The effect of nitecapone on early graft function in experimental single lung transplantation.

Nitecapone is an antioxidant molecule which has been shown to protect the heart against ischemia-reperfusion injury. We investigated whether a similar effect could be detected on lung graft preservation in a porcine model of single lung transplantation. Donors received either nitecapone or placebo in a modified Euro-Collins pulmonary flush solution. After cold storage for 19 h the left lung was transplanted. Patients in the nitecapone group received a nitecapone infusion during the graft reperfusion. A right-side heart bypass was used to measure flow distribution and pulmonary vascular resistance (PVR) in the recipient's transplanted and native lungs, respectively. Pulmonary vein blood samples were analyzed for blood gases, free radical trapping capacity and diene conjugates. PVR was high in the transplanted lung, which received only 20% of the blood flow. Oxygen tension in the transplanted lung was low (2.3-26.7 kPa). Nitecapone treatment increased the plasma free radical trapping capacity threefold. In spite of this increase in antioxidative capacity nitecapone could not protect the lung against ischemia-reperfusion injury when pulmonary hemodynamics, gas exchange or plasma diene conjugates were used as measures of lung graft function.

Magnetic resonance imaging angiography in patency evaluation of bronchial artery revascularization grafts.

In this report we present our experience of non-invasive magnetic resonance imaging (MR) angiography and selective catheter angiography in assessing the patency of bronchial artery revascularization grafts after an en bloc double-lung and heart-lung transplantation. We studied 8 patients who had undergone pulmonary transplantation with direct bronchial artery revascularization. Catheter angiography was performed 10 days to 63 months postoperatively. MR angiography was performed within 24 h of the catheter procedure and the results were compared with the findings from catheter angiography. Catheter angiography showed the bronchial revascularization graft to be patent in 6 patients and occluded in 2. At MR angiography, the patency of bronchial artery revascularization grafts was reliably identified in 7 of the 8 patients. One patient had inadequate image quality because of void artefacts caused by haemostatic clips. It is concluded that MR angiography is a reliable method for assessing the patency of bronchial artery revascularization grafts.

Bronchial artery revascularization improves tracheal anastomotic healing after lung transplantation.

The study aimed to clarify the role of direct bronchial artery revascularization (BAR) after en bloc double-lung (DLT) and heart-lung transplantation (HLT). Group I comprised eight patients with en bloc DLT or HLT and successful BAR, while group II included 14 DLT or HLT cases without BAR or with failed BAR. From these groups, 2 subgroups were extracted: group III, including 6 cases of en bloc DLT with successful BAR and group IV 10 HLT cases without or with failed BAR. Airway healing was evaluated at bronchoscopy and patency of BAR with angiography. Pulmonary viral, bacterial and fungal infections, rejections and bronchiolitis obliterans syndrome (BOS) were registered. Tracheal healing at 2 weeks and 3 months was better in group I than in group 1 (p = 0.003 and p = 0.05, respectively). Compared with group IV, tracheal anastomotic healing at 2 weeks was better in group III (p = 0.007) and tended to be better also after 3 months (p = 0.07). The incidence of infections, rejection or BOS did not differ between groups I and II. BAR thus improved healing of tracheal anastomosis.

The role of pulmonary and systemic circulation in the tracheal blood supply in rats.

The different roles of bronchial and pulmonary circulation in the tracheal blood supply were investigated in 26 female rats: a control group (CG, n = 7), a group with pulmonary hilar ligation (PL, n = 5), another with tracheal transsection (TL, n = 9) and a group with both these procedures (TL&PL, n = 5). Technetium 99-m was injected into the left ventricle postoperatively, and the radioactivity of tracheal samples was calculated as a percentage of injected activity/g tissue (%ID/g). The tracheal uptake averaged 1.9 in group CG, and 1.7, 1.3 and 1.5% ID/g in groups PL, TL and TL&PL, respectively. Tracheal transsection (TL) thus reduced the tracheal blood supply by 29.7% compared with the control group (p < 0.05), whereas the reduction of tracheal blood supply following pulmonary hilar ligation (PL) was only 10.9% (n.s.). Tracheal transsection combined with hilar ligation (TL&PL) effected a reduction of 19.9% (n.s.). We conclude that only 10.9% of the tracheal blood supply comes from the pulmonary circulation.

Nitecapone inhibits myeloperoxidase in vitro and enhances functional performance after 8 h of ischemia in experimental heart transplantation.

