Fibrinolysis-adjusted perioperative low-dose aprotinin reduces blood loss in bypass operations

BACKGROUND: Postoperative bleeding still remains a serious problem in bypass surgery. This study evaluated fibrinolysis and perioperative low-dose antifibrinolytic regimens adjusted to the time course of fibrinolysis. METHODS: In a prospective, randomized study of 42 patients undergoing bypass grafting, patients received low-dose aprotinin (group A; n = 14) or low-dose tranexamic acid (group TA; n = 14) intraoperatively and postoperatively, respectively, with no antifibrinolytics for comparison (group C; n = 14). Parameters of procoagulation, fibrinolysis, and activated factor VII were measured preoperatively, intraoperatively, and postoperatively. Blood loss was determined up to 24 hours. RESULTS: The level of thrombin-antithrombin III complex was significantly decreased postoperatively in the treatment groups (group A and TA versus C: 25 +/- 14 and 19 +/- 10 microg/L, respectively, versus 40 +/- 21 microg/L; p < 0.05). Levels of plasmin-antiplasmin complexes were significantly decreased postoperatively in group A (607 +/- 231 microg/L) versus group C (825 +/- 225 microg/L) (p < 0.05) but were increased in group TA (1,145 +/- 394 microg/L) versus group C (p < 0.05). At all times intraoperatively and postoperatively, levels of D-dimers were significantly decreased in group A and group TA versus control (p < 0.001), indicating that fibrinolysis persists after the operation. Intraoperatively, the factor VIIa level decreased significantly in group A (20 +/- 8 mU/mL) versus group C (31 +/- 15 mU/mL) (p < 0.05), but not in group TA (32 +/- 15 mU/mL). Blood loss was significantly lower in group A (135 +/- 37 mL) and group TA (155 +/- 71 mL) versus group C (354 +/- 170 mL) (p < 0.001). CONCLUSIONS: This low-dose aprotinin regimen adjusted to perioperative fibrinolysis reduces blood loss significantly in coronary bypass grafting. For further progress in this subject, clinical investigations of individual fibrinolysis-adjusted antifibrinolytic treatment seems warranted.     

Aprotinin and recombinant human erythropoietin reduce the need for homologous blood transfusion in cardiac surgery

The effects of low dose aprotinin (Trasylol) and preoperative administration of recombinant human erythropoietin (EPO) were evaluated in 144 patients undergoing cardiopulmonary bypass divided into four groups. Group I (n = 43) received a subcutaneous administration of EPO (18,000 U) one week before operation and intraoperative administration of low-dose aprotinin (mean; 1.38 +/- 0.26 x 10(6) kallikrein inactivator units; KIU) from extracorporeal circulation, group II (n = 39) received only preoperative administration of EPO, group III (n = 28) received only intraoperative administration of low-dose aprotinin (mean; 1.46 +/- 0.25 x 10(6) KIU), and group IV (n = 34) were not administered either drug. Compared with group IV, the intraoperative blood loss was significantly lower in group I (p < 0.01), and in group II or III (p < 0.05). The postoperative drainage in 24 hours was significantly lower in groups I and III receiving aprotinin than in the other groups. The mean volume of total homologous blood transfusion and the percentage of cases not requiring a homologous blood transfusion in each group was, respectively, 74 +/- 235 ml and 88.4% in group I, 282 +/- 1289 ml and 87.2% in group II, 414 +/- 584 ml and 60.7% in group III, and 976 +/- 1931 ml and 44.1% in group IV. Significant differences were recognized between group I and group IV (p < 0.05). These findings indicate that when used in combination, both drugs reduce blood loss and the need for a homologous blood transfusion more effectively than either drug alone.     

Effect of modified ultrafiltration in high-risk patients undergoing operations for congenital heart disease

