Improved cerebral recovery from hypothermic circulatory arrest after remote ischemic preconditioning.

BACKGROUND: Remote ischemic preconditioning is a novel method of reducing ischemia-reperfusion injury in which a transient ischemic period of the limb provides systemic protection against a prolonged ischemic insult. This method of preconditioning has shown some potential in ameliorating ischemia-related injury in various organs and experimental settings. We hypothesized that remote ischemic preconditioning might also improve the recovery from hypothermic circulatory arrest (HCA). METHODS: Twenty-four juvenile pigs underwent 60 minutes of HCA at 18 degrees C with either transient right hind leg ischemic preconditioning or no ischemic preconditioning. Preconditioning was induced by four cycles of 5-minute ischemia periods with three 5-minute reperfusion periods in between. Microdialysis and electroencephalography (EEG) data were recorded to detect any possible changes during the recovery phase. RESULTS: The EEG data showed that the remote ischemic preconditioning group had significantly better EEG recovery time and a lower burst suppression ratio throughout the follow-up period. Cerebral extracellular glucose and glycerol content rose significantly immediately after HCA in the control group compared with the remote ischemic preconditioning group, and significantly higher lactate concentrations were measured in the control group at 5 and 6 hours after reperfusion, indicating a difference in cerebral metabolism. CONCLUSIONS: Our data imply that remote ischemic preconditioning improves the recovery from HCA. It provides a faster recovery of cortical neuronal activity and protection against potential oxygen radical-mediated ischemia damage during and after HCA. In addition, it seems to protect from a late phase lactate and pyruvate burst, mitigating possible damage from an anaerobic metabolism phase.

Acute homing of bone marrow-derived mononuclear cells in intramyocardial vs. intracoronary transplantation.

OBJECTIVES: Cell homing optimisation after transplantation is critical in myocardial infarction (MI) cell therapy. DESIGN: Eight pigs were randomized to receiving autologous purified (111)indium-labeled bone marrow mononuclear cells (BMMCs) (10(8) cells/2 ml) by intramyocardial (IM) (n=4) or by intracoronary (IC) (n=4) transplantation after 90 minutes occlusion of the CX-coronary artery. Dual isotope SPECT imaging was performed 2 and 24 hours postoperatively. Two animals were additionally analyzed on the sixth postoperative day. Tissue samples from the major organs were analyzed. RESULTS: In SPECT imaging revealed that BMMCs administered using IM injection remained in the injured area. In contrast, minor proportion of IC transplanted cells remained in the myocardium, as most of the cells showed homing in the lungs. Analysis of the biopsies showed a seven-fold greater number of cells in the myocardium for the IM method and a 10-fold greater number of cells in the lungs in the IC group (p < 0.001). CONCLUSIONS: In producing persistently high cell homing at the infarction site, the IM transplantation is superior to the IC transplantation. However, the IC administration might be more specific in targeting injured capillaries and epithelial cells within the infarcted myocardium.

Acute edematous and necrotic pancreatitis in a porcine model.

OBJECTIVE: It is unclear why pancreatitis progresses either to mild edematous disease or to severe necrotic disease. The aim of the study was to shed some light on this topic by investigating differences during the early stages of necrotic and edematous pancreatitis. MATERIAL AND METHODS: Piglets were randomized into two groups. Necrotic pancreatitis was induced with retrograde injection of 20% taurocholic acid (1 ml/kg), and edematous pancreatitis was induced with 0.9% NaCl (1 ml/kg). Central hemodynamics was measured, and pancreatic microcirculation was directly examined by intravital microscopy. Vascular permeability to proteins and albumin was measured by microdialysis. Apoptosis and claudins 2, 3, 4, 5, and 7 were analyzed from pancreatic tissue samples. Blood samples were taken for analysis of blood cell counts, blood gases, lipase, and amylase. RESULTS: Hemodynamic changes were similar in both groups, whereas microcirculatory impairment was more pronounced in necrotic pancreatitis. Necrosis was associated only with necrotic pancreatitis. Apoptosis increased only in edematous pancreatitis. The number of blood neutrophils and monocytes increased and lymphocyte and platelet counts decreased in both groups. Necrotic pancreatitis was associated with increased permeability to albumin and proteins. Expression of claudins 3, 4, 5, and 7 was not changed during pacreatitis, but in acinar cells, membranous expression of claudin-2 increased in both groups. CONCLUSIONS: The results show that acute edematous pancreatitis is characterized by induction of apoptosis, whereas full-blown pancreatitis is characterized by necrosis. Impaired vascular permeability to albumin and protein is related to the early phase of necrotic pancreatitis. Claudin-2 increases during acute necrotic and edematous pancreatitis and may be related to impaired permeability.

The use of statins and fate of small abdominal aortic aneurysms.

