Inhibition of complement, neutrophil, and platelet activation by an anti-factor D monoclonal antibody in simulated cardiopulmonary bypass circuits.

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 microg/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.

Percutaneous and surgical interventions for in-stent restenosis: long-term outcomes and effect of diabetes mellitus.

OBJECTIVE: We examined long-term outcomes of patients with in-stent restenosis (ISR) who underwent different percutaneous interventions at the discretion of individual operators: balloon angioplasty (BA), repeat stent or rotational atherectomy (RA). We also examined long-term outcomes of patients with ISR who underwent coronary artery bypass surgery (CABG). BACKGROUND: In-stent restenosis remains a challenging problem, and its optimal management is still unknown. METHODS: Symptomatic patients (n = 510) with ISR were identified using cardiac catheterization laboratory data. Management for ISR included BA (169 patients), repeat stenting (117 patients), RA (107 patients) or CABG (117 patients). Clinical outcome events of interest included death, myocardial infarction, target vessel revascularization (TVR) and a combined end point of these major adverse cardiovascular events (MACE). Mean follow-up was 19+/-12 months (range = 6 to 61 months). RESULTS: Patients with ISR treated with repeat stent had significantly larger average post-procedure minimal lumen diameter compared with BA or RA (3.3+/-0.4 mm vs. 3.0+/-0.4 vs. 2.9+/-0.5, respectively, p < 0.05). Incidence of TVR and MACE were similar in the BA, stent and RA groups (39%, 40%, 33% for TVR and 43%, 40%, 33% for MACE, p = NS). Patients with diabetes who underwent RA had similar outcomes as patients without diabetes, while patients with diabetes who underwent BA or stent had worse outcomes than patients without diabetes. Patients who underwent CABG for ISR, mainly because of the presence of multivessel disease, had significantly better outcomes than any percutaneous treatment (8% for TVR and 23% for MACE). CONCLUSIONS: In this large cohort of patients with ISR and in the subset of patients without diabetes, long-term outcomes were similar in the BA, repeat stent and RA groups. Tissue debulking with RA yielded better results only in diabetic patients. Bypass surgery for patients with multivessel disease and ISR provided the best outcomes.

Global and regional cerebral blood flow in neonatal piglets undergoing pulsatile cardiopulmonary bypass with continuous perfusion at 25 degrees C and circulatory arrest at 18 degrees C.

To investigate the influence of hypothermic cardiopulmonary bypass (HCPB) at 25 degrees C and circulatory arrest at 18 degrees C on the global and regional cerebral blood flow (CBF) during pulsatile perfusion, we performed the following studies in a neonatal piglet model. Using a pediatric physiologic pulsatile pump, we subjected six piglets to deep hypothermic circulatory arrest (DHCA) and six other piglets to HCPB. The DHCA group underwent hypothermia for 25 min, DHCA for 60min, cold reperfusion for 10 min, and rewarming for 40 min. The HCPB group underwent 15 min of cooling, followed by 60 min of HCPB, 10min of cold reperfusion, and 30 min of rewarming. The following variables remained constant in both groups: pump flow (150 ml/kg/min), pump rate (150 bpm), and stroke volume (1 ml/kg). During the 60-min aortic crossclamp period, the temperature was kept at 18 degrees C for DHCA and at 25 degrees C for HCPB. The global and regional CBF (ml/100g/min) was assessed with radiolabeled microspheres. The CBF was 48% lower during deep hypothermia at 18degrees C (before DHCA) than during hypothermia at 25 degrees C (55.2 +/- 14.3ml/100g/min vs 106.4 +/- 19.7 ml/100 g/min; p < 0.05). After rewarming, the global CBF was 45% lower in the DHCA group than in the HCPB group 48.3 +/- 18.1 ml/100g/min vs (87 +/- 35.9ml/100g/min; p < 0.05). Fifteen minutes after the termination of CPB, the global CBF was only 25% lower in the DHCA group than in the HCPB group (42.2 +/- 20.7 ml/100 g/min vs 56.4 +/- 25.8ml/100g/min; p = NS). In the right and left hemispheres, cerebellum, basal ganglia, and brain stem, blood flow resembled the global CBF. In conclusion, both HCPB and DHCA significantly decrease the regional and global CBF during CPB. Unlike HCPB, DHCA has a continued negative impact on the CBF after rewarming. However, 15 min after the end of CPB, there are no significant intergroup differences in the CBF.

