BACKGROUND: There is controversy regarding the application of transfusion triggers in cardiac surgery. The goal of this study was to determine if lowering the hemoglobin threshold for red cell (RBC) ...transfusion to 8 g per dL after coronary artery bypass graft surgery would reduce blood use without adversely affecting patient outcome.
STUDY DESIGN AND METHODS: Consecutive patients (n = 428) undergoing elective primary coronary artery bypass graft surgery were randomly assigned to two groups: study patients (n = 212) received RBC transfusions in the postoperative period if the Hb level was <8 g per dL or if predetermined clinical conditions required RBC support, and control patients (n = 216) were treated according to individual physician's orders (hemoglobin levels <9 g/dL as the institutional guideline). Multiple demographic, procedure‐related, transfusion, laboratory, and outcome data were analyzed. Questionnaires were administered for patient self‐assessment of fatigue and anemia.
RESULTS: Preoperative and operative clinical characteristics, as well as the intraoperative transfusion rate, were similar for both groups. There was a significant difference between the postoperative RBC transfusion rates in study (0.9 ± 1.5 RBC units) and control (1.4 ± 1.8 RBC units) groups (p = 0.005). There was no difference in clinical outcome, including morbidity and mortality rates, in the two groups; group scores for self‐assessment of fatigue and anemia were also similar.
CONCLUSIONS: A lower Hb threshold of 8 g per dL does not adversely affect patient outcome. Moreover, RBC resources can be saved without increased risk to the patient.
Rhythmic gamma-band communication within and across cortical hemispheres is critical for optimal perception, navigation, and memory. Here, using multisite recordings in both rats and mice, we show ...that even faster ~140 Hz rhythms are robustly anti-phase across cortical hemispheres, visually resembling splines, the interlocking teeth on mechanical gears. Splines are strongest in superficial granular retrosplenial cortex, a region important for spatial navigation and memory. Spline-frequency interhemispheric communication becomes more coherent and more precisely anti-phase at faster running speeds. Anti-phase splines also demarcate high-activity frames during REM sleep. While splines and associated neuronal spiking are anti-phase across retrosplenial hemispheres during navigation and REM sleep, gamma-rhythmic interhemispheric communication is precisely in-phase. Gamma and splines occur at distinct points of a theta cycle and thus highlight the ability of interhemispheric cortical communication to rapidly switch between in-phase (gamma) and anti-phase (spline) modes within individual theta cycles during both navigation and REM sleep.
Gamma-rhythmic communication within and across cortical hemispheres is critical for optimal perception, navigation, and memory. Here, Ghosh et al. identify even faster ~140 Hz rhythms, named splines, that reflect anti-phase neuronal synchrony across hemispheres. The balance of anti-phase spline and in-phase gamma communication is dynamically controlled by behavior and sleep.
Summary
Background Atherosclerotic lesions are heterogeneous and prognosis cannot easily be predicted, even with intracoronary ultrasound and angioscopy. Serial angiographic and necropsy studies ...suggest that the risk of plaque rupture correlates only weakly with the degree of stenosis. Most ruptured plaques are characterised by a large pool of cholesterol or necrotic debris and a thin fibrous cap with a dense infiltration of macrophages. The release of matrix-digesting enzymes by these cells is thought to contribute to plaque rupture. Other thromboses are found on non-ruptured but inflamed plaque surfaces. We postulated that both types of thrombotic events may be predicted by heat released by activated macrophages either on the plaque surface or under a thin cap.
Methods To test the hypothesis, we measured the intimal surface temperatures at 20 sites in each of 50 samples of carotid artery taken at endarterectomy from 48 patients. The living samples were probed with a thermistor (24-gauge needle-tip; accuracy 0-1°C; time contrast 0·15 s). The tissues were then fixed and stained.
Findings Plaques showed several regions in which the surface temperatures varied reproducibly by 0·2-0·3°C, but 37% of plaques had substantially warmer regions (0·4-2·2°C). Points with substantially different temperatures could not be distinguished from one another by the naked eye; such points could also be very close to one another (<1 mm apart). Temperature correlated positively with cell density (
r=0·68, p=0·0001) and inversely with the distance of the cell clusters from the luminal surface (
r=-0·38, p=0·0006). Most cells were macrophages. Infrared thermographic images also revealed heterogeneity in temperature among the plaques.
Interpretation Living atherosclerotic plaques show thermal heterogeneity, which raises the possibility that an infrared catheter or other techniques that can localise heat or metabolic activity might be able to identify plaques at high risk of rupture or thrombosis.
Little information is available about changes in left ventricular diastolic function during pregnancy. We used mitral inflow and pulmonary venous flow profiles to evaluate left ventricular diastolic ...function in 37 healthy pregnant women 26 to 41 years old (mean, 32 years).
