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  • Frei U
  • Harms A
  • Bakovic-Alt R
  • Pichlmayr R
  • Koch KM
J Cardiovasc Pharmacol. 1990;16 Suppl 6:S11-5.

Acute postischemic renal failure (ARF) is a major complication in surgery and in particular in renal transplantation. Calcium channel blockers (CCBs) are able to prevent or ameliorate ARF in different experimental models when given before ischemic injury. Because ARF, which is observed in 20-60% of graft recipients, carries the risk of undetected rejections and nephrotoxic injury and is also expensive, we tested the hypothesis, suggested by animal experiments, that there is also a beneficial effect of CCBs when given after ischemic injury. A total of 134 recipients of first or second cadaver grafts were randomly assigned to a diltiazem pretreatment (DZ) or control (C) group. Kidney grafts were pretreated immediately prior to transplantation by reperfusion with 500 ml Euro-Collins (preservation fluid), with or without DZ. The DZ patients also received a 74-h infusion of DZ (0.12 mg/kg/h), starting 2 h prior to surgery. DZ was continued (90 mg b.i.d. p.o.) until day 30. Immunosuppression consisted of low-dose steroids and cyclosporine A (CSA) (10 mg/kg p.o.). CSA was instituted 6 h after surgery and later adjusted to achieve whole-blood trough levels of 300-600 ng/ml [by polyclonal radioimmunoassay (RIA)]. A total of 129 patients were available for efficacy analysis. There were no significant differences concerning donor demographics, human lymphocyte antigen (HLA) match, or ischemic times. ARF was defined as a need for dialysis in the first week. Our data show a significant reduction in ARF in grafts pretreated with DZ.(ABSTRACT TRUNCATED AT 250 WORDS)

  • Brouwer ML
  • Wenting GJ
  • Vincent HH
  • Hendriks GF
  • Jeekel J
  • et al.
  • Millis JM
  • Baquerizo A
  • Saleh S
  • Danovitch GM
  • Busuttil RW
Transplant Proc. 1989 Jun;21(3):3551-2.
  • Jaffers GJ
  • Banowsky LH
  • Millis JM
  • McDiarmid SV
  • Hiatt JR
  • Brems JJ
  • Colonna JO
  • et al.

A group of 52 liver transplant patients was prospectively randomized to receive prophylactic immunosuppressive therapy consisting of either Orthoclone OKT3 for 14 days, azathioprine, and steroids (25 patients); or cyclosporine, azathioprine, and steroids (27 patients). The groups were similarly matched for age, diagnosis, and Child's classification. The patients were studied to determine the effect of these two regimens on the incidence of rejection, infection, renal dysfunction, and mortality. Seven rejection episodes, as determined by clinical and histological criteria, occurred in seven of 25 patients (28%) receiving OKT3 compared with 18 episodes in 27 patients (67%) receiving cyclosporine during the first 14 days after transplantation (P less than 0.02). In 20% of the OKT3 patients, CD3+ levels of greater than 10% developed during therapy, and 16% of the patients developed anti-OKT3 antibodies during OKT3 treatment. Five patients were retreated with OKT3 for steroid-resistant acute rejection episodes; all had resolution of the rejection episode. Infectious complications were similar in each group. Renal function, as measured by serum creatinine, was significantly better with OKT3 than with cyclosporine (P less than 0.003) at 14 days. We conclude that prophylactic OKT3 is effective in reducing the number of early rejection episodes after liver transplantation; after 14 days the incidence of rejection is similar; reuse of OKT3 has been successful in liver transplant patients; infectious complications are similar between OKT3 and cyclosporine; and OKT3 preserves renal function better than cyclosporine and is thus indicated in patients with compromised preoperative renal function.

  • Hausen B
  • Fieguth HG
  • Schäfers HJ
  • Winter A
  • Spring EA
  • et al.
Transpl Int. 1988 Oct;1(3):140-5.

In distant heart procurement, optimal storage conditions remain to be defined, especially with respect to the electrolytic concentrations of storage solutions. Between December 1986 and April 1987, heart transplants were carried out in 18 patients. After cardioplegic arrest (St. Thomas), the hearts were randomly stored in either Euro-Collins' solution (ECS; n = 9) or Ringer's solution (RS; n = 9) at 4 degrees C. For the first 24 h postsurgery, atrial pressures (LAP, RAP), systemic (MAP) and pulmonary pressures (PAP), and cardiac output (CO) were monitored. In addition, catecholamine and nitroglycerin requirements as well as the type of cardiac rhythm were documented. There was no significant difference between the groups in terms of the period of graft ischemia (ECS, 162 +/- 28 min; RS, 141 +/- 47 min); the MAP, RAP, LAP, and CO were also similar in both groups. The total amount of epinephrine needed to maintain the MAP between 60 and 80 mm Hg was 10.5 mg/24 h +/- 4.1 mg in ECS compared with 19.9 mg/24 h +/- 12 mg in RS (P less than 0.05). Despite less inotropic support, the left cardiac work index was considerably higher in the ECS group (P less than 0.05). In the first few postoperative hours, 8/9 RS patients needed either atrial (n = 4) or ventricular pacing (n = 4) for a heart rate of 90-100 beats/min (bpm), whereas only three ECS patients required atrial pacing (P less than 0.05). All other ECS hearts showed a spontaneous sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