Patency and life-spans of failing hemodialysis grafts in patients undergoing repeated percutaneous de-clotting.

We set out to determine retrospectively the primary and secondary patency rates, as well as the life-spans, of failing polytetrafluoroethylene dialysis grafts after repeated percutaneous mechanical de-clotting. The study group consisted of all patients who had undergone percutaneous mechanical de-clotting, balloon angioplasty, or angiography of theirpolytetrafluoroethylene hemodialysis grafts at our institution from 1 January through 30 April 1999. Patency of the hemodialysis grafts was calculated using Kaplan-Meier analysis. A total of 161 percutaneous de-clotting procedures were performed on 59 of 71 patients. At 1 year, the primary and secondary surgical patency rates of the grafts were 29% and 61.4%, respectively The life-spans of the polytetrafluoroethylene grafts after repeated percutaneous de-clotting and surgical interventions was 93.5% at 6 months, 78% at 1 year, 58.8% at 2 years, and 35% at 3 years. The patency rates after the 1st, 2nd, and 3rd de-clotting procedures were 55.9%, 61.9%, and 55.8% at 3 months and 32.2%, 40.8%, and 31.4% at 6 months, respectively (P=0.40). The patency rate of grafts after mechanical de-clotting using the Arrow-Trerotola thrombectomy device was not statistically different from that of the crossed angioplasty balloon technique alone (P=0.38). Further, there was no difference in the life-spans of grafts whether they were located in the upper or lower extremity Because reocclusion rates are similar following 1st, 2nd, and 3rd occlusions, regardless of the percutaneous mechanical de-clotting technique used, repeated percutaneous management should be undertaken to preserve each graft regardless of the number of previous de-clotting procedures.

Predictors of conversion to sinus rhythm using ibutilide for atrial fibrillation or flutter.

To determine what factors can predict conversion to sinus rhythm, we retrospectively studied 201 consecutive patients who received ibutilide for treatment of atrial fibrillation or flutter. On multivariate analysis, the following factors were significantly associated with conversion: recent onset of arrhythmia, an underlying atrial flutter rhythm, lack of a history of congestive heart failure, and lack of concomitant digoxin therapy.

The effects of cardiopulmonary bypass and deep hypothermic circulatory arrest on blood viscoelasticity and cerebral blood flow in a neonatal piglet model.

The purpose of this study is to determine the effects of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) on the viscoelasticity (viscosity and elasticity) of blood and global and regional cerebral blood flow (CBF) in a neonatal piglet model. After initiation of CPB, all animals (n = 3) were subjected to core cooling for 20 min to reduce the piglets' nasopharyngeal temperatures to 18 degrees C. This was followed by 60 min of DHCA, then 45 min of rewarming. During cooling and rewarming, the alpha-stat technique was used. Arterial blood samples were taken for viscoelasticity measurements and differently labeled microspheres were injected at pre-CPB, pre- and post-DHCA, 30 and 60 min after CPB for global and regional cerebral blood flow calculations. Viscosity and elasticity were measured at 2 Hz, 22 degrees C and at a strain of 0.2, 1, and 5 using a Vilastic-3 Viscoelasticity Analyzer. Elasticity of blood at a strain = 1 decreased to 32%, 83%, 57%, and 61% (p = 0.01, ANOVA) while the viscosity diminished 8.4%, 38%, 22%, 26% compared to the baseline values (p = 0.01, ANOVA) at pre-DHCA, post-DHCA, 30 and 60 min after CPB, respectively. The viscoelasticity of blood at a strain of 0.2 and 5 also had similar statistically significant drops (p < 0.05). Global and regional cerebral blood flow were also decreased 30%, 66%, 64% and 63% at the same experimental stages (p < 0.05, ANOVA). CPB procedure with 60 min of DHCA significantly alters the blood viscoelasticity, global and regional cerebral blood flow. These large changes in viscoelasticity may have a significant impact on organ blood flow, particularly in the brain.

