Matrix metalloproteinase activity and immunohistochemical profile of matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 during human dermal wound healing

Proteolytic activity is required for the turnover of the extracellular matrix during wound healing. Matrix metalloproteinases can collectively cleave all components of the extracellular matrix, with the endogenous tissue inhibitor of metalloproteinase-1 regulating their activity. Breast tissue taken at varying postoperative times (n= 92) or during surgery (controls, n= 17), was used to investigate the temporal and spatial activity of matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 during human wound healing. Matrix metalloproteinase activity, determined using a quenched fluorescence substrate assay, increased during early healing (3-8 weeks) compared to controls, and then decreased between 24 and 36 weeks after surgery (p < 0.05 until 24 weeks, Mann-Whitney U-test). Immunohistochemistry scores for matrix metalloproteinase-9 expression were significantly elevated compared to controls in scar endothelial cells and fibroblasts from 2 until 12 and 20 weeks, respectively. Matrix metalloproteinase-2 staining was observed exclusively in fibroblasts, reaching maximum levels 8-12 weeks after surgery, decreasing by 1.5 years but remaining significantly increased. Tissue inhibitor of metalloproteinase-1 staining was relatively sparse but was significantly increased until 8 weeks after surgery. These results show that matrix metalloproteinases are present at elevated levels during early wound healing, when angiogenesis occurs, and suggest that matrix metalloproteinase-9 may play a significant role. The later expression of matrix metalloproteinase-2 and -9 in fibroblasts suggests a role in extracellular matrix remodeling.     

Cardiac surgery increases the activity of matrix metalloproteinases and nitric oxide synthase in human hearts

OBJECTIVES: Heart function is variably impaired after cardiopulmonary bypass. We hypothesized that, similar to other myocardial injury states, cardiopulmonary bypass leads to enhanced activity of nitric oxide synthase and matrix metalloproteinases. METHODS: We obtained right atrial biopsy specimens and plasma samples at the onset and termination of cardiopulmonary bypass in 10 patients. Biopsy specimens were analyzed for nitric oxide synthase activity by using a citrulline assay, whereas plasma and tissue were analyzed for matrix metalloproteinase-9 and matrix metalloproteinase-2 activity by using zymography. Tissue inhibitor of metalloproteinase-4 was analyzed by means of Western blotting. The cellular expression of inducible nitric oxide, endothelial nitric oxide synthase, matrix metalloproteinase-2, and matrix metalloproteinase-9 was determined in right atrial biopsy samples from 3 additional patients by using the appropriate conjugated antibodies. RESULTS: Nitric oxide synthase activity increased from the beginning to the end of bypass (4.46 +/- 1.07 vs 16.77 +/- 4.86 pmol citrulline/mg of protein per minute, respectively; P =.018). Pro-matrix metalloproteinase-9 activity increased in hearts (199 +/- 41 vs 660 +/- 177 density units/mg protein; P =.008) and plasma (14.1 +/- 4.6 vs 52.2 +/- 5.9 density units/mg protein; P =.008). Pro-matrix metalloproteinase-2 activity increased in the heart (201 +/- 23 vs 310 +/- 35 density units/mg protein, P <.05) but not in plasma. Tissue inhibitor of metalloproteinase-4 expression in the heart decreased (1574 +/- 280 vs 864 +/- 153 density units, P =.014). CONCLUSIONS: Cardiopulmonary bypass activates enzymes mediating acute inflammation and organ injury (ie, nitric oxide synthase, matrix metalloproteinase-9, and matrix metalloproteinase-2). Decreased tissue inhibitor of metalloproteinase-4 expression allows relatively unopposed increases in matrix metalloproteinase tissue activity. We postulate that these changes play a role in the pathogenesis of heart dysfunction after bypass surgery.     