BACKGROUND: Modified ultrafiltration (MUF) after cardiopulmonary bypass (CPB) in children decreases body water, removes inflammatory mediators, improves hemodynamics, and decreases transfusion requirements. The optimal target population for MUF needs to be defined. This prospective, randomized study attempted to identify the best candidates for MUF during operations for congenital heart disease. METHODS: Informed consent was obtained from 100 consecutive patients with complex congenital heart disease undergoing operations with CPB. They were randomized into a control group (n = 50) of conventional ultrafiltration during bypass and an experimental group using dilutional ultrafiltration during bypass and venovenous modified ultrafiltration after bypass (MUF group, n = 50). Postoperative arterial oxygenation, duration of ventilatory support, transfusion requirements, hematocrit, chest tube output, and time to chest tube removal were compared between the groups stratified by age and weight, CPB technique, existence of preoperative pulmonary hypertension, and diagnosis. RESULTS: There were no MUF-related complications. In patients with preoperative pulmonary hypertension, MUF significantly improved postoperative oxygenation (445 +/- 129 mm Hg versus control: 307 +/- 113 mm Hg, p = 0.002), shortened ventilatory support (42.9 +/- 29.5 hours versus control: 162.4 +/- 131.2 hours, p = 0.0005), decreased blood transfusion (red blood cells: 16.2 +/- 18.2 mL/kg versus control: 41.4 +/- 27.8 mL/kg, p = 0.01; coagulation factors: 5.3. +/- 6.9 mL/kg versus control: 32.3 +/- 15.5 mL/kg, p = 0.01), and led to earlier chest tube removal. In neonates (< or =30 days), MUF significantly reduced transfusion of coagulation factors (5.4 +/- 5.0 mL/kg versus control: 39.9 +/- 25.8 mL/kg, p = 0.007), and duration of ventilatory support (59.3 +/- 36.2 hours versus 242.1 +/- 143.1 hours, p = 0.0009). In patients with prolonged CPB (>120 minutes), MUF significantly reduced the duration of ventilatory support (44.7 +/- 37.0 hours versus 128.7 +/- 133.4 hours, p = 0.002). No significant differences were observed between MUF and control patients for any parameter in the presence of ventricular septal defect without pulmonary hypertension, tetralogy of Fallot, or aortic stenosis. CONCLUSIONS: Modified ultrafiltration after CPB is safe and decreases the need for homologous blood transfusion, the duration of ventilatory support, and chest tube placement in selected patients with complex congenital heart disease. The optimal use of MUF includes patients with preoperative pulmonary hypertension, neonates, and patients who require prolonged CPB.     

Aprotinin does not decrease early graft patency after coronary artery bypass grafting despite reducing postoperative bleeding and use of donated blood

Forty-five male patients with planned coronary artery bypass operation were randomized in a double blind fashion to receive either 6 million kallikrein inactivator units of aprotinin (high-dose group), 2 million kallikrein inactivator units of aprotinin (low-dose group), or placebo (control group). Postoperative bleeding was significantly decreased in both aprotinin groups in comparison to that in the control group (590 ml [290 to 1800 ml] high-dose group and 650 ml [280 to 1900 ml] low-dose group versus 920 ml (350 to 2700 ml) control group, p < 0.001). There was no difference between the two aprotinin groups. The need for postoperative blood transfusion was significantly lower in the aprotinin groups (1.46 [0 to 4] blood units high-dose group and 1.65 [0 to 5] blood units low-dose group versus 2.43 [0 to 7] blood units control group, p < 0.05). All patients underwent coronary angiography between the seventh and twelfth postoperative day. No difference was found among the three groups in patency of vein grafts-93.8% in the high-dose group, 94.5% in the low-dose groups, and 93.3% in the control group. Therefore, aprotinin significantly reduced postoperative bleeding and transfusion requirement after coronary artery bypass grafting without influencing early graft patency.     

Reduction of allogeneic blood transfusions after open heart operations by lowering cardiopulmonary bypass prime volume

BACKGROUND: Despite recent advances in blood conservation techniques, up to 30% to 80% of patients undergoing open heart operations require allogeneic blood transfusions. A prospective, randomized study was performed to test the effect of lowering cardiopulmonary bypass prime volume (as an additional component of an integrated blood conservation strategy) on clinical outcome and allogeneic blood transfusion. METHODS: One hundred fourteen patients undergoing open heart operations were randomized to either full prime (FP) volume (1,400 mL of Plasmalyte solution) or reduced prime (RP) volume (600 to 800 mL). The reduction of prime volume was achieved by slowly draining the cardiopulmonary bypass circuit into a cell-saving device before the initiation of bypass. Firm transfusion thresholds were observed. RESULTS: There were no significant differences between the groups with respect to baseline characteristics, body surface area, type and urgency of the procedures, perfusion technique, and hematologic profile. Mortality (FP, 1.7%; RP, 0%; p approximately 1.0) and overall morbidity (FP, 28.1%; RP, 22.8%; p = 0.53) were similar. However, transfusion requirements were significantly lower in the RP group: total donor exposure, 3.8 +/- 10.1 versus 1.0 +/- 2.4 units (p = 0.044); percentage of patients transfused, 54% (n = 31) versus 35% (n = 20) (p = 0.036). Twenty-four-hour chest tube drainage was similar: 455 +/- 223 mL for FP versus 472 +/- 173 mL for RP (p = 0.66). The lowest hematocrit on bypass was significantly higher in the RP group: 29.3% +/- 4% versus 26.3% +/- 5.3% (p = 0.009). CONCLUSIONS: Lowering cardiopulmonary bypass prime volume resulted in a significant decrease in allogeneic blood product use. Because postoperative 24-hour chest tube drainage was similar in both groups, and hematocrit during bypass was higher in the RP group, the reduction in allogeneic blood transfusions appears to be related to a decrease in prime-induced hemodilution. This technique is effective, simple, and safe. It therefore should be strongly considered for patients undergoing operations using normothermic or near-normothermic cardiopulmonary bypass who are at high risk for allogeneic blood transfusion.     