Impact of the "stent-when-feasible" policy on in-hospital and 6-month success and complication rates after coronary angioplasty: single-center experience with 17,956 revascularization procedures (1993-1997).

This retrospective, observational, single-center study analyzed the results of a "stent-when-feasible" policy in a real-world setting. The study began in the "pre-stent" period (1993) and ended after the beginning of the "routine stent" period (1997). When the 1993 and 1997 global data were compared, the early and 6-month results included significant improvements in the rates of angiographic success (89.3% vs 97.1%), emergency surgical revascularization (1.0% vs 0.3%), freedom from in-hospital major events (91.2% vs 95.9%), and freedom from 6-month major events (77.2% vs 85.1%). The 6-month redo revascularization rate was reduced by almost half for "any catheter intervention" (19.6% vs 10.7%) and was lowest after stent use (7.7% in 1997).

Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome.

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.

Left ventricular diastolic function in normal human pregnancy.

BACKGROUND: 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). METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Estrogen replacement therapy and outcome of coronary balloon angioplasty in postmenopausal women.

Estrogen replacement therapy (ERT) in women after menopause is associated with prevention of clinical coronary artery disease. However, few studies have investigated possible benefits from ERT in postmenopausal women undergoing treatment for established coronary disease. We therefore retrospectively reviewed the clinical outcomes of 428 postmenopausal women undergoing percutaneous transluminal coronary balloon angioplasty (PTCA) to test the hypothesis that ERT has a beneficial effect in this setting. The women were divided into 2 groups based on ERT status at the time of the procedure. Estrogen users were younger (60 +/- 10 vs 68 +/- 9 years, p <0.001), more commonly had family histories of coronary heart disease (54% vs 41%, p = 0.04), had less incidence of hypertension (63% vs 76%, p = 0.02), and had slightly fewer diseased vessels per patient (1.3 +/- 0.5 vs 1.5 +/- 0.7, p = 0.03) compared with nonusers. No in-hospital deaths occurred in estrogen users compared with 5% hospital mortality in nonusers (p = 0.01). The combined outcome of death or myocardial infarction (MI) also was lower in estrogen users (4% vs 12%, p = 0.04). Of 348 women discharged after successful PTCA, 336 (97%) were able to be contacted at an average follow-up interval of 22 +/- 17 months (range 5 to 82). Estrogen users had superior event-free survival both for death as well as for death or nonfatal MI. Repeat revascularizations were similar in both groups (32% vs 24%, p = 0.15). In a Cox proportional-hazards model, nonusers had 4 times the likelihood of death after angioplasty compared with estrogen users (OR = 4.025, 95% CI = 1.3 to 13.4, p = 0.02). We conclude that estrogen replacement may offer protection against clinical coronary events in postmenopausal women who already have established coronary disease and are undergoing balloon angioplasty. The benefit was independent of age, smoking, presence of diabetes mellitus, or the number of diseased coronary vessels. However, it did not include a reduction in repeat revascularization procedures, suggesting no reduction in restenosis.

Low serum cholesterol levels predict high perioperative mortality in patients supported by a left-ventricular assist system.

BACKGROUND: Although the use of a left-ventricular assist system (LVAS) provides circulatory support for end-stage heart failure patients awaiting heart transplantation, this procedure is accompanied by a relatively high perioperative mortality. The aim of this retrospective study was to identify those patients preoperatively which have the highest perioperative mortality. METHODS AND RESULTS: Forty-five consecutive patients undergoing LVAS implantation were evaluated for preoperative risk factors, including body mass index, hemodynamic data, and blood chemistry studies by multivariate analysis. They were divided into (1) patients who were successfully transplanted (n = 25) and (2) patients who died before transplantation (n = 20). The nonsurvivors were subclassified into patients who died within 14 days after surgery (n = 11) and patients who died after 2 weeks of device implantation (n = 9). Hemodynamic parameters were the same in both groups, but total cholesterol was significantly lower in the nonsurvivors than in the survivors (90 +/- 7 vs. 144 +/- 8 mg/dl, respectively, p < 0.0001). The sensitivity of predicting perioperative death with a serum cholesterol below 100 mg/dl was 100%, the specificity of predicting survival with a serum cholesterol above 120 mg/dl was 87%. CONCLUSION: In this small retrospective study, there was a correlation between total cholesterol levels and survival of patients with advanced heart failure on mechanical support. A cholesterol level below 100 mg/dl was accompanied by a high perioperative mortality. In contrast, a cholesterol level above 120 mg/dl was accompanied by a 87% chance of survival. The results suggest a predictive value of cholesterol which is independent of the hemodynamic status.

Reduction of canine infarct size by bolus intravenous administration of liposomal prostaglandin E1: comparison with control, placebo liposomes, and continuous intravenous infusion of prostaglandin E1.

Prostaglandin E1 (PGE1) reduces experimental infarct size when administered by prolonged low-dose left atrial infusion during coronary occlusion. Liposomal delivery of PGE1 may enhance biologic activity and limit adverse hemodynamic effects. The purpose of this study was to test the hypothesis that intravenous bolus administration of liposomal PGE1 (TLC C-53, The Liposome Company, Princeton, N.J.) during coronary occlusion would result in myocardial salvage. We compared TLC C-53 (0.5 microgram/kg intravenous bolus at 10 and 100 min of occlusion of the left anterior descending coronary artery [LAD]), free PGE1 (0.1 microgram/kg/min infused 10 min after LAD occlusion until reperfusion), placebo liposomes, and control (n = 7 for each group) in an open-chest canine model of 2 hours of LAD occlusion and reperfusion. Infarct size as a percentage of risk area (mean +/- SD) in the control group (58.4% +/- 20.0%) was similar to that in animals given placebo liposomes (53.1% +/- 12.6%) but was significantly reduced in the groups given TLC C-53 (33.5% +/- 9.2%; p < 0.01) or free PGE1 (37.2% +/- 4.8%; p < 0.05) groups. Infarct salvage was significant (p < 0.05) for the TLC C-53-and PGE1-treated dogs compared with the control dogs, independent of collateral blood flow by analysis of covariance. Moreover, the ischemic-zone blood flow during reperfusion was significantly higher in the TLC C-53 group compared with the control group or the group receiving free PGE1. Neutrophil infiltration of ischemic myocardium was significantly inhibited by TLC C-53 as determined by myeloperoxidase assay. Unlike free PGE1, TLC C-53 did not cause significant tachycardia or hypotension during therapy. In conclusion, TLC C-53 administered intravenously during coronary occlusion significantly reduced infarct size, limited neutrophil infiltration, and improved myocardial blood flow during reperfusion without adverse hemodynamic consequences.

PTCA in angulated segments: effects of balloon material, balloon length, and inflation sequence on straightening forces in an in vitro model.

We sought to determine the effect of balloon material, balloon length, and inflation sequence on the straightening forces generated during percutaneous transluminal coronary angioplasty (PTCA) in angulated segments. Using an in vitro model consisting of a curved channel (3/4" radius) with a displaceable pressure sensor, we examined four different balloon materials: compliant (POC), semicompliant (PE600 and Duralyn), and noncompliant (PET), two balloon lengths (20 mm and 40 mm), and two inflation sequences (rapid and slow) with continuous recording of straightening force during each balloon inflation. Three balloons were tested for each combination of materials, length, and inflation sequence. Long balloons exerted significantly lower straightening forces. There were significantly higher straightening forces with noncompliant, particularly short, balloons. Varying the inflation sequence had no significant effect. For PTCA in angulated segments: (1) long balloons produce lower straightening force, (2) noncompliant balloons produce higher straightening force, particularly with short balloons, and (3) varying the inflation sequence has no significant effect on straightening force.

Comparison of angioscopy, intravascular ultrasound imaging and quantitative coronary angiography in predicting clinical outcome after coronary intervention in high risk patients.