Neutrophil-mediated secretion and activation of matrix metalloproteinase-9 during cardiac surgery with cardiopulmonary bypass

Cardiopulmonary bypass (CPB) induces neutrophil activation, degranulation, and a systemic inflammatory response. Matrix metalloproteinase (MMP)-9 exists in neutrophils and is released on neutrophil activation. Increased levels of MMP-9 have been observed in patients undergoing CPB. We designed the present study to determine whether MMP-9 is derived from neutrophils during CPB. Twenty-one patients undergoing elective coronary artery bypass grafting with or without CPB were included in this study. Blood was collected and analyzed for MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1. Neutrophils were also isolated and examined for MMP-9 production and mRNA expression. Plasma levels and activity of MMP-9 increased significantly 2-6 h after beginning CPB, whereas the MMP-9 levels in patients with off-pump cardiac surgery did not increase. The neutrophil content of MMP-9 and mRNA increased significantly 2 h after beginning CPB. The plasma levels of TIMP-1 increased gradually for 6 h, whereas the MMP-9/TIMP-1 ratios were increased 2-4 h after beginning CPB. The present study demonstrated that CPB causes an increase in the concentration and activity of plasma MMP-9. The corresponding increase in neutrophil MMP-9 expression and production suggests that MMP-9 is derived primarily from neutrophils and may contribute to the inflammatory response associated with CPB.     

Superior biocompatibility of heparin-bonded circuits in pediatric cardiopulmonary bypass.

BACKGROUND: Heparin bonding of pediatric cardiopulmonary bypass circuits may decrease activation of blood compartments as inflammatory responses. We studied the biocompatibility of heparin-bonded circuits in infant cardiac surgery. METHODS: Twenty-four infants undergoing elective cardiac surgery were randomly assigned to either a nonheparin-bonded control circuit (n = 12) or a fully heparin-bonded circuit (n = 12) including membrane oxygenator, reservoir, and all tubing. Blood samples were used to identify differences in complement activation and cytokine release between groups during and after cardiopulmonary bypass. The postbypass oxygenation index was also compared. RESULTS: The C3 activation product in the heparin-bonded group was significantly lower during (p < 0.01) and just after (p < 0.05) cardiopulmonary bypass. No statistically significant difference in C4 activation products was observed. Lower interleukin-6 and tumor necrosis factor-alpha were found immediately after cardiopulmonary bypass (p < 0.05) and a higher mean postbypass oxygenation index was also seen (p < 0.05) in the heparin-bonded group. CONCLUSION: We found that a heparin-bonded cardiopulmonary bypass circuit reduced inflammatory response and improved oxygenation in pediatric cardiac surgery. These results suggest that the superior biocompatibility of the bonded circuit may reduce pulmonary complications.     

The effect of intravenous quinaprilat on plasma cytokines and hemodynamic variables during cardiac surgery

OBJECTIVES: Perioperative treatment with angiotensin-converting enzyme (ACE) inhibitors in cardiac surgery with cardiopulmonary bypass is still controversial. Using ACE inhibitors during cardiac surgery might be associated with an increased risk of critical hypotensive episodes. On the other hand, ACE inhibitors could have beneficial effects with respect to the development of the systemic inflammatory response syndrome. DESIGN: The effect of acute administration of quinaprilat on hemodynamic variables and plasma cytokines was assessed under double-blind, randomized, and placebo-controlled conditions. SETTING: Department of anesthesiology and cardiovascular surgery clinic in a university hospital. PARTICIPANTS: Forty patients without preexisting cardiac failure, undergoing coronary artery bypass grafting. INTERVENTIONS: Patients received 0.08 mg/kg of intravenous quinaprilat or intravenous isotonic saline solution after induction of anesthesia. MEASUREMENTS AND RESULTS: Blood samples were taken after induction of anesthesia (T0), before cardiopulmonary bypass (T1), at the end of surgery (T2), and 4 hours after the end of surgery (T3). There was no difference between the 2 groups regarding mean arterial pressure and inotropic or vasopressor support. Systemic vascular resistance index was significantly lower in the quinaprilat group at T2 (p = 0.016) and T3 (p = 0.017). No difference in proinflammatory cytokine levels was observed between the 2 groups. CONCLUSIONS: The present investigation shows that acute administration of an intravenous ACE inhibitor, quinaprilat, has no influence on proinflammatory cytokines during cardiac surgery with cardiopulmonary bypass. The patients treated with quinaprilat showed an improved systemic vascular resistance index with no increased risk of deleterious hemodynamic episodes.     