Nitecapone (NC) has been shown to have beneficial effects on the functional recovery of rat hearts in Langendorff-preparation. The present study was executed to evaluate the effect of NC on preservation of grafts in heart transplantation and the role of NC in the inhibition of granulocyte infiltration. Donor hearts were perfused and stored at +4 degrees C for 8 h in either Ringer solution in the control-group (C-group, n = 26) or in NC (50 microM) added Ringer solution (NC-group, n = 18). The heterotopic heart transplantation was performed. The rats in both groups were killed at either 10 min or 60 min after release of the aortic clamp and tissue samples were obtained for antioxidative capacity, myeloperoxidase activity, and lipid peroxidation measurements. In vitro studies were performed using sodium azide or nitecapone to inhibit myeloperoxidase (MPO) activity of isolated human leukocytes. A total of 61% of the grafts began to beat in the NC-group, compared to 46% in the control group. Using an arbitrary scale of functional performance, only 33% (4/12) of the grafts were classified as well functioning in the control group, compared to 82% (9/11) in the NC-group (P<0.05). MPO activity was equal in both groups after 10 min but significantly lower after 60 min in the NC-group as compared to the control group (P<0.05). In vitro studies demonstrated that NC inhibits 50% of purified MPO activity at a concentration of 10 microM. NC did not significantly affect lipid peroxidation or the preservation of endogenous antioxidants. Since NC inhibited myeloperoxidase both in vitro and in vivo, it seems that the positive effects of NC on graft preservation may be mediated via the inhibition of granulocyte infiltration.

Abdominal aortic aneurysm surgery in octogenarians.

BACKGROUND: It is difficult to decide whether to operate on a symptomless, abdominal aortic aneurysm in an elderly person almost in the last decade of their life. PATIENTS AND METHODS: A comparative retrospective review was undertaken of 77 octogenarians and 692 other patients aged less than 80 treated for infrarenal abdominal aortic aneurysms between January 1980 and July 1992 at the Department of Thoracic and Cardiovascular Surgery of Helsinki University Central Hospital, Finland. Of these 77 octogenarians, 60 underwent surgery and 17 were treated non-surgically. Of the 60, 48 (80%), and 284 of the 692 (41%) non-octogenarians underwent emergency surgery either because of ruptured aneurysm (RAAA group: 35 octogenarians and 213 non-octogenarians) or because of non-ruptured but impending rupture (NRAAA group: 13 octogenarians and 71 non-octogenarians). RESULTS: Emergency surgery was more frequent among octogenarians than among younger patients (p < 0.001) and was associated with significantly higher 30-day mortality rates in the RAAA group: 71% (22/35) versus 36% (76/213) (p < 0.01) and in the NRAAA group: 38% (5/13) versus 14% (10/71) (p < 0.05). Elective surgery for symptomless abdominal aortic aneurysms (AAA group) was associated with 8% (1/12) 30-day mortality rates in octogenarians and 8% (33/408) in non-octogenarians. Survival rates for non-surgically treated symptomless octogenarians were statistically significantly lower (log rank test) than for electively treated octogenarians and for an age- and sex-matched Finnish population. Median survival for non-surgically treated octogenarians was 2.5 years (SE 0.13), with 50% of the patients dying from rupture of their aneurysms during the follow-up period. CONCLUSION: These findings support the active treatment of abdominal aortic aneurysms on an elective basis among the elderly.

Treatment of Barrett's esophagus by endoscopic laser ablation and antireflux surgery.

OBJECTIVE: The regeneration of intestinal metaplasia by squamous epithelium in 17 patients with Barrett's esophagus after endoscopic laser ablation in a reflux-free environment after successful antireflux surgery was prospectively examined. METHODS: All patients had antireflux surgery, and healing of reflux was verified at postoperative endoscopy and 24-hour esophageal pH monitoring. Thereafter, in 11 patients, the whole Barrett's epithelium was ablated using endoscopic Nd-YAG laser energy in 1 to 8 sessions (mean, 4). The needed energy was 965 to 11,173 joules (mean 4709), or about 1000 joules per centimeter of Barrett's esophagus. Six patients had no laser ablation but were treated by antireflux surgery and served as a control group. RESULTS: In all laser-treated patients, the regenerated epithelium was histologically of squamous type in the tubular esophagus, but two patients still had intestinal metaplasia in the gastric cardia. In controls, the length of Barrett's esophagus and intestinal metaplasia remained unchanged. The length of follow-up was 26 months after the last laser session and 21 months in the control group. CONCLUSIONS: The regenerated esophageal epithelium arising after laser ablation in reflux-free environment surgery is of squamous type. This treatment may have a role in preventing the development of esophageal adenocarcinoma arising in Barrett's esophagus.

