Lasse Heikkilä

Malignancies after heart transplantation: presence of Epstein–Barr virus and cytomegalovirus

The presence of Epstein–Barr virus (EBV), human papilloma virus (HPV), and cytomegalovirus (CMV) was studied in 20 patients who developed malignancies after heart transplantation in the Helsinki University Central Hospital. The tumors were analyzed for the presence of HPV by polymerase chain reaction and for EBV by in situ hybridization. Clinical CMV infection was verified by immunochemical quantitation of CMV antigen in peripheral blood cells. HPV was detected in one of the eight epithelial malignant tumors studied. Three of the six lymphomas were positive for EBV. Two (67%) of 3 patients with EBV‐positive lymphomas and one (33%) of the other three lymphomas but only 2 (14%) of 14 patients who developed other malignancies had a history of a manifest post‐transplantation CMV infection prior to the development of malignancy. These results confirm the presence of EBV in lymphomas of heart transplant recipients and suggest that CMV might have a contributory role in the development of EBV‐associated lymphomas.

Heart transplantation in repaired transposition of the great arteries.

Cardiac transplantation was carried out in a 40-year-old man with the diagnosis of repaired transposition of the great arteries and right-sided aortic arch who had end-stage cardiac failure due to myopathy of the ventricles. Because of several previous surgical repairs and the orientation of the great vessels, the operation presented some technical problems. Therefore, modifications of operative procedures were used, including recipient hypothermia, circulatory arrest, and changes in the donor heart implantation. The removal of the donor heart was modified in such a way that the graft included the aortic arch and both pulmonary arteries. With the extra length of ascending aorta and transverse arch, the innominate, left carotid, and left subclavian vessels were excised as a button, thereby leaving the distal orifice of the aorta in the superior portion of the transverse arch. For the recipient, the operation was performed using hypothermic total circulatory arrest to dissect free the huge pulmonary artery and the short right-sided aortic arch to place the clamp. Implantation of the donor heart was modified accordingly. The technical results were confirmed one and a half months later on a control digital angiogram. Thirty-five days postoperatively the patient was discharged. Six months after operation, the patient is doing better than ever before in his life. Our findings suggest that a complicated conotruncal development does not preclude cardiac transplantation.

Plasma cell granuloma of lung and pleura

A report is presented of seven patients with plasma cell granuloma of the lung or pleura. Two were operated on in 1970, three in 1971, one in 1973 and one in 1984. None of the patients had smoked cigarettes. Five had a history of infection. Most of the patients were young, healthy and working. The surgical treatment was lobectomy in four cases, bilobectomy in one case and resection of tumour in two cases. The histology of the tumours was re-evaluated, and was similar in all cases. They were composed mainly of plasma cells, lymphocytes and granulocytes, and small foci of calcification were also seen. No recurrence of tumour was found in observation up to 13 years postoperatively. One patient died of pancreatic carcinoma after 6 years. The others are doing well.

Prostaglanding E1 or prostacyclin in euro-collins solution fails to improve lung preservation

BACKGROUNDnIn 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.nnnMETHODSnTwenty-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.nnnRESULTSnCarbon 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.nnnCONCLUSIONnThe use of prostaglandins as constituents of the flush solution was not followed by any improvement of early graft function after cold ischemia.

L-Arginine in lung graft preservation and reperfusion.

BACKGROUNDnInhaled nitric oxide has been shown to ameliorate early lung graft dysfunction. It improves oxygenation by inducing pulmonary vasodilatation in well-ventilated lung areas, and it also modulates leukocyte-endothelium interactions. We used a porcine, single lung transplantation model to evaluate whether the benefits of exogenously administered gas could be achieved easier by adding L-arginine, the substrate of endogenous nitric oxide synthesis, as an additive to the flush solution and intravenously during reperfusion.nnnMETHODSnSix pig lungs were flushed with modified Euro-Collins solutions containing L-arginine (2 g/liter). After cold (4 degrees C) storage, the left lung was transplanted. Ischemic time was 260 minutes. The recipients received intravenous boluses of L-arginine (30 mg/kg), followed by infusion (20 mg/kg/min) during the first 30 minutes of reperfusion. Six control animals received saline as placebo. We measured the blood flow and pulmonary vascular resistance (PVR) in the transplanted and in the native lung using a right heart bypass model. We measured blood gases, leukocyte counts, plasma free-radical trapping capacity, and diene conjugates in pulmonary venous blood and myeloperoxidase activity of the lung tissue.nnnRESULTSnPulmonary vascular resistance was 4 to 5-fold higher in the transplanted lung than in the native lung, which received 80% of the total blood flow. L-arginine reduced PVR by 30% in the native lung (p < 0.001), but not in the transplanted lung. L-arginine had no effect on oxygenation or carbon dioxide exchange of the transplanted lung. Nor did L-arginine treatment have any effect on leukocyte sequestration or myeloperoxidase activity in the transplanted lung. The plasma antioxidant capacity in venous blood of the transplanted lung almost doubled shortly during early reperfusion without influence of L-arginine.nnnCONCLUSIONSnL-arginine reduced PVR in the native lung but did not improve pulmonary hemodynamics, gas exchange, or reduce leukocyte sequestration of the transplanted lung.