The aim of this study was to evaluate the value of statins in reducing abdominal aortic aneurysm (AAA) growth rate and improving freedom from aneurysm repair or rupture. One hundred and twenty-one patients with AAA undergoing ultrasonographic surveillance for at least one year were included in this retrospective study. Patients treated with statins had a decreased linear aneurysm growth rate than those not receiving statins (1.9+/-1.8 mm/year vs. 2.6+/-2.4 mm/year, P=0.27), but this difference did not reach statistical significance. Statin users had a better survival freedom from aneurysm repair or rupture (at 5 years: 72.3% vs. 52.5%, P=0.048). The impact of treatment with statins was even more evident in patients with a baseline aneurysm diameter<40 mm (at 5 years: 84.0% vs. 58.8%, P=0.022). When adjusted for age, coronary artery disease and baseline aneurysm diameter, treatment with statins had significantly better survival freedom from aneurysm repair or rupture (P=0.012, RR 0.34, 95% CI 0.14-0.78). The use of statins seems to slightly decrease the AAA growth rate and to significantly improve freedom from aneurysm repair and rupture.

Effects of pH management during selective antegrade cerebral perfusion on cerebral microcirculation and metabolism: alpha-stat versus pH-stat.

BACKGROUND: Selective cerebral perfusion (SCP) is used for extending the period during which surgical procedures can be safely performed. We sought to determine the direct effects of pH management on cerebral microcirculation and metabolism during SCP. METHODS: An experimental SCP porcine model was created by selectively allowing cold perfusate only into the bicarotid brachiocephalic trunk during the SCP period. Twenty-four piglets (6 to 8 weeks; mean weight, 26.1 +/- 4.1 kg) underwent 15-minute normothermic cardiopulmonary bypass, 45-minute cooling cardiopulmonary bypass, 60-minute SCP at 25 degrees C, and 45-minute rewarming cardiopulmonary bypass with either alpha-stat or pH-stat perfusion strategy randomly assigned. A cranial window was created over the parietal cortex for visualization of the cerebral vessels with intravital microscopy. Rhodamine-stained leukocytes were observed in cerebral postcapillary venules for adhesion and rolling. Microdialysis analysis was used for determination of brain metabolism. RESULTS: Brain concentration of lactate was significantly higher in the alpha-stat group at 45 minutes of SCP, and at 15- and 45-minute rewarming intervals (p = 0.03; p = 0.003; and p = 0.05; respectively), reaching borderline statistical significance when assessed throughout the experiment (p = 0.06 for differences between groups). Further, at the end of cooling, the oxygen delivery tended to be higher in the pH-stat group (p = 0.07), whereas at the 30-minute rewarming interval, the oxygen extraction tended to be higher in the alpha-stat group (p = 0.06). There were no statistically significant differences between the groups in leukocyte-endothelial interaction, arterial diameter, or tissue oxygenation. CONCLUSIONS: The higher concentration of brain lactate and the tendency to higher oxygen extraction levels during rewarming with alpha-stat strategy suggests anaerobic metabolism occurred during SCP. No major differences between pH management strategies in cerebral microcirculation could be shown during SCP.

Bone marrow-derived mononuclear cell transplantation improves myocardial recovery by enhancing cellular recruitment and differentiation at the infarction site.

OBJECTIVE: Stem cell therapy in myocardial infarction is under intensive investigation; however, the mechanisms of recovery and the optimal transplantation technique remain controversial. The goal of this controlled and randomized study was to test the hypothesis that locally injected bone marrow-derived mononuclear cells can focus in on the damaged myocardium and improve cardiac function by means of active participation in remodeling. METHODS: Myocardial infarction was introduced through occlusion of the circumflex coronary artery for 90 minutes in 14 piglets (24.0 +/- 4.9 kg) that were randomized to a cell-therapy group (n = 7) and a control group (n = 7). At reperfusion, autologous purified prelabeled or unlabeled cells (10(8) cells/2 mL) or saline were injected into the myocardium. Cardiac function was measured by using echocardiography preoperatively and postoperatively and at 3 weeks, when hearts were collected for histopathologic examination. RESULTS: The ejection fraction recovered in the cell-therapy group (P = .02) but failed to recover in the control group, and at 3 weeks, it remained at the lower level compared with that in the cell-therapy group (P = .067). The number of living cells in the necrotic area was significantly greater in the cell-therapy group (P < .001). Labeled cells were detected in the infarcted area, and they showed signs of myocyte differentiation. Furthermore, the proportional area of muscle actin-positive cells at the granulation area was higher in the cell-therapy group (P = .035). CONCLUSIONS: Autologous bone marrow-derived mononuclear cells at the infarcted area localize in the myocardium. The exact mechanism of recovery remains to be determined, but our findings may give new information concerning the cellular events that occur during cell therapy-enhanced recovery.

Postoperative stroke after off-pump versus on-pump coronary artery bypass surgery.