Nitecapone is of benefit to functional performance in experimental heart transplantation.

In heart transplantation, global ischemia of a graft is followed by reperfusion injury. The formation of oxygen free radicals induces arrhythmias and impairs functional recovery of the graft. This study was executed to evaluate the effect of the new antioxidant, nitecapone, on ischemia-reperfusion injury in heart transplantation in rats. Donor hearts were perfused and stored at +4 degrees C for 2 h in either Ringer's solution in the control group (C-group, n = 26) or Ringer's solution with nitecapone (NC) added (NC-group, n = 18). The donor aorta was anastomosed to the recipient's abdominal aorta and the pulmonary artery to the recipient's inferior vena cava. The grafts were classified into three categories based on the functional recovery. The rats in both groups were killed at 10, 30, or 60 min after release of the aortic clamp. Tissue samples for chemiluminescence were obtained from the left ventricle, the right ventricle, and the septum of the heart. All grafts in the NC-group (18/18) began beating after release of the aortic clamp, whereas only 50% (13/26) of the grafts in the C-group recovered (P < 0.0004). Chemiluminescence analysis showed lipid peroxidation values to be higher in the C-group than the NC-group up to 1 h after reperfusion. Also, the right ventricle samples showed lower chemiluminescence values in the NC-group than in the C-group. In conclusion, our results do not support the theory that different regions of the heart have different vulnerability to ischemia-reperfusion injuries. Nitecapone has a beneficial effect on the preservation of the grafts in terms of functional recovery.

pH-metric analysis after successful antireflux surgery: comparison of 24-hour pH profiles in patients undergoing floppy fundoplication or Roux-en-Y duodenal diversion.

Fundoplication is the most widely used antireflux method, whereas Roux-en-Y duodenal diversion (partial gastrectomy, vagotomy, and Roux-en-Y reconstruction) has been used in fewer patients with more complicated gastroesophageal reflux disease. Abnormal esophageal pH values are normalized after successful fundoplication. However, very little is known about possible changes in the pH profile after successful Roux-en-Y duodenal diversion. A total of 37 patients with severe gastroesophageal reflux disease were treated by fundoplication (n=22) or Roux-en-Y duodenal diversion (n=15). Postoperatively all patients in both groups were symptom free and healing of esophagitis was verified endoscopically. After fundoplication, the 24-hour esophageal acid exposure decreased significantly (P=0.03) and the pH profile normalized (pH<4 in 5.8%+/-2.4% of the recorded time). However, the decrease in esophageal acid exposure was not significant (P=0.77) after successful Roux-en-Y reconstruction and the pH profile remained abnormal (pH<4 in 15.1%+/-4.3%). It was concluded that 24-hour esophageal pH monitoring is a reliable means of assessing the results of fundoplication, but the current test criteria should be reexamined in evaluating the results of Roux-en-Y duodenal diversion. Healing of esophagitis after Roux-en-Y duodenal diversion despite abnormal acid reflux, as shown by 24-hour pH measurements, suggests that duodenal contents also have a role in the pathogenesis of esophagitis in an acid milieu.

Tuberculous fistula of the esophagus.

BACKGROUND: Tuberculous involvement of the esophagus has been extremely rare during the past 40 years. It will be, however, more frequently encountered in the future, as the number of immunocompromised patients is growing. This condition is usually secondary to infection in other thoracic sites, such as lungs, larynx, or mediastinum. The diagnosis is difficult if the suspicion of tuberculosis is not raised. Dysphagia and cough after ingestion of fluids and food are common symptoms without any other specific signs in these patients. Diagnosis is based on combination of esophagography, esophagoscopy, bronchoscopy, and computed tomographic scan. METHODS: We present 3 patients with tuberculous fistulas of the esophagus. Two of our 3 patients were treated successfully with the combination of operation and antituberculous chemotherapy. Fistulas were resected and closed directly. Suture lines were secured with pedicled pleural flaps. RESULTS: Both patients who underwent operation recovered without complications. One patient died without definitive diagnosis and treatment. CONCLUSIONS: Treatment of tuberculous fistulas consists of operation and antituberculous chemotherapy, although antituberculous medication alone has been suggested to be effective if the diagnosis is early. However, operation is usually necessary to establish the correct diagnosis. Therefore, we believe that if the cause of the esophageal fistula cannot be verified, thoracotomy should be performed. If the fistula is left untreated the consequences are usually fatal.