OBJECTIVES: The purpose of this study was to identify qualitative or quantitative variables present on angioscopy, intravascular ultrasound imaging or quantitative coronary arteriography that were associated with adverse clinical outcome after coronary intervention in high risk patients. BACKGROUND: Patients with acute coronary syndromes and complex lesion morphology on angiography are at increased risk for acute complications after coronary angioplasty. Newer devices that primarily remove atheroma have not improved outcome over that of balloon angioplasty. Intravascular imaging can accurately identify intraluminal and intramural histopathologic features not adequately visualized during coronary arteriography and may provide mechanistic insight into the pathogenesis of abrupt closure and restenosis. METHODS: Sixty high risk patients with unstable coronary syndromes and complex lesions on angiography underwent angioscopy (n = 40) and intravascular ultrasound imaging (n = 46) during interventional procedures. In 26 patients, both angioscopy and intravascular ultrasound were performed in the same lesion. All patients underwent off-line quantitative coronary arteriography. Coronary interventions included balloon (n = 21) and excimer laser (n = 4) angioplasty, directional (n = 19) and rotational (n = 6) atherectomy and stent implantation (n = 11). Patients were followed up for 1 year for objective evidence for recurrent ischemia. RESULTS: Patients whose clinical presentation included rest angina or acute myocardial infarction or who received thrombolytic therapy within 24 h of procedure were significantly more likely to experience recurrent ischemia after intervention. Plaque rupture or thrombus on preprocedure angioscopy or angioscopic thrombus after intervention were also significantly associated with adverse outcome. Qualitative or quantitative variables on angiography, intravascular ultrasound or off-line quantitative arteriography were not associated with recurrent ischemia on univariate analysis. Multivariate predictors of recurrent ischemia were plaque rupture on preprocedure angioscopy (p < 0.05, odds ratio [OR] 10.15) and angioscopic thrombus after intervention (p < 0.05, OR 7.26). CONCLUSIONS: Angioscopic plaque rupture and thrombus were independently associated with adverse outcome in patients with complex lesions after interventional procedures. These features were not identified by either angiography or intravascular ultrasound.

Thermal detection of cellular infiltrates in living atherosclerotic plaques: possible implications for plaque rupture and thrombosis.

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 degree 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 degrees C, but 37% of plaques had substantially warmer regions (0.4-2.2 degrees 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.

Blood use in patients undergoing repeat coronary artery bypass graft procedures: multivariate analysis.

BACKGROUND: The prevailing clinical opinion is that patients undergoing repeat coronary artery bypass graft (CABG) operation require more blood transfusions than do patients undergoing primary CABG operation. To determine the extent of this increased demand and the variables responsible for it, the cases of 196 patients who had undergone primary procedures and 65 patients who had had repeat procedures at the same institution were reviewed. STUDY DESIGN AND METHODS: To analyze the differences in transfusion requirements for these two groups, the following data were obtained: number of transfusions given between the time of surgery and the time of hospital discharge; preoperative hemoglobin (Hb), hematocrit (Hct), prothrombin time, and platelet count; Hb and Hct at hospital discharge; time the patient was on cardiopulmonary bypass; number and type of grafts; estimates of intraoperative blood loss; and chest-tube blood shed during the first 48 hours after surgery. RESULTS: The groups were comparable with respect to age, body weight, preoperative Hb and Hct, number of grafts, and aspirin exposure. Patients in the repeat group had 35-percent greater blood loss and required 75-percent more blood components than did the patients undergoing primary procedures. The mean number of blood components transfused per patient was as follows: red cells, 3.8 +/- 0.5 units in repeat patients and 2.2 +/- 0.2 units in primary patients (p = 0.002); platelets, 2.9 +/- 0.9 vs. 1.1 +/- 0.2 (p = 0.043); fresh-frozen plasma, 1.6 +/- 0.4 vs. 0.8 +/- 0.1 (p = 0.044). Analysis of variables by regression method for repeat patients showed a predictive effect of blood loss (p < 0.0001), prolonged time on cardiopulmonary bypass (p < 0.0001), preoperative Hb (p = 0.0003), and aspirin exposure (p = 0.0094) on red cell transfusion rate in repeat patients (R-square = 0.7778, Prob > f = 0.0001). CONCLUSION: Repeat CABG patients have higher transfusion rates. These findings may be attributed to the increased microvascular bleeding, prolonged time on cardiopulmonary bypass, lower preoperative Hb, and the use of preoperative antiplatelet medications.

