Comparison of radionuclide and contrast ventriculography for detection and quantitation of regions of myocardial ischemia in dogs.

Radionuclide and contrast ventriculography were evaluated for their ability to estimate myocardial ischemia. In 14 closed-chest, sedated dogs, a small and larger region of ischemia were produced by inflating balloon occluders on the left anterior descending coronary artery. The systemic arterial pressure, atrial-paced heart rate, global ejection fraction by radionuclide and contrast ventriculography, regional wall-motion abnormalities (as the percentage of abnormally contracting segments), and regional myocardial blood flow (using the microsphere technique) were measured during an initial control period, two separate ischemic periods, and a final control period. The regional ischemic weights based on myocardial blood flow ranged from 0 to 38.5 g and were grouped as zero, small (range 0 to less than 10 g, mean 3.40 g), and large regions of ischemia (greater than 10 g, mean 24.8 g). Regional wall-motion abnormalities were sensitive qualitative indicators of ischemia. Receiver operating characteristic analysis showed that both ventriculographic methods were highly sensitive, specific, and accurate for detecting regional ischemia. Contrast ventriculography was slightly superior for detecting small regions less than 4 g, but the methods were equal for regions greater than 4 g. The arterial pressure and heart rate were unchanged during ischemia. For small regions of ischemia, the global ejection fraction did not fall using either the contrast or radionuclide technique, but it fell significantly when large regions were produced. There was a quantitative relationship between the percentage of abnormally contracting segments and the grams of myocardial ischemia (for radionuclide ventriculography, r = 0.65, P = 0.003, and for contrast ventriculography, r = 0.75, P less than 0.001), but for many small regions of ischemia, wall-motion changes were greater than anticipated, suggesting hypofunction of the continguous normal tissue. This study demonstrated that both radionuclide and contrast ventriculography were quite sensitive and specific for detecting measured amounts of regional ischemia. The functional changes resulting from ischemia are quantitatively related to the extent of regional ischemia, small areas resulting in regional wall motion abnormalities, and large areas producing both reduced global ejection fraction and wall motion changes.

Beneficial long-term effect of intracoronary perfluorochemical on infarct size and ventricular function in a canine reperfusion model.

The administration of a drug soon after reperfusion that could enhance myocardial salvage would have important clinical application. The aim of this study was to assess the long-term effect of the perfluorochemical, Fluosol DA 20%, on infarct size, infarct morphology, ventricular ectopic activity and serial regional ventricular function in a 2 week closed chest canine model. After 90 minutes of proximal left anterior descending artery occlusion, animals randomly received either oxygenated Fluosol DA (n = 9) or saline solution (n = 9) intracoronary at 15 ml/kg body weight over 20 to 30 minutes. Hemodynamic variables were similar in the two groups except for transient elevation of left ventricular filling pressure immediately after infusion in the treated group. Infarct size was markedly reduced in the perfluorochemical-treated animals when expressed as a percent of the risk region (10.8 +/- 1.8% versus 28.9 +/- 5.5%, p less than 0.02) or as a percent of the total left ventricle (3.7 +/- 1% versus 10.8 +/- 8%, p less than 0.006). This was associated with greater improvement in radial shortening in the jeopardized zone at 2 weeks after reperfusion (15.3 +/- 2.8% versus 5.2 +/- 2.1%, p less than 0.01). Histologic examination revealed adequate healing in the treated animals with an increased number of swollen mononuclear cells in the border zones. Holter electrocardiographic recordings demonstrated a low frequency of ventricular ectopic beats in both groups. This study suggests that the perfluorochemical, Fluosol DA, may be a potentially useful agent in enhancing myocardial salvage after successful reperfusion.

Determinants of left ventricular aneurysm formation after anterior myocardial infarction: a clinical and angiographic study.

To determine factors involved in left ventricular aneurysm formation after transmural anterior myocardial infarction, 79 patients with a first myocardial infarction who underwent cardiac catheterization within 6 months of infarction were evaluated. Patients who had received thrombolytic therapy were excluded. Patients were divided into four groups depending on the status of the left anterior descending artery and the presence or absence of a left ventricular aneurysm: Group I (n = 25): aneurysm with occluded left anterior descending artery; Group II (n = 27): no aneurysm and occluded left anterior descending artery; Group III (n = 23): no aneurysm and patent left anterior descending artery; and Group IV (n = 4): aneurysm with patent left anterior descending artery. Single vessel disease was more common in Group I (aneurysm) compared with Groups II and III (no aneurysm) (chi 2(4) = 12.8; probability value equal to 0.012). Collateral blood supply in the presence of an occluded left anterior descending artery was significantly less in Group I (aneurysm) compared with Group II (no aneurysm) (0.9 versus 2.4, p less than 0.001). The extent of coronary artery disease and collateral blood supply in Groups I and II were directly related (p = 0.012). Neither age, sex nor risk factors for coronary disease correlated with aneurysm formation. At a mean follow-up of 48 months, no differences were observed in the incidence of recurrent angina, new myocardial infarction, embolic events or sudden death. More patients in Group II underwent coronary artery bypass surgery. Total occlusion of the left anterior descending artery in association with inherent poor collateral blood supply is a significant determinant of aneurysm formation after anterior myocardial infarction. Multivessel disease with either good collateral circulation or a patent left anterior descending artery is uncommonly associated with the development of left ventricular aneurysm.

Right ventricular hypertrophy is an important determinant of right ventricular infarction complicating acute inferior left ventricular infarction.

To explore the role of right ventricular hypertrophy and chronic obstructive pulmonary disease in the pathogenesis of right ventricular infarction, 27 consecutive patients with a first inferior left ventricular infarction were prospectively studied. Right ventricular infarction was diagnosed using established hemodynamic criteria. Right ventricular hypertrophy was defined as right ventricular free wall thickness greater than or equal to 5 mm. Patients were classified into two groups: Group I patients with right ventricular infarction (n = 15), and Group II patients without right ventricular infarction (n = 12). The ratio of forced expiratory volume over forced vital capacity (FEV1/FVC) and forced expiratory flow between 25 and 75% expired volume (FEF) as a percent of predicted values were significantly reduced in Group I versus Group II (90 +/- 5 versus 105 +/- 6% and 63 +/- 13 versus 103 +/- 15%, respectively; p less than 0.05). This was associated with increased right ventricular wall thickness (Group I 5.5 +/- 0.3 mm versus Group II 3.9 +/- 0.2 mm, p less than 0.001). Multiple logistic regression analysis demonstrated that right ventricular wall thickness was the strongest predictor of right ventricular infarction (p less than 0.0005). No significant difference was found in the site of right coronary occlusion, collateral blood supply or extent of coronary artery disease between the two groups. These findings suggest that right ventricular hypertrophy predisposes patients with acute inferior myocardial infarction to right ventricular infarction independent of the site or extent of coronary artery disease.

Enhanced thrombolysis, reduced coronary reocclusion and limitation of infarct size with liposomal prostaglandin E1 in a canine thrombolysis model.

OBJECTIVES: The purpose of this study was to test the hypothesis that liposomal prostaglandin E1 (TLC C-53) would result in more rapid thrombolysis, less reocclusion and smaller infarct size when administered with heparin and streptokinase in a canine thrombolysis model. BACKGROUND: In experimental animals, prostaglandin E1 has been shown to augment thrombolysis, improve coronary flow and reduce infarct size when infused directly into the left atrium. TLC C-53 is a stable preparation of prostaglandin E1 bound by phospholipid microspheres that produces fewer adverse hemodynamic effects during intravenous use. METHODS: To investigate the effects of TLC C-53 on coronary patency and infarct salvage, we studied 30 conditioned open chest dogs. After coil-induced left anterior descending coronary artery occlusion and 1 h of clot maturation, the dogs were randomly assigned to receive a 10-min intravenous infusion of either TLC C-53 (2 micrograms/kg body weight) or placebo. Both groups then received intravenous heparin and streptokinase. Hemodynamic variables and Doppler coronary flow were monitored, and myocardial blood flow was determined using radioactive microspheres. Infarct size was assessed with triphenyltetrazolium chloride staining. RESULTS: Thrombolysis time was accelerated from 79 +/- 38 to 47 +/- 9 min (mean +/- SD), and coronary patency was greater (100% vs. 50%) with TLC C-53 than with placebo (p < 0.05). Moreover, for arteries that recanalized, coronary Doppler flow and myocardial perfusion were more severely impaired with placebo. Infarct size as a percent of the area at risk was higher (p < 0.05) with placebo (51 +/- 15%) than with TLC C-53 (33 +/- 14%). Neutrophil infiltration into ischemic myocardium determined by myeloperoxidase assay was also significantly greater in the placebo group. CONCLUSIONS: TLC C-53 administered intravenously before thrombolytic therapy resulted in a significant acceleration of thrombolysis time, improvement in coronary patency and blood flow during reperfusion and a reduction in infarct size.

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.

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.

Dexamethasone suppression testing in chronic renal failure: pharmacokinetics of dexamethasone and demonstration of a normal hypothalamic-pituitary-adrenal axis.

The status of the hypothalamic-pituitary-adrenal axis in chronic renal failure (CRF) was examined by dexamethasone suppression testing (DST) using oral overnight, oral and iv 8-h daytime, and standard 48-h oral dosage protocols. Based on data obtained after iv administration of dexamethasone, the daytime study was used to calculate pharmacokinetic parameters for dexamethasone (clearance, volume of distribution at steady state, and terminal t1/2). None of a group of seven uremic patients had suppressed plasma cortisol concentrations after administration of 1 mg dexamethasone, orally, the night before. Six normal subjects and six patients with CRF participated in the pharmacokinetic study. There was no significant difference between the groups with respect to clearance, volume of distribution at steady state, or t1/2 of dexamethasone, indicating that patients with CRF metabolize dexamethasone in a fashion similar to that of normal subjects. Daily patterns of plasma cortisol determined between 0800-1600 h on a day when dexamethasone was not administered were similar in normal subjects and CRF patients. However, the degree of suppression of plasma cortisol after dexamethasone was significantly greater in the normal subjects (P less than 0.01), possibly due to a prolonged cortisol t1/2 in CRF. Nevertheless, the CRF patients did have decreased plasma cortisol levels from 4-8 h after iv and from 4-7 h after oral dexamethasone. The bioavailability of dexamethasone was not significantly different between the groups. When 48-h oral DSTs were performed in the CRF group, four of five patients had normal responses. The one patient who did not suppress had low levels of plasma dexamethasone, presumably due to decreased gastrointestinal absorption of dexamethasone. These results indicate that the metabolism of dexamethasone is similar in CRF patients and normal subjects, that normal suppression of plasma cortisol can be achieved in uremia if the duration of dexamethasone administration is prolonged sufficiently to compensate for the prolongation of cortisol t1/2 in CRF, and that it is essential to measure plasma dexamethasone as well as cortisol levels to interpret the results of a DST in CRF patients.

The use of "marginal" donors for organ transplantation. The influence of donor age on outcome.

The influence of donor age on outcome was studied in the recipients of 12,131 cadaveric renal allografts, 3026 heart allografts, and 2913 liver allografts with followup information in the UNOS data base for transplants performed between 10/1/87 and 12/31/89. For recipients of kidney transplants, donors of ages 6-15 had significantly better 1-year graft survival than donors of ages 56-65, but the difference was only 7.0%. Donors of age greater than 65 actually did better than donors ages 56-65, but donors less than or equal to 5 were less satisfactory. Kidneys from older donors survived as well as kidneys from younger donors in patients with repeat transplants, diabetes, black race, age over 45, O HLA or 5 and 6 HLA matches, delayed graft function, shared kidneys and PRA greater than 50. For kidney recipients, multifactorial analysis by Cox regression showed that donor age was less important than the use of ALG, donor race, diabetes or peak PRA in ages 16-45, delayed function, repeat transplant, and HLA match. Recipients of heart transplants from donors ages 45-55 had 1-year graft survival that was 8.4% less than recipients of hearts from donors age 16-45. However, 32.7% of heart patients died during the first 12 months after listing without benefit of a transplant. Liver transplant recipients of donor ages 16-45 had 10.8% better 1-year graft survival than recipients of donors greater than 45, but a greater percentage of older donors were transplanted to high risk and older recipients. Tragically, 24.3% of patients listed for liver transplantation died within 12 months without a transplant. This analysis shows that satisfactory graft survival can be achieved using older donors and that age in itself should not be a barrier to organ donation, providing that organ function is normal and that specific disease of the organ is absent.

