Heart transplantation in Finland 1985-1995.

BACKGROUND AND AIMS: Since improved immunosuppression in the 1980's, heart transplantation is a well established procedure to treat patients with end-stage heart failure. The first heart transplantation in Finland was performed in 1985. Since then the activity has gradually increased to a level of about 25 annual transplants. The aim of this report is to sum up the clinical experience during the first 11 years. MATERIALS AND METHODS: From February 1985 till the end of 1995, 190 heart transplantations were performed in our institution. There were 176 males and 14 females ranging from 15 to 62 (mean 42.2) years of age. End-stage preoperative cardiac disease was dilating cardiomyopathy in 108 cases, coronary artery disease in 65 cases, valvular disease in 12 cases and congenital heart disease in five cases. RESULTS: The 30-day hospital mortality was 29 out of 190 (15.2%). The actuarial survival was 77% at one year, 75% at two years and 73% at 10 years. The most common causes of death were rejection (11 cases), graft failure (11 cases), abdominal complications (six cases) and cytomegalovirus (CMV) infection (four cases). A total of 87 rejection episodes occurred in 53 patients consisting 28 per cent of patients. 44 rejections occurred within three months post transplantation. Significant infections were noted in 198 instances in 97 patients. These were of bacterial origin in 92, viral in 48, fungal in 12 and protozoal in 10 cases, and 36 such infections which responded to antibiotics favourably but in which the microbe remained unidentified. 138 infections (i.e. 80%) occurred within 6 months post transplantation. In viral infections cytomegalovirus (CMV) predominated (29 out of 48). The CMV infection was significantly milder in patients who were seropositive preoperatively than in preoperatively seronegative patients with seropositive donors. CMV infection was associated with increased risk of post-transplant coronary artery disease. Three years after transplantation some restoration of sympathetic nervous response was observed at orthostatic test in heart rate and blood pressure. CONCLUSIONS: It can be concluded that 1) if a patient survives the three immediate postoperative months, his prognosis is good for the forthcoming years, 2) clinically significant rejections occur in less than one third of the patients, 3) cytomegalovirus is the most harmful agent post transplantation and a risk factor for post-transplant coronary artery disease and that 4) some restoration of sympathetic nervous control of the heart occurs within three years after transplantation.

En bloc heart and lung transplantation in Finland 1988-1996.

UNLABELLED: The purpose of the study was to review the first clinical experience in combined heart-lung transplantation in our institution. MATERIAL: From June 1988 to December 1996 15 en bloc heart and lung transplantations were performed. There were nine men and six women, aged 17-61 (mean 42.3) years. The indications for operation were primary pulmonary hypertension with right heart failure in five, Eisenmenger's syndrome in five, pulmonary embolism and right heart failure in three and emphysema with right heart failure in two cases. RESULTS: The hospital (30 day) mortality was four patients (26.6%). The causes of mortality were graft failure in two cases, infection and bleeding after transbronchial biopsy in one case and sepsis and aspergillosis in one case. Postoperative complications included eight cytomegalovirus (CMV), two Pneumocystis Carinii, five bacterial and five fungal (one Aspergillus and four Candida) infections. Rejection episodes (of the lungs) occurred in four patients (in 27%). During the follow-up to four years two patients developed diabetes mellitus (insulin therapy), one patient renal failure (dialysis), two patients tracheal stricture (laser resection), one patient fracture of the spine and one patient epilepsy. One patient died from prolonged CMV infection and chronic rejection eight months postoperatively. Four patients underwent bronchial artery revascularization (two with the internal thoracic artery and two with a vein graft). This was followed by improved airway healing and resistance towards infections. After a follow-up to four years 10 patients out of 15 (66.7%) were living an active life. CONCLUSION: Combined heart-lung transplantation offers a good mid-term outcome for patients with end-stage cardiopulmonary disease. The results compare favourably with the corresponding international statistics.

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.

Time course of beta 2-integrin CD11b/CD18 (Mac-1, alpha M beta 2) upregulation on neutrophils and monocytes after coronary artery bypass grafting. CD11b upregulation after CABG surgery.

