Effect of a glutathione S-transferase inhibitor on oxidative stress and ischemia-reperfusion-induced apoptotic signalling of cultured cardiomyocytes.

Oxidative stress and ischemia-reperfusion (I/R) injury are crucial in the pathogenesis of cardiovascular diseases. The antioxidant glutathione S-transferase (GST) is responsible for the high-capacity metabolic inactivation of electrophilic compounds and toxic substrates. The main objective of the present study was to examine the effect of GST inhibition (with the administration of ethacrynic acid [EA]) on the viability and apoptosis of cardiomyocytes when these cells are exposed to various stress components of I/R and mitogen-activated protein kinase (c-Jun N-terminal kinase, p38 and extracellular signal-regulated kinase [ERK]) inhibitors. The primary culture of neonatal rat cardiomyocytes was divided into six experimental groups: control group of cells (group 1), cells exposed to H(2)O(2) (group 2), I/R (group 3), I/R and EA (group 4), H(2)O(2) coupled with EA (group 5), and EA alone (group 6). The viability of cardiomyocytes was determined using a colorimetric MTT assay. The apoptosis ratio was evaluated via fluorescein isothiocyanate-labelled annexin V and propidium iodide staining. c-Jun N-terminal kinase, p38, Akt/protein kinase B and ERK/p42-p44 transcription factors were monitored with flow cytometry. c-Jun N-terminal kinase activation increased due to GST inhibition during I/R. EA administration led to a significant increase in p38 activation following both H(2)O(2) treatment and I/R. ERK phosphorylation increased when GST was exposed to I/R. A pronounced decrease in Akt phosphorylation was observed when cells were cotreated with EA and H(2)O(2). GST plays an important role as a regulator of mitogen-activated protein kinase pathways in I/R injury.

Effect of cardiopulmonary bypass on cytokine network and myocardial cytokine production.

BACKGROUND: In addition to the well-investigated proinflammatory cytokine expression, there is an ever increasing interest in the field of anti-inflammatory response to cardiopulmonary bypass (CPB). Evidence suggests that myocardium serves as an important source of cytokines during reperfusion and application of CPB. The effect of coronary artery bypass graft (CABG) without CPB on myocardial cytokine production has not as yet been investigated. HYPOTHESIS: Cardiopulmonary bypass can cause long-term disturbance in pro- and anti-inflammatory cytokine balance, which may impede a patient's recovery following surgery. Therefore, the effect of CPB on the balance of the pro-/anti-inflammatory cytokines network and myocardial cytokine outflow was assessed throughout a longer period after surgery. METHODS: Twenty patients were scheduled for CABG with CPB and 10 had off-pump surgery. Blood samples were taken before, during, and over the first week following surgery. Coronary sinus blood samples were collected during surgery. The ratio of pro- and anti-inflammatory cytokines was calculated and the cytokine concentration of peripheral and coronary sinus blood were compared in both groups. RESULTS: Pro-/anti-inflammatory cytokine ratio decreased early after CPB followed by a delayed and marked increase. A more balanced ratio was present following off-pump surgery. Coronary sinus levels of certain cytokines exceeded the concentration of systemic blood in the course of CPB but not during off-pump operation. CONCLUSION: Patients show pro-inflammatory predominant cytokine balance at a later stage after CPB in contrast to those without CPB. The heart produces a remarkable amount of cytokines only in the course of surgery with CPB.

Expression of CD97 and adhesion molecules on circulating leukocytes in patients undergoing coronary artery bypass surgery.

OBJECTIVE: Leukocyte activation is thought to be responsible for the adverse effects and postoperative complications following cardiopulmonary bypass (CPB). A novel cell surface molecule, CD97, is a sensitive marker of leukocyte and primary lymphocyte activation. The present study aimed to determine the activation of different leukocyte subsets by comparing the expression of CD97 and adhesion molecules (CD11, CD18) in patients receiving coronary surgery with or without CPB. METHODS: 30 patients were enrolled and scheduled for coronary bypass surgery under CPB (20 patients, group A) and with off-pump (OP) operation (10 patients, group B). Blood samples were taken before and during surgery, and over the following first week. RESULTS: Here, we report an early decrease in CD97 expression of granulocytes (PMN) and monocytes (MC) followed by an intensive increase reaching the maximum on postoperative days 2 and 3 in patients operated with CPB. The rate of active CD97-positive lymphocytes showed a marked, gradual increase until postoperative day 3 and remained elevated up to day 7 after CPB. OP surgery resulted in moderate alteration in the presence of CD97 on PMN, MC and lymphocytes. The expression of adhesion molecules was similar to CD97 in all leukocyte subsets. CONCLUSION: The findings about CD97 expression suggest considerable leukocyte activation following coronary bypass with CPB compared to OP surgery. The collected data show that the lymphocytes are highly activated and involved in leukocyte sequestration after CPB. Moreover, the importance of CD97 in CPB-related inflammatory response can be stated.