Responses of interleukin-6 and tumor necrosis factor during and after cardiac surgery undergoing cardiopulmonary bypass and pancreatoduodenectomy

To evaluate the effect of cardiopulmonary bypass on immunological function, we measured interleukin-6 (IL-6) and tumor necrosis factor (TNF) in 12 patients undergoing cardiac surgery during and after cardiopulmonary bypass, and in 10 patients with pancreatoduodenectomy. Plasma IL-6 levels were determined using the Human Interleukin 6 ELISA Kit, and TNF levels were determined using a highly sensitive sandwich enzyme immunoassay. In patients with cardiac surgery, plasma levels of IL-6 and TNF increased during cardiopulmonary bypass, and in patients with pancreatoduodenectomy, IL-6 and TNF levels significantly increased at the end of intraabdominal manipulation. These results suggest that endotoxin may have activated the immune system and stimulated cytokine production after pancreatoduodenectomy and during bypass.     

Acute mesenteric ischemia after cardiopulmonary bypass.

Acute mesenteric ischemia is an uncommon but catastrophic event after cardiopulmonary bypass. From 1980 to 1990, 16,951 cardiac procedures requiring cardiopulmonary bypass were performed at Emory University Hospital in Atlanta, Ga. Eighteen patients (0.1%) had acute mesenteric ischemia that resulted in intestinal infarction. Emergency cardiac surgery had been performed in 16 of the 18 patients, and all 18 patients were vasopressor dependent for hemodynamic support after surgery. Diagnostic difficulties resulted in the diagnosis of intestinal infarction an average of 9 1/2 days after cardiopulmonary bypass. Nonocclusive mesenteric arterial ischemia was the determined cause in all cases. Statistically significant risk factors associated with acute mesenteric ischemia after cardiopulmonary bypass surgery included (1) emergency cardiac surgery (p less than 0.0001), (2) the use of an intraaortic balloon pump (p less than 0.0001), (3) failed angioplasty requiring emergency surgery (p = 0.0074), (4) prolonged pump time (p = 0.0093), and (5) advanced age (p = 0.0016). A high index of suspicion for mesenteric ischemia after cardiopulmonary bypass in patients with identified risk factors may decrease the diagnostic delay and lead to an improvement in the 67% mortality rate seen in this series.     

Transient rise in serum soluble Fas (APO-1/CD95) in patients undergoing cardiac surgery

The Fas molecule, also designated APO-1/CD95, belongs to the tumor necrosis factor (TNF) receptor family. It is a widely expressed membrane-anchored protein that induces apoptosis by Fas/Fas ligand (Fas-L) mediation. It was reported that Fas-mediated apoptosis plays an important role in regulation of the immune system, systemic inflammatory response, and ischemia/reperfusion injury. A soluble form of Fas (sFas) is produced either through the proteolytic cleavage of membrane-bound receptors or by alternative splicing, and sFas is thought to be implicated in apoptosis. In addition, sFas released damaged cells, and elevated serum levels of sFas reflect systemic tissue damage. To examine the specificity of sFas production during cardiac surgery with cardiopulmonary bypass, we serially measured the serum sFas levels in 13 patients during and after surgery. Blood samples were obtained before surgery, at the end of cardiopulmonary bypass, at the end of surgery, and at 12 h after surgery. Levels of serum sFas were determined by sandwich ELISA. Seven patients undergoing other types of surgeries served as controls. Although increased sFas was not observed in the control group, a significantly higher sFas level was detected in cardiac surgical patients at the end of surgery than before surgery (p = 0. 028), and the level decreased at 12 h after surgery. A significant correlation was observed between the maximum sFas values and the length of surgery (r = 0.659, p = 0.012) and cardioplegic arrest (r = 0.559, p = 0.046). Elevated serum sFas levels were observed in patients undergoing cardiac surgery, and these serum sFas levels reflect the severity of a surgery. sFas may play an important role in the pathophysiology of surgical damage caused by cardiac surgery with cardiopulmonary bypass.     