Although upregulation of CD11b/CD18 receptor, i.e. activation of neutrophils and monocytes, during cardiopulmonary bypass is well documented, the duration of the active state after uncomplicated operation is less understood. We therefore investigated CD11b expression of phagocytes in blood samples collected 2-4, 24, 48 and 72 h after coronary artery bypass grafting. CD11b expression on neutrophils was significantly elevated at 2-4 and 24 hours after operation as compared with baseline. On monocytes, expression peaked at 24 h and returned to baseline by 72 h. Because CD11b is a sensitive marker, effects of different sampling techniques on its expression were also studied. CD11b expression was similar in samples collected with a syringe from arterial or central venous catheter or with open technique from cubital vein. On neutrophils from healthy subjects, sampling with syringe caused small (10%) but statistically significant increase of expression. We conclude that activated neutrophils disappear from circulation within hours after CABG surgery while activated monocytes may continue circulating for 2-3 days, and that CD11b sampling can be done with a syringe.

Perivascular sympathectomy does not remove adrenergic nerves from distal vessels. The effect of various denervations on the rat saphenous bundle: a histochemical study.

It has been claimed earlier that perivascular sympathectomy removes distal adrenergic innervation of the vessels. Based on preliminary results suggesting the contrary, the purpose of this work was to reconsider the denervation effect of perivascular sympathectomy. We operated on 40 rats using different denervation methods mainly to test the effects of perivascular sympathectomy on the distal saphenous vessels of the leg. The operations were performed on the right leg, while the left leg was used as a control. Samples were taken 2 days after the operations for glyoxylic acid-induced fluorescence examination for the histochemical demonstration of adrenergic nerves. Perivascular sympathectomy seemed to remove the adrenergic innervation only from the operated segment of the vessel. There was a short segment of diminished innervation a few millimeters in length just distal to the perivascular sympathectomy while the more distal adrenergic nerves around the vessels appeared to be normal. When the saphenous nerve was cut the adrenergic innervation seemed to disappear for 1 cm and to continue to be diminished at the medial malleolus site. Lumbar sympathectomy did not seem to remove the distal adrenergic nerves around the vessels, but caused only a slight decrease in innervation. It can be concluded that the peripheral adrenergic innervation is apparently normal after perivascular sympathectomy and that the operation does not have the previously assumed denervation effects.

Surgical treatment of ventricular septal defect secondary to myocardial infarction.

13 patients were operated on during 1974-88 for ventricular septal defect secondary to myocardial infarction. 7 infarctions were inferior and 6 anterior. At the time of operation 5 patients were in shock. Besides the correction of ventricular septal defect coronary artery by-pass grafting was performed in 6 patients and left ventricular aneurysmectomy in 3 patients. The operative mortality was 31%. The cause of death was low output syndrome in 3 cases and a new rupture through the left ventricular free wall in one case. Postoperative shunting was detected in 5 patients. During an average follow-up time of 6.3 years (range 0.5-15 years) 3 patients died from a new myocardial infarction. The mean performance levels of the patients still living was NYHA II. Prompt diagnosis of a ventricular septal defect due to myocardial infarction and its immediate surgical treatment is recommended. The results are poor in the presence of primary shock and for inferior infarction.

Popliteal artery entrapment.

External compression of the popliteal artery is probably still underdiagnosed. Young patients with atypical claudication, with isolated popliteal changes, deserve thorough investigation. Subdividing the entrapment syndrome into three subgroups (I-III) highlights the clinically important characteristics of the different types. Delayed diagnosis leads to arterial occlusion with clinical and radiological resemblance to arteriosclerotic occlusive disease. At this stage a medial approach with reversed saphenous vein bypass is recommended. If the artery is still patent, a posterior S-shape approach offers good exposure for arterial decompression, rerouting and possible ancillary measures. In addition to reviewing the literature and outlining the classification criteria and surgical treatment, five cases of our own are presented including two rarities. In one both type I and type III existed simultaneously. In the other the popliteal artery entrapment was combined with cystic adventitial disease.

Early and late results of surgery for atrial septal defect in patients aged over 60 years.

To assess the risks and benefits attending the surgical repair of atrial septal defect in the elderly the case histories of all patients operated on at the age of 60 years or more were reviewed and follow-up study, including cardiac catheterization, was performed. A total of 17 patients (12 females and 5 males) were identified. The left-to-right shunt ratio averaged 2.7. Fifteen patients had abnormally high systolic (greater than 30 mmHg) or mean (greater than 20 mmHg) pulmonary artery pressure and the pulmonary arterial resistance was elevated (greater than 1.5 units) in eight. One patient died shortly after surgery (operative mortality, 6%) and major postoperative complications were found in four additional patients (24%). Three months after surgery the effort capacity had improved by at least one class in all survivors. After an average of 8.2 years follow-up 12 patients were alive. Ten of them felt better than preoperatively. Eight agreed to cardiac catheterization. The pulmonary blood flow was markedly decreased in all (means, 5.6 l/min postoperatively, vs 11.2 l/min preoperatively) even though a hemodynamically significant shunt persisted in two patients. The mean pulmonary artery pressure had decreased in all who were hypertensive before operation (mean, 25 mmHg vs 33 mmHg). It had slightly increased in patients who had normal pulmonary pressure preoperatively (mean, 27 mmHg vs 19 mmHg). The pulmonary arterial resistance was higher than before surgery in all except one patient (mean, 2.2 units vs 1.5 units).(ABSTRACT TRUNCATED AT 250 WORDS)

Life-threatening complications of cardiac operations and occurrence of myocardial catecholamine bombs.

