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Biomedical subjects

L Martinelli

Publications and source records attributed to L Martinelli.

At least 37 records · Page 2Linked to original sources

A pump-prime aprotinin dose in cardiac surgery: appraisal of its effects on the hemostatic system.

OBJECTIVES: To examine pump-prime aprotinin action on coagulation and fibrinolysis in patients undergoing primary coronary revascularization. DESIGN: A prospective randomized study. SETTING: A university hospital. PARTICIPANTS: Forty-three patients were randomly assigned to either group A, 21 patients treated with 2 x 10(6) kallikrein inhibitor units (KIU) of aprotinin in the cardiopulmonary bypass (CPB) prime, or group B, 22 patients, untreated. INTERVENTIONS: Patients, scheduled for elective coronary surgery, were treated with 2 x 10(6) KIU of aprotinin in the CPB prime. Markers of coagulation and fibrinolysis were evaluated. MEASUREMENTS AND MAIN RESULTS: Surgical times, number of reopenings, and allogeneic blood requirements were collected for each patient. Blood samples were obtained before and after surgery for assessing coagulation (prothrombin time [PT], activated partial thromboplastin time [aPTT], ethanol test, factor VII, antithrombin III [AT III], thrombin-antithrombin III complex [TAT], fragment 1.2 of prothrombin [F1.2]) and fibrinolysis (fibrin degradation products [FOP], plasmin-antiplasmin complexes [PAP], D-dimers) markers variations. In group A surgical times were faster, there were fewer reopenings (0 v 3), and fewer blood transfusions (1 patient v 4 patients). The two groups did not differ for PT, aPTT, and fibrinogen measurements. Postoperative FDP (measurable in more patients of group B at the end of the operation), PAP, and D-dimers postoperatory levels (less increased in aprotinin group) show the antifibrinolytic properties of the drug. Regarding the coagulation markers, factor VII decreased, whereas TAT and F1.2 increased, all to a lesser extent in the aprotinin group compared with the untreated patients, at the end of operation. CONCLUSION: Pump-prime aprotinin minimized, even if not completely inhibited, the activation of coagulation and fibrinolysis during CPB, possibly ensuring a less complicated and safer postoperative recovery. It seemed to allow the maintenance of a correct balance of hemostatic systems, avoiding the risk of thrombotic phenomena.

Adult↗

Lung transplantation: the experience of the Thoracic Organ Transplantation Centre of Pavia.

Between January 1991 and September 1995 at the Thoracic Organ Transplantation Centre of Pavia, 193 patients entered the waiting list for heart-lung or lung transplantation. Indications for heart-lung transplantation (HLT) were mainly primary or secondary pulmonary vascular diseases. Parenchymal lung diseases were the most frequent reasons for single- (SLT) or double-lung (DLT) transplantation. During the same period, 21 patients underwent HLT, 16 SLT and 14 DLT. Early deaths (within 30 days of surgery) occurred in 2 (10%) HLT, in 3 (19%) SLT, and in 3 (21%) DLT. Nineteen (90%) patients with HLT, 11 (69%) with SLT, and 10 (71%) with DLT survived up to 3 months; and 11 (52%) patients with HLT, 8 (50%) with SLT, and 5 (36%) with DLT survived up to 12 months. At the time of writing, the following patients are still alive: 10 (48%) with HLT, after a mean +/- SEM follow-up of 37.2 +/- 6 (range 28-46) months, 12 (75%) with SLT, after a mean follow-up of 16 +/- 11 (range 1-35) months, and finally 7 (50%) with DLT, after mean follow-up of 14 +/- 9 (range 1-23) months.

Adult↗

Afterload mismatch-related problems after "domino" heart transplantation.