Echocardiographic studies were performed at the end of each trimester. Eight subjects (control group) underwent similar testing 1 to 3.5 months (mean, 1.7 months) postpartum. During pregnancy, the cardiac output increased significantly as a result of an increased heart rate and, to a lesser degree, stroke volume. Significantly decreased systemic vascular resistance and increased left ventricular mass were also noted. Peak mitral flow velocity in early diastole (E) increased 13. 3% during the first trimester and remained at the high end of normal throughout pregnancy. Peak A-wave velocity (A) increased maximally in the third trimester. Compared with control subjects, first-trimester subjects had a significantly increased E/A ratio. The ratio subsequently decreased, reflecting the augmented A-wave velocity. Pulmonary venous peak systolic forward flow velocity increased, peaking in the second trimester (nonsignificant), but returned to baseline levels postpartum. The pulmonary venous diastolic time-velocity integral decreased significantly from the first to the third trimester. Peak pulmonary venous reverse flow velocity at atrial contraction increased significantly, without being markedly changed in duration.
Pregnancy, a chronic, natural volume-overload state, has important effects on hemodynamic and echocardiographic variables. Based on pulmonary venous flow and left ventricular inflow velocities, our results provide a standard reference concerning diastolic filling dynamics by trimester.
Bone marrow-derived stem cells are under investigation as a treatment for ischemic heart disease. Mesenchymal stem cells (MSCs) have been used preferentially in the acute ischemia model; data in the ...chronic ischemia model are lacking.
Twelve dogs underwent ameroid constrictor placement. Thirty days later, they received intramyocardial injections of either MSCs (100x10(6) MSCs/10 mL saline) (n=6) or saline only (10 mL) (controls) (n=6). All were euthanized at 60 days. Resting and stress 2D echocardiography was performed at 30 and 60 days after ameroid placement. White blood cell count (WBC), C-reactive protein (CRP), creatine kinase MB (CK-MB), and troponin I levels were measured. Histopathological and immunohistochemical analyses were performed. Mean left ventricular ejection fraction was similar in both groups at baseline but significantly higher in treated dogs at 60 days. WBC and CRP levels were similar over time in both groups. CK-MB and troponin I increased from baseline to 48 hours, eventually returning to baseline. There was a trend toward reduced fibrosis and greater vascular density in the treated group. MSCs colocalized with endothelial and smooth muscle cells but not with myocytes.
In a canine chronic ischemia model, MSCs differentiated into smooth muscle cells and endothelial cells, resulting in increased vascularity and improved cardiac function.
In an effort to minimize transfusions in patients undergoing elective coronary artery bypass grafting operations after recent clopidogrel exposure, we studied laboratory tests predictive of platelet ...dysfunction and used a strict algorithm-driven treatment of bleeding.
Forty-five patients receiving clopidogrel within 6 days of the operation and 45 control subjects were studied. Prothrombin time, activated partial thromboplastin time, platelet count, and platelet function test results were measured before heparinization, after protamine administration, and then every 2 hours. No transfusions were administered unless a patient met both laboratory and clinical criteria.
Algorithm-driven treatment of bleeding significantly reduced the mean units of all blood components transfused by about one third, as shown by comparison with current control and historical data. Compared with current control subjects, clopidogrel recipients required significantly more transfusions of platelets (9.0 +/- 1.7 vs 1.2 +/- 0.5 U; P <.0001) and packed red blood cells (4.3 +/- 0.6 vs 2.3 +/- 0.5 U; P =.01) and required longer periods of controlled ventilation (12.4 +/- 1.3 vs 8.6 +/- 0.8 hours; P =.02). Preoperative platelet dysfunction before heparin administration for cardiopulmonary bypass, as measured by using adenosine diphosphate aggregometry (response <40%), predicted all but 1 case of severe coagulopathy requiring multiple transfusions (16.6 +/- 2.8 U of platelets and 5.8 +/- 1.0 U of packed red blood cells).
A strict transfusion algorithm can reduce the transfusion requirement for all blood components. Preheparin testing of platelet function with adenosine diphosphate aggregometry can identify patients at highest risk for perioperative bleeding and transfusions and might further reduce the perioperative transfusion requirement.
Objectives: Patients undergoing cardiopulmonary bypass frequently manifest generalized systemic inflammation and occasionally manifest serious multiorgan failure. Inflammatory responses of bypass are ...triggered by contact of blood with artificial surfaces of the bypass circuits, surgical trauma, and ischemia-reperfusion injury. We studied the effects of specific inhibition of the alternative complement cascade by using an anti-factor D monoclonal antibody (166-32) in extracorporeal circulation of human whole blood used as a simulated model of cardiopulmonary bypass. Methods: Five healthy blood donors were used in the study. Monoclonal antibody 166-32 was added to freshly collected, heparinized human blood recirculated in a pediatric cardiopulmonary bypass circuit at a final concentration of 18 μg/mL. An irrelevant monoclonal antibody was used as a negative control with the same donor blood in a parallel bypass circuit on the same day. Blood samples were collected at different time points during recirculation for measurement of activation of complement, neutrophils, and platelets by immunofluorocytometric methods and enzyme-linked immunosorbent assays. Results: Monoclonal antibody 166-32 inhibited the alternative complement activation and the production of Bb, C3a, sC5b-9, and C5a. Upregulation of CD11b on neutrophils and CD62P on platelets was also significantly inhibited by monoclonal antibody 166-32. This is consistent with the inhibition of the release of neutrophil-specific myeloperoxidase and elastase and platelet thrombospondin. The production of proinflammatory cytokine interleukin 8 was also suppressed by the antibody. Conclusions: The alternative complement cascade is predominantly activated during extracorporeal circulation. Anti-factor D monoclonal antibody 166-32 is effective in inhibiting the activation of complement, neutrophils, and platelets. Inhibition of the alternative complement pathway by targeting factor D could be useful in reducing systemic inflammation in patients undergoing cardiopulmonary bypass.