Value of high-resolution computed tomography in routine evaluation of lung transplantation recipients during development of bronchiolitis obliterans syndrome.

BACKGROUND: Chronic rejection is a major long-term complication after lung transplantation. The purpose of our study was to evaluate the role of repeated high-resolution computed tomographic examinations in monitoring the development of bronchiolitis obliterans syndrome after lung transplantation. METHODS: A total of 126 high-resolution computed tomographic examination in 13 lung transplant recipients was analyzed. During a mean follow-up period of 23 months, bronchiolitis obliterans syndrome developed in eight of the patients. A scoring system from 0 to 10 based on the number of chronic changes on high-resolution computed tomography was developed, and the score of each patient was compared with decline in the forced expiratory volume in 1 second and maximal forced expiratory flow rate of 50% of the forced vital capacity. RESULTS: The score of chronic changes, measured at 1 year after transplantation, correlated inversely with the values of forced expiratory volume in 1 second and maximal forced expiratory flow rate at 50% of the forced vital capacity (p < 0.05). Stage I bronchiolitis obliterans syndrome was associated with scores of 4 to 6 (mean 5.0), stage 2 with scores of 6 to 9 (mean 7.0), and stage 3 with scores of 6 to 9 (mean 7.7). The sensitivity of high-resolution computed tomography was 93% and its specificity was 92% when five chronic changes were used as a cutoff level. CONCLUSIONS: The progress of chronic changes on high-resolution computed tomography occurs concurrently with the development of bronchiolitis obliterans syndrome. High-resolution computed tomography may provide additional morphologic information for noninvasive evaluation of chronic lung rejection.

Prostaglandin E1 or prostacyclin in Euro-Collins solution fails to improve lung preservation.

BACKGROUND: In search of the ideal composition of the flush solution for pulmonary preservation, we studied the effects of prostaglandin E1 (PGE1) and prostacyclin as an additive to Euro-Collins solution (ECS) on pulmonary hemodynamics and gas exchange in a porcine single lung transplantation model using extracorporeal circulation and right heart bypass. METHODS: Twenty-two pigs served as donors. The animals were randomized to receive either modified ECS alone (control group, n = 8), ECS with 100 micrograms/L of PGE1 (PGE1 group, n = 6), or ECS with 200 micrograms/L of prostacyclin (prostacyclin group, n = 8). Left lung transplantation was performed in 22 recipients after approximately 4 hours of cold ischemia. RESULTS: Carbon dioxide elimination was significantly depressed in the two prostaglandin groups, and the use of PGE1 was associated with a significant decrease in arterial oxygen tension compared with the control group. Both drugs were inefficient in alleviating the increase in pulmonary vascular resistance after transplantation. CONCLUSION: The use of prostaglandins as constituents of the flush solution was not followed by any improvement of early graft function after cold ischemia.

Congenital bronchoesophageal fistula in the adult.

Congenital bronchoesophageal fistula is a rare clinical entity in adult patients. This anomaly may cause various symptoms such as respiratory infections, coughing bouts when eating or drinking, and even hemoptysis. We present a report on 9 patients with bronchoesophageal fistulas who were treated in our hospital during the last 30 years. One patient died of pulmonary complications before definitive treatment of the fistula. Other patients recovered from surgical closure of the fistula without complications. Based on our experience, these patients should be treated surgically without delay. Observation may result in fatal pulmonary complications.

Video-assisted thoracoscopic pleurectomy in the treatment of recurrent spontaneous pneumothorax.