UNLABELLED: The heart transplants with domino technique, which uses donor hearts from heart-lung recipients, increases the pool of donors, provides the advantage of shortening the ischemic time and makes suitable hearts for patients with pulmonary hypertension. The present study aimed to characterise the pre- and post-transplant clinical and hemodynamic profiles of patients that underwent domino transplant in Pavia. METHODS: Between 1991 and 1992, 9 heart transplants were performed with the domino procedure at I.R.C.C.S. Policlinico S. Matteo of Pavia. Domino donors (6 with primary pulmonary hypertension, 2 with Eisenmenger's syndrome due to atrial septal defect, 1 with cystic fibrosis) underwent electrocardiographic, echocardiographic, chest roentgenogram studies, and right heart catheterization and coronary angiography (for donor older than 40). Domino recipients, 6 males and 3 females with a mean age of 44 years, had dilated cardiomyopathy (4 cases), coronary artery disease (4 cases) and valvular heart disease (1 case) (group 1). Seven of the 9 cases entered the study; 2 were excluded: one because had undergone heterotopic transplantation, the other had received the heart from another country and therefore the graft had suffered from a very long ischemic time. Controls group consisted of 12 patients who had consecutively undergone cardiac transplantation with non-domino donors during the same period (group 2). Immunosuppression was similar in both groups, and consisted of a combination of cyclosporin A, azathioprine and corticosteroids, plus a 7-day-course of antithymocyte globulin. Hemodynamic and echocardiographic controls were performed at 2, 3 and 4 weeks (short-term control) and at 2 and 6 months (mid-term control) after surgery. RESULTS: Domino donors (39 +/- 12.5 years) had significantly higher mean right ventricular end-diastolic diameter and lower left ventricular diameter than normal mean values. Domino recipients had significantly higher mean pulmonary arteriolar resistances than controls; mean ischemic time was also significantly lower in group 1 than in group 2. Short- and mid-term controls after surgery in group 1 showed persistently higher systemic vascular resistances and pulmonary vascular resistances and lower cardiac output than in group 1. Two patients developed an early and unexpected increase in pulmonary wedge pressure accompanied by severe paroxysmal nocturnal dyspnea and mitral regurgitation. In all cases, the left ventricles were relatively inadequate; the combination of low cardiac output and of high systemic vascular resistances favoured the occurrence of an afterload mismatch condition that was worsened by chronic hypoxia. This condition must be known and expected in these patients after transplantation in order to provide timely and effective treatment to potentially life-threatening left ventricular failure episodes. IN CONCLUSION, the subset of transplanted patients that receives domino donors may develop left-side afterload mismatch which, combined with low cardiac output, with high systemic vascular resistances and with the effects of chronic hypoxia originally suffered by the heart, may cause sudden and unexpected left-side heart failure which has to be timely recognised and managed. Although hemodynamic adaptation of this patients is highly problematic, it does not limit the value of the domino procedure.

Adult↗

[Heart transplant over 55 years].

BACKGROUND: The age of recipient has been thought for several years to be one of the most important predictors of survival after heart transplantation. Therefore patients older than age 50 years were usually excluded from heart transplantation. The marked improvement in survival after clinical introduction of cyclosporine made a critical revision of selection criteria for heart recipients. In this article we retrospectively analyze the outcome of heart transplantation dividing the patients into two groups: Group A < or = 55 years, Group B > 55 years respectively. METHODS: We analyzed 437 patients who underwent heart transplantation, immunosuppressive protocol for all the patients was cyclosporine, azathioprine and prednisone. Group A included 284 patients, Group B 153 patients. We studied demographic, clinical and haemodynamic data pre- and post-operatory in both groups. RESULTS: In Group A was more frequent dilated cardiomyopathy (p < 0.01) and the patients arrived at heart transplantation in worse haemodynamic conditions requiring more frequently inotropic infusion and/or mechanical support (intraaortic balloon pump, left ventricular assist device). Post-operatory course was more complicated in Group B patients where ischemic cardiomyopathy was more frequent (p < 0.001); intensive care stay, inotropic drugs infusion, mechanical ventilation and hospital mortality were higher in Group B, although non significantly. The donor age was significantly higher in Group B (p < 0.001), anyway the statistical analysis did not show a correlation between donor age and more complicated post-operative course. Follow-up did not show significative differences in the two groups considering haemodynamic data, metabolic disorders, graft coronary disease, infection and rejection rates. On Group B is significantly higher tumor incidence (p < 0.05) and peripheral vascular complications (p < 0.01). Actuarial survival at 5 and 7 years is respectively in Group A 80.3 and 72.9%, in Group B 75.4 and 71% (p = ns). CONCLUSIONS: Heart transplantation in patients older than 55 years with end-stage heart disease is a valid therapeutic option with excellent long-term survival; pre-operative screening must be particularly accurate and older donors should be considered.

Aged↗

Factors increasing the risk of allograft vascular disease in heart transplant recipients.

Allograft vascular disease is the major cause of late cardiac graft failure. A multifactorial etiopathogenesis is supposed. Our study investigated factors associated with allograft vascular disease occurrence. After stratifying our series on the basis of potential risk factors, we calculated allograft vascular disease incidence rate in 267 grafts from 258 patients who underwent transplant between November 1985 and August 1996. Chi-square test was used for the identification of univariate risk factors to be included in a multivariate model. Multivariate analysis was based on a Poisson model. Seventy of the 267 grafts (26.2%) were diagnosed with allograft vascular disease. Heart disease other than idiopathic dilated cardiomyopathy, donor's age, number of mismatches for HLA-B = 2, presence of systo-diastolic hypertension, number of acute rejection positive endomyocardial biopsies > or = 7 and the association of human Cytomegalovirus and hepatitis C virus infections proved to be univariate risk factors, and were included in the Poisson multivariate model. The association of Cytomegalovirus and hepatitis C infections multiplied allograft vascular disease incidence rate by 3.9, systo-diastolic hypertension by 2.2, occurrence of 2 HLA-B mismatches by 2, a high number (> or = 7) of acute rejection positive-endomyocardial biopsies by 1.8, and heart disease other than idiopathic dilated cardiomyopathy by 1.8. The association of human Cytomegalovirus and hepatitis C virus infections, of HLA-B mismatches, of acute rejection-positive endomyocardial biopsies, as well as post-transplantation hypertension and native heart disease other than idiopathic dilated cardiomyopathy, proved to be positively associated with an increased risk of allograft vascular disease. Given the concordance of our data with those of numerous prior series, we are going to adopt a special surveillance angiographic protocol for patients with these factors.

Adolescent↗

FK506 effectiveness in reducing acute rejection after heart transplantation: a prospective randomized study.

BACKGROUND: Tacrolimus (FK506) has recently become available clinically as an alternative to cyclosporine-based immunosuppression. This study reports the middle-term results of a prospective, randomized trial that compared FK506 with cyclosporine-based immunosuppression in heart transplant recipients. METHODS: Twenty-five consecutive patients were randomized at a 2:1 ratio into two groups, one of which received FK506 (15 patients), the other cyclosporine (10 patients). Both groups received similar concomitant immunosuppression. The patients were followed up for 12 months. The following outcome parameters were analyzed: survival, rejection and infection rate, lymphocyte subsets, new-onset diabetes, renal and hepatic function, hypertension, right-sided heart catheterization data, graft coronary artery disease, and neurologic side effects. RESULTS: The mortality rate (two patients) in the FK506 group was 13% versus 0% in the cyclosporine group (p = NS). The two deaths were the consequences of early infections and higher doses of FK506. From the outset, the FK506 group presented a lower prevalence of acute rejection, a lower requirement for rejection treatments and a higher incidence of infections. Accordingly, we reduced overall immunosuppression for the last seven patients in the FK506 group; the decrease in FK506 and prednisone dosage led to a decrease in the early infection rate without an increase in the rejection rate. There was no difference between the two groups in diabetes incidence, renal and hepatic function, right-sided heart catheterization data, or coronary angiograms. Hypertension was less frequent and milder in the FK506 group. CONCLUSIONS: This experience suggests that FK506 can be safely used in heart transplantation. It can decrease the frequency of rejection episodes. Low-dose administration allows a lower infection rate without an increase in rejection. With a protocol of delayed starting and low dosing, side effects such as renal toxicity, hypertension, and neurologic toxicity seem to be unlikely. Further studies are needed to establish the exact dosage and therapeutic levels of the drug.

Acute Disease↗

Echo-controlled endomyocardial biopsy in orthotopic heart transplantation with bicaval anastomosis.

Starting in January 1995, we performed heart transplantation, randomly using standard and bicaval techniques. In the latter technique, the anatomy of the right atrium is maintained, since the venae cavae are anastomosed. In 38 patients who received heart transplantation with bicaval anastomosis, 339 endomyocardial biopsies (EMB) were performed. EMB was done under echocardiographic control in 309 cases, whereas the remaining 30 were done under fluoroscopy. When EMB was echo-guided there was one major complication, namely right hemothorax in a 29-year-old man, who had had heart transplantation one week before, and this required surgical exploration. Other complications, correlated to venipuncture were: left hemothorax in a 65-year-old woman determined by arterial puncture, treated by means of chest tube drainage; pneumothorax (1 case). Echocardiographic guidance during EMB allows a better choice of biopsy site, reduces the risk of damaging cardiac structures and allows immediate monitoring of heart performance. Moreover the risk of X-ray exposure to both patient and operators is reduced. In any case, because the superior vena cava suture line is not visualized by two-dimensional echocardiography, if the bioptome cannot be introduced easily through superior vena cava, fluoroscopic control should be immediately applied, particularly in the early post-operative period when cicatrization is not complete.

Adult↗

Frequency and characteristics of coronary thrombosis in the epicardial coronary arteries after cardiac transplantation.

We investigated at autopsy or at retransplantation the frequency and characteristics of coronary thrombosis in 76 cardiac allografts: 37 in place for < or = 2 months (early) and 39 in place >2 to 99 months (late). The 76 allografts were inserted in 69 patients: a single 1 in 56 patients and 2 allografts in 13 patients, 7 of whom subsequently died and had an autopsy. An average of 140 sections from 70 5-mm-long segments of 8 epicardial coronary arteries were examined from each of the 76 allografts with both hematoxylin-eosin and Movat pentachrome stains. Thrombus was found in only 1 coronary artery (3%) (the right one) of the 37 early allografts, and in 24 of 39 late allografts (61%). Of the latter 39 grafts, 29 (79%) had allograft vascular disease (AVD) and 24 (83%) of them had coronary thrombosis. Of the 312 epicardial coronary arteries (4 major and 4 minor) examined in the 39 late cases, 66 arteries (21%) contained thrombus. Of the 24 late cases with thrombus in at least 1 artery, thrombus was present in 66 (34%) of the 192 epicardial coronary arteries examined: in 6 of the 8 arteries in 3 patients; in 5 arteries in 2 patients; in 4 arteries in 1 patient; in 3 arteries in 5 patients; in 2 arteries in 6 patients, and in a single artery in 7 patients. In all 66 arteries with thrombus (24 patients) the thrombus was longer than 5 mm. The thrombus in the late cases was entirely nonocclusive (mural) in 51 (77%) of the 66 epicardial coronary arteries containing thrombus and entirely occlusive in 10 arteries (15%). It consisted exclusively of multiluminal channels in 6 arteries (9%) and combinations in 1 artery (2%). Acute myocardial infarcts were present in 3 patients, all of whom had occlusive thrombi. In all 10 arteries with occlusive thrombi, the thrombus was larger than the underlying plaque and no occlusive thrombi were located over ulcerated plaques. These observations demonstrate that thrombus is common in epicardial coronary arteries >2 months after cardiac transplantation.

Adolescent↗

Human cytomegalovirus early infection, acute rejection, and major histocompatibility class II expression in transplanted lung. Molecular, immunocytochemical, and histopathologic investigations.

The present study aimed to investigate the relationship between acute rejection and human cytomegalovirus (HCMV) infection, as well as the coexpression of HLA-DR and immediate-early (IE) viral antigens, in 143 transbronchial biopsies and bronchoalveolar lavage fluids of 32 lung transplant recipients. We investigated the occurrence of morphologically overt viral infection with conventional histopathology, the expression of IE antigens with single labeling immunohistochemistry, the coexpression of IE antigens and HLA-DR molecules with double labeling techniques, and the presence of viral IE genes with polymerase chain reaction. Histopathologic study showed overt viral infections (12.6%) in 18 of the 143 biopsies; 8 were in a context of pneumonia and 10 were localizations without surrounding inflammatory cells; immunohistochemistry showed IE viral antigen expression in 31 (21.67%); PCR detected viral IE genes in 73/143 lavage fluids and biopsies (51%). The double labeling immunohistochemical technique showed that most IE antigen-expressing, noncytopathic cells were either HLA-DR negative in areas without infiltrates, or HLA-DR positive in those areas where inflammatory infiltrates were consistent, in the absence of viral cytopathy, with acute rejection. The results indicate that, in transplanted lung, the frequency of morphologically occult HCMV infection (as detected by immunohistochemically and/or PCR) is much higher than that of morphologically overt viral infection. The occurrence of inflammatory infiltrates (consistent with acute rejection) around morphologically occult infected cells and the possible lack of inflammation around both early- and late-infected cells suggest that in biopsies with occult infection the infiltrates should be attributed to allograft reaction. This conclusion would be in keeping with the coexpression of HLA-DR and HCMV IE in infiltrate-rich biopsies that are consistent with acute rejection, as well as with the absence of HLA-DR expression in IE antigen-positive cells in infiltrate-free-areas.

Acute Disease↗

Biochemical changes during regeneration of sunflower (Helianthus annuus L.).

The main developmental stages in Helianthus annuus organogenesis have been studied in the sunflower hybrid "Giove". Shoot regeneration was obtained with high efficiency from mature seed cotyledons. Two-dimensional electrophoresis of protein extracts as well as the isozyme patterns of acid phosphatase, alcohol dehydrogenase, esterase, gluconate-6-phosphate dehydrogenase and phosphoglucomutase were compared during growth, callusing and regeneration. Two-dimensional protein patterns were similar, although polypeptides specific for each developmental phase could be identified. Different 2,4-dichlorophenoxyacetic acid concentrations or the sampling of specific regions of the seed did not result in significant differences in protein patterns. The activity of alcohol dehydrogenase and phosphoglucomutase appeared very low. For gluconate-6-phosphate dehydrogenase no difference, related either to the genotype or to different morphological stages, could be observed; the expression of acid phosphatase varied in a nonsystematic fashion. The isozyme pattern of esterase was related to the genotype as well as to the morphogenic phase.

Acid Phosphatase↗

Modified method for Novacor left ventricular assist device implantation.

We have developed and applied in 7 cases an alternative "orthodromic" technique for Novacor left ventricular assist device implantation. After sternotomy, the pocket is tailored, dividing the insertion of the diaphragm to the lower ribs, for easier bleeding control. On cardiopulmonary bypass, the aorta is cross-clamped and cardioplegia administered. Apical cannulation is performed first on a dry, still field. The device is then easily deaired, with blood flowing in the physiologic direction. The aorta is declamped and the outflow conduit is anastomosed. Before the suture is tied, the final deairing is obtained. This technique allows extreme precision in apical cannulation, easier control of bleeding, and accurate deairing of the pump. The ischemic time is short and damage to the right ventricle negligible.

Heart-Assist Devices↗

Use of the radial artery for myocardial revascularization.

BACKGROUND: The radial artery was first used as a coronary graft by Carpentier and associates in 1973 but, due to the disappointing results, it was abandoned. In 1992 its revival coincided with the widespread use of calcium-channel blockers in cardiovascular surgery, in the belief they could prevent spasm. METHODS: From January 1993 to October 1995 we operated on 109 patients for myocardial revascularization employing the radial artery with two different surgical techniques: in 95 patients (group 1) it was "pretreated" by opening its fascia after a gentle hydrostatic dilation and then anastomosed to the aorta; in 14 patients (group 2) it was branched to another conduit. We had two operative deaths (1.82%). RESULTS: At a mean interval of 532.42 days 105 patients are still alive, 2 (1.86%) having died of abdominal tumors. Fifty-six patients (52.33%) underwent angiography at a mean interval of 334.42 days: the patency of the radial artery was 88.88% in group 1 and 62.50% in group 2. Indications and contraindications are discussed. CONCLUSIONS: The radial artery is an easily manageable conduit whose early patency is very promising, although a longer follow-up is mandatory.

Adult↗

Effect of different interventions on heart rate variability after heart transplantation: non-autonomic vs autonomic factors.

1. The human transplanted heart is initially denervated, hence any fluctuation present in the RR interval variability can be either due to reacquired innervation, or to the effect of some non autonomic activity, such as a direct effect of respiration on atrial (sinus node) stretch. 2. In order to distinguish between sympathetic, vagal and non autonomic factors we examined the effects of various physical and pharmacologic manoeuvres on the respiratory and non-respiratory components of heart rate variability. 3. We found that sinusoidal neck suction appears a useful, noninvasive tool to characterise the relative importance of the different factors, which can influence heart rate variability in the transplanted heart.

Autonomic Nervous System↗

Determinants of heart rate variability in heart transplanted subjects during physical exercise.

Respiratory sinus arrhythmia has been described in heart transplanted subjects. In order to investigate the mechanisms involved in the generation of this condition in the transplanted heart and its evolution after surgery, graded exercise was performed (0-75 W in 25 W steps) on a cycle ergometer by 41 subjects (mean age 44 years) who had undergone heart transplantation 28 months (range 3-60) earlier and by six age matched-control subjects. R-R interval, respiratory signal, O2 consumption (VO2) and CO2 production (VCO2) were measured. Respiratory sinus arrhythmia was assessed by the autoregressive power spectrum of the R-R interval and respiration. All subjects reached the anaerobic threshold (heart transplants: 60% at 50 W, 40% at 75 W Controls: 150 W). In control subjects, the respiratory sinus arrhythmia was higher than in heart transplanted subjects (5.80 +/- 0.30 vs 1.45 +/- 0.16 1n ms2) and it decreased significantly (4.66 +/- 0.30 1n ms2, P < 0.05) during exercise, despite the increase in breathing rate and depth. When, the group of heart transplanted subjects was considered as a whole, respiratory sinus arrhythmia was found to be present in all conditions. It significantly increased at 25 W (from 1.45 +/- 0.16 to 2.00 +/- 0.17 1n ms2, P < 0.01), then significantly fell below baseline during recovery (to 0.97 +/- 0.23 1n ms2, P < 0.01). Multiple regression analysis showed that a linear combination of heart rate (inverse correlation) and VO2 (direct correlation) together with months having passed since transplantation surgery, could explain the observed changes in heart rate during exercise (multiple regression: r = 0.658, P < 0.0001). In five long-term transplanted subjects, non respiratory-related low frequency (0.1 Hz) waves were present on the R-R spectrum, but respiratory sinus arrhythmia is also present in the recently transplanted heart and depends on the opposing effects of ventilation and heart rate. In a few cases, sympathetic modulation (re-innervation) could not be excluded.

Adult↗