OBJECTIVE: The value of off-pump over conventional coronary artery bypass surgery in reducing the risk of postoperative stroke is controversial. This issue has been evaluated in light of our recent clinical experience. METHODS: Off-pump coronary artery bypass surgery was performed in 557 patients, and conventional coronary artery bypass surgery was performed in 445 patients. Preoperative stroke risk was calculated according to the Northern New England Cardiovascular Disease Study Group stroke risk-scoring method. RESULTS: Off-pump coronary artery bypass surgery was associated with a lower but not significant rate of postoperative stroke in the overall series (1.8% vs 2.5%, P = .45), a difference that slightly increased in the highest tertile of the Northern New England Cardiovascular Disease Study Group score (2.8% vs 4.2%, P = .75). The postoperative stroke rate was significantly lower when the operation was performed by off-pump coronary artery bypass surgeons using routinely epiaortic ultrasonographic scanning compared with conventional coronary artery bypass surgeons not using epiaortic ultrasonographic scanning (0.4% vs 3.9%, P = .015). The Northern New England Cardiovascular Disease Study Group score (mean, 4.6 +/- 2.1 vs 4.9 +/- 2.2; P = .189) was similar in these groups. Logistic regression showed that when adjusted for Northern New England Cardiovascular Disease Study Group stroke risk score and critical preoperative status, the treatment approach (off-pump coronary artery bypass surgery and routine epiaortic ultrasonographic scanning) was an independent predictor of postoperative stroke (P = .012; odds ratio, 34.1; 95% confidence interval, 2.2-533.7). CONCLUSIONS: The neuroprotective efficacy of off-pump coronary artery bypass surgery is marginal compared with that of conventional coronary artery bypass surgery. A decreased risk of postoperative stroke after off-pump coronary artery bypass surgery is expected, mostly in high-risk patients and when epiaortic ultrasonographic examination is routinely used for better planning of operative strategy, aiming to minimize the risk of intraoperative embolism.

Leukocyte filtration to decrease the number of adherent leukocytes in the cerebral microcirculation after a period of deep hypothermic circulatory arrest.

OBJECTIVE: Cardiopulmonary bypass and hypothermic circulatory arrest induce a systemic inflammatory response, including a cascade of leukocyte and endothelial cell activity, during the postischemic reperfusion phase. Accumulation of leukocytes in the brain can lead to neurologic problems after cardiac surgery. The beneficial effects of a leukocyte-depleting filter have been documented, but because of contradictory results the underlying function of the filter remains unclear. METHODS: Twenty-two juvenile piglets (6 to 8 weeks) were randomly assigned to undergo cardiopulmonary bypass with or without a leukocyte-depleting filter 60 minutes before and 60 minutes after a 75-minute hypothermic circulatory arrest at 18 degrees C. The cerebral vessels were visualized with intravital microscopy through a cranial window placed over the parietal cortex. Rhodamine staining was used to observe adherent and rolling leukocytes in the cerebral postcapillary venules. The animals were electively killed 1 hour after weaning from cardiopulmonary bypass. RESULTS: There were no significant differences between the study groups regarding hemodynamic data. Numbers of adherent activated leukocytes were lower in the leukocyte filtration group, reaching borderline statistical significance when assessed throughout the experiment (between-groups P = .069) and actual statistical significance when assessed during the rewarming period (between-groups P = .029). CONCLUSION: The leukocyte-depleting filter succeeded in reducing the number of adherent leukocytes during the reperfusion period in an experimental operation with deep hypothermic circulatory arrest. Such a filter thus could mitigate cerebral reperfusion injury after cardiac surgery.

Predictors of diseased ascending aorta in patients undergoing off-pump coronary artery bypass surgery.

OBJECTIVE: To identify the preoperative risk factors associated with increased prevalence of atherosclerotic lesions of the ascending aorta among patients undergoing off-pump coronary artery bypass surgery (OPCAB). MATERIAL AND METHODS: OPCAB was performed in 241 patients who were intraoperatively investigated by epiaortic ultrasound for the presence of atherosclerotic lesions of the ascending aorta. The Northern New England Cardiovascular Disease Study Group (NNECVDSG) and the Multicenter Study of Perioperative Ischemia (McSPI) stroke risk scores were retrospectively calculated. RESULTS: A diseased ascending aorta was detected by intraoperative epiaortic ultrasound in 74 patients (30.7%). Patient's age (P = .002, odds ratio [OR] 1.067, 95% confidence interval [CI] 1.025-1.110), diabetes (P = .023; OR, 2.211; 95% CI, 1.117-4.378), extracardiac arteriopathy (P = .014; OR, 2.567; 95% CI, 1.214-5.428) and urgent/emergency operation (P < .0001; OR, 3.066; 95% CI, 1.685-5.580) were independent preoperative predictors of a diseased ascending aorta. The area under the ROC curve of the NNECVDSG score in predicting a diseased ascending aorta was 0.710 (95% CI, 0.642-0.778), and that of the McSPI score was 0.722 (95% CI, 0.655-0.788). The prevalence of a diseased ascending aorta was 11.2%, 34.7%, and 49.4% among the NNECVDSG score tertiles (P < .0001), and 11.3%, 31.7%, and 49.4% among the McSPI score tertiles (P < .0001). CONCLUSIONS: These findings confirm the reported high incidence of a diseased ascending aorta in patients undergoing coronary artery bypass surgery. Current stroke risk scores, particularly the simple NNECVDSG score, are valuable predictors of increased prevalence of a diseased ascending aorta.