Correlation between interleukin-6 and matrix metalloproteinase-9 in early wound healing in children

Interleukin-6 and matrix metalloproteinase-9 concentrations in the wound fluid and their associations to cellular changes were determined in early wound healing. Wound healing of 75 children who underwent elective operations was studied with the Cellstick(R) device, which was inserted into the wound at the end of the operation and removed 3 or 24 hours post-wounding. Differential counts of the wound cells and interleukin-6 and matrix metalloproteinase-9 concentrations in the wound fluid were analyzed. Interleukin-6 and the matrix metalloproteinase-9 concentrations increased in parallel (r = 0.81). The proportion of wound neutrophils increased (p < 0.0001) and lymphocytes decreased (p < 0. 0001) between the observation times. The number of wound neutrophils had a strong correlation with both interleukin-6 (adjusted R2 = 0.41, p < 0.0001) and matrix metalloproteinase-9 concentrations (adjusted R2 = 0.37, p < 0.0001). The extracellular matrix degradation process of the early wound healing seems to be closely linked to the inflammatory response. Both of these measured markers are associated significantly with the neutrophil proportion in the wound.     

Superior biocompatibility of heparin-bonded circuits in pediatric cardiopulmonary bypass

Background: Heparin bonding of pediatric cardiopulmonary bypass circuits may decrease activation of blood compartments as inflammatory responses. We studied the biocompatibility of heparin-bonded circuits in infant cardiac surgery.Methods: Twenty-four infants undergoing elective cardiac surgery were randomly assigned to either a nonheparin-bonded control circuit (n = 12) or a fully heparin-bonded circuit (n = 12) including membrane oxygenator, reservoir, and all tubing. Blood samples were used to identify differences in complement activation and cytokine release between groups during and after cardiopulmonary bypass. The postbypass oxygenation index was also compared.Results: The C3 activation product in the heparin-bonded group was significantly lower during (p < 0.01) and just after (p < 0.05) cardiopulmonary bypass. No statistically significant difference in C4 activation products was observed. Lower interleukin-6 and tumor necrosis factor-α were found immediately after cardiopulmonary bypass (p < 0.05) and a higher mean postbypass oxygenation index was also seen (p < 0.05) in the heparin-bonded group.Conclusion: We found that a heparin-bonded cardiopulmonary bypass circuit reduced inflammatory response and improved oxygenation in pediatric cardiac surgery. These results suggest that the superior biocompatibility of the bonded circuit may reduce pulmonary complications.     

Preoperative statin therapy does not reduce cognitive dysfunction after cardiopulmonary bypass

OBJECTIVE: The purpose of this study was to determine if patients receiving statin therapy before coronary artery bypass grafting surgery would have less cognitive dysfunction after cardiopulmonary bypass as a consequence of a diminished inflammatory response. DESIGN: Retrospective observational study of patients undergoing coronary artery bypass grafting surgery. SETTING: Referral center for cardiothoracic surgery at a university hospital. PARTICIPANTS: Four hundred forty patients undergoing coronary artery bypass grafting surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-five percent of patients received statins in the preoperative period. Multivariable analysis revealed no effect of preoperative statin therapy on cognitive function (p = 0.67). Post hoc analysis revealed that statin therapy at hospital discharge was associated with less improvement in cognitive performance at 6 weeks after surgery (p = 0.011). No significant differences were found between statin therapy groups in either range or maximum value of any of the cytokines (p > 0.05). CONCLUSIONS: Preoperative statin therapy did not decrease the inflammatory response to cardiopulmonary bypass or the cognitive dysfunction commonly seen after cardiac surgery.     

Heparin-coated circuits reduce occult myocardial damage during CPB: a randomized, single blind clinical trial.