[Hemodynamic effects of propofol induction administered with target controlled infusion pump in patients scheduled for open heart surgery]. / Célkoncentráció-vezérelt módszerrel adagolt propofol hemodinamikai hatásai a narkózis bevezetése során nyitott szívmútétre kerüló betegekben.

Target controlled infusion systems have been developed to provide improved convenience and control during intravenous anaesthesia. The anaesthetist sets and adjust the target blood concentration and depth of anaesthesia--as required on clinical grounds. Infusion rates are altered automatically according to a validated pharmacokinetic model. Haemodynamic effects during induction of anaesthesia with target controlled infusion pump have been documented in this prospective study. Twenty patients scheduled for open heart surgery. Mean age 62.2 +/- 9.93 years. The surgical procedures were: 16 coronary bypass, 2 artificial valve replacement, 2 coronary bypass combined valve replacement. Anaesthesia was induced with alfentanil, 20-40 micrograms/kg, and propofol administered with target control infusion pump, 1.5-4 micrograms/ml target concentration. Pulse contour analysis was used for haemodynamic measurements. They were repeated before induction (T0), after induction--before intubation (T1), after intubation in two minutes intervals (T2-T5). Compared with values obtained in awake patients, there was a significant decrease in mean arterial pressure (-30%), in cardiac output (-25%), in heart rate (-8%), in vascular resistance (-9%), in contractility (-37.4%), in stroke volume (-17.5%). No ECG changes were observed during that period. The haemodynamic changes observed do not differ from the published data in patients presenting for cardiac surgery and anaesthetized with manually controlled infusion techniques using propofol.

Immunological and histopathological changes in the atrial tissue during and after cardiopulmonary bypass.

BACKGROUND: Ischemia and reperfusion injury occur in cardiac operations using cardiopulmonary bypass (CPB). Little is known about the immunological and histopathological changes in the atrial tissue under these conditions. OBJECTIVES: To investigate and compare multiple right atrial biopsy specimens by means of a self-developed pathological and immunohistochemistry panel. PATIENTS AND METHODS: Thirty-six nonselected adult patients (mean age 59+/-11.6 years, range 34 to 75) who had undergone different types of heart surgery (26 with and 10 without the use of CPB). RESULTS: Circumscribed necrosis was not found in any of the samples. Contractile bundle necrosis deteriorated only moderately with CPB. The share of hibernated myocardium seemed to increase during CPB, reaching 30% regardless of the basic disease. From the subepicardial toward the subendocardial surface, the amount of contractile proteins decreased continuously. Features similar to those seen with the phenomenon of 'stunning', which develops due to acute ischemia, were also noted. The apoptosis index did not exceed 1%. Apoptotic cells were generally randomly spread. It was very characteristic that with the use of CPB neither pro- nor antiapoptotic peptides (Bax, Bcl-2) were seen. In samples taken from patients who underwent surgery performed without the use of CPB both proteins were detected. The occurrence of cellular stress (heat shock protein 70 reaction) was rather variable in the samples. CONCLUSIONS: These investigations should be continued on homogeneous patient populations with the inclusion of proinflammatory cytokine determination.

[Successful surgical treatment of ruptured left ventricular aneurysm]. / Rupturált bal kamra aneurysma sikeresen operált esete.

Authors report on the successful surgical treatment of a ruptured left ventricular aneurysm that resulted in cardiogenic shock. Pathogenesis and complications of left ventricular aneurysm as well as the diagnostic and treatment modalities are summarized. Authors emphasize that the quick and close co-operation between their departments was a prerequisite of the success.

[Adult respiratory distress syndrome after open heart surgery]. / Adult respiratory distressz-szindróma nyitott szívmútétek után.

