Total excision of the right atrium with a minimal cuff of left atrium remaining around the four pulmonary veins, followed by direct anastomoses on venae cavae, has been proposed as an alternative to the standard procedure described by Shumway and Lower for orthotopic cardiac transplantation. To investigate whether this "anatomic" transplantation should be proposed as the optimal procedure, we prospectively randomized 78 patients having 81 procedures since 1991 into two groups: group I, standard transplantation (n = 40), and group II, "anatomic" transplantation (n = 41). The two groups were statistically similar in recipient age, sex, weight, disease, and status at the time of transplantation. Also similar were donor age, sex, weight, and drug dependency at the time of harvesting. All patients could be weaned from cardiopulmonary bypass with comparable graft ischemic times (group I, 136 +/- 46 minutes; group II, 138 +/- 51 minutes). Immediate recovery of sinus rhythm occurred in 20 cases of group I and 36 cases of group II. Delayed recovery of sinus rhythm in the first postoperative week occurred in 15 cases of group I and 5 cases of group II. Persistence of atrial arrhythmia occurred in 5 cases of group I and never in group II. These differences were highly significant (p < 0.001). Postoperative hemodynamics showed a higher cardiac index at day 1 in group II (4.12 +/- 0.85 L/min per square meter) than in group I (3.77 +/- 0.65 L/min per square meter) (p = 0.04). There were 13 early deaths in group I and 8 early deaths in group II. One death in group I was related to an acute atrioventricular block at 3 weeks with no evidence of cardiac rejection at histologic examination. Two patients in group I (5%) required definitive pacemaker implantation for prolonged sinus node dysfunction. Echocardiographic and Doppler studies of survivors have been performed 2 to 3 months after transplantation. Right atrial area was significantly reduced (p < 0.01) in group II (18 +/- 4.7 cm2) versus group I (24 +/- 7 cm2), as was left atrial area (group I, 24 +/- 4.5 cm2; group II, 20 +/- 5 cm2) (p = 0.01). Mild tricuspid regurgitation was observed in 82% of group I patients versus 57% of group II patients (p < 0.05), inasmuch as mitral regurgitation was comparable (71% in group I, 67% in group II).(ABSTRACT TRUNCATED AT 400 WORDS)

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We have investigated perforin and granzyme B expression in graft-infiltrating lymphocytes of patients who underwent heart transplantation. Those proteins are commonly present in the cytoplasmic granules of cytotoxic T lymphocytes and are released upon effector-target cell interaction. From 28 patients 103 endomyocardial biopsies were obtained and examined by histology and immunocytochemical analysis using relevant monoclonal antibodies. We found that "high" biopsy histological grades were associated with perforin and granzyme B expression in graft-infiltrating lymphocytes of patients with acute severe rejection crisis. In contrast, these markers were not detected in patients without rejection or during graft stabilization. Interestingly, in patients with mild rejection and "low" histological grades, two groups could be distinguished with a differential expression of the two intracytoplasmic proteins. The presence of perforin and granzyme B-expressing cells was found to be predictive of rapid progression to severe rejection, so that this situation required additional treatment; in contrast, their absence seemed to correlate with a good graft outcome without additional treatment. Moreover, perforin and granzyme B expression seemed to be down-regulated by immunosuppressive drugs, which coincided with graft stabilization. In conclusion, our data suggest that detection of granzyme B and perforin in graft-infiltrating lymphocytes might be helpful for routinely monitoring heart transplant patients.

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