Parietal pleurectomy is the most effective method of preventing a recurrence of spontaneous pneumothorax. Until recently, however, it has required thoracotomy which is associated with significant morbidity. The advent of video-assisted thoracoscopic surgery (VATS) has offered a less traumatizing method of performing parietal pleurectomy, but experience in this operation is limited. In this study we compared the operative results of our first twelve patients treated using VATS (VATS-group) with twelve consecutive patients operated on via thoracotomy (T-group) before we started using VATS. The groups were comparable in terms of age, sex ratio and the length of preoperative pleural drainage. In the VATS-group peroperative blood loss was markedly less, but the mean operative time was 16 min longer than in the T-group. There was practically no difference in the number of opioid dosages given postoperatively between the groups, but the hospital stay was approximately three days shorter in the VATS-group than in the T-group. Inability to work lasted two weeks longer in the T-group than in the VATS-group. In the T-group there were no recurrences of pneumothorax, but in the VATS-group pneumothorax recurred in two patients. They were both treated using a Roeder loop to excise bullae. One patient was reoperated via thoracotomy and another was treated by pleural suction. The initial Finnish experience of VATS-pleurectomy shows that parietal pleurectomy can be performed safely with less morbidity in the treatment of recurrent spontaneous pneumothorax. However, recurrences in the VATS-group underlines the proper selection of technical methods when using this method of treatment.

Altered regulation of breathing after bilateral lung transplantation.

In our previous animal studies on dogs, regulation of breathing was found to be altered after en bloc transplantation of the heart and both lungs. During carbon dioxide (CO2) inhalation the minute volume was increased due to an increase of tidal volume after transplantation whereas before transplantation both respiratory frequency and tidal volume increased. The success of the heart-lung transplantation was based on experiments on baboons as no long-term survivors were obtained in dogs. It was thought that the regulation of breathing is different in dogs and primates. We therefore decided to study the regulation of breathing in humans after bilateral lung transplantation during CO2 stimulation. The regulation of breathing was tested 2 to 4 months after bilateral lung transplantation in six patients. Six healthy subjects with intact lungs were tested as controls. The test persons were allowed to breathe first room air, then 5% CO2 in air for 4 min and then room air again. The frequency of respiration, tidal volume and minute ventilation were recorded using a phneumotachograph. Simultaneously samples of arterial blood were drawn from a cannulated brachial artery for analysis of pressure of arterial oxygen (PaO2), pressure of arterial carbon dioxide (PaCO2), base excess (BE) and pH. During inhalation of CO2 for 4 min the minute volume doubled in both transplant patients and in controls. The tidal volume of the transplant patients increased significantly more than that of the controls (P < 0.005) whereas respiratory frequency increased significantly only in the controls with intact lungs (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cytomegalovirus infection-associated generalized immune activation in heart allograft recipients: a study of cellular events in peripheral blood and endomyocardial biopsy specimens.

An association between cytomegalovirus (CMV) infection, heart allograft rejection, and arteriosclerosis has been reported. To investigate the mechanisms of this association, the cellular immune response in peripheral blood and the inflammation in heart allografts during antigenemia were studied. CMV antigenemia occurred in 13 recipients. In recipients with severe CMV infection, a significantly weaker immune response was recorded in peripheral blood: fewer lymphoid blast cells (max. 2.4% +/- 0.4%) and large granular lymphocytes (LGL; max. 9.3% +/- 1.4%) were seen than in patients with mild or asymptomatic CMV infection (lymphoid blast cells max. 6.5% +/- 0.8% P < 0.01 and LGLs max. 20% +/- 2.3%, P < 0.05). Thus, a strong immune response with lymphoid activation was associated with clinically good outcome of CMV infection. In heart allograft histology, subendothelial inflammation of small intramyocardial vessels was a characteristic finding during CMV antigenemia compared to CMV-free recipients (at the peak P < 0.01). However, no difference in this mild and short-lived inflammatory response was observed between clinically mild or severe CMV infection. The CMV-linked generalized immune activation and inflammation of the vascular structures might contribute to the initiation of allograft vasculopathy and to the pathogenesis of chronic heart allograft rejection.

Management of delayed esophageal perforation with mediastinal sepsis. Esophagectomy or primary repair?

Ninety patients with esophageal perforations were operated on at our institutions between 1970 and 1992. Thirty-four of them were seen after delayed diagnosis (> 24 hours) with mediastinal sepsis caused by perforation of the thoracic esophagus. There were 18 patients with spontaneous ruptures, 11 with instrumental perforations (including one caused during laparotomy), and 3 perforations caused by foreign bodies. One patient had perforation of an esophageal ulcer into the pericardium and another had perforation of an esophageal diverticulum into the mediastinum. Nineteen patients underwent primary repair of the perforation with cleansing and drainage of the mediastinum and the pleural cavity. The remaining 15 had primary extirpation of the thoracic esophagus, irrigation of the mediastinum with antibiotics, cervical esophagostomy, gastrostomy, and drainage of the mediastinum and pleural cavity. Nineteen of the 34 patients survived (hospital mortality 44%). Of patients with primary repair, only six survived (in-hospital mortality 68%), whereas only two patients treated with esophagectomy died (in-hospital mortality 13%). The difference was highly significant (p = 0.001). The most common cause of death was multiorgan failure resulting from sepsis. Postoperative complications developed in four patients treated with primary repair (two sepsis, one empyema, and one anuria) and in seven patients treated with esophagectomy (two empyema, two sepsis, one pneumonia, one mediastinal abscess, and one brain abscess). After healing of the mediastinitis, the esophagogastric continuity was reconstructed with colon in 11 patients and stomach in two patients. In the management of delayed esophageal perforation with mediastinal sepsis, esophagectomy is superior to primary repair alone, which often leads to mediastinal leakage, continued sepsis, and death.