OBJECTIVES: Cardiopulmonary bypass is associated with a diffuse systemic inflammatory response that can cause considerable morbidity, including organ dysfunction and bleeding. Heparin-coated circuits have been shown to give a reduced inflammatory response with clinical benefits during open-heart surgery. However, the effects on lipid peroxidation, neutrophil activation and myocardial ischemic damage in the human have remained unknown. METHODS: In a randomized single blind trial, complement activation, neutrophil counts, malondialdehyde, and cardiac enzymes were studied in 39 patients undergoing open-heart surgery. Two groups were perfused with cardiopulmonary bypass circuits with (n=20) or without heparin-coating (n=19). RESULTS: The different complement factors (C3, C4, C3d, C3d/C3 and the C-function), neutrophil levels, MDA and the cardiac enzyme levels were comparable before CPB was started and significantly increased in both groups during bypass. There were significant intergroup differences in the neutrophil levels and MDA after reperfusion (P<0.0001). Furthermore, significant positive correlations between the lipid peroxidation, expressed as MDA levels, and the levels of neutrofils and the cardiac enzyme, CK-MB were seen within the groups. CONCLUSIONS: Heparin coated circuits did lead to a decreased neutrophil response and MDA level. The correlations between CK-MB and neutrophil and MDA levels suggest neutrophil activation leading to lipid peroxidation that may influence myocardial damage. Heparin coating improved biocompatibility and was associated with less occult myocardial ischemic damage in patients undergoing open heart surgery.     

Effects of propofol on pulmonary inflammatory response and dysfunction induced by cardiopulmonary bypass

The pulmonary inflammatory response and pulmonary dysfunction after cardiopulmonary bypass is a major problem in patients undergoing cardiac surgery. Propofol has anti-inflammatory and immunomodulatory properties which may attenuate this response. Thirty patients undergoing cardiopulmonary bypass were randomly assigned to receive saline (control group) or propofol (propofol group). Pulmonary thoracic compliance, respiratory index, malondialdehyde and interleukin-8 concentrations and intrapulmonary polymorphonucleocyte sequestration were measured at pre-bypass and 5, 30, 60, 90 and 120 min after unclamping the aorta. Plasma levels of interleukin-8, malondialdehyde and the respiratory index increased and reached peaks 30 min after unclamping in both groups. However, in the propofol group the increases were less than in the control group (p < 0.01). Intrapulmonary polymorphonucleocytes sequestration in the propofol group was less than in the control group 5 min after unclamping (p < 0.0001). Pulmonary thoracic compliance decreased significantly after unclamping in both groups, but the reduction was less in the propofol group (p < 0.01). These findings suggest that propofol administered during bypass could reduce the severity of pulmonary dysfunction.     

Tumor necrosis factor and clinical and metabolic courses after cardiac surgery in children

OBJECTIVE: This study was undertaken to determine the relationship between plasma tumor necrosis factor concentrations and hemodynamic and metabolic parameters during the postoperative clinical course in children undergoing cardiac surgery. METHODS: Tumor necrosis factor levels of 10 consecutive children undergoing surgery for repair of congenital heart defects were analyzed in blood samples drawn at predetermined time points during surgery and up to 24 hours thereafter. Clinical data were collected at these times for correlation to tumor necrosis factor levels. RESULTS: All the patients survived. Tumor necrosis factor was detected in all 10 children. Tumor necrosis factor levels declined after induction of general anesthesia (201 +/- 65 pg/mL) steadily decreasing during surgery, reaching 80 +/- 50 pg/mL at 24 hours after the operation. Tumor necrosis factor levels were found to be inversely correlated with mean blood pressure values and indicators of acidosis (bicarbonate levels and base excess, P <.03). They were not correlated with the durations of cardiopulmonary bypass and aortic crossclamping. CONCLUSIONS: Tumor necrosis factor released into the circulation during and after pediatric cardiac surgery under cardiopulmonary bypass may be related to the hemodynamic and acid-base changes observed after cardiac surgery. Elucidation of the relationship between tumor necrosis factor and patient outcome in high-risk patients awaits further studies.     