J Thorac Cardiovasc Surg 2001;122:113-22
Statin therapy in nonsurgical patient populations is associated with a significant reduction in adverse cardiovascular events, including death, myocardial infarction (MI), and stroke. Recently, ...statin therapy was shown to be associated with a reduced incidence of postoperative mortality in patients undergoing major noncardiac vascular surgery. We investigated the influence of preoperative statin therapy on adverse outcomes after primary coronary artery bypass graft (CABG) surgery.
A retrospective cohort study of patients undergoing primary CABG surgery with cardiopulmonary bypass (CPB) (n=1663) between January 1, 2000 and December 31, 2001 at the Texas Heart Institute was performed. Patients were classified into 2 groups: patients receiving preoperative statin therapy (n=943) and patients not receiving preoperative antihyperlipidemic therapy (n=720). To determine if preoperative statin therapy was independently associated with a reduction in the risk of adverse postoperative outcomes, multivariate stepwise logistic regression was performed controlling for patient demographics, medical history, and preoperative medications. Multivariate logistic regression analysis demonstrated that preoperative statin therapy was independently associated with a significant reduction ( approximately 50%) in the risk of 30-day all-cause mortality (3.75% versus 1.80%; P<0.05). The adjusted odds ratio for early mortality in patients receiving preoperative statin therapy compared with patients not receiving antihyperlipidemic agents was 0.53 (95% CI, 0.28 to 0.99). Statin therapy was not independently associated with a reduced risk of postoperative MI, cardiac arrhythmias, stroke, or renal dysfunction. In an attempt to further control for selection bias related to the choice of therapy, multivariate analysis of a propensity-matched cohort of 1362 patients revealed that preoperative statin therapy was independently associated with a significant reduction in the composite endpoint of 30-day all-cause mortality and stroke (7.1% versus 4.6%; P<0.05).
Preoperative statin therapy may reduce the risk of early mortality after primary CABG surgery with CPB.
Three genetic complementation groups of rodent cells are defective for both repair of x-ray-induced double-strand breaks and V(D)J recombination. Cells from one group lack a DNA end-binding activity ...that is biochemically and antigenically similar to the Ku autoantigen. Transfection of complementary DNA (cDNA) that encoded the 86-kilodalton subunit of Ku rescued these mutant cells for DNA end-binding activity, x-ray resistance, and V(D)J recombination activity. These results establish a role for Ku in DNA repair and recombination. Furthermore, as a component of a DNA-dependent protein kinase, Ku may initiate a signaling pathway induced by DNA damage.
The influence of donor age on outcome was studied in the recipients of 12,131 cadaveric renal allografts, 3026 heart allografts, and 2913 liver allografts with followup information in the UNOS data ...base for transplants performed between 10/1/87 and 12/31/89. For recipients of kidney transplants, donors of ages 6-15 had significantly better 1-year graft survival than donors of ages 56-65, but the difference was only 7.0%. Donors of age greater than 65 actually did better than donors ages 56-65, but donors less than or equal to 5 were less satisfactory. Kidneys from older donors survived as well as kidneys from younger donors in patients with repeat transplants, diabetes, black race, age over 45, O HLA or 5 and 6 HLA matches, delayed graft function, shared kidneys and PRA greater than 50. For kidney recipients, multifactorial analysis by Cox regression showed that donor age was less important than the use of ALG, donor race, diabetes or peak PRA in ages 16-45, delayed function, repeat transplant, and HLA match. Recipients of heart transplants from donors ages 45-55 had 1-year graft survival that was 8.4% less than recipients of hearts from donors age 16-45. However, 32.7% of heart patients died during the first 12 months after listing without benefit of a transplant. Liver transplant recipients of donor ages 16-45 had 10.8% better 1-year graft survival than recipients of donors greater than 45, but a greater percentage of older donors were transplanted to high risk and older recipients. Tragically, 24.3% of patients listed for liver transplantation died within 12 months without a transplant. This analysis shows that satisfactory graft survival can be achieved using older donors and that age in itself should not be a barrier to organ donation, providing that organ function is normal and that specific disease of the organ is absent.
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