Cardiopulmonary bypass used in open heart surgery is responsible for nearly 15% of adult respiratory distress syndrome. The condition has a high mortality rate and still today we do not have a specific therapy for it. The aim of this study was to reveal the factors that are responsible for the adult respiratory distress syndrome developing after open heart operations. A retrospective statistical analysis of the database of 837 consecutive open heart operations was performed. Those patients in whom the adult respiratory distress syndrome has not developed have served as control group. chi 2 probe, Student t test and the Mann-Whitney test were used for the analysis. The authors applied logistic regression analysis for the multivariate investigation. Adult respiratory distress syndrome has developed in 10 patients (1.2%) in the postoperative period. One patient in whom the adult respiratory distress syndrome was accompanied by multiorgan failure has been lost. Between the two subgroups the authors found significant difference in the amount of blood and fresh frozen plasma transfusion, in the duration of ischaemic period and cardiopulmonary bypass, in anaesthesia time, and also in the occurrence of postoperative low cardiac output syndrome and acute myocardial infarction. Fresh frozen plasma can be a risk factor in the development of postoperative adult respiratory distress syndrome. In order to avoid the occurrence of this syndrome a great emphasis must be put on the pulmonary prevention.

[Low cardiac output following open heart surgery and catecholamine therapy]. / Nyitott szívmütéteket követö alacsony perctérfogat szindróma és katecholamin terápia.

The authors have studied the possible risk factors and complications of low cardiac output (LCO) following open heart operations. A retrospective analysis of 537 consecutive open heart operations has been performed with regards to the patients past medical and perioperative data. For statistical analysis the authors have applied the Chi-square test, T-probe, Mann-Whitney-test and logistical regression analysis by means of the SPSS software. Occurrence of various types of operations was as follows: coronary bypass (CABG): n = 266, 49.5%, combined CABG: n = 62, 11.5%, aortic valve replacement (AVR): n = 73, 13.6%, mitral valve replacement (MVR): n = 59, 11%, multiple valve replacement: n = 39, 7.3%, adult congenital surgery: n = 25, 4.7%. Aortic dissection repair: n = 6, 1.1%, miscellaneous: n = 7, 1.3%. LCO has developed in 7.3% (n = 39) of the patients. The authors have concluded that in the studied group of patients the independent risk factors of postoperative LCO are as follows: atrial fibrillation in the patient history, mitral valve disease, perioperative myocardial infarction, length of anaesthesia, NYHA stage, number of transfused units of blood, and the perioperative LDH value. Beyond these variables the cause of LCO in some cases was surely an intra or perioperative myocardial necrosis. At least a certain part of this perioperative myocardial damage must have been or might have been caused by the catecholamines given under compulsion for the treatment of LCO.

Gauze swabs left intrapericardially following cardiac surgery.

The occurrence of surgical gauze swabs left in the body following operations is not as rare as one would suspect, however the actual incidence is difficult to estimate. This accident seems to be occurring most frequently in general and gastro-intestinal surgery followed by operations in gynaecology and obstetrics and orthopaedics. There have been only a few papers in the literature dealing with the topic of foreign bodies left in place after cardiac surgical procedures. In this paper two cases of gauze swabs left intrapericardially following cardiac surgery are presented. The issue goes far beyond professional significance alone, but raises important and critical questions of medical ethics let alone legal implications.

[Simultaneous heart valve implantation and coronary bypass following kidney transplantation]. / Egy ülésben végzett mübillentyü implantáció és coronaria bypass mütét vesetranszplantáció után.

The authors report simultaneous aortic valve replacement and coronary artery bypass grafting surgery successfully performed in a patient with functioning transplanted kidney. The patient's cardiac status was classified as NYHA class III. The indication of the cardiac operation was a heavily calcified, stenotic and insufficient aortic valve and severe coronary artery disease. Renal function and blood biochemistry tests did not show significant changes in the postoperative period. The patient was discharged on the 15. postoperative day after an uneventful postoperative period. He remained asymptotic for two and a half years after operation. His cardiac status judged by postoperative treadmill stress was NYHA class I. The outcome of this case in accordance with results found in the literature further confirms that, if the clinical indications are appropriate, a kidney transplant patient can survive and benefit from cardiac surgery. To our knowledge our patient has been the only one who has survived aortic valve replacement and double coronary artery bypass grafting after kidney transplantation, and this is the first case that has ever been reported in Hungary.