Single-Lung Allotransplantation in Pigs Following Donor Pretreatment with Intravenous Prostaglandin E-1: Morphologic Changes after Preservation and Reperfusion

Single left lung allotransplantation with ligation of the right pulmonary artery was performed on 11 pigs after donor pretreatment with prostaglandin E-1 and pulmonary artery flush with modified Euro-Collins solution. Sequential morphologic changes in pulmonary artery flow surface and lung structure were studied after 6-hour storage and after 4-hour reperfusion, using light microscopy and scanning and transmission electron microscopy. Morphologic observations were compared with functional changes. After 6-hour preservation slight degenerative changes were found in the pulmonary artery flow surface and changes in lung tissue suggestive of increased vascular permeability and edema. During 4-hour reperfusion the changes progressed. Preservation was in general moderate. Lung tissue showed vascular congestion and slight inflammation. Localized areas of reperfusion damage could adjoin near-normal looking alveoli. Oxygenation and gas exchange, though low in the beginning of reperfusion, tended to improve during the reperfusion period. The method was concluded to afford good morphologic preservation of the graft after 6-hour storage, and moderately good morphologic and functional preservation after 4-hour reperfusion.

Inhaled NO and prostacyclin during porcine single lung transplantation.

BACKGROUNDnIncreased pulmonary vascular resistance (PVR) and decreased arterial oxygenation frequently complicate lung transplantation. Inhaled nitric oxide (NO) and aerosolized prostacyclin (PGI2) both dilate the pulmonary vasculature and improve oxygenation in adult respiratory distress syndrome. We investigated whether similar effects would occur during early reperfusion of a lung graft.nnnMETHODSnEighteen pigs underwent left lung transplantation. We measured blood flow distribution, mean pulmonary artery pressure, PVR, and gas exchange in each lung separately. Animals were randomized into three groups to receive NO (10 ppm/30 minutes, 40 ppm/30 minutes), nebulized PGI2 (25 microg/mL/30 minutes, 50 microg/mL/30 minutes), or no drugs (control).nnnRESULTSnIn the transplanted lung, PVR was significantly higher than in the native lung. Pulmonary vascular resistance of the transplanted lung was lower in the NO and PGI2 groups in comparison with the control group. During the first hour of inhalation, NO decreased PVR more than PGI2. Neither drug improved oxygenation in the graft.nnnCONCLUSIONSnNitric oxide and PGI2 decreased PVR of the transplanted lung slightly, but the effect did not produce a normal pressure in pulmonary vasculature.

The effect of nitecapone, a new antioxidant, on myocardial function after aortic cross-clamping in experimental heart ischemia

During aortic cross-clamping, the myocardium suffers from global ischemia, which is followed by reperfusion after declamping. The generation of free oxygen radicals increases during reperfusion, resulting in arrhythmias and impaired cardiac function. This study was conducted to evaluate the effect of a novel antioxidant nitecapone (NC) on cardiac reperfusion injuryin vivo. Twelve pigs were anesthetized and after sternotomy the aorta and the right atrium were cannulated for cardiopulmonary bypass. The heart was arrested with either +4°C crystalloid cardioplegia alone in the control group (n=6) or cardioplegia with NC (50 µM) added in the NC group (n=6). Cardioplegia was added every 20 minutes. After 1 hour of aortic crossclamping, blood samples for oxidative stress analysis were taken, and hemodynamic profile surveillance continued for 90 minutes. Heart rate (p=0.04) and left ventricular end diastolic pressure (LVEDP) (p=0.04) were significantly lower in the NC group than in the C group after aortic declamping. Cardiac output and myocardial contractility (dP/dtmax) were also enhanced in the group receiving NC, but the difference was not statistically significant. At 30 minutes after reperfusion, the coronary production (coronary sinus-aorta) of thiobarbituric acid reactive substances correlated inversely with cardiac output (r=−0.90,p=0.001) and stroke volume (r=−0.82,p=0.007). The effect of NC on lipid peroxidation seems to be modest and therefore the target of NC is unclear. NC would appear, however, to be a beneficial additive in the crystalloid cardioplegia in terms of functional recovery.

Donor Lung Pretreatment with Prostaglandin E1 Does Not Improve Lung Graft Preservation

Prostaglandin E1 (PGE1) is widely used to improve early graft function after lung transplantation, but some studies have questioned its benefits. Therefore we evaluated the effect of donor pretreatment with PGE1 in our porcine model of single lung transplantation. Donors received PGE1 or placebo intravenously before flushing the pulmonary artery with modified Euro-Collins solution. After cold storage, the excised left lung was transplanted. Ischemic time was 4 h. We used our right side heart bypass model to measure standardized pulmonary vascular resistance and to study blood flow distribution between recipient’s native and transplanted lung. Systemic and pulmonary hemodynamics and gas exchange were also measured. After transplantation, pulmonary vascular resistance was significantly higher in the transplanted lung, which received only one fourth of the total pulmonary blood flow. PGE1 pretreatment did not improve pulmonary hemodynamic parameters, or gas exchange.

The Pulmonary Vasodilatory Properties of PGE1 are Blunted after Experimental Single Lung Transplantation

Prostaglandin E1 (PGE1 is a short-lived powerful vasodilator, which modifies platelet and neutrophil function and exerts a cytoprotective effect. In search of improved pulmonary preservation techniques PGE1 has been extensively studied as an adjunct to the crystalloid flush solutions or in donor pretreatment. Less attention has been paid to its possible usefulness when administered during the reperfusion period. Therefore, we evaluated the effects of PGE1-infusion on pulmonary hemodynamics and gas exchange during the first four hours of reperfusion of a pig left lung allotransplantation.