Cytomegalovirus infection and accelerated cardiac allograft vasculopathy in human cardiac allografts.

Cardiac allograft vasculopathy is a major limiting factor of the long-term survival of heart transplant patients. An association of cytomegalovirus infection and cardiac allograft vasculopathy has been described. We analyzed 104 endomyocardial biopsy specimens obtained from 53 heart transplant recipients and correlated the histologic findings with 115 angiograms obtained from the same patients during 4 postoperative years. The frequency of vascular changes in endomyocardial biopsy specimens was significantly higher than in angiograms during the first 3 posttransplantation years (P < 0.001, P < 0.005, P < 0.03, respectively). Also, in patients with angiographically documented cardiac allograft vasculopathy, significantly higher scores of capillary and arteriolar endothelial cell accumulation and arteriolar intimal thickness were recorded when compared with the recipients with normal angiograms (P < 0.02, P < 0.05, P < 0.005, respectively). Altogether, 29 of 53 recipients underwent cytomegalovirus infection during the first posttransplant year. Cytomegalovirus infection was associated with arteriolar endothelial cell accumulation and with increased intimal thickness of intramyocardial vessels of 1-year endomyocardial biopsy specimens when compared with cytomegalovirus-free recipients (P < 0.02 and P < 0.005, respectively). After the second year, the cytomegalovirus-associated endothelial cell response subsided, but the thickness of intima had increased when compared with cytomegalovirus-free patients (P < 0.05). Thereafter, the cytomegalovirus-associated histologic changes reached a plateau. In coronary angiography, the cardiac allograft vasculopathy changes were detected in a slower pace. Thus only after 2 posttransplantation years, cytomegalovirus-associated acceleration of cardiac allograft vasculopathy was observed, compared with cytomegalovirus-free patients (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitation of cytomegalovirus infection-associated histologic findings in endomyocardial biopsies of heart allografts.

To investigate whether histologic changes in heart allografts may be associated with cytomegalovirus infection, 46 heart transplant recipients were monitored for cytomegalovirus. Altogether, 762 endomyocardial biopsy specimens were analyzed. The histologic changes were semiquantitatively scored from mild to severe, and special attention was paid to inflammatory infiltrates and vascular changes. Cytomegalovirus infection occurred in 27 of 46 patients, shown by cytomegalovirus-antigenemia test. The endomyocardial biopsy findings were investigated in relation to cytomegalovirus-antigenemia. In the acute phase of cytomegalovirus infection during antigenemia, an inflammatory infiltrate, subendothelial lymphocytosis, was a characteristic finding in the endomyocardial biopsy specimens. An intense arteriolar endothelial cell proliferation and thickening of intima occurred. Long-term histologic findings with two years follow-up revealed a cytomegalovirus-associated enhanced vascular intimal thickening that narrowed the lumen of small intramyocardial arterioles. Acute rejection episodes were diagnosed in 15 of 27 patients with cytomegalovirus and in 9 of 19 patients free of cytomegalovirus. The inflammatory infiltrate of acute rejection was more peripheral to the vessels and did not obscure the findings characteristic to cytomegalovirus infection. The arteriolar endothelial proliferation and intimal thickening were significantly more prominent in cytomegalovirus infection than in biopsy specimens from patients with rejection only. In long-term follow-up, arteriolar endothelial proliferation declined, but the intimal thickness persisted and increased. The increase was significantly higher in patients with cytomegalovirus than in patients with rejection. In conclusion, an inflammatory response in vessel walls with alterations of small intramyocardial arterioles leading to narrowing of the vascular lumen of the graft was associated with cytomegalovirus infection in heart transplant patients.