Aprotinin reduces homologous blood transfusions when pediatric cardiac surgery must be redone

The hemostatic effect of aprotinin in pediatric cardiac surgery is controversial. This study demonstrated the usefulness of aprotinin in cases undergoing additional surgery. In a retrospective study, three groups of children were investigated. In group I (n = 10), no aprotinin or Cell saver was used (control). In group II (n = 12), Cell saver was used intraoperatively. In group III (n = 14), aprotinin 30,000 KIU/kg was added to the prime of cardiopulmonary bypass, and another 10,000 KIU/kg was given every hour during extracorporeal circulation. Both blood loss and use of homologous blood during operation were significantly (p < 0.01) reduced in group III compared to those in the other two groups. In group III, blood loss both 12 and 48 hours postoperatively were one-third less than those in group I (no significant difference). The use of homologous blood 48 hours postoperatively was significantly reduced in group III compared to that in group I (p < 0.01) or group II (p < 0.05). We conclude that aprotinin administration during cardiopulmonary bypass reduced blood loss and homologous blood requirements both operatively and postoperatively when pediatric cardiac surgery must be redone.     

Intrapericardial delivery of L-arginine reduces the increased severity of ventricular arrhythmias during sympathetic stimulation in dogs with acute coronary occlusion: nitric oxide modulates sympathetic effects on ventricular electrophysiological properties

BACKGROUND: Nitric oxide (NO) modulates autonomic effects on myocardial contractility and sinus and atrioventricular nodal function of the heart. Whether NO influences autonomic actions on ventricular electrophysiological properties and arrhythmogenesis is not known. METHODS AND RESULTS: Four groups consisting of 43 autonomically denervated dogs were studied. To "superfuse" sympathetic nerves innervating the ventricles, test drugs were introduced into the pericardial sac for 30 minutes, and their effects on ventricular effective refractory period (ERP) and arrhythmia development were assessed before and during sympathetic stimulation (SS). In group 1 (n=12), ventricular ERPs showed no significant difference between control and superfusion with L-arginine, a NO precursor (222+/-20 versus 222+/-19 ms, P=.485). However, L-arginine significantly reduced SS-induced ERP shortening compared with control (9+/-7 versus 13+/-7 ms, P<.001). Simultaneous administration of N(G)-monomethyl-L-arginine (2 mg/mL) abolished the inhibitory effects of L-arginine (13+/-7 versus 13+/-7 ms, P=.885). In group 2 (n=15), the severity of ventricular arrhythmias significantly increased during SS. L-Arginine reduced this increase caused by SS. In group 3 (n=8), plasma norepinephrine spillover measured from the coronary sinus significantly increased during SS and was reduced by pericardial superfusion with L-arginine compared with control (6005.2+/-1525.6 versus 8503.4+/-2044.5 pg/min, P=.012). In group 4 (n=8), L-arginine pericardial superfusion significantly increased NO overflow measured from the coronary sinus during SS (93.25+/-59.20 versus 114.82+/-74.92 nmol/min, P=.043). CONCLUSIONS: Pericardial L-arginine reduces ERP shortening and increased severity of ischemic ventricular arrhythmias during SS in dogs. NO-induced reduction of norepinephrine release in the heart may be one of the underlying mechanisms.     