Evidence of increased matrix metalloproteinase-9 concentration in patients following cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response, which can result in acute lung injury known as "postperfusion syndrome." Neutrophil activation with concomitant serine protease release has been implicated in the pathogenesis of "postperfusion syndrome." Increased plasma levels of neutrophil elastase (NE) have been demonstrated in patients undergoing CPB, and it is well documented that both NE and matrix metalloproteinase-9 (MMP-9) have a synergistic role in pulmonary injury. We, therefore, hypothesized that plasma levels of MMP-9 would be elevated in patients after CPB. Human plasma was obtained after informed consent from eight patients undergoing CPB. Plasma was collected at the start of CPB, 5 minutes after the initiation of CPB, and at the termination of CPB (156 +/- 17 min). All samples were analyzed by both standard enzyme-linked immunosorbent assay (ELISA) and gelatin zymography for MMP-9 (free and total enzyme) concentration. Data were expressed as means +/-SE and assessed by analysis of variance (ANOVA). Plasma MMP-9 concentration was significantly increased at the end of CPB (191 +/- 30.4 ng/mL; p <.05) as compared to both the start of CPB (28.3 +/- 13.2 ng/mL) and 5 minutes after the initiation of CPB (44.3 +/- 15.4 ng/mL). Patients undergoing CPB show an increase in serum MMP-9 levels. Prior studies utilizing an animal model of "postperfusion syndrome" have shown that inhibition of MMP-9 and NE prevented pulmonary injury following CPB. The results of the current study suggest that such an approach may also have merit in the clinical setting of cardiopulmonary bypass.     

The inflammatory response to colloids and crystalloids used for pump priming during cardiopulmonary bypass

Background: Systemic inflammatory response frequently occurs after coronary artery bypass surgery and is strongly correlated with the risk of postoperative morbidity and mortality. This study tests the hypothesis that the priming of the extracorporeal circuit with colloid solutions results in less inflammation in patients undergoing cardiac surgery than priming with crystalloid solutions. Methods: A prospective, randomized study was designed. Forty‐four patients undergoing elective coronary artery bypass grafting were randomly allocated to one of two groups: 22 patients primed with Ringer's lactate (RL) solution and 22 patients primed with gelatin‐containing solution during the surgery. Plasma levels of interleukin (IL)‐6, IL‐8, tumor necrosis factor (TNF)‐α, C‐reactive protein (CRP) and, complement 4 were measured during the surgical intervention and over the following 48 postoperative hours. Cytokine levels were measured by enzyme‐linked assays from plasma samples obtained at specific time points pre‐ and post‐operatively. Results: In both groups the serum levels of the pro‐inflammatory cytokines (IL‐6, IL‐8, TNF‐α), CRP, complement 4, and leukocytes increased significantly over the baseline, although no significant differences were observed between the two groups. The operation time, blood loss, need for inotropic support, extubation time, and length of intensive care unit stay did not differ significantly between the two groups. Conclusion: Priming with gelatin vs. RL produces no significant differences in the inflammatory response in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.     

Tumor necrosis factor gene polymorphism is associated with enhanced systemic inflammatory response and increased cardiopulmonary morbidity after cardiac surgery

Cardiopulmonary bypass induces a systemic inflammatory response characterized by alterations in cardiopulmonary function. Mediators for this morbidity are the cytokines tumor necrosis factor (TNF)-alpha and interleukins. A genomic polymorphism within the TNF locus is associated with increased TNF-alpha levels and high mortality in severe trauma and sepsis. We assessed the relationship of biallelic polymorphisms of the TNF locus in patients undergoing elective cardiac surgery to release of proinflammatory cytokines and cardiopulmonary morbidity. TNF genotypes, plasma concentrations of TNF-alpha, interleukin-6, and cardiopulmonary morbidity were studied in 95 unselected, consecutive patients undergoing routine cardiac surgery. TNF genotypes were determined by the solid-phase minisequencing method. Patients homozygous for the TNFB2 allele (n = 42) displayed larger peak concentrations of TNF-alpha (11.3 +/- 1.3 versus 7.8 +/- 0.7 pg/mL; P = 0.013) and interleukin-6 (153 +/- 27 versus 87 +/- 7 pg/mL; P = 0.010) when compared with patients homozygous or heterozygous for TNFB1 (n = 53). The TNFB2 homozygotes had a higher incidence of left ventricular dysfunction (31% versus 9%; P = 0.029; odds ratio 3.84 [95% confidence interval, 1.40-24.3]), postoperative pulmonary dysfunction (24% versus 6%; P = 0.016; odds ratio 5.21 [95% confidence interval, 1.49-18.3]), and a lower pulmonary oxygenation index (29 +/- 1.9 versus 36.1 +/- 1.8; P = 0.013). Patients homozygous for the TNFB2 allele may develop an enhanced systemic inflammatory response with an increased risk of cardiopulmonary morbidity after cardiac surgery. IMPLICATIONS: The associations between tumor necrosis factor (TNF) gene polymorphism, plasma cytokines, and cardiopulmonary function after elective cardiac surgery were evaluated. Patients homozygous for the TNFB2 allele displayed larger concentrations of TNF-alpha and interleukin-6 and had an increased risk of developing left ventricular and pulmonary dysfunction compared with TNFB1 homo- or heterozygotes.     

