Pentoxifylline affects cytokine reaction in cardiopulmonary bypass.

BACKGROUND: Cardiac surgery is associated with an inflammatory response that may cause myocardial dysfunction after cardiopulmonary bypass. We examined the efficacy of pentoxifylline to attenuate the cardiopulmonary bypass-induced inflammatory response during heart operations. METHODS: In a prospective, randomized study, 30 patients undergoing coronary artery bypass graft surgery received either pentoxifylline (group P, n = 15) (continuous infusion of 1.5 mg/kg per hour during operation) or not (group C [control], n = 15). Blood samples for measurements of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, and IL-10 were taken from the arterial line in both groups at 5 different time points. RESULTS: TNF-alpha, IL-6, and IL-8 plasma levels increased in both groups after cardiopulmonary bypass, with a higher increase in the control group (P < .05). CONCLUSIONS: Our results indicate that pentoxifylline infusion during cardiac surgery inhibits the proinflammatory cytokine release caused by cardiopulmonary bypass.

Trimetazidine reduces oxidative stress in cardiac surgery.

BACKGROUND: Trimetazidine is an anti-ischemic agent that is used to treat angina and it has cardioprotective effects without inducing any significant hemodynamic changes. It inhibits the long-chain mitochondrial 3-ketoacyl coenzyme A thiolase enzyme in the myocyte and can improve cardiac mitochondrial metabolism, as well as scavenge free radicals. The aim of this double-blind prospective randomized study was to investigate the effect of preoperative use of trimetazidine on the reduction of oxidative stress during coronary artery bypass grafting (CABG) under cardiopulmonary bypass (CPB). METHODS AND RESULTS: The study group (group T) and the control group (group C) each comprised 12 patients. Pretreatment began 2 weeks before CABG with trimetazidine (60 mg/day po); the control group did not receive any medication. Serial blood samples were collected before and after CPB for measurement of the serum concentrations of these major endogenous antioxidant enzyme systems, which are markers for oxidative degradation of the cellular membranes; postoperative levels were significantly different between the groups (p<0.05). There were no significant difference in hemodynamic values. CONCLUSION: The findings suggest that pretreatment with trimetazidine alleviates malondialdehyde production and preserves endogenous antioxidant capacity during CABG with CPB and cardioplegic arrest.

Cardioprotective effect of calcium dobesilate during open-heart surgery.

OBJECTIVE: The purpose of this double-blind, controlled, prospective randomized study was to investigate the possible effects of the preoperative use of calcium dobesilate (CLS2210) on the biochemical markers of myocardial injury during open-heart surgery, and to determine if it has any myocardial protective effects. METHODS: Twenty-four patients undergoing elective cardiac surgery were included in this study and randomized into two groups. CLS2210 was given orally to 12 patients for 14 days before the operation (CD group), but not to the other 12 patients (control group). Serum CK, CK-MB, myoglobin and troponin-T levels were measured from venous blood samples before and after the operation for evaluation of the effect of this drug against myocardial damage. Blood samples were also taken from the radial artery and the coronary sinus before the institution of cardiopulmonary bypass (CPB), and 2 and 15 minutes after the removal of the cross-clamp in order to measure the lactate levels and calculate the lactate extraction of the myocardium. RESULTS: First, CK-MB levels in patients of the CD group were significantly lower than those of the control group (p < 0.05) at the 2nd and 18th postoperative hour. Second, myoglobin and troponin-T levels in the CD group were significantly lower than those of the control group (p < 0.05) at the 2nd, 18th and 48th postoperative hour. Third, there was a significant difference in lactate extraction calculation values between the groups at the 2nd minute after removal of the cross-clamp (p < 0.05). CONCLUSIONS: We concluded that preoperative use of CLS2210 has some beneficial effects in protecting the myocardium and decreasing the myocardial injury during the cardioplegic arrest period in open-heart surgery.

The effect of cardiopulmonary bypass on the expression of inducible nitric oxide synthase, endothelial nitric oxide synthase, and vascular endothelial growth factor in the internal mammary artery.

OBJECTIVE: Endothelial function of a vessel may be impaired by local or systemic inflammation initiated by cardiopulmonary bypass (CPB) during coronary artery bypass graft (CABG) surgery. The present study was designed to investigate the early effects of CPB on nitric oxide production and vascular endothelial growth factor (VEGF) expression in internal mammary artery (IMA). DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Twenty patients who were scheduled for elective CABG with CPB. INTERVENTIONS: IMA sections were studied immunohistochemically from these patients. The samples were taken from the distal end of the IMA before the institution of CPB and just before the construction of the IMA-left anterior descending artery anastomosis. MEASUREMENT AND MAIN RESULTS: After CPB, VEGF and endothelial nitric oxide synthase immunoreactivity increased significantly when compared with baseline values in the endothelium (p = 0.0156, p = 0.0313) and adventitia (p = 0.0313, p = 0.0001), respectively. No significant change was observed in inducible nitric oxide synthase immunoreactivity. CONCLUSIONS: The increase in eNOS expression may have been induced by the inflammation caused by CPB.

The role of brain natriuretic peptide in the prediction of cardiac performance in coronary artery bypass grafting.

The relationship between brain natriuretic peptide and cardiopulmonary bypass has not been examined sufficiently. In this study, we prospectively examined brain natriuretic peptide levels in the plasma of 26 patients undergoing coronary artery bypass grafting. Brain natriuretic peptide measurements were carried out at 4 times: preoperatively, 3 hours after institution of cross-clamping, 24 hours after institution of cross-clamping, and on the 5th postoperative day. In addition, we measured individual variables and compared them to brain natriuretic peptide levels. Mean preoperative brain natriuretic peptide levels were significantly higher in patients with histories of myocardial infarction (P = 0.0047) and heart failure (ejection fraction < or = 0.40) (P = 0.0001). There was a significant correlation between preoperative brain natriuretic peptide levels and cross-clamp times (P = 0.028), and an inverse correlation between those levels and preoperative cardiac indices (P = 0.001). The preoperative brain natriuretic peptide level also correlated inversely with left ventricular ejection fraction before (P = 0.001) and 5 days after (P = 0.01) operation. When the Clinical Severity Scoring System was applied, preoperative brain natriuretic peptide plasma concentrations in 19 patients with risk scores of 0-2 were significantly lower than in the 7 patients whose risk scores were 3-6 (P = 0.006). There was also a significant relationship between preoperative brain natriuretic peptide plasma concentrations and the postoperative requirement for inotropic agents (P = 0.027). This study suggests that plasma brain natriuretic peptide concentration could be one of the predictors of risk in patients undergoing coronary artery bypass grafting.

Diagnosis of asymptomatic atrial septal aneurysms using two-dimensional color Doppler and contrast transthoracic echocardiography.

OBJECTIVE: To evaluate the dimensions of atrial septal aneurysm (ASA), the presence and characteristics of interatrial shunt, the movement of the wall of the aneurysm, and correlation between these findings and sign and/or symptoms suggesting embolism in Manisa, a district of a western Anatolian city of Turkey. METHODS: Two thousand five hundred cases were examined by routine transthoracic echocardiography (TTE) in both pediatric and adult cardiology outpatient clinics. ASA was detected in 20 cases and evaluated by two-dimensional color Doppler echocardiography (CDE). The length of the base, the maximum radius and the maximum displacement of ASA were measured. The shunt between the atria was examined by CDE. In cases where a shunt could not be found, galactose and palmitic acid was injected. Standard 12-lead electrocardiogram (ECG) and exercise stress test were also performed. RESULTS: No clinical signs or symptoms were found, suggesting a systemic or cerebral embolism. The maximum displacement of ASA was between 2 and 5 mm. All of the aneurysms were localized in the right atrium, and the walls of the aneurysm did not move beyond the base of the left atrium during the maximum displacement. Interatrial shunt was detected in 14 of 20 patients (70%) by CDE and in the remaining six cases by contrast TTE. Frequent ventricular ectopic beats were observed in one patient. CONCLUSIONS: During routine TTE we observed 0.8% asymptomatic ASA in our population. The use of a contrast agent was found to be a valuable additional method in patients with ASA when the shunt could not be detected by CDE. The risk for embolism is not high when the maximum displacement of the wall of ASA was 5 mm or less and no bulge into the left atrium was observed. Based on our experience with this method, TTE is easy to perform, well-tolerated and acceptable.

Ischaemic preconditioning reduces spinal cord injury in transient ischaemia.

OBJECTIVE: Paraplegia remains a devastating complication after thoracic and thoracoabdominal aortic surgery for coarctations, dissections or aneurysms. Since the advent of ischaemic preconditioning of the myocardium, attention has been directed to the nervous system. This study was designed to evaluate the acute protective effect of ischaemic preconditioning on the spinal cord. MEDHODS AND RESULTS: Thirty-six New Zealand white rabbits were randomly assigned to one of three groups. The preconditioning group had 5 minutes of aortic occlusion, 25 minutes reperfusion and 20 minutes of ischaemia, whereas the controls had only 20 minutes of ischaemia. The sham group was anaesthetized and subjected to laparotomy without aortic occlusion. Physiological parameters and somatosensory evoked potentials were monitored during the experiment. Neurological outcome was clinically evaluated up to 48 hour after ischaemia and motor function was scored. Then the animals were sacrificed. Their spinal cord, abdominal aorta and its branches were removed and processed for histopathological examination. Histhopathological changes of the gray matter in the lumbosacral segments were scored from 0 to 6 according to a semi-quantitative scala. The changes in amplitudes of evoked potentials during ischaemia and recovery periods were similar in preconditioning and control groups. The average motor function score was significantly higher in the preconditioning group than the control group at 24 and 48 hours after the ischaemic event (p < 0.05). Histological observations were consistent with the neurological findings. The histopathological scores in the control group and the preconditioning group were 3.2 (1.4-5.2) and 2.4 (0.8-4.4), respectively (p < 0.05). CONCLUSIONS: The results suggest that ischaemic preconditioning reduces the spinal cord injury and improves neurological outcome in transient ischaemia in rabbits. This protective mechanism is rapidly invoked within only 25 minutes interval between the preconditioning stimulus and the ischaemic insult.