Myocardial catecholamine bombs (huge local intra-axonal accumulations of catecholamine, mainly norepinephrine, within cardiac tissue) were observed in (right auricular) myocardial biopsy specimens in 16 of 65 adult patients selected randomly from a series of elective cardiac operations. The occurrence of catecholamine bombs was in highly significant correlation (p less than 0.001) with the occurrence of life-threatening complications of cardiac operations (life-threatening arrhythmias [ventricular tachycardias, ventricular fibrillation, asystole], clinically evident perioperative myocardial infarction/postoperative low-output syndrome, death). There was a very close correlation between the occurrence of catecholamine bombs and life-threatening arrhythmias. Life-threatening arrhythmias occurred in 13 patients. Eight of them belonged to the group of 16 patients with catecholamine bombs and five belonged to the group of 49 patients with no bombs; the difference (8/16 versus 5/49) is very clear (p less than 0.001). It was our experience that dangerous arrhythmias related to catecholamine bombs may occur as late as during the second postoperative week. We believe our observations are of considerable clinical importance, because catecholamine bombs are easily identified by fluorescence microscopic examination of right auricular myocardial specimens retrieved intraoperatively, and patients at high risk can then be selected (during the operation) for more extensive and prolonged surveillance and possibly prophylactic treatment.

Adrenergic innervation of aortic patch-grafts in rats.

The regeneration of vascular adrenergic nerves was studied using the glyoxylic acid-induced fluorescence method for the specific demonstration of adrenergic nerves in syngeneic patch-grafts of the right atrium of the heart, vena cava and glutaraldehyde-treated vena cava transplanted into the abdominal aorta of the rat. Glutaraldehyde-treated segments of the supradiaphragmatic inferior vena cava were transplanted into the abdominal aorta of rats as well. At the end of the observation period of 24 weeks limited, patchy and defective innervation was observed in the syngeneic vena cava and atrial patches. No adrenergic nerves were found in the glutaraldehyde-treated vein patch-grafts or vein grafts. Owing to the very poor innervation of atrial and venous patch-grafts the results are not entirely in agreement with the target organ concept of adrenergic nerve regeneration. In this study the suture line around the patch graft probably hampers regeneration of vascular adrenergic nerves in the patches.

Bronchospasm during cardiopulmonary bypass--a potentially fatal complication of open-heart surgery.

Severe bronchospasm at the termination of cardiopulmonary bypass is an unusual but dangerous complication of open-heart surgery. We report two cases. In both of them the final etiology remained unsettled. In one of the cases vigorous and immediate bronchodilatory therapy resulted in a favourable remission. In the second case bronchospasm contributed to a very harmful bulging of the left lung through the opened mediastinal pleura, stretching and damaging the left internal mammary artery graft, which obviously contributed to the fatal outcome. We emphasize especially the following points: 1) a carefully evaluated medical history of patients scheduled for open-heart surgery may reveal some details pointing to an increased risk of bronchospasm during cardiopulmonary bypass; in such cases prophylactic measures may be indicated; 2) immediate vigorous bronchodilatory therapy early at the onset of bronchospasm during the weaning from cardiopulmonary bypass may reverse the alarming situation.

Abdominal aortic aneurysm and dissection after blunt trauma.

A case of abdominal aortic aneurysm and dissection after blunt trauma is presented. Unlike traumatic lesions of the thoracic aorta, this condition seems to be extremely rare, and may therefore deserve publication. Conservative surgery (resection of the dissected intimal flaps, closure of the aortotomy with a Blalock-type vascular suture) gave good early and late (6 years follow-up) results.

Effect of addition of magnesium to potassium-containing fluorocarbon cardioplegic preparations. An experimental study.

