摘要:

Background Abdominal aortic aneurysm (AAA) disease is characterized by an increase in proteolysis and loss of matrix components.The cytokines tumor necrosis factor- alpha (TNF- alpha) and interleukin-1 beta (IL-1 beta), products of activated macrophages and T cells, are known to increase the production of matrix-degrading enzymes in some pathological states.Methods and Results Seven AAA and five control aortic tissue extracts were assayed for TNF-alpha and IL-1 beta with ELISA. TNF- alpha was elevated significantly in AAA extracts compared with controls (86+-34 pg/mg of total protein versus 1+-1 pg/mg of total protein; P<.001). IL-1 beta concentration also was significantly increased in the AAA specimens (48+-14 pg/mg of total protein versus 12+-5 pg/mg of total protein; P<.05). Immunoblotting demonstrated secreted forms of TNF- alpha in the AAA extracts, and possible membrane-bound forms were observed when the tissues were detergent-extracted. Known forms of IL-1 beta also were observed on immunoblots of AAA tissue extracts.Conclusions The presence of TNF-alpha and IL-1 beta in AAA tissue underscores the importance of the infiltrating inflammatory cells present in the media and adventitia of aneurysmal aortic wall and further implicates an inflammatory process in the pathogenesis of AAA. (Circulation. 1994;90 (part 2):II-224-II-227.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Despite major advances in both surgical and percutaneous revascularization techniques, limb salvage and relief of ischemic pain cannot be achieved in many patients with diffuse peripheral vascular disease.Vascular endothelial growth factor (VEGF) is a heparin-binding, endothelial cell-specific mitogen. Previous studies have suggested that VEGF is a regulator of naturally occurring physiological and pathological angiogenesis. In this study, the therapeutic potential of intramuscularly administered VEGF was investigated in a rabbit model of chronic hindlimb ischemia.Methods and Results Ischemia was induced in the hindlimb of 24 New Zealand White rabbits by ligation of the distal external iliac artery and complete excision of the femoral artery.Ten days after the induction of limb ischemia (day 0), saline (group A, n=7) or the 165-amino acid isoform of recombinant human VEGF (group B: 200 micrograms, n=6; group C: 500 micrograms, n=7; group D: 1000 micrograms, n=4) was administered intramuscularly into the ischemic limb daily for 10 days. Angiography on day 30 after initiation of therapy revealed statistically significant dose-dependent augmentation of collateral vessels in the ischemic limb (angiographic score: group A, 13.0+-1.1; group B, 21.2+-1.8; group C, 27.3+-1.4; group D, 31.5+-2.5). Capillary density in the thigh muscles on day 30 was 1.6 times greater in VEGF groups versus controls (176+-15.3 versus 113+-27.3 per square millimeter, P<.05). Amelioration of the hemodynamic deficit in the ischemic limb was documented by calf systolic blood pressure ratio (group A, 0.52+-0.02; group B, 0.67+-0.02; group C, 0.73+-0.01; group D, 0.82+-0.03). "Clinical" improvement (incidence of calf muscle atrophy and distal limb necrosis: group A, 85.7%; group B, 33.3%; group C, 14.3%; group D, 0%) was greater in VEGF- treated than in control animals, again in a dose-dependent fashion.Conclusions These findings demonstrate a significant dose-dependent augmentation in limb perfusion accompanied by evidence of increased collateral formation after intramuscular administration of VEGF in ischemic rabbit hindlimbs. This study thus supports the hypothesis that administration of VEGF to stimulate angiogenesis may represent a new therapeutic modality in the management of arterial insufficiency. (Circulation. 1994;90(part 2):II-228-II-234.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Aortic dissection is one of the most lethal potential complications in patients with the Marfan syndrome.Methods and Results Among 360 patients undergoing operative treatment of aortic dissection between 1963 and 1992, 40 had the Marfan syndrome.There were 24 men and 16 women with a mean age of 35+-9 years (+-1 SD; range, 15 to 54 years). These patients included 16 with acute type A, 2 with acute type B, 18 with chronic type A, and 4 with chronic type B aortic dissections. The aortic arch was involved in 29 cases. Preoperative complications included acute aortic valvular insufficiency in 13 patients, rupture into the pericardial space in 3, and loss of peripheral pulses in 9. The site of primary intimal tear was the ascending aorta in 25 patients, the aortic arch in 2, the descending aorta in 7, and not identified in 6. Operations included ascending aortic and aortic valvular replacement (with or without coronary artery reimplantation) in 22 patients, ascending aortic replacement alone in 5, and descending thoracic aortic replacement in 9. Four operative deaths (10+-5% (+-70% confidence limits)) occurred in 3 acute patient-years and 1 chronic type A patient-years. Long-term follow-up (216 patient-years; range, 1 month to 22 years; mean, 5.4 years) revealed 15 late deaths, 7 from late aortic sequelae. The overall actuarial survival estimates were 71+-8%, 54+-10%, and 22+-11% at 5, 10, and 15 years, respectively. Twenty late aortic operations were required in 14 patients.Conclusions Despite satisfactory early results, the long-term survival of patients with the Marfan syndrome was suboptimal (albeit similar to those without the Marfan syndrome). Future progress will pivot on reducing the incidence of aortic dissection in these patients with medical therapy and/or earlier surgical intervention and enhanced postoperative serial imaging surveillance of the entire aorta. (Circulation. 1994;90(part 2):II-235-II-242.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Age is a predictor of cognitive dysfunction after cardiac surgery, but the mechanism is unknown.The purpose of our study was to determine whether age-related decrements in cognition are associated with cerebral blood flow (CBF) autoregulation during cardiopulmonary bypass (CPB).Methods and Results Cognitive function testing was completed before surgery and before hospital discharge in 215 patients undergoing elective coronary artery bypass grafting (CABG) surgery.The battery consisted of seven tests with nine measures designed to evaluate memory, mood changes, and visuomotor speed and function. Pressure-flow and metabolic-flow cerebral autoregulation during hypothermic cardiopulmonary bypass were determined using the Xenon-133 clearance CBF method and radial artery and jugular bulb effluent to calculate cerebral metabolic rate (CMRo2) and cerebral AV difference (C(AV)o2=20%. Metabolism-flow autoregulation was tested by varying the temperature (CMRo2) and measuring the coupling of CBF and CMRo2. Individual patient autoregulation was correlated with changes in cognitive measures. Cognitive performance declined in 6 of 9 measures after CABG surgery. Age predicted cognitive decline in 7 of 9 measures; short-term memory showed the greatest effect of age. Pressure-flow autoregulation during hypothermic CPB showed a small but significant (P<.0001) effect of pressure on CBF. There was no effect of age on the slope of CBF response to changes in MAP (pressure-flow autoregulation). There was a major effect of temperature on CBF during CPB (P<.0001). Coupling CBF and CMRo2with changing temperature was unaffected by age. Changes in cognition were not associated with measures of cerebral autoregulation. However, increasing C(AV)o2is associated with cognitive deficits in 5 of 9 measures; these associations were independent of age.Conclusions Increased age predisposes to impaired cognition after cardiac surgery.This decline in cognitive function in the elderly is not associated with age-related changes in cerebral blood flow autoregulation. The association of increased oxygen extraction with decline in some measures of cognitive function suggests that an imbalance in cerebral tissue oxygen supply, which is unrelated to age, contributes to acute cognitive dysfunction after cardiac surgery. Cognitive dysfunction after CPB in the elderly cannot be explained by impaired CBF autoregulation. (Circulation. 1994;90(part 2):II-243-II-249.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Neurological injury is an important cause of morbidity and mortality after cardiac surgery.With the advent of warm heart surgery, the neuroprotective role of hypothermic cardiopulmonary bypass (CPB) has come under increasing scrutiny. Preliminary work by us in the area found no increased risk of neurological morbidity with normothermic CPB in a small group of patients and suggested a possible benefit. The purpose of the present study is to compare the incidence of neurological and neuropsychological dysfunction in a larger number of patients randomized to warm or cold aortocoronary bypass surgery.34 degrees C; cold, <=28 degrees C). Statistical analysis was performed using the sas statistical software package. Two hundred one patients were enrolled in the study. Of these, 155 patients completed the entire protocol and were included in the final analysis (warm group, n=78; cold group, n=77). One patient in the warm group died perioperatively from a massive hemispheric stroke. Another warm group patient was unable to complete neuropsychological evaluation because of a perioperative stroke. Thus, 153 patients completed the entire series of neuropsychological tests. A total of 6 patients (warm group, n=2; cold group, n=4; P=NS) suffered from perioperative focal neurological deficits. There was a consistent deterioration in scores from tests of psychomotor speed/coordination (trail making, digit symbol, pegboard) in the early postoperative period, which resolved by the 3-month follow-up. Tests of memory (Buschke, Wechsler memory scale) showed no evidence of patient deterioration in the postoperative period. No difference was seen between the warm and cold groups.Conclusions In this randomized trial of normothermic versus hypothermic CPB, we found deterioration in scores of tests of psychomotor speed but not of memory in the early postoperative period.We were unable to demonstrate any neuroprotective effect from moderate hypothermia in this patient population. (Circulation. 