  • Keon WJ
  • Hendry PJ
  • Taichman GC
  • Mainwood GW
Ann Thorac Surg. 1988 Sep;46(3):337-41 doi: 10.1016/s0003-4975(10)65939-5.

The ideal preservation method and cooling temperature for transport of donor hearts are not known. Serious derangements in myocardial relaxation are well described with different methods of cooling. To assess this problem, human right atrial trabeculae contracting isometrically at 34 degrees C in vitro were subjected to hypothermic arrest at 1, 4, 12, and 20 degrees C for 1, 2, 4, 24, and 48 hours. Control conditions were resumed, and myocardial mechanical recovery was assessed over 1 hour. Contraction was 50% depressed after a 1- to 2-hour exposure to 1 degree C and was almost completely arrested following a 4-hour exposure. Muscles cooled to 4 degrees C recovered poorly, whereas those cooled to 12 and 20 degrees C did well. In the latter 2 groups, force development increased rapidly on rewarming and exceeded the precooling contraction force (p less than 0.05). A 100% increase in relative resting force was seen in muscles cooled to 1 and 4 degrees C (p less than 0.05). This finding suggests a failure of calcium homeostasis at very low temperatures. We conclude that atrial preservation is optimal at about 12 degrees C.

  • Matas AJ
  • Tellis VA
  • Quinn TA
  • Glicklich D
  • Soberman R
  • et al.
Transplantation. 1988 Feb;45(2):406-9.

In patients with delayed graft function (DGF), the use of cyclosporine (CsA) has been reported to prolong DGF, increase the number of required dialyses, increase the duration of hospitalization, and be associated with decreased graft survival. Routine postoperative antilymphocyte globulin (ALG) use has been advocated, but ALG is associated with increased viral infection. We studied outcome of individualization of immunosuppression. Between 11/84 and 8/86, first-cadaver transplant recipients whose serum creatinine (Cr) fell greater than or equal to 30% in the first 24 hr (immediate function) were started on CsA and prednisone (P) (group 1, n = 26). The remainder were randomized to P and azathioprine (group 2, n = 32) or P and ALG (group 3, n = 26), and switched to CsA when serum Cr fell greater than 30% (minimum 5 days ALG for the ALG group). P taper was the same in all groups. Patients with DGF (groups 2 and 3) had longer preservation time and higher peak PRA (P less than .05) than group 1. Groups were otherwise equivalent. One and 2-year patient survival was 96% (3 cardiovascular deaths; all with functioning grafts). One-year graft survival was 87% for group 1, 87% for group 2, and 82% for group 3(NS). In patients requiring dialysis, mean day off dialysis was 12 +/- 3 in both groups 2 and 3. Mean hospital stay was 12.5 +/- 1.3 days for group 1, 21.6 +/- 2.1 days for group 2 (P less than .05 vs. 1 & 3), and 14.5 +/- 1.2 days for group 3 (NS vs. 1). The increased hospital stay for group 2 patients was mainly due to increased in-hospital rejections: 75% for group 2, (P less than .05 vs. group 1 [35%], and group 3 [11.5%]). In addition, more group 2 in-hospital 1st rejections were steroid resistant as compared to group 1; 46% group 1 patients have remained rejection free as compared to 0% group 2 (P less than .05 vs. 1 and 3) and 35% of group 3 (P less than .05 vs. 1 and 2). Mean serum creatinine at 6-12 months remained higher in patients with DGF (group 1 P less than .05 vs. 2 and 3). Rejection was the major cause of graft loss in all groups.(ABSTRACT TRUNCATED AT 400 WORDS)

  • Fries D
  • Hiesse C
  • Charpentier B
  • Lantz O
  • Bensadoun H
  • et al.
Clin Transpl. 1988;115-29.
  • Frei U
  • Margreiter R
  • Harms A
  • Bösmüller C
  • Neumann KH
  • et al.
Transplant Proc. 1987 Oct;19(5):3539-41.