Immune and inflammatory role of hydroxyethyl starch 130/0.4 and fluid gelatin in patients undergoing coronary surgery.

OBJECTIVES: Compare the effects on inflammatory (TNF-α, IL-6, IL-8 and IL-10) and immunologic (CD3(+), CD4(+), CD8(+), CD11b(+), CD16(+)/56(+) T cells and total lymphocyte concentration) variables of hydroxyethyl starch 130/0.4, 4% modified fluid gelatin, or crystalloid when used as volume replacement fluids for acute normovolemic hemodilution (a blood conservation technique) in coronary artery bypass graft patients. METHODS: Thirty patients undergoing coronary artery bypass graft surgery were randomized to receive Isolyte S® (Group ISO), 6% hydroxyethyl starch 130/0.4 (Group HES) or 4% modified gelatin solution (Group GEL) for acute normovolemic hemodilution. Blood samples were taken immediately after induction of anaesthesia (T0), and 2 h (T1), 12 h (T2), 24 h (T3), and 48 h (T4) after separation from cardiopulmonary bypass. TNF-α, IL-6, IL-8 and IL-10 levels were determined with commercially available ELISA kits. CD3(+) (mature T cells), CD4(+) (T helper cells), CD8(+) (suppressor cytotoxic T cells), CD16(+)/56(+) (natural killer lymphocytes), and CD11b(+) (Mac-1, adhesion receptor) levels were measured using flow-cytometry reagents. The CD4(+):CD8(+) ratio was calculated. RESULTS: Between-group comparisons showed significantly higher levels of TNF-α at T1 (2 h after weaning from cardiopulmonary bypass) in Group HES compared to Group ISO (p=0.003). IL-8 was significantly lower in Group HES than Group GEL at T1 (p=0.0005). IL-10 was significantly higher in Group HES than in Group GEL at T1 (p=0.0001). The CD4(+):CD8(+) ratio in Group ISO was significantly lower than that in Group HES at T2 (p=0.003). CD11b(+) levels in Group HES were also higher than those in Group GEL and group ISO at T2, but not significantly. CD16/56(+) levels in Group HES were higher than those in Group GEL at T2 (p<0.003). No excessive hemorrhage occurred in any patient. Mediastinal drainage during the first 24 h after surgery in Group HES (347±207 mL) was not significantly different from that of Group GEL (272±177 mL) or Group ISO (247±109) (p>0.05). CONCLUSION: Hydroxyethyl starch 130/0.4 reduced pro-inflammatory responses and increased anti-inflammatory responses to a greater degree than gelatin solution and isolyte S®. The use of hydroxyethyl starch, compared to gelatin solution and isolyte S®, resulted in less decrease in the CD4(+):CD8(+) ratio, suggesting less immunosuppression.

Superior mesenteric artery branch--jejunal artery aneurysm.

Visceral artery aneurysm (VAA) is a relatively uncommon disorder and it shows some vague symptoms. Therefore, the clinical diagnosis is difficult and these aneurysms are discovered and diagnosed only after rupture in many cases. This case report describes the history of a woman who had a superior mesenteric artery (SMA) branch aneurysm. A 62-year-old woman presented with fatigue and moderate to severe epigastric and mid-back pain. A computed tomography of the abdomen and pelvis demonstrated a partially thrombosed aneurysm (38×40 mm) rising from the jejunal branch of the SMA. The aneurysm which contains mural thrombus is resected, and a saphenous vein graft interposition is performed between the ends of the same jejuno-jejunal artery. The patient's recovery was unremarkable, and she was discharged on postoperative day 7. Rapid diagnosis, localization, and surgical or endovascular interventions are necessary to avoid devastating consequences in VAAs. Saphenous vein graft interposition is a good choice for surgical intervention for patients not suitable for endovascular treatment.

Trimetazidine may protect the myocardium during cardiac surgery.

BACKGROUND: Trimetazidine is an anti-ischemic agent with cardioprotective effects. The purpose of this double-blind, controlled, prospective randomized study was to investigate the possible effects of the preoperative use of trimetazidine on the biochemical markers of myocardial injury during open heart surgery and to determine if it has any myocardial protective effects. METHODS: Thirty patients undergoing coronary artery bypass grafting surgery, received either trimetazidine (study group, n = 15) or not (control group, n = 15). Pretreatment began 2 weeks before the operation with trimetazidine (60 mg/day orally), and the control group received no medication. We measured the levels of serum creatine kinase (CK), CK isoenzyme MB (CK-MB), myoglobin, and troponin T in venous blood samples obtained before and after the operation to evaluate the effect of this drug against myocardial damage. We also took serial blood samples from the radial artery and the coronary sinus before the institution of cardiopulmonary bypass (CPB) and at 2 and 15 minutes after the removal of the cross-clamp to measure lactate levels and calculate the lactate extraction of the myocardium. RESULTS: Postoperative levels of myoglobin, troponin T, CK, and CK-MB were significantly lower in the trimetazidine group than in the control group (P < .05). There was also a significant difference in the values for the lactate extraction calculation between the groups at minute 2 after the removal of the cross-clamp (P < .05). CONCLUSION: We conclude that pretreatment with trimetazidine has some beneficial effects in protecting the myocardium and decreasing myocardial injury during the cardioplegic arrest period in open heart surgery without affecting postoperative hemodynamics.

Preoperative oral pentoxifylline for management of cytokine reactions in cardiac surgery.

BACKGROUND: Cardiopulmonary bypass may lead to many inflammatory responses that may cause myocardial dysfunction after open heart surgery. We aimed to investigate the effect of preoperative pentoxifylline treatment to reduce the occurrence of cardiopulmonary bypass-induced inflammatory response. METHODS: In a prospective, randomized study, 40 patients undergoing coronary artery bypass graft surgery received either pentoxifylline (study group, n = 21) or not (control group, n = 19). Pretreatment with pentoxifylline (800 mg/day orally) was started 5 days before the operation. Blood samples for measurements of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8 from the arterial line, and venous blood samples for creatine kinase (CK) and CK isoenzyme fraction MB (CK-MB) were taken in both groups at 5 different time points. Hemodynamic parameters were measured with the thermodilution technique. RESULTS: TNF-alpha, IL-6, and IL-8 plasma levels increased in both groups after cardiopulmonary bypass, with a greater increase in the control group (P < .05). There were no significant differences between the groups for the values of CK-MB and hemodynamic parameters. CONCLUSIONS: We conclude that pretreatment with oral pentoxifylline before cardiac surgery inhibits proinflammatory cytokine release caused by cardiopulmonary bypass and has some beneficial effects in protecting the myocardium during the cardioplegic arrest period in open-heart surgery, without affecting postoperative hemodynamics.

Sleep disturbances after cardiac surgery with or without elevated S100B levels.

OBJECTIVE: The aim of the study was to investigate sleep disturbances of cardiac surgery patients with or without elevated S100B levels. METHODS AND RESULTS: Twenty-two patients with serum S100B > 0.3 microg/l (study group) 12 hours after cardiac surgery with cardiopulmonary bypass and 23 patients with serum S100B < 0.3 (control group) were investigated in a prospective study. They were evaluated with the use of objective sleep tests. Cardiopulmonary bypass has negatively affected the sleep characteristics in the postoperative period for both groups. Maintenance wakefulness test, total sleep time, total activity score and sleep efficiency scores were significantly shorter in the study group in the postoperative period. Sleep latency, percentage of wakefulness after sleep onset, daytime napping episodes and total nap duration in the same period were significantly higher than in the control group. CONCLUSION: Cardiac surgery affects a patient's sleep characteristics. Patients with elevated S100B values have more sleep disturbances after cardiac surgery than patients with normal S100B values.

N-terminal ProBNP levels can predict cardiac failure after cardiac surgery.

BACKGROUND: The aim of this study was to evaluate the relationship between the preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and the need for the inotropic support in the early postoperative period of patients undergoing coronary artery bypass graft surgery. METHODS AND RESULTS: The patients were divided into 2 groups: NT-proBNP level<220 pg/ml (group A, n=26) or >220 pg/ml (group B, n=26). The normal value for NT-proBNP level was accepted as <220 pg/ml. The cardiac output was measured on arrival in intensive care and at the 16th hour. The groups were compared with respect to early postoperative hemodynamic measurements, urinary output, use of inotropic agents and requirement for additional cardiac-assist devices. Left ventricular ejection fraction, cardiac output and cardiac index were lower in group B and inotropic agents were used for a longer period of time and at higher doses in this group (p<0.05). CONCLUSION: Measurement of the NT-proBNP level in the period before cardiac surgery can indicate the postoperative prognosis of the patient and may be a predictor of the need for postoperative inotropic treatment.

The effect of piroxicam on the prevention of postoperative retrosternal and pericardial adhesions.

BACKGROUND: The presence of adhesions after heart operations increases the risk of life-threatening damage to the heart and extracardiac grafts. Infections, tissue injury and inflammations are suspected aetiologic agents. The main purpose of our study is to evaluate the effect of an antiinflammatory agent piroxicam on the formation of retrosternal and pericardial adhesions in a rabbit model. MATERIAL AND METHODS: 23 of forty-two New Zealand white rabbits were labelled as group P (piroxicam group) and the others as group C (n = 19, control group). All animals were subjected to median sternotomy and abrasion was applied to the epicardium and pericardium. Piroxicam was given only to group P animals 10 mg/kg/day intramuscularly on the day of operation and twice daily for 2 days postoperatively. All animals were sacrificed on the 10th postoperative day. After cardiectomy, the pericardium was totally excised; retrosternal and pericardial adhesions were evaluated and scored. t-PA (tissue plasminogen activator), PAl-I (plasminogen activator inhibitor-I) levels and pericardial tissue myeloperoxidase activities were measured. RESULTS: More severe retrosternal and pericardial adhesions were observed in the control group (P < 0.05). Mean levels of t-PA were higher in the study group than in the control group (P < 0.05). Mean levels of PAI-I were lower in the study group (P < 0.05). Hence pericardial fibrinolytic capacity was significantly higher in the piroxicam group than in the control group. Myeloperoxidase activities in the pericardium were significantly lower in the study group than in the control group (P < 0.05). CONCLUSION: The use of piroxicam in the perioperative period prevents inflammation, preserves the fibrinolytic capacity of the pericardium and decreases the postoperative pericardial and retrosternal adhesions.

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.

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.