The association of pretransplant native nephrectomy with decreased renal allograft rejection.

Analysis of 2808 first and 823 second or subsequent cadaveric renal allograft recipients transplanted between June 1977 and July 1982 as part of the Southeastern Organ Procurement Foundation (SEOPF) Prospective Study was performed to determine the influence of pretransplant bilateral native nephrectomy (BNN) on graft and patient outcome. A highly significant increase in overall graft survival was associated with BNN in first transplant recipients (P less than 0.003) but not in regrafted patients. However, no increased graft survival was seen in patients receiving BNN at the time of the transplant operation. Interestingly, the improvement in graft survival associated with BNN appeared to be the result of a significant decrease in the incidence of graft loss caused by rejection--and especially accelerated acute rejection (P less than 0.007). Comparing actuarial graft survival for first graft recipients that had BNN prior to transplantation (n = 434) with those who had no nephrectomy (n = 2240) showed differences of 62% +/- 3 vs. 52% +/- 1 and 46% +/- 3 vs. 38% +/- 2 at one and three years, respectively. Analysis of first graft survival stratified for other factors known to influence outcome showed that the beneficial influence of BNN was independent of transfusion status or the number of transfusions given, use of antilymphocyte serum, pretransplant splenectomy, HLA match, or time on dialysis. The most striking increase in graft survival associated with BNN was seen in patients with evidence of presensitization as manifested by a positive panel reactive antibody (PRA) and in patients having delayed function (ATN) posttransplantation. The beneficial association of BNN was also found to be independent of the primary cause of renal failure or the specific indication leading to nephrectomy. These results suggest that patients receiving native bilateral nephrectomy prior to transplantation have a reduced incidence of graft loss from rejection by some as yet unexplained mechanism.

The timing of pretransplant transfusions and renal allograft survival.

Analysis of over 3000 cadaveric renal allograft recipients transplanted between June 1977 and June 1982 as part of the South-Eastern Organ Procurement Foundation Prospective Study was performed to determine the influence of timing of blood transfusions (BT) on patient and graft survival. Four mutually exclusive BT groups were identified for 2480 first-transplant and 655 regrafted patients studied: group 1 (n = 348, 29, respectively) received no BT; group 2 (n = 256, 29, respectively) received perioperative BT only (i.e., at the time of, or within 10 days of transplant); group 3 (n = 972, 287, respectively) received preoperative BT only (i.e., 10 or more days pretransplant); group 4 (n = 904, 310, respectively) received both preoperative and perioperative BT. For first graft recipients, actuarial graft survival for group 2 was significantly greater (P less than 0.035) than group 1 (49% vs. 41% at one year; 35% vs. 25% at 4 years), but to a lesser degree than groups 3 or 4, which were equivalent (58% at one year and 38% at 4 years). For regrafted patients, actuarial graft survival was again significantly greater (P less than 0.03) for group 2 patients, as compared with group 1 (59% vs. 29% at one year), and group 3 and 4 patients were not significantly different from each other (45% and 48% at one year, respectively) or from group 2. Interestingly, for regrafted patients who were presensitized at the time of transplant, those in group 4 (n = 94) had significantly better graft survival than group 3 (n = 111) at all time points examined (54% vs. 47% at one year, 46% vs. 22% at 3 years). In all comparisons, increases in graft survival were associated with decreased graft loss resulting from rejection, and no significant differences in patient survival were seen between any of these groups. These findings indicate that: (1) perioperative transfusions alone may have benefit in decreasing allograft rejection; (2) perioperative transfusions provide no apparent risk for patients who have already received pretransplant transfusions; and, (3) sensitized regrafted patients who receive pretransplant transfusions may gain an additional benefit from perioperative transfusions.

