Ischemic intestinal injury during cardiopulmonary bypass does not show an association with neutrophil activation: a porcine study.

BACKGROUND: Neutrophil activation and tissue sequestration are crucial events in intestinal ischemia-reperfusion injury, but their role in the gut wall after clinical cardiopulmonary bypass (CPB) remains unclear. We tested whether local post-CPB inflammatory response in the gut wall would be associated with intestinal mucosal perfusion. METHODS: Twenty pigs underwent 60 min of aortic clamping and 75 min of normothermic perfusion. Intestinal biopsies were taken after 120 min of reperfusion. Based on ileal myeloperoxidase activity (MPO), the animals were divided into 2 groups, CPB-induced increase in MPO (MPO+) versus no such increase (MPO-), for comparison of the parameters that measure gut mucosal perfusion. Ileal p(CO)((2)) and intramucosal pH were determined, and arterial gases were analyzed. Additionally, several hemodynamic parameters and blood thrombin-antithrombin complexes (TAT) were measured. RESULTS: Myocyte degeneration, endothelial activation and vasculitis were more pronounced in the MPO+ group (p < 0.05), while the MPO- group showed significantly increased pi(CO)((2)) and lower mucosal pH values during reperfusion. Hemodynamics and TAT levels did not differ between the groups. CONCLUSION: Tissue sequestration of neutrophils was poorly associated with perturbed mucosal perfusion after CPB. Mechanisms of gut wall injury after a low-flow/reperfusion setting can differ from those in reperfusion injury after total ischemia.

Antithrombin reduces pulmonary hypertension during reperfusion after cardiopulmonary bypass in a pig.

BACKGROUND: Antithrombin (AT) may alleviate many cardiopulmonary bypass (CPB) and ischemia-reperfusion (I/R)-related adverse effects. Using a porcine model of clinical cardiac surgery on CPB, we tested the effects of supplementary AT on myocardial and lung I/R injury. METHODS: Twenty pigs undergoing 60-min aortic clamping and 75-min normothermic perfusion were randomized in a blinded setting to receive an intravenous (i.v.) bolus of AT (250 IU/kg) (AT group, n = 10) or placebo (n = 10) 15 min before aortic declamping. An additional group of five animals received 500 IU/kg AT in an open-label setting (AT+). Thrombin-antithrombin complexes (TAT), activated clotting times (ACT), AT and myeloperoxidase (MPO) activities, troponin T, and several hemodynamic parameters were measured before CPB and after weaning from CPB up to 120 min after aortic declamping. After 120 min of reperfusion, myocardial and lung biopsies were taken for histological examination. RESULTS: AT effectively inhibited coagulation as assessed by ACT. In the AT and AT+ groups only, cardiac output (CO) and stroke volume (SV) showed a trend of post-ischemic recovery during the first 15 min after CPB. AT-attenuated reperfusion induced an increase in pulmonary arterial diastolic pressure (PAPD) but did not have significant effects on systemic or pulmonary vascular resistance. The effects of AT on SV, CO, and PAPD were fortified in the AT+ group. AT did not show effects on inflammatory changes in either myocardial or pulmonary tissue specimens. AT did not reduce post-ischemic troponin T release. CONCLUSION: Supplementary AT, in doses with significant anticoagulant effect, did not alleviate myocardial I/R injury in terms of histological inflammatory changes or post-ischemic troponin T release. Instead, however, AT-attenuated reperfusion induced an increase in pulmonary pressure after CPB. Mechanisms and clinical implications of these effects remain to be explored.

Vasopressin, when added to norepinephrine, was not associated with increased predicted mortality after cardiac surgery.

BACKGROUND AND AIMS: Arginin vasopressin (AVP) is a potent vasoconstrictor which has been used in vasodilatory shock when therapy with catecholamines and fluids has failed. In this study we evaluated the association of AVP with organ failure and mortality in cardiac surgical patients suffering from vasodilatory shock refractory to norepinephrine (NE) treatment. MATERIAL AND METHODS: Cardiac surgical patients who received AVP in addition to NE (N=33, AVP-group) and 33 control patients (NE group) who were treated with an equal dose of NE compared with AVP patients when AVP infusion started. Data on preoperative risk factors according to EuroSCORE and predicted mortality calculated by logistic EuroSCORE were collected preoperatively. Data on hemodynamics, organ dysfunctions, length of intensive care unit stay and mortality were collected. RESULTS: EuroSCORE did not differ between the groups, AVP:10.4 +/- 3.9 vs. NE 8.9 +/- 4.0. Observed 30 day mortality was lower than predicted in both groups, AVP: 7 (21.7%) vs. predicted mortality 25.9% and NE: 2 (6.1%) vs. 16.0%, respectively. There were more renal complications (36.4% vs. 9.1%, p = 0.008) and infections (30.3% vs. 3.0%, p = 0.003) in patients receiving AVP. Cardiovascular complications did not differ between the groups. CONCLUSIONS: In this prospectively observed cohort of cardiac surgical patients, AVP did not increase mortality predicted by Euroscore. Anyhow renal and infection complications were common.