1994;90(part 2):II-250-II-255.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Hypertension commonly occurs after cardiac surgery and requires therapy to prevent the potentially deleterious effects.=3 (mean score, 2.0). Both isradipine and nitroprusside produced statistically significant reductions in systolic and diastolic blood pressures, a decrease in systemic vascular resistance, and increases in heart rate, cardiac index, and stroke volume index. Isradipine produced no significant decreases in pulmonary artery occlusion wedge pressure compared with nitroprusside.Conclusions Intravenous isradipine was effective and well tolerated in patients with hypertension after CABG and offers an additional therapeutic option to treat patients after cardiac surgery.(Circulation. 1994;90(part 2):II-256-II-261.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background We have established that thromboxane B2(TX) blood levels increase across the pulmonary circulation after total cardiopulmonary bypass (CPB) but not after partial CPB.In the present study, we used the same model and examined the parameters of pulmonary injury after total or partial CPB.Methods and Results Fourteen anesthetized sheep were placed on total CPB (n=7), without ventilation and with occlusion of the pulmonary artery, or partial CPB (n=7), with ventilation and an open pulmonary artery.After 90 minutes, the sheep were separated from CPB, and the pulmonary artery was perfused normally. After 30 minutes, we elevated left atrial pressure in all sheep. Plasma TX, plasma leukotriene B4, platelet counts, white blood cell counts, and plasma protein concentration were measured before CPB and every 15 minutes after CPB for 1 hour. The right and left atrial blood samples were obtained simultaneously. Pulmonary arterial pressure, left atrial pressure, and pulmonary arterial flow were measured. Pulmonary vascular resistance (PVR) was calculated for 30 minutes after CPB. Lung lymph protein, TX, leukotriene B4, and flow were measured before CPB and every 30 minutes after CPB for 1 hour. Pulmonary biopsies and bronchoalveolar lavage fluid were obtained before CPB and at the end of the experiment. After total CPB, levels of TX across the pulmonary circulation increased significantly, but leukotriene B4remained constant. Platelets and white blood cells were consumed across the pulmonary circuit after total CPB but not after partial CPB. PVR increased by 170%, lymph flow increased by 233%, lung water content increased by 15%, and the ratio of lymph to plasma protein decreased by 20% after total CPB, but similar changes did not occur after partial CPB.Conclusions During total CPB, the lungs are totally dependent on oxygen supply provided by nonpulsatile bronchial arterial flow.Lung injury seen with restoration of pulmonary artery flow and ventilation may be the result of an inflammatory response associated with TX elevation after a period of relative pulmonary ischemia. Pulmonary injury was not seen after less severe pulmonary arterial flow deprivation, with maintenance of ventilation (partial CPB). Although the specific cause is undetermined from these data, the occurrence of elevated TX levels and lung damage after total CPB is clearly established. (Circulation. 1994;90(part 2):II-262-II-268.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Thrombocytopenia and impaired platelet function after cardiopulmonary bypass (CPB) contribute to postoperative bleeding and may increase blood transfusion requirements.We tested the hypothesis that reversible inhibition of glycoprotein IIb/IIIa integrin-mediated platelet adhesion would reduce postoperative bleeding after CPB.Methods and Results Twelve mongrel dogs (21 to 24 kg) underwent 2.5 hours of hypothermic CPB followed by 6 hours of observation. The study group (n=6) received a 90- micrograms/kg IV bolus of the glycoprotein IIb/IIIa inhibitor Integrelin, followed by continuous infusion (2 micrograms/kg per minute) during CPB; the control group (n=6) received only drug vehicle. Platelet number and aggregometry, Pao2, and chest tube output were assessed serially. Lung wet weight, histology, and myeloperoxidase activity were also measured. At 120 minutes after CPB, the control group had significantly lower platelet counts (expressed as percent of pre-CPB values) when compared with the Integrelin