Living-donor renal transplantation in SEOPF. The impact of histocompatibility, transfusions, and cyclosporine on outcome.

The impact of haplotype match (HM), pretransplant transfusions, and cyclosporine use were examined for living-donor renal transplants performed among 49 centers in the South-Eastern Organ Procurement Foundation (SEOPF) from November 1983 to June 1988 with follow-up through March 1989. During this period, 750 2-HM, 1246 1-HM, and 120 0-HM living-donor transplants were performed at 46, 47, and 27 centers, respectively. Demographic comparisons of the HM categories demonstrated the greatest use of cyclosporine and donor-specific transfusions in the 0-HM group, and the greatest use of random blood transfusions (RBT) or no blood transfusions (NBT) in the 2-HM group. By univariate and multivariate (Cox regression) analyses, actuarial graft survival was significantly associated with haplotype match, although excellent 3-year graft survival was seen for 0-HM as well as 1-HM and 2-HM first transplant recipients: 74 +/- 5%, 80 +/- 2%, and 85 +/- 2%, respectively. Comparisons were also made among patients receiving DST +/- CsA, RBT +/- CsA, and NBT +/- CsA for each HM group by univariate and multivariate analyses. For 0-HM recipients, DST + CsA was most frequently used and associated with the best long-term survival (86 +/- 5% at 3 years) by univariate analysis. For 1-HM recipients, there were no apparent differences in graft survival between DST and RBT groups +/- CsA by univariate analysis, but the absence of transfusion (NBT +/- CsA) was associated with the poorest 3-year survival (79 +/- 4%). This was confirmed by multivariate analysis, where DST (P less than 0.06) and RBT (P less than 0.02) were each significantly associated with graft survival, and provided relative benefits (vs. NBT) of 0.56 and 0.44, respectively; CsA use was not significantly associated with outcome or a significant benefit. For 2-HM recipients, the poorest results were seen with DST + CsA (78 +/- 6% at 3 years) by univariate analysis; multivariate analysis suggested no benefit with DST or RBT, and an increased risk of graft loss with CsA. These results indicate that the use of pretransplant transfusions and CsA therapy may have differential benefits depending upon HM in living-donor renal transplantation.

Multivariate analysis of risk factors in cadaver donor kidney transplantation.

Data collected prospectively on 3811 kidney transplants performed between June 1977 and July 1982 with follow-up to July 1984 by the 42 member institutions of the South-Eastern Organ Procurement foundation were analyzed to identify factors associated with graft and patient outcome in patients not receiving cyclosporine. Multivariate Cox regression analysis was used to examine the association and relative risk of 24 variables with three actuarial outcomes: overall graft failure, irreversible rejection, and patient death. Factors having no suggested association with any outcome included: recipient sex, history of pregnancy, blood group, and time on dialysis; organ preservation method, time and source; donor race; crossmatch test sensitivity; and annual center transplant rate. In decreasing order of relative risk, the factors most significantly associated with irreversible rejection were: loss of two or more prior grafts, low HLA-A,B match, lack of pretransplant blood transfusion, high (greater than 60%) pretransplant sensitization to leukocyte (HLA) antigens, and delayed graft function. Splenectomy, insulin-dependent diabetes, and antilymphocyte serum therapy provided the greatest risk of patient death. Factors such as recipient age, race, and native nephrectomy had suggested associations with outcome. By adding each center as a separate covariate in the analysis, other center-dependent factors were quantitated and found in some cases to have a highly significant association with graft and patient outcome. These results provide a basis for evaluating the potential risk of graft loss or patient death for those prospective cadaver kidney transplant recipients not being considered for cyclosporine therapy.

The effect of first cadaver renal transplant HLA-A, B match on sensitization levels and retransplant rates following graft failure.

Data were collected retrospectively on all 449 first-transplant cadaver renal allograft recipients transplanted at four centers between 1/1/78 an 12/31/82 who had graft failure by 1/1/85. A total of 383 of these patients had information available regarding subsequent disposition. Of these, 182 (47.5%) were placed on an active waiting list for retransplantation. There were no associations found between placement on a waiting list and the following variables: panel reactive antibody (PRA) prior to first transplant or subsequent to graft failure, recipient age at first transplant or at the time of graft failure, recipient race, PRA after first graft loss, or HLA-A, B match of the first transplant. When stratified by level of HLA-A, B match as poor (0-1 antigen, n = 150) or good (2-4 antigens, n = 233) the poorly matched recipients as a group had a significantly lower mean PRA prior to first transplant (9.4 +/- 1.6 vs. 15.5 +/- 1.7, P less than 0.01), but a significantly higher PRA within the first year following graft failure (48.1 +/- 4.8 vs. 36.2 +/- 3.2, P less than 0.04). In addition, the poorly matched (vs. well-matched) group had a significantly higher mean increase in PRA following graft failure (45.1 +/- 4.4 vs. 33.7 +/- 3.5), and a significantly higher percentage of patients with PRA level greater than or equal to 60% within a year after graft failure (40% vs. 25%). Of the 182 patients who were placed on a waiting list, 113 (62.1%) were regrafted. As a group, regrafted patients had a significantly lower PRA within the first year following graft failure compared with the group not regrafted (33.6 +/- 3.9 vs. 54.0 +/- 5.0, P less than 0.002). Patients with a good first transplant HLA match had a higher overall regraft rate compared with those with a poor match (70.0% vs. 50.0%, P less than 0.01). Likewise, the percentage of well-matched patients regrafted within two years of first graft failure was significantly higher (55.5% vs. 32.5%, P less than 0.02). By multivariate analysis using the Cox proportional hazard model with 13 separate variables and considering all patients, the relative risk (RR) of not being regrafted was significantly (P less than 0.012) associated with poor HLA-A, B matching of the first transplant (RR = 1.7).(ABSTRACT TRUNCATED AT 400 WORDS)

Identification of donor factors predisposing to high discard rates of cadaver kidneys and increased graft loss within one year posttransplantation--SEOPF 1977-1982. South-Eastern Organ Procurement Foundation.

From 1977 to 1982, the South-Eastern Organ Procurement Foundation (SEOPF) conducted a prospective study to determine the fate of all cadaver kidneys retrieved by member institutions. During the study period, 6152 kidneys were retrieved, 1264 being discarded. Donor factors predisposing to wastage included AB and A blood groups, donor age greater than 30, hospitalization greater than 3 days, serum creatinine greater than 2.0 mg%, average systolic blood pressure less than 80, last-hour urine output less than 100 ml, proteinuria, heart not beating at time of nephrectomy, and kidneys not removed en bloc. Donor factors affecting graft survival rate at one year include age, length of hospitalization, last-hour urine output, and changing serum creatinine. The data suggest that certain donor kidneys are less likely than others to be transplanted depending on donor characteristics and retrieval practices. Furthermore, some of these factors have a negative impact on long-term success when kidneys are transplanted.

The detrimental effects of delayed graft function in cadaver donor renal transplantation.

Data collected prospectively on over 3800 cadaveric renal transplants performed between June 1977 and July 1982 by the 41 member institutions of the South-Eastern Organ Procurement Foundation were analyzed to determine the influence of delayed graft function (DGF) on patient and graft outcome. Approximately 35% of first graft recipients and 47% of regrafted patients were found to have DGF, as determined by the necessity for dialysis at one week posttransplant. First-graft recipients with DGF tended to include more black recipients, patients with higher peak levels of panel reactive antibody (PRA), less use of antilymphocyte serum (ALS) posttransplant, slightly longer organ preservation times and the more frequent use of organs by ice alone. Multivariate (Cox) regression analysis considering DGF simultaneously with ten other potentially confounding variables showed a highly significant association between DGF and overall graft loss from all causes (P less than 10(-5], irreversible graft rejection (P less than 0.001) as well as patient death (P = 0.012). The differences in graft survival between first graft recipients with DGF (n = 961) versus those without DGF (n = 1769) at one and four years posttransplant were 46% +/- 2 vs. 60% +/- 1 and 28% +/- 3 vs. 40% +/- 2, respectively. The detrimental effect of DGF was highly significant irrespective of the source of donor organs or the type of preservation used. For first transplant recipients who recovered good graft function by one month following DGF (n = 564), there was a significant decrease in eventual graft survival, as compared with patients who had graft function at one month but no prior history of DGF (n = 1407; P = 0.008). However, patients with history of DGF who had good graft function at six months (n = 361) showed no significant difference in longer-term graft survival when compared with similar patients with good graft function at six months but no history of DGF (n = 912). Interestingly, first transplant recipients with DGF were found to have significantly better graft survival if they had received bilateral native nephrectomy at least one month prior to transplantation. These results indicate that delayed graft function following cadaver donor renal transplantation provides a significant risk for eventual graft and patients survival that is principally manifested during the first six months posttransplant. In addition, patients who recover graft function following DGF appear to also remain at higher risk for early graft loss, while pretransplant bilateral native nephrectomy may afford some protection against the detrimental effects of DGF.

The influence of pretransplant transfusions, using different blood products, on patient sensitization and renal allograft survival.

An analysis of data collected during the South Eastern Organ Procurement Foundation (SEOPF) Prospective Study from 1977-1982 was performed to identify the relative effects of different blood products on patient sensitization and graft survival in cadaveric donor renal transplant recipients. More than 2700 primary and 800 regrafted patients from 40 transplant centers were included in this study. A significant increase in actuarial graft survival was seen in primary recipients who had pretransplant transfusions with only frozen blood (P less than 0.003), washed blood (P less than 0.0005), packed blood (P less than 0.0001), or any combination of blood products (P less than 0.002) as compared with those who received no transfusions. No blood product was found to provide a significantly greater increase in graft survival than any other blood product. Likewise, regrafted patients had significant and equivalent increases in graft survival associated with each type of blood product examined. The increased graft survival associated with each blood product was the result of decreased graft rejection, and not apparently related to other differences among patients receiving different types of blood. Furthermore, the type of blood used in pretransplant transfusions did not significantly influence the degree of patient sensitization for first-graft recipients, although regrafted recipients who received packed blood or a combination of blood products showed a slightly greater degree of sensitization than those who received only frozen or washed blood. First-graft recipients given packed or mixed blood had a small, statistically insignificant increase of hepatitis B virus (HBV) antigenemia, compared with those receiving frozen, washed, or no blood. Regrafted patients given any type of transfusion had a 3-4-fold increased incidence of HBV antigenemia as compared with nontransfused patients, but this difference also was statistically not significant. These findings suggest that the benefits of increased graft survival and the risks of sensitization or HBV infection associated with pretransplant transfusions are not significantly affected by the type of blood used.

Cadaver renal transplantation ignoring peak-reactive sera in patients with markedly decreasing pretransplant sensitization.

A review of more than 3000 cadaver donor renal allograft recipients transplanted between June 1977 and July 1982 as part of the South-Eastern Organ Procurement Foundation (SEOPF) Prospective Study was performed to identify patients who received a transplant following a significant decrease in pretransplant sensitization as measured by the percentage of panel-reactive antibody (PRA). Such patients were identified as having had a most reactive (historical peak sera) PRA level at least 40 percentage points higher than their last sample tested prior to transplant (current sera). Additional data were obtained on 157 of these patients, who also had no history of pretransplant immunosuppression and had a negative pretransplant crossmatch with current sera. Data included the dates of pretransplant sera samples, the specific techniques used for each serum sample that was crossmatched or screened for PRA, and the serological results. The population studied included 17 of 87 first-transplant recipients and 17 of 70 regrafted recipients whose pretransplant crossmatches with peak sera were positive or not done. These subgroups showed no decrease in graft or patient survival compared with cohorts (70/87 first-transplant recipients and 53/70 regrafted recipients) for whom peak sera crossmatching was performed with negative results. Additional stratification for the techniques used in crossmatching and screening, as well as the interval between peak and current PRA levels, showed no significant associations with eventual graft or patient outcome. These results suggest that crossmatch testing using peak sera may not be important in predicting eventual graft or patient outcome for patients with a marked decrease in PRA prior to transplantation and a negative crossmatch with current sera.