Activated protein C and inflammation in human myocardium after heart surgery.

To assess possible interactions between inflammation and activation of the anticoagulant protein C system during post-ischemic reperfusion protein C, APC, neutrophil L-selectin expression and myocardial myeloperoxidase activity (MPO) were measured in 19 patients undergoing cardiopulmonary bypass. After reperfusion for 10 min, APC to protein C ratio (APC/PC) increased from pre-reperfusion value 1.43 +/- 0.12 (mean +/- SEM) to 2.25 +/- 0.29, p = 0.015. Negative correlations were observed between APC/PC and MPO activity (Spearman r -0.64, p = 0.007) and APC/PC and neutrophil L-selectin expression (r = -0.7, p = 0.007, demonstrating that post-ishemic protein C activation was associated with decreased neutrophil tissue sequestration. Thus, physiological protein C activation may be involved in regulation of the inflammatory injury during reperfusion of human ischemic coronary circulation.

Cardiopulmonary bypass and activation of antithrombotic plasma protein C.

OBJECTIVE: We hypothesized that antithrombotic plasma-activated protein C plays a defensive antithrombotic role during coronary ischemia and postischemic reperfusion. METHODS AND RESULTS: We evaluated protein C activation during cardiopulmonary bypass and coronary reperfusion in 20 patients undergoing coronary bypass surgery. During cardiopulmonary bypass and during the 10 minutes after aortic unclamping, the plasma levels of protein C (mean +/- standard error of the mean) decreased from 123% +/- 7% to 74% +/- 5% of normal mean. In contrast, the levels of activated protein C in plasma increased from 122% +/- 8% to 159% +/- 21%, and the activated protein C/protein C ratio increased from 1.04 +/- 0.08 to 2.29 +/- 0. 31 (P =.006, 2-tailed Wilcoxon signed rank test). Patients were stratified on the basis of the increase in activated protein C in the coronary sinus plasma at 10 minutes after reperfusion by means of the arbitrary value of 1.5 for the activated protein C/protein C ratio. Within 24 hours, the patients with low increases in activated protein C (ratio < 1.5, n = 8) had a significantly (P <.05) lower cardiac output and mean pulmonary artery pressure, as well as a higher systemic vascular resistance, than patients (n = 11) with high increases in activated protein C (ratio > 1.5). The rapid increase in activated protein C during the first 10 minutes after aortic unclamping indicated protein C activation in the reperfused vascular beds. CONCLUSIONS: The antithrombotic protein C pathway was significantly activated during cardiopulmonary bypass mainly during the minutes after aortic unclamping in the ischemic vascular beds. Suboptimal protein C activation during ischemia may impair the postischemic recovery of human heart and circulation.

Nitecapone as an additive to crystalloid cardioplegia in patients who had coronary artery bypass grafting.

BACKGROUND: Nitecapone has been shown to have a protective effect against ischemia-reperfusion injury in experimental heart transplantation and in Langendorff preparations. This prospective, randomized study assessed the effects of nitecapone in patients who had coronary artery bypass grafting. METHODS: Thirty patients with normal myocardial function were randomly divided into control patients (n = 15), who received crystalloid (Plegisol) cardioplegia, and nitecapone patients, who received nitecapone in a 50 microM solution (n = 15) in Plegisol. Cardioplegia was administered as an initial dose of 15 mL/kg of body mass after cross-clamping and 2 mL/kg every 15 minutes. Simultaneous coronary sinus and aortic blood samples, and myocardial biopsies were taken at 1, 5, and 10 minutes after unclamping. Hemodynamics were measured invasively for 24 hours and with transesophageal echocardiography for 3 hours after cardiopulmonary bypass. RESULTS: There were no adverse effects. The incidence of ventricular arrhythmias was significantly lower in the treatment group during the recovery period (p = 0.02). Cardiac output and stroke volume did not differ significantly between the groups. The conjugated dienes gradient between the aorta and the coronary sinus increased significantly during the first minute of reperfusion in the control group (p = 0.02) compared with the nitecapone group. Myeloperoxidase activity in myocardial biopsies was higher in the control group (2.3 times higher at 5 minutes and 3.2 times higher at 10 minutes) than in the nitecapone group (p = 0.13). CONCLUSIONS: Nitecapone did not exert any significant hemodynamic effects in patients with normal ejection fraction.

Nitecapone reduces cardiac neutrophil accumulation in clinical open heart surgery.

BACKGROUND: To study the effect of nitecapone, a novel antioxidant, on cardiac neutrophil activation during cardiopulmonary bypass in patients. METHODS: In a double-blind, placebo controlled trial, 30 male patients undergoing coronary artery bypass grafting were randomly assigned to control (crystalloid cardioplegia, n = 15) and nitecapone groups (cardioplegia supplemented with nitecapone, n = 15). Leukocyte differential counts, neutrophil and monocyte CD11b and L-selectin expressions and neutrophil hydrogen peroxide production were measured in blood samples parallelly obtained from the coronary sinus and aorta before cardiopulmonary bypass and at 1, 5, and 10 min after aortic declamping. Myocardial myeloperoxidase activity was analyzed in biopsies taken at 1, 5, and 10 min after declamping. RESULTS: Transcoronary neutrophil difference (i.e., aorta--sinus coronarius) at 1 min after aortic declamping was significantly lower in nitecapone-treated patients (0.41 [-0.42-0.98] x 10(9) cells/l) than in controls (0.68 [-0.28-2.47] x 10(9) cells/l; P = 0.032). At 5 min after aortic declamping, significant transcoronary reduction of neutrophil hydrogen peroxide production and CD11b expression were observed in controls but not in nitecapone patients. At 24 h postoperatively, left ventricular stroke volume was better in nitecapone-treated patients (94 [51-118] ml) than controls (66 [40-104] ml; P= 0.018). Data are median [range]. CONCLUSION: Nitecapone added to cardioplegia solution reduces cardiac neutrophil accumulation and transcoronary neutrophil activation during clinical cardiopulmonary bypass. Reflected by better left ventricular stroke volume, nitecapone treatment may be an additional way of reducing the deleterious effects of neutrophil activation during cardiopulmonary bypass.

Nitecapone inhibits myeloperoxidase in vitro and enhances functional performance after 8 h of ischemia in experimental heart transplantation.

Nitecapone (NC) has been shown to have beneficial effects on the functional recovery of rat hearts in Langendorff-preparation. The present study was executed to evaluate the effect of NC on preservation of grafts in heart transplantation and the role of NC in the inhibition of granulocyte infiltration. Donor hearts were perfused and stored at +4 degrees C for 8 h in either Ringer solution in the control-group (C-group, n = 26) or in NC (50 microM) added Ringer solution (NC-group, n = 18). The heterotopic heart transplantation was performed. The rats in both groups were killed at either 10 min or 60 min after release of the aortic clamp and tissue samples were obtained for antioxidative capacity, myeloperoxidase activity, and lipid peroxidation measurements. In vitro studies were performed using sodium azide or nitecapone to inhibit myeloperoxidase (MPO) activity of isolated human leukocytes. A total of 61% of the grafts began to beat in the NC-group, compared to 46% in the control group. Using an arbitrary scale of functional performance, only 33% (4/12) of the grafts were classified as well functioning in the control group, compared to 82% (9/11) in the NC-group (P<0.05). MPO activity was equal in both groups after 10 min but significantly lower after 60 min in the NC-group as compared to the control group (P<0.05). In vitro studies demonstrated that NC inhibits 50% of purified MPO activity at a concentration of 10 microM. NC did not significantly affect lipid peroxidation or the preservation of endogenous antioxidants. Since NC inhibited myeloperoxidase both in vitro and in vivo, it seems that the positive effects of NC on graft preservation may be mediated via the inhibition of granulocyte infiltration.

Nitecapone is of benefit to functional performance in experimental heart transplantation.

In heart transplantation, global ischemia of a graft is followed by reperfusion injury. The formation of oxygen free radicals induces arrhythmias and impairs functional recovery of the graft. This study was executed to evaluate the effect of the new antioxidant, nitecapone, on ischemia-reperfusion injury in heart transplantation in rats. Donor hearts were perfused and stored at +4 degrees C for 2 h in either Ringer's solution in the control group (C-group, n = 26) or Ringer's solution with nitecapone (NC) added (NC-group, n = 18). The donor aorta was anastomosed to the recipient's abdominal aorta and the pulmonary artery to the recipient's inferior vena cava. The grafts were classified into three categories based on the functional recovery. The rats in both groups were killed at 10, 30, or 60 min after release of the aortic clamp. Tissue samples for chemiluminescence were obtained from the left ventricle, the right ventricle, and the septum of the heart. All grafts in the NC-group (18/18) began beating after release of the aortic clamp, whereas only 50% (13/26) of the grafts in the C-group recovered (P < 0.0004). Chemiluminescence analysis showed lipid peroxidation values to be higher in the C-group than the NC-group up to 1 h after reperfusion. Also, the right ventricle samples showed lower chemiluminescence values in the NC-group than in the C-group. In conclusion, our results do not support the theory that different regions of the heart have different vulnerability to ischemia-reperfusion injuries. Nitecapone has a beneficial effect on the preservation of the grafts in terms of functional recovery.

Delayed intrathoracic herniation of the stomach with pleural empyema due to diaphragmatic stab wound.

A 32-year-old man received a left-sided thoracic stab wound, which was primarily treated with percutaneous tube thoracostomy. Ipsilateral empyema appeared 8 weeks later and subsequent investigations revealed herniation of the stomach through the diaphragm. The diaphragmatic rupture and a perforation in the gastric wall were repaired at thoracotomy. The literature on such wounds is reviewed.