group (control, 35.2+-4.6%; Integrelin, 68.2+-4.9%; mean+-SEM; P<.05). Three hundred sixty minutes after CPB, platelet function (expressed as percent of pre-CPB aggregation induced by 10 micromole/L ADP) was better preserved in the Integrelin group (Integrelin, 20.8+-3.0%; control, 43.9+-10.4%; P<.05). The Integrelin group also had less total postoperative blood loss (control, 447+-97 mL; Integrelin, 248+-30 mL; P<.05). Pao2, lung wet weight, histology, and myeloperoxidase activity did not differ significantly between groups.Conclusions This study demonstrates that inhibition of platelet adhesion during CPB results in (1) less platelet consumption, (2) better preservation of platelet function, and (3) less postoperative bleeding.Reversible platelet inhibition may have clinical utility in minimizing postoperative bleeding and reducing blood transfusions. (Circulation. 1994;90(part 2):II-269-II-274.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background The use of warm blood cardioplegia is usually associated with that of warm cardiopulmonary bypass (CPB).Little is known, however, about the effect of temperature during bypass on neutrophil-endothelium interactions, which are currently considered a key component of the inflammatory response to CPB.Methods and Results Twenty-five patients operated on under CPB were studied. Core temperature during bypass was kept normothermic (33.5 degrees C to 37 degrees C) in 14 and lowered to 28 degrees C to 30 degrees C in the 11 remaining patients. The two groups were otherwise comparable. Arterial blood samples were collected before CPB and 30 minutes, 4 hours, and 24 hours thereafter. Samples were assayed for interleukin-1 receptor antagonist (IL-1ra), soluble intercellular adhesion molecule 1 (sICAM- 1), and elastase, which are markers of cytokine production, cytokine-upregulated endothelial ligands for neutrophil adhesion molecules, and degranulation secondary to adhesion of neutrophils to endothelial cells, respectively. IL-1ra levels (mean+-SEM) peaked 4 hours after bypass and were significantly higher in the warm group (87 926+-24 067 versus 18 090+-5798 mg/L, P<.02). Peak values of sICAM-1, which occurred 24 hours after bypass, were correspondingly higher in warm patients (414+-74 versus 298+-23 micrograms/L in cold patients). In keeping with these data, warm patients released significantly more elastase at both the 30-minute (703+-101 versus 349+-55 micrograms/L, P<.01) and 4-hour (627+-116 versus 324+-31 micrograms/L, P<.03) post-CPB study points.Conclusions Temperature profoundly affects neutrophil-endothelium interactions, which leads one to question the use of systemic normothermia in patients at higher risk of suffering from postbypass inflammation-mediated organ damage. (Circulation. 1994;90(part 2):II-275-II-279.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Postoperative cardiac arrest that is not responsive to conventional resuscitation is uniformly fatal.Sixteen patients who experienced postoperative ventricular fibrillation (VF) and arrest over a 6-year period and did not respond to open chest resuscitation were placed on an emergency basis on cardiopulmonary bypass (CPB) in the cardiac surgical intensive care unit (CSICU).Methods and Results Data were reviewed by retrospective analysis.Nine of the 16 patients (56.3%) survived, and they spent a mean of 9+-2.8 days in the CSICU and a mean of 17+-4.6 days in the hospital. They all are alive 1 month to 51/2 years later. The mean interval between VF/arrest and CPB in the CSICU was 50+-6.7 minutes (range, 25 to 83 minutes) for survivors and 51+-6.1 minutes (35 to 83 minutes) for nonsurvivors (P=.98). The duration of CPB in the CSICU was 111+-16.0 minutes (range, 55 to 189 minutes) for survivors and 167+-20.7 minutes (range, 80 to 232 minutes) for nonsurvivors (P=.05). There were no apparent differences between survivors and nonsurvivors in age, history of arrhythmias, use of antiarrhythmics, congestive heart failure, recent myocardial infarction, ejection fraction, preoperative intra-aortic balloon pump, urgency, or type of operation. Surgical variables and postoperative medications and electrolytes (after the primary procedure) were similar. The use of cardioplegic arrest during CPB in the CSICU was higher among survivors (3 of 9) compared with 0 of 7 for nonsurvivors (P=.21). There was no mediastinitis and only two minor soft tissue infections among survivors.Conclusions The use of CPB in the CSICU can achieve significant survival in patients who have otherwise irreversible cardiac arrest and/or VF after surgery; the incidence of infection in patients undergoing CPB in the CSICU is very low; and the use of warm cardioplegic arrest may enhance the chances of survival in this type of patient.(Circulation. 1994;90 (part 2):II-280-II-284.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID