PubMed Health⌕ Search

Biomedical subjects

L Heikkilä

Publications and source records attributed to L Heikkilä.

At least 19 recordsLinked to original sources
PubMed2001

L-Arginine in lung graft preservation and reperfusion.

BACKGROUND: Inhaled 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. METHODS: Six 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. RESULTS: Pulmonary 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. CONCLUSIONS: L-arginine reduced PVR in the native lung but did not improve pulmonary hemodynamics, gas exchange, or reduce leukocyte sequestration of the transplanted lung.

Animals↗
PubMed2001

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.

Adult↗
PubMed2000

Survival in operable non-small-cell lung cancer: role of p53 mutations, tobacco smoking and asbestos exposure.

Validated markers are needed to identify operable lung cancer patients with poor prognosis. About one-half of non-small-cell lung cancers (NSCLCs) carry a mutation in the p53 tumor-suppressor gene. We examined 101 NSCLC patients for surgical stage, completeness of resection, tobacco smoking, asbestos exposure, age, gender and p53 gene mutations as prognostic factors after a follow-up period of 4 years. Cox's multivariate regression model was applied to quantify the associations with overall and cancer-related survival. Patients with a wild-type p53 gene had an overall 4-year survival of 43% and those with a mutated p53 gene, 35%. In squamous-cell carcinoma, stage and heavy smoking, defined as the median of pack-years smoked, had prognostic significance for overall survival. Only stage was associated with poor cancer-related survival. Asbestos exposure was not associated with overall survival or cancer-related survival in squamous-cell carcinoma or adenocarcinoma. In adenocarcinoma, p53 mutation, in addition to stage, emerged as a significant predictor of poor cancer-related survival.

Adult↗
PubMed2000

Adventitial mast cells connect with sensory nerve fibers in atherosclerotic coronary arteries.

BACKGROUND: The number of activated mast cells is increased in the adventitia of coronary segments with plaque rupture and in spastic atherosclerotic coronary segments. Neurogenic activation of mast cells has been demonstrated previously in other tissues. Here we identified and quantified contacts between mast cells and nerves in the adventitia of normal and atherosclerotic coronary segments. METHODS AND RESULTS: Normal (types 0 or I) and atherosclerotic (lesion types II, III, and IV) coronary segments from 22 unselected autopsy cases were stained for mast cells and sensory nerves by a histochemical double-labeling method. Contacts between mast cells and sensory nerves were quantified morphometrically and also identified by confocal microscopy. Coronary arteries obtained during heart transplantation were stained for the neuropeptides capable of stimulating mast cells, ie, substance P and calcitonin gene-related peptide. In the adventitia of atherosclerotic coronary segments with type IV lesions, the numbers of mast cells and mast cell-nerve contacts (104+/-15 mast cells/mm(2) and 30+/-5 nerve contacts/mm(2); mean+/-SEM) were significantly greater than in segments with type III lesions (79+/-12 [P<0.001] and 24+/-6 [P<0.001]), those with type II lesions (54+/-4 [P<0.001] and 12+/-2 [P<0.001]), or those with normal intima (31+/-3 [P<0.001] and 4+/-1 [P<0.001]). The nerve fibers connected with mast cells contained both substance P and calcitonin gene-related peptide, which identified them as sensory nerves. CONCLUSIONS: Neurogenic stimulation of mast cells in the adventitia of coronary arteries may release vasoactive compounds, such as histamine and leukotrienes, which can contribute to the complex neurohormonal response that leads to abnormal coronary vasoconstriction.

Calcitonin Gene-Related Peptide↗
PubMed2000

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.

Animals↗
PubMed1999

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 injury in 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 degreesC 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 cross-clamping, 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.

Journal Article↗
PubMed1999

Signs of massive intraoperative pulmonary embolism with extensive invasive monitoring.

A 71-year-old patient suffered a massive pulmonary tumor embolism during removal of a renal carcinoma. He had extensive invasive monitoring, and the data were stored for later analysis. This shows that most of the known signs of pulmonary embolism were present in the tracings. It is discussed how none of them alone was sufficient for clinical diagnosis, but the comparison of several simultaneous variables together may be of great help. This report shows also the importance of the data-storing devices in the anesthesia monitors to make these comparisons possible in quickly changing emergency situations.

Aged↗
PubMed1999

Donor lung pretreatment with prostaglandin E(1) does not improve lung graft preservation.

Prostaglandin E(1) (PGE(1)) 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 PGE(1) in our porcine model of single lung transplantation. Donors received PGE(1) 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. PGE(1) pretreatment did not improve pulmonary hemodynamic parameters, or gas exchange.

Alprostadil↗
PubMed1998

Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting.

AIMS: The aim of the study was to evaluate the effects on systemic and coronary haemodynamics and myocardial substrate utilization of a new calcium sensitizer, levosimendan, after coronary artery bypass grafting. METHODS AND RESULTS: Twenty-three low-risk patients were included in this randomized and double-blind study. They received placebo (n = 8), 8 (n = 8) or 24 (n = 7) micrograms.kg-1 of levosimendan after coronary artery bypass operation. Systemic and coronary sinus haemodynamics with thermodilution and myocardial substrate utilization were measured. The heart rate increased 11 beats.min-1 after the higher dose (P < 0.05). Cardiac output increased by 0.7 and 1.61.min-1 (P < 0.05 for both) after 8 and 24 micrograms.kg-1 of levosimendan, respectively. Systemic and pulmonary vascular resistance decreased significantly after both doses. Coronary sinus blood flow increased by 28 and 42 ml/(P = 0.054 for the combined effect) after the lower and higher dose, respectively. Myocardial oxygen consumption or substrate extractions did not change statistically significantly. CONCLUSION: Despite improved cardiac performance, levosimendan did not increase myocardial oxygen consumption or change myocardial substrate utilization. Thus levosimendan has the potential to treat low cardiac output states after cardiopulmonary bypass surgery.

Adult↗
PubMed1998

Comparison of sotalol and metoprolol in the prevention of atrial fibrillation after coronary artery bypass surgery.

New-onset atrial fibrillation (AF) is frequent after coronary artery bypass grafting (CABG), and beta-blockers decrease its incidence. To examine whether a beta-blocker with class III properties is superior to a pure one, 191 consecutive patients undergoing CABG were randomized to receive oral sotalol, 120 mg daily (n = 93), or metoprolol, 75 mg daily (n = 98), postoperatively. The doses were adjusted if beta-blockade was inadequate or excessive. AF occurred in 16 (16%) of 98 sotalol patients and in 30 (32%) of 93 metoprolol patients (p < 0.01). Symptoms related to beta-blockade or proarrhythmia did not appear. After CABG, sinus heart rate increased in both groups (p < 0.001) but less in the sotalol patients (p < 0.001) throughout the postoperative period. Corrected QT duration (by the Bazett equation) was prolonged after the operation in both groups (p < 0.001), whereas uncorrected QT duration at similar heart-rate levels were prolonged only in sotalol patients (mean increase, 31 ms; 95% confidence interval, 2042 ms; p < 0.01). Uncorrected QT durations at similar heart-rate levels were longer during sotalol (compared with metoprolol) treatment (p < 0.05). Heart rates or QT durations did not differ between the patients with or without AF. In conclusion, sotalol significantly reduces the incidence of AF after CABG. Although a marked class III effect is demonstrated with relatively low doses (as prolonged ventricular repolarization) in direct comparison unbiased by any rate correction, its contribution as an enhanced antifibrillatory mechanism in the postoperative state remains unconfirmed.

Anti-Arrhythmia Agents↗
PubMed1997

Experimental piglet lung transplantation: histological bioptic changes and autopsy findings.

To investigate difficulties in diagnosing pulmonary rejection and to create a new model to observe long-term histological consequences, 21 piglets were subjected to left single lung transplantation. Five of these transplants served as targets for unmodified rejection in piglets without immunosuppression (Group I), 13 recipients were treated with cyclosporin A, azathioprine and methylprednisolone (Group II), and in 3 cases reimplantation of an autograft was performed (Group III). In the course of postoperative graft monitoring, transthoracic/bronchial biopsies were obtained on days 3, 5, 7, 10, 14, and 20, and thereafter less frequently up to 134 days. In the unmodified rejection group, grafts consolidated in one week and histologically presented perivascular mononuclear cell infiltrates, except for one case which showed vasculitis. Lymphocytic bronchiolitis and or peribronchiolar infiltrate was present in three of the four autopsied grafts. In Group II acute rejection was detected six times in three piglets, and all except one of these specimens had a peribronchiolar component. Although no incontestable bronchiolitis obliterans developed, mild to moderate chronic obliterative vascular lesions were detected in all immunosuppressed piglets (n = 3) surviving more than 80 days. Contralateral lungs and Group III autografts showed mild changes related to the operation itself and interstitial swine endemic pneumonia (SEP). Chronic changes related to rejection were limited to the vascular wall. The mainly inflammatory bronchiolar changes are thought to present an incipient phase leading to obliterative lesions.

Anastomosis, Surgical↗
PubMed1997

Assessment of xanthine oxidase in human lung and lung transplantation.

Oxygen free radical generation by xanthine oxidase (XO) is a possible mechanism in the injury following reperfusion of transplanted organs. This study was undertaken to investigate XO in human lung, and to investigate whether XO is released into the blood stream during the immediate postoperative period after lung transplantation. XO activity was measured in healthy human lung tissue, and XO protein and the adenine nucleotide catabolic products hypoxanthine, xanthine and uric acid were analysed in the plasma samples collected during human heart-lung transplantation (n=4), double lung transplantation (n=2), and single lung transplantation (n=1). Neutrophil degranulation was assessed by plasma lactoferrin measurements. The results indicated that XO activity (detection limit 5 pmol x min(-1) x mg(-1) protein) and protein (detection limit 5 ng x mg-1 protein) were undetectable in the lungs of five healthy individuals. Similarly, no XO protein could be found in the plasma samples from the right ventricle or left atrium during and after the transplantation in any of the cases. Plasma xanthine and hypoxanthine concentrations were elevated 2-10 fold immediately after the reperfusion of the transplant, indicating washout of high-energy phosphate degradation products from the ischaemic lung. Plasma uric acid decreased rather than increased immediately after the surgery and during the following 24 h. Lactoferrin was elevated during the surgery. In conclusion, these results show that XO activity in human lung is low, it is not released into the blood stream during human heart-lung transplantation, and it is unlikely to contribute to postoperative complications in these patients.

Chromatography, High Pressure Liquid↗
PubMed1997

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.

Adult↗
PubMed1997

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.

Adult↗
PubMed1997

St. Jude versus CarboMedics: follow-up after prosthetic valve replacement.

BACKGROUND: The purpose of the present study was to evaluate the immediate and long-term outcome of patients with two types of mechanical bileaflet heart valves operated on in the same institution by the same group of surgeons. METHODS: A comparative analysis was made in 229 consecutive patients receiving either the St. Jude Medical (SJM) or CarboMedics (CMS) bileaflet mechanical valve in 1990-1991. There were no differences in the preoperative demographics between the two groups. At operations simultaneous coronary bypass operation was performed in 40 patients out of 134 (30%) in the SJM group and 95 (44%) in the CMS group (p=0.026). Sixteen patients in the SJM group underwent replacement of the ascending aorta with a composite graft and none in the CMS group. RESULTS: There was no difference in hospital mortality between the SJM (6.7%) and CMS (6.3%) groups or in other immediate postoperative complications. The patients were followed up to 32 months. There were more patients in the NYHA class I and II in the CMS group (88%) than in the SJM group (69%), p<0.002. Three were 11 thromboembolic events (0.051% per patient year) in the SJM group and one thromboembolic event (0.008% per patient year) in the CMS group. There were no other differences between the groups in long-term survival, rate of bleeding, infective endocarditis or perivalvular leakage. CONCLUSIONS: With the exception of a little more favourable exercise tolerance and fewer thromboembolic events in the CMS group there were no other differences in the outcome of patients with these two types of bileaflet mechanical valves.

Adult↗
PubMed1996

Delayed intrathoracic herniation of the stomach with pleural empyema due to diaphragmatic stab wound.

A 32-year-old man received a left-sided thoracic stab wound, which was primarily treated with percutaneous tube thoracostomy. Ipsilateral empyema appeared 8 weeks later and subsequent investigations revealed herniation of the stomach through the diaphragm. The diaphragmatic rupture and a perforation in the gastric wall were repaired at thoracotomy. The literature on such wounds is reviewed.

Adult↗
PubMed1996

Thromboxane receptor blockade does not attenuate pulmonary pressor response in porcine single lung transplantation.

BACKGROUND: The ischemia-reperfusion lung injury is characterized by increased pulmonary vascular resistance, edema, and subsequent deterioration of oxygenation. Other models of acute lung injury suggest that thromboxane A2 may contribute to the pulmonary hypertension after transplantation. METHODS: We studied the effects of the selective thromboxane A2 receptor antagonist SQ 30741 on pulmonary hemodynamics and gas exchange in porcine single lung transplantation using extracorporeal circulation (right heart bypass) with separate cannulations of the right and left pulmonary arteries. Pulmonary vascular resistance was measured at equal and constant flow to each lung. Flow distribution between the lungs was registered at equal pulmonary artery pressures. Twelve pigs (weight 17 to 23 kg) were studied. At the onset of reperfusion a bolus dose of the drug (5 mg/kg) was injected into both pulmonary arteries followed by an infusion (5 mg/kg/hr) for 1 hour (SQ group, n = 6). The control group (n = 6) received an equal amount of vehicle. The systemic and pulmonary hemodynamics and blood gas values were registered during 2 hours of reperfusion. RESULTS: The pulmonary vascular resistance of the transplanted lung was significantly higher compared with the native lung (p < 0.001). Administration of SQ 30741 failed to ameliorate the pulmonary pressor response of the graft in comparison with the control group. No difference was found in the systemic arterial oxygen tension between the two groups. CONCLUSIONS: Thromboxane does not seem to be among the principal mediators in the pulmonary hypertension after transplantation.

Animals↗