004). Multivariate independent predictors of POAF included left-atrial diameter, hypertension, bypass duration, pre-randomization and pre-operative heart rates, carvedilol plus NAC group vs. metoprolol group, and carvedilol plus NAC group vs. carvedilol group. CONCLUSION: Carvedilol plus NAC decreased POAF incidence and duration of hospitalization compared with metoprolol and decreased POAF incidence compared with carvedilol.

The protective effect of adrenomedullin on renal injury, in a model of abdominal aorta cross-clamping.

Renal injury induced by aortic ischemia-reperfusion (IR) is an important factor in the development of postoperative acute renal failure following abdominal aortic surgery. The aim of this study was to examine the effect of adrenomedullin (AM) on kidney injury induced by infrarenal abdominal aortic IR in rats. Thirty-two Wistar Albino rats were randomized into four groups (eight per group) as follows: Control group, IR group (120-minute ischemia and 120-minute reperfusion), IR + AM group (a bolus intravenously of 0.05 µg/kg/min AM), and control + AM group. At the end of the experiment, blood and kidney tissue specimens were obtained for biochemical analysis. Immunohistological evaluation of the rat kidney tissues was also done. IR significantly increased (p < 0.05 vs control group) and AM significantly decreased (p < 0.05 vs. IR group) all of the biochemical parameters. Immunohistological evaluation showed that AM attenuated morphological changes as apoptosis associated with kidney injury. The results of this study indicate that AM attenuates both biochemically and immunohistopathologically kidney injury induced by aortic IR in rats.

Adrenomedullin attenuates aortic cross-clamping-induced myocardial injury in rats.

BACKGROUND: In this study we investigate the effects of adrenomedullin on myocardial injury after ischemia-reperfusion (I/R) after abdominal aortic surgery. METHODS: Thirty-two Wistar rats were randomized into 4 groups (n = 8) as follows: control group (sham laparotomy), the aortic I/R group, aortic I/R plus adrenomedullin group (underwent aortic I/R periods, and received a bolus intravenous injection of .05 µg/kg/min adrenomedullin), and the control plus adrenomedullin group. RESULTS: Biochemical analysis showed that aortic I/R significantly increased (P < .05) the plasma levels of troponin-I and tumor necrosis factor-α, and the myocardial tissue levels of malondialdehyde, superoxide dismutase, catalase, and angiotensin II, whereas aortic I/R plus adrenomedullin significantly decreased these same factors (P < .05). Aortic I/R significantly increased (P < .05) myocardial tissue levels of nitric oxide whereas aortic I/R plus adrenomedullin significantly increased the same factor (P < .05). CONCLUSIONS: These results indicate that adrenomedullin has protective effects against myocardial injury induced by abdominal aortic I/R in rats.

Mitral valve replacement in a patient with idiopathic hypereosinophilic syndrome and pulmonary arterial hypertension.

BACKGROUND AND AIMS: Idiopathic hypereosinophilic syndrome, a rarely seen systemic disease, may cause cardiac valvular lesions by eosinophilic infiltration. This report describes management of a 25-year-old woman with idiopathic hypereosinophilic syndrome, severe mitral stenosis, and pulmonary arterial hypertension. METHODS: The patient was presented with haemoptysia and dyspnea on exertion. Echocardiography showed severe mitral stenosis and pulmonary arterial hypertension. RESULTS: After hematological stabilization, she underwent mitral valve replacement using a No. 27 bovine pericardial valve. In the intensive care unit she had a pulmonary hypertensive crisis, which ameliorated gradually with sedation and nitroglycerin. She was extubated and discharged on the second and seventh days, respectively. CONCLUSION: Surgical experience for the patients with mitral dysfunction caused by idiopathic hypereosinophilic syndrome is limited. When mitral valve replacement is needed, the ideal type of prosthesis remains unclear and the presence of pulmonary arterial hypertension further complicates the management. We think that bioprosthetic valves would be the appropriate choice in eosinophilic mitral dysfunction requiring valve replacement.