Infarct salvage with liposomal prostaglandin E1 administered by intravenous bolus immediately before reperfusion in a canine infarction-reperfusion model.

BACKGROUND: Prostaglandin E1 (PGE1) inhibits leukocyte and platelet function and reduces infarct size during left atrial infusion. Intravenous liposomal PGE1 (TLC C-53) accelerates thrombolysis and prevents reocclusion in canine coronary thrombosis. We tested the hypothesis that intravenous TLC C-53 would attenuate reperfusion injury in a canine infarction-reperfusion model. METHODS AND RESULTS: Twenty-one open-chest dogs were randomized to receive a 10-minute intravenous infusion of either liposome diluent (placebo), free PGE1 (2 micrograms/kg), or TLC C-53 (2 micrograms/kg PGE1) after 2 hours of left anterior descending (LAD) occlusion just before reperfusion. Hemodynamic assessment, regional myocardial blood flow determination with radioactive microspheres, myocardial leukocyte infiltration by myeloperoxidase assay, and estimation of infarct size using triphenyl tetrazolium chloride staining were performed. Regional fractional shortening was measured with sonomicrometer crystals implanted in the midmyocardium. Infarct size as a percentage of the risk region was significantly reduced (P < .05) with TLC C-53 (37.9 +/- 17.4%) compared with PGE1 (56.7 +/- 13.9%) or placebo (58.0 +/- 9.9%) infusion. Infarct salvage with TLC C-53 was independent of collateral blood flow by ANCOVA. There was a dramatic reduction in myeloperoxidase activity in the infarct, risk, and border regions of dogs treated with TLC C-53 compared with placebo. Enzyme activity was also significantly reduced (P < .05) in the infarct zone with TLC C-53 (0.11 +/- 0.1 U/100 mg) treatment compared with PGE1 (0.38 +/- 0.3 U/100 mg). No significant differences in regional myocardial blood flow or myocardial function among treatment groups were identified, although there was a trend toward improved function in the TLC C-53 dogs. CONCLUSIONS: Bolus intravenous administration of TLC C-53 immediately before reperfusion results in reduced leukocyte infiltration and substantial infarct salvage. TLC C-53 mah be useful in limiting reperfusion injury during treatment of acute myocardial infarction.

Neonatal outcome of premature infants of mothers with preeclampsia.

Our objective was to compare the outcome of premature infants of mothers with preeclampsia and hypertension with properly matched controls to examine whether infants of mothers with preeclampsia are at a lesser risk. We designed a retrospective cohort study of 99 infants of mothers with preeclampsia and hypertension (IHM) at < or = 36 weeks' gestation. Infants of nonhypertensive women matched for gestational age, gender, asphyxia, maternal diabetes mellitus, twin gestation, and mode of delivery served as controls. Data were analyzed by dividing all cases into three gestational age groups: group I, 26 to 30 weeks' gestation (IHM n = 21, control n = 39); group II, 31 to 33 weeks (IHM n = 32, control n = 61); and group III, 34 to 36 weeks (IHM n = 46). Because detailed data on nonhypertensive infants at 34 to 36 weeks' gestation were available only for intensive care unit admissions, group III was excluded from the comparative analysis. The incidence of hyaline membrane disease was significantly lower in IHM compared with the controls in groups I and II (group I, 19.1% vs 46.2%, p < 0.005; group II, 12.5% vs 32.8%, p < 0.04). Symptomatic patent ductus arteriosus occurred less frequently in groups I and II compared with controls (group I, 28.6% vs 46.2%, p < 0.001; group II, 3.1% vs 13.1%, p < 0.005). Intraventricular hemorrhage was less frequent in group I compared with controls (4.8% vs 20.5%, p < 0.001). The incidence of intraventricular hemorrhage in group II was similar at 3.1% versus 1.6% for controls.(ABSTRACT TRUNCATED AT 250 WORDS)