Influence of changes in pretransplant sensitization on patient and graft survival in cadaver renal transplantation.

Analysis of 2778 primary and 606 regrafted cadaveric donor renal allograft recipients transplanted between June 1977 and July 1982 as part of the South-Eastern Organ Procurement Foundation (SEOPF) Prospective Study was performed to determine the influence of changes in presensitization on graft and patient outcome. Four mutually exclusive groups of patients were identified based on the relative difference in the percentage of panel-reactive antibody (PRA) from highest ever (peak) to most recent (current) pretransplant levels as follows: group 1 (unsensitized): peak = current PRA = 0; group 2 (rising or stable PRA): (peak = current PRA) greater than 0; group 3 (small decrease): (peak - current PRA) = 1-40%;) and group 4 (large decrease): (peak - current PRA) greater than 40%. First-transplant recipients in group 4 had significantly higher mortality when compared with groups 1-3 (P less than 0.002). This decrease in patient survival was evident at 6 months (81% +/- 4 vs 91% +/- 1) and persisted to three years (68% +/- 8 vs 78% +/- 2), and it was associated with a significant (P less than 0.037) increase in death from infectious causes. This finding was even more striking when only transfused recipients were considered: at three years the difference in patient survival was 63% +/- 11 vs. 77% +/- 2. In addition, transfused patients with a decrease in pretransplant PRA of greater than 40% had significantly lower overall graft survival (P less than 0.02) and a higher incidence of irreversible graft rejection (50% +/- 8 vs 33% +/- 1 at two years). For regrafted recipients, there were no differences in patient survival among groups, but those in group 4 had significantly lower graft survival (P less than 0.0033) than groups 1-3. These findings suggest that a substantial decrease in PRA prior to transplant does not necessarily indicate a decrease in potential donor alloreactivity, and in first-graft recipients it may reflect an increased susceptibility to life-threatening infections following transplantation.

Renal allograft cell infiltrates associated with irreversible rejection.

All 74 renal transplant biopsies performed between 11/78 and 8/84 at Duke University and Durham VA Medical Centers having cellular infiltrates that could be phenotyped by immunoperoxidase labeling were examined to identify histologic and immunopathologic features which correlated with rejection. Monoclonal antibodies identifying hematopoietic cells, T cells, T helper cells, T cytotoxic-suppressor cells, macrophages, and B cells were used, and each phenotype population was graded separately based on pattern of infiltration: cortical-diffuse (CD), perivascular (PV), and cortical-aggregate (CA). Histologic and immunofluorescent studies were used to evaluate acute (humoral) and cellular types of vascular and interstitial inflammation. By univariate analysis, patients having irreversible rejection within 10 weeks postbiopsy (n = 23) had significantly higher grades of both acute vascular (humoral) inflammation and TC-S cell infiltrates in a CD pattern as compared with those who had good graft function. Multivariate (Cox regression) analysis was also performed considering biopsy changes, therapy before and after biopsy, and intervals between transplant, rejection onset, and biopsy--as well as other factors potentially affecting the biopsy or graft outcome. Of nine cell phenotype-pattern combinations, only TC-S infiltrates in a CD pattern were associated with a significant (P less than 0.03) relative risk (RR) of subsequent failure from rejection (RR = 8.2). When those cases with significant acute (humoral) inflammation (n = 10) were excluded, the relative risk of TC-S-CD infiltrates increased to 46.4 (P less than 0.04). These findings indicate that the location, as well as the number and type of cell infiltrates are critical in evaluating cellular forms of rejection, and that the extent of diffuse, cortical TC-S infiltration on biopsy provides the greatest predictor of subsequent irreversible graft failure.