Safety and cost-effectiveness of MIDCABG in high-risk CABG patients

BACKGROUND: Myocardial revascularization without cardiopulmonary bypass has been proposed as a potential therapeutic alternative in high-risk patients undergoing coronary artery bypass grafting. To evaluate this possibility we compared 15 high-risk (HR) patients in whom minimally invasive direct coronary artery bypass grafting was used as the method of revascularization with 41 consecutive patients who underwent conventional coronary artery bypass grafting during 1 month. METHODS: Patients undergoing myocardial revascularization without cardiopulmonary bypass were significantly older than their low-risk (LR) counterparts (72.2 +/- 11.6 versus 63.3 +/- 9.7 years, p = 0.006). The demographic profile for HR versus LR patients was as follows: female patients, 60.0% versus 26.8%, p = 0.02; diabetes, 20.0% versus 24.4%, p = 0.7; prior stroke, 33.3% versus 7.4%, p = 0.03; chronic obstructive pulmonary disease, 60.0% versus 9.8%, p < 0.0001; peripheral vascular disease, 33.3% versus 12.2%, p = 0.03, congestive heart failure, 26.6% versus 9.8%, p = 0.09; impaired left ventricular (ejection fraction < 0.40), 40.0% versus 17.0%, p = 0.07; urgent operation, 86.6% versus 46.3%, p < 0.0001; and redo operation, 20.0% versus 0%, p = 0.003. RESULTS: There were no deaths in the HR group and one death in the LR group. The average intensive care unit stay was 1.1 +/- 0.5 days in HR patients versus 1.6 +/- 1.6 days in LR individuals (p = 0.2), and the average hospital stay was 6.1 +/- 1.8 versus 7.3 +/- 4.4 days, respectively (p = 0.3). We used an acuity risk score index developed by the Adult Cardiac Care Network of Ontario to predict outcome in the HR group. The expected intensive care unit stay in HR patients was 4.1 +/- 1.2 days (versus the observed stay of 1.1 +/- 0.5 days, p < 0.0001), and the expected hospital stay was 12.5 +/- 1.5 days (versus the observed stay of 6.1 +/- 1.8 days, p < 0.0001). The expected mortality in the HR group was 6.1% versus 0%, p = 0.3. A cost regression model was used to examine predicted versus actual cost (in Canadian dollars) for the HR patient cohort (based on Ontario Ministry of Health funding). The expected cost for the HR cohort would have been $11,997 per patient. In contrast, the average cost for these 15 patients was $5,997 per patient, an estimated cost saving of 50%. CONCLUSIONS: Myocardial revascularization without cardiopulmonary bypass appears to be a safe and cost-effective therapeutic modality for HR patients requiring myocardial revascularization.     

Perfluorocarbons are effective oxygen carriers in cardiopulmonary bypass

Intravascular perfluorochemical (PFC) emulsions together with a high oxygen (O2) tension may increase the delivery of dissolved O2 to useful levels. A severely anemic model of cardiopulmonary bypass (CPB) was used to test the hypothesis that a novel PFC emulsion (PFCE; Oxygent [Alliance Pharmaceutical Corp., San Diego, CA] 90% w/v perflubron) used at a high PO2 during bypass delivers sufficient O2 to ameliorate hypoxic myocardial contractile dysfunction. Acutely anemic dogs (N = 42; hematocrit = 15.8 +/- 0.6% [mean +/- SEM] before CPB and 10.9 +/- 0.1% during CPB) were divided into four groups. Group 1 was a control (n = 12). As CPB was initiated, groups 2 (n = 10), 3 (n = 10), and 4 (n = 10) had 1.35 g PFC.kg-1, 2.7 g PFC.kg-1, or 5.4 g PFC.kg-1 added via the venous return cannula. Pre-CPB and post-CPB cardiac function was measured by the first derivative of left ventricular pressure (dP/dtmax). The dP/dtmax on separation from CPB was: group 1, 619 +/- 96; group 2, 738 +/- 56; group 3, 782 +/- 101; and group 4, 828 +/- 100 (p < 0.05 groups 3 and 4 versus group 1). Mortality during the first hour after separation from CPB was higher in group 1 than in PFCE treated dogs; however, this trend did not attain statistical significance (p < 0.065). The PFC dose was higher in survivors than in nonsurvivors (2.6 +/- 0.4 g PFC.kg-1 versus 1.2 +/- 0.5 g PFC.kg-1; p < 0.05). A PFCE used at a high PO2 provides sufficient physically dissolved O2 to relieve myocardial hypoxic injury in a severely anemic model of CPB. Current PFCEs are effective O2 carriers. This finding suggests that they can be used as a temporary erythrocyte substitute to diminish the need for allogeneic transfusions during cardiac operations.     

Cryosurgical treatment of professional chronic radiodermatitis

The results of open cholecystectomy ([OC] n = 7) versus laparoscopic cholecystectomy ([LC] n = 7) in cirrhotic patients were analyzed prospectively. Groups were well matched for surgical indication, presence of ascites/bleeding tendency, and Child's grade. There was no mortality. Mean operating time was significantly longer in the LC group (155 +/- 47 vs. 103 +/- 25 min, p < 0.05). Operative blood loss was significantly greater in the OC group (128 +/- 125 vs. 642 +/- 467 ml, p < 0.05). No patient in LC group required blood transfusion in contrast to three patients in OC group. Compared with 0% postoperative complications in LC group, wound infections developed in 43% of the patients in OC group (p < 0.05). Mean hospital stay in LC group was significantly less (6.7 +/- 4 vs. 17.4 +/- 7.3 days, p < 0.01). Thus, contrary to previous belief, cirrhosis per se is not a contraindication to LC. Laparoscopic cholecystectomy may be the procedure of choice whenever cholecystectomy is indicated in a cirrhotic patient because it may be associated with less bleeding and fewer incision-related complications.     

Dilutional and modified ultrafiltration reduces pulmonary hypertension after operations for congenital heart disease: a prospective randomized study

OBJECTIVE: A prospective randomized study was performed to test whether removal of endothelin-1, by ultrafiltration techniques, will reduce pulmonary hypertension after operations for congenital heart disease. METHODS: Twenty-four patients with pulmonary hypertension (systolic pulmonary/systemic arterial pressure ratio > 60%) undergoing cardiac operations were randomized into a control group (n = 12) having conventional ultrafiltration and an experimental group (n = 12) undergoing dilutional ultrafiltration during and modified ultrafiltration after cardiopulmonary bypass. Plasma endothelin-1, nitric oxide metabolites, and cyclic guanosine monophosphate were assayed before bypass, 10 minutes into bypass, after bypass, and 0, 3, 6, and 12 hours after the operation in both groups, as well as in the ultrafiltrates and after modified ultrafiltration in the experimental group. Both groups received alpha-blockers (chlorpromazine and/or prazosin) postoperatively using the same guidelines. RESULTS: The ultrafiltrates contained significant amounts of endothelin-1 (1.81 +/- 0.86 pg/ml, dilutional, and 6.44 +/- 1.82 pg/ml, modified ultrafiltrate). Endothelin-1 and the pulmonary/systemic pressure ratio were significantly lower in experimental compared with control patients. Nitric oxide metabolites and cyclic guanosine monophosphate increased similarly in both groups for 12 hours after the operation (p = not significant). Three of 12 control patients (25%) but no experimental patients had pulmonary hypertensive crises (p = 0.07). The experimental patients required significantly less ventilatory support (67 +/- 47 hours vs 178 +/- 139 hours for control patients, p = 0.048). CONCLUSIONS: Dilutional and modified ultrafiltration reduce endothelin-1 and the pulmonary/systemic pressure ratio postoperatively and may become an important adjunct for preventing pulmonary hypertension after operations for congenital heart disease in high-risk patients.     

The prophylactic effect of aprotinin on intraoperative bleeding in liver transplantation: a randomized clinical study

Fibrinolysis has been recognized as an important cause of intraoperative bleeding during orthotopic liver transplantation (OLT). Several investigators have used prophylactic administration of aprotinin in patients to inhibit fibrinolysis and to decrease transfusion requirements, morbidity, and mortality. Nevertheless, the role of aprotinin in this situation is not yet clear. The goal of this study was to determine the effects of prophylactic administration of aprotinin on intraoperative bleeding and blood requirements, and on hemostatic changes during OLT. Eighty consecutive patients were included in a double-blind, prospective study and were randomized in two groups. In group A (n = 39), an initial dose of 2 x 10(6) kallikrein inactivator units (KIU) of aprotinin was administered in the induction of anesthesia followed by infusion of 5 x 10(5) KIU/h until the end of the procedure. The control group (n = 41) received an identical volume of saline solution. The majority of the operations were performed with vena cava preservation (piggy-back technique) without venovenous bypass. During the anhepatic phase, a significant increase in levels of tissue plasminogen activator, thrombin-antithrombin complexes (TAT) and D-dimers (DD) was noted in both groups. A significant increment of TAT was observed in group A during reperfusion. The remaining hemostatic parameters were similar in both groups. Intraoperative requirements of packed red cells, fresh-frozen plasma (FFP), platelets, and cryoprecipitate were similar in the two groups. Our results suggest that prophylactic administration of aprotinin is not useful in reducing bleeding and blood product requirements during OLT.     

Morbidity, cost, and six-month outcome of minimally invasive direct coronary artery bypass grafting

BACKGROUND: Minimally invasive direct coronary artery bypass grafting (MIDCABG) promises to reduce the morbidity of coronary bypass, but this has not been proved. METHODS: This retrospective study compares the morbidity, mortality, cost, and 6-month outcome of patients less than 80 years old undergoing elective left internal mammary artery to left anterior descending artery bypass grafting via MIDCABG (n = 60) or sternotomy (n = 55) between January 1995 and December 1996. There were no differences between the groups in mean age, sex distribution, or preoperative risk level. The left internal mammary artery was mobilized from the fifth costal cartilage to the subclavian artery in all patients. The anastomoses were done with a beating heart in the MIDCABG group and with cardioplegic arrest in the sternotomy group. RESULTS: There were no operative deaths in either group. The MIDCABG patients had a lower transfusion incidence (10/60 [17%] versus 22/55 [40%]; p< or =0.02) and a shorter postoperative intubation time (2.1+/-4.2 versus 12.6+/-9 hours; p< or =0.0001). One patient in each group was reexplored for bleeding. Three sternotomy patients (3/55, 5%) required ventilatory support for greater than 48 hours, but no MIDCABG patient was ventilated for more than 24 hours. Median postoperative length of stay was 4 days for MIDCABG and 7 days for sternotomy. Estimated hospital costs were $11,200+/-3100 for MIDCABG and $15,600+/-4200 for CABG (p < 0.001). The reduced morbidity and cost of MIDCABG was found mostly in high-risk patients. At 6-month follow-up, 5 MIDCABG patients (5/60, 8%) had evidence of recurrent ischemia involving the left anterior descending artery, primarily the result of anastomotic stricture. CONCLUSIONS: This analysis shows that MIDCABG reduces the initial morbidity and cost of coronary bypass, but some patients require subsequent reintervention. Long-term follow-up is needed before MIDCABG can be judged better than traditional bypass, but the initial results are promising, especially in high-risk patients.     

Clinical trial of retrograde warm blood reperfusion versus standard cold topical irrigation of transplanted hearts

BACKGROUND: A prospective, randomized clinical study involving 34 patients undergoing heart transplantation compared myocardial preservation of donor hearts maintained with continuous reperfusion with retrograde warm blood cardioplegia during surgical implantation versus the standard cold topical irrigation. METHODS: Hearts in both groups were arrested with a standard crystalloid solution and maintained in a cold saline solution during transportation. In the retrograde group, cardioplegia was administered through a catheter in the coronary sinus during surgical implantation. An average of 471 +/- 30 mL of hyperkalemic crystalloid solution diluted 1:4 in warm blood from the oxygenator was infused. In the standard group, the heart was kept cold by topical irrigation of cold saline solution and was reperfused only when the ascending aorta was unclamped. RESULTS: Preoperative characteristics of donors and recipients were similar in the two cohorts. Ischemic time average 139 +/- 12 minutes in the retrograde group compared with 130 +/- 11 minutes in the standard group (p = 0.57). Cardiopulmonary bypass time averaged 89 +/- 4 minutes in the retrograde group and 110 +/- 12 minutes in the standard group (p = 0.12). Defibrillation at reperfusion was performed in 4 patients (4/17, 24%) in the retrograde group and 12 patients (12/18, 67%) in the standard group (p = 0.01). There were no deaths in the retrograde group (0/17), whereas in the standard group, 3 patients (3/17) died of early graft failure (p = 0.11). Four early graft failures occurred in the standard group (p = 0.06). Two patients (2/17, 12%) were weaned from bypass with ventricular assist devices in the standard group. The number of subendocardial necrotic cells in the first two weekly endomyocardial biopsy specimens averaged 2.7 +/- 0.8 cells/mm2 in the retrograde group and 5.9 +/- 2.4 cells/mm2 in the standard group (p = 0.12). CONCLUSIONS: Retrograde warm blood reperfusion appears to improve the initial recovery of transplanted hearts. The technique is easy to use and may be a useful approach to graft protection during surgical implantation.     

Predictive value of contact investigation for identifying recent transmission of Mycobacterium tuberculosis

BACKGROUND: Abciximab (ReoPro; Eli Lilly and Co, Indianapolis, IN) is a monoclonal antibody that binds to the platelet glycoprotein IIb/IIIa receptor and produces powerful inhibition of platelet function. Clinical trials of abciximab in patients undergoing coronary angioplasty have demonstrated a reduction in thrombotic complications and have encouraged the widespread use of this agent. We have observed a substantial incidence of excessive bleeding among patients who receive abciximab and subsequently require emergency cardiac operations. METHODS: The records of 11 consecutive patients who required emergency cardiac operations after administration of abciximab and failed angioplasty or stent placement were reviewed. RESULTS: The interval from the cessation of abciximab administration to operation was critical in determining the degree of coagulopathy after cardiopulmonary bypass. The median values for postoperative chest drainage (1,300 versus 400 mL; p < 0.01), packed red blood cells transfused (6 versus 0 U; p = 0.02), platelets transfused (20 versus 0 packs; p = 0.02), and maximum activated clotting time (800 versus 528 seconds; p = 0.01) all were significantly greater in the early group (cardiac operation < 12 hours after abciximab administration; n = 6) compared with the late (cardiac operation >12 hours after abciximab administration; n = 5) group. CONCLUSIONS: This report suggests that the antiplatelet agent abciximab is associated with substantial bleeding when it is administered within 12 hours of operation.     

Alterations in renal microcirculation during cardiopulmonary bypass

BACKGROUND: This study was designed to investigate renal microvascular changes during cardiopulmonary bypass. METHODS: Kidneys were harvested from each of four groups of 6 pigs. Group A were anesthetized and heparinized only. The remaining three groups underwent cardiopulmonary bypass at 28 degrees C, group B for 30 minutes and groups C and D for 120 minutes; group D had an additional 30 minutes of normothermic perfusion at the end of the experiment. Renal cortical blood flow was measured using radiolabeled microspheres. Microvascular morphology was defined by corrosion casting and scanning electron microscopy. RESULTS: In group A, renal vascular resistance was 61+/-5.1 mm Hg x mL(-1) x min(-1). This value decreased to 28+/-7.8 in group B and 25+/-4.0 in group C (p < 0.05), and increased in group D to 40+/-4.1 (p < 0.05 versus groups A, B, and C). Cortical thickness, as measured by microvascular casts in groups A, B, and C, was 33, 34, and 31 mm, respectively, with equal distribution of the resin to the superficial and deep cortex but was significantly reduced in group D to 22 mm (p < 0.05 versus groups A, B, and C), with failure of the resin to fill the superficial cortical layer. Diameters of glomeruli as seen on the casts were 111+/-10.38 microm in group A, 100+/-9.24 microm in group B, and 82+/-4.4 microm in group C (p < 0.05 group A versus group C). The glomeruli from group D were still significantly smaller than group A (93+/-10.35 microm, p < 0.05). Mean glomerular capillary diameters were 4.65+/-0.26 microm in group A, 3.9+/-0.16 microm in group B, 3.6+/-0.19 microm in group C, and 3.65+/-0.3 microm in group D (p < 0.05 group A versus groups B, C, and D). CONCLUSIONS: Hypothermic nonpulsatile cardiopulmonary bypass decreased renal vascular resistance, but the superficial and deep layers of the cortex were perfused equally. Glomeruli were reduced in size because of capillary narrowing. This was consistent with diversion of blood through bypass channels. With restoration of normothermia, underperfusion of the superficial cortex occurred, with potential for damage to these nephrons during the increased metabolic demands of rewarming.     

An experimental study of coronary arteriosclerosis after heart transplantation

The purpose of this study is to evaluate the effects of Cyclosporine (CsA), FK-506 (FK) and 15-Deoxyspergualin (DOS) on coronary arteriosclerosis after rat heart transplantation. Three groups of Lewis rats (n = 7, each) received heterotopic heart transplants from F-344 donors and were treated with CsA (Group Cs), FK (Group FK) and DOS (Group DOS) intraperitoneally. All rats were sacrificed 60 days later and assessed microscopic grading score (GS) of rejection and arteriosclerosis, and measured serum lipid. There was no significant difference in the GS of rejection but the GS of arteriosclerosis in the groups Cs was significantly higher than the group DOS (1.71 +/- 0.24 versus 1.11 +/- 0.34, p < 0.01). Triglyceride in the groups Cs was significantly higher than the group FK and group DOS (99 +/- 23 versus 66 +/- 21, 56 +/- 30 mg/dl, p < 0.02), and LDL in the group Cs and group FK was significantly higher than group DOS (104 +/- 17, 81 +/- 23 versus 31 +/- 17 mg/dl, p < 0.01). We concluded that DOS had a superior protective effect against coronary arteriosclerosis after heart transplantation and it may depend on the different mechanism of immunosuppression and lipid metabolism abnormality causing by immunosuppressants.     

Modifying risk for extracorporeal circulation: trial of four antiinflammatory strategies

BACKGROUND: Despite recent rediscovery of beating heart cardiac surgical techniques, extracorporeal circulation remains appropriate for most heart operations. To minimize deleterious effects of cardiopulmonary bypass, antiinflammatory strategies have evolved. METHODS: Four state-of-the-art strategies were studied in a prospective, randomized, preoperatively risk stratified, 400-patient study comprising primary (n = 358), reoperative (n = 42), coronary (n = 307), valve (n = 27), ascending aortic (n = 9), and combined operations (n = 23). Groups were as follows: standard, roller pump, membrane oxygenator, methylprednisolone (n = 112); aprotinin, standard plus aprotinin (n = 109); leukocyte depletion, standard plus a leukocyte filtration strategy (n = 112); and heparin-bonded circuitry, centrifugal pumping with surface modification (n = 67). RESULTS: Analysis of variance, linear and logistic regression, and Pearson correlation were applied. Actual mortality (2.3%) was less than half the risk stratification predicted mortality (5.7%). The treatment strategies effectively attenuated markers of the inflammatory response to extracorporeal circulation. Compared with the other groups the heparin-bonded circuit had highly significantly decreased complement activation (p = 0.00001), leukocyte filtration blunted postpump leukocytosis (p = 0.043), and the aprotinin group had less fibrinolysis (p = 0.011). Primary end points, length of stay, and hospital charges, were positively correlated with operation type, age, pump time, body surface area, stroke, pulmonary sequelae, predicted risk for stroke, predicted risk for mortality, and risk strata/treatment group interaction (p = 0.0001). In low-risk patients, leukocyte filtration reduced length of stay by 1 day (p = 0.02) and mean charges by $2,000 to $6,000 (p = 0.05). For high-risk patients, aprotinin reduced mean length of stay up to 10 fewer days (p = 0.02) and mean charges by $6,000 to $48,000 (p = 0.0007). CONCLUSIONS: These pharmacologic and mechanical strategies significantly attenuated the inflammatory response to extracorporeal circulation. This translated variably into improved patient outcomes. The increased cost of treatment was offset for selected strategies through the added value of significantly reduced risk.     

Prevalence and aspects of arteriopathies in non-insulin-dependent diabetes mellitus with severe hypertension

Severe hypertension may lead to macroangiopathy complications especially when a major vascular risk factor as diabetes exists. We have studied the prevalence of macroangiopathy in a group of 40 consecutive NIDDM patients with severe hypertension (> or = 3 hypotensive drugs) (grS) that we have compared to 80 consecutive NIDDM patients with controlled hypertension (1 or 2 hypotensive drugs) (grC). All patients have had metabolic, blood pressure (ABPM) and vascular (color duplex) investigations. The two groups were similar for age (years): 61.9 > or = 9 versus 65.2 +/- 9.5, diabetes duration (years): 10.7 +/- 7 versus 12.1 +/- 8 and hypertension duration: (years) 8.9 +/- 8 versus 11.7 +/- 7.3. The mean level of blood pressure was the same in all patients (mmHg): SBP = 138 +/- 14 versus 144 +/- 20; DBP = 80 +/- 9 versus 83 +/- 13; MBP = 100 +/- 10 versus 105 +/- 15. The frequency (%) of escape SBP (> 140): 50 versus 80, p < 0.01), and DBP (> 90): 29 versus 35, p < 0.05 was significantly higher in grS. Twenty (25%) patients in grC and 20 (50%) in grS had one or more macroangiopathy which was dispatched as follow: coronary heart disease n = 8 (7%) versus 13 (32.5%), p < 0.01; lower limb arteritis n = 12 (15%) versus n = 9 (22%), NS; carotid atheroma n = 5 (25) versus n = 6 (15%), NS. All significant renal artery stenosis (RAS) n = 8 (20%) were found in grS (p < 0.001). Only plasma triglyceride level (mmol/L) was statistically higher in grS 2.5 +/- 1.2 versus +/- 1 while BMI, plasma cholesterol, HbA1C, and creatininemia were NS. The sex-ratio (F/M) 1.28 versus 3, insulin requirement (%): 11 versus 42.5, retinopathy (%) 14 versus 45 and micromacroalbuminuria were statistically significant p < 0.01. Conclusion: macroangiopathy is frequent in severe hypertension (50%) versus controlled hypertension (25%) in NIDDM patients especially coronary heart disease (32.5%); the prevalence of RAS is high in grS (20%). The following criteria are frequently noticed in high risk patients: insulin requirement, micro or macroalbuminuria and high plasma triglyceride.     

Aprotinin reduces the expression of p-selectin on the surface of platelet and leukocyte-platelet conjugates

P-Selectin, an adhesion molecule expressed on the surfaces of activated platelets and the vascular endothelium, mediates platelet binding to monocytes and neutrophils. Monocytes and neutrophils produce superoxide anion by activated platelets through p-selectin. Aprotinin, a serine protease inhibitor, inhibits plasmin to activate platelets during cardiopulmonary bypass (CPB). A total of 25 patients were studied to clarify the effects of aprotinin on p-selectin expression during CPB. Nine patients were not given aprotinin (control group), and 16 were given aprotinin of 2 million U in the priming solution (aprotinin group). The platelet count and soluble p-selectin in the plasma, p-selectin on the surface membranes of platelets, and leukocyte-platelet conjugate levels were measured during and after CPB. The platelet count was maintained well in the aprotinin group. The increases of soluble p-selectin in the plasma, platelet surface p-selectin, and leukocyte-platelet conjugates were less in the aprotinin group than in the control group (p < 0.05). In conclusion, aprotinin in patients undergoing CPB may reduce the early inflammatory reactions induced by p-selectin.