The effect of magnesium on potassium fluorocarbon cardioplegia was studied in 20 rabbits. Isolated hearts with ascending aortas were perfused with oxygenated and cooled (+4 degrees C) fluorocarbon solutions. In 10 experiments, the solution contained 20 mmol/l of potassium, in 10 further experiments, 20 mmol/l of potassium and 15 mmol/l of magnesium. Ultrastructural preservation of the myocardium was studied using transmission electron microscopy. In addition, the cation contents of the myocardium were studied by flame atomic absorption spectrophotometry (calcium, magnesium) or electrothermal atomic absorption spectrophotometry (copper). After 120 minutes of ischaemia, areas of moderate or severe ultrastructural myocardial cell damage were observed in both groups but severe damage was more extensive and commoner in the group with no access to magnesium. Preservation of the capillary endothelium was also worse in that group. There was a highly significant increase in magnesium content, a decrease in calcium content and an increase in the magnesium/calcium ratio following magnesium-potassium fluorocarbon infusion. The copper content remained unchanged. A protective effect of magnesium was observed. The electrolyte content of cardioplegic solutions also alters the electrolyte content of the myocardium. This may be important in reperfusion.

Congruence of adrenergic and cholinergic intrinsic innervation of human and rat atria.

Right atrial biopsies from rat and human hearts were studied using combined methods for the demonstration of glyoxylic acid-induced fluorescence (GIF) of catecholamines and acetylcholinesterase (AChE) reactions in the same specimens. In specimens from the rat heart, the GIF and AChE reactions were performed either simultaneously or consecutively. In biopsies of the human right atrium, obtained at right atria cannulation during open-heart surgery, the reactions were performed consecutively. It was found that in both rat and human atria the adrenergic nerves and AChE reactive nerves, which are probably cholinergic, run partly separately and partly together. In the rat atrial specimens, close relations between adrenergic nerves and clusters of AChE reactive cells were observed. In addition, clusters of fluorescent cells were observed in the vicinity of AChE reactive nerve bundles. This indicates that there may be several possible means of peripheral interaction between the intrinsic adrenergic and cholinergic systems of the rat heart.

Long-term survival rates after prolonged aortic cross-clamping with St. Thomas' Hospital cardioplegia.

Prolonged aortic cross-clamping (in excess of 120 min) was necessary in 154 cardiac surgical patients. St. Thomas' Hospital cardioplegia was used for myocardial preservation. Quantitative polarization microscopy enabling quantitative birefringence measurements to assess the change in birefringence of the muscle fibres in response to the addition of buffer containing ATP and calcium (i.e. myocardial contractility) was used to detect whether there had been any deterioration in right or left ventricular myocardium during the bypass period. 30 day survival was 90%, long-term (60 months) survival was 80%. In single valve replacements, patients with aortic valvular replacement had 100% survival up to 92 months, whereas patients with mitral valvular replacement had survival rates of 83% after 12 months and 27% after 60 months. Survival rates after 60 months were 89% for coronary artery bypass grafting, 80% for multiple valve replacements, and 74% for combined valvular and coronary artery bypass grafting surgery. Quantitative birefringence assessment of function showed that in the surviving patients 5% had functional deterioration during bypass whereas in the non-surviving patients 70% had functional deterioration. It may be concluded that after cardiac surgery necessitating prolonged aortic cross-clamping--once the initial operative problems are overcome--reasonable long-term results can be obtained by using St. Thomas' Hospital cardioplegia.

Peptidergic innervation of human atrial myocardium: an electron microscopical and immunocytochemical study.

Nerve terminals of human cardiac muscle were studied using an electron microscope. Substance P-, Leu-enkephalin- and vasoactive intestinal polypeptide-like (VIP) immunoreactive nerves were demonstrated by use of the light microscope. In addition, VIP- and substance P-like immunoreactive nerves were localized ultrastructurally by the peroxidase-antiperoxidase-method. Muscle specimens were obtained from right auricula of patients undergoing open-heart surgery. In the nerve fibres and terminals, which were situated close to the blood vessels and cardiac muscle cells several vesicle populations were identified. On the morphological basis the terminals could be tentatively categorized as cholinergic, mixed cholinergic-peptidergic, adrenergic, sensory or baroreceptor type, peptidergic and degenerating nerve endings. Substance P-, Leu-enkephalin- and VIP-like immunoreactive nerves were localized between cardiac muscle cells. Nerve terminals, which showed substance P-immunoreaction were observed also close to blood vessels. In substance P- and VIP-immunoreactive nerve terminals the immunoprecipitation was localized in large dense-cored vesicles of about 120 nm in diameter. It is concluded that the intrinsic control of the human heart is most probably regulated by several transmitter candidates. The peptidergic nerves may exert their modulatory interactions in the nerve bundles where they are situated close to each other but a direct effect on the blood vessels and muscle cells cannot be excluded.