Human cytokine responses to coronary artery bypass grafting with and without cardiopulmonary bypass.

BACKGROUND: Coronary artery bypass grafting (CABG) is associated with a systemic inflammatory response. This has been attributed to cytokine release caused by extracorporeal circulation and myocardial ischemia. This study compares the inflammatory response after CABG with cardiopulmonary bypass and after minimally invasive direct coronary artery bypass grafting (MIDCABG) without cardiopulmonary bypass. METHODS: Cytokine release and complement activation (interleukin-6 and interleukin-8, soluble tumor necrosis factor receptors 1 and 2, complement factor C3a, and C1 esterase inhibitor) were determined in 24 patients before and after CABG or MIDCABG. The maximum body temperature, chest drainage, and fluid balance were recorded for 24 hours after operation. RESULTS: Release of interleukin-6, interleukin-8, and tumor necrosis factor receptors 1 and 2 was significantly higher (p < or = 0.005) in the CABG group than the MIDCABG group just after operation. After 24 hours, a significant increase in interleukin-6 was also found in the MIDCABG group (p = 0.001) compared with preoperative value. Body temperature and fluid balance were significantly higher after CABG (p < or = 0.001). CONCLUSIONS: Minimally invasive direct coronary artery bypass grafting represents a less traumatizing technique of surgical revascularization. The reduction in the inflammatory response may be advantageous for patients with a high degree of comorbidity.     

Factores implicados en el desarrollo de vasoplejía tras cirugía cardiaca con circulación extracorpórea. Estudio prospectivo observacional

ObjectiveThe incidence and risk factors for vasoplegia in the early postoperative period and at 24 h are investigated in patients subjected to cardiopulmonary bypass surgery. Vasoplegia following cardiac surgery with cardiopulmonary bypass is associated with a high morbimortality. The risk factors described emerged from retrospective, non-controlled studies.MethodsObservational prospective study of 188 consecutive patients subjected to cardiac surgery with cardiopulmonary bypass in a single hospital between November 2011 and May 2012. Emergency surgery or complex procedures were excluded. Vasoplegia was assessed during the immediate postoperative period, and at 24 h after surgery, and was defined as a mean arterial pressure below 50 mmHg, and the need for a noradrenaline perfusion of more than 0.08 μg/kg/min, monitored by cardiac output and systemic vascular resistances. The anaesthetic and cardiopulmonary bypass protocols, as well as haemodynamic management, were the same in all patients.ResultsAlmost half (48%) of patients had vasoplegia in the immediate postoperative period, and 34% at 24 h. Risk factors for immediate vasoplegia development were preoperative use of angiotensin converting enzyme inhibitor drugs, a mean arterial pressure < 50 mmHg immediately after beginning cardiopulmonary bypass, duration of aortic clamping as well as the cardiopulmonary bypass, and minimum temperature in cardiopulmonary bypass. Vasoplegia at 24 h after surgery was correlated to preoperative angiotensin converting enzyme inhibitor drug treatment and cardiopulmonary bypass duration.ConclusionThe incidence of vasoplegia after cardiac surgery with cardiopulmonary bypass is high during the first 24 postoperative hours. Preoperative treatment with angiotensin converting enzyme inhibitor and the mean arterial pressure at the beginning of cardiopulmonary bypass are the more easily controllable risk factors. In patients arriving to surgery with those drugs, treatment or prevention of vasoplejia should be planned.