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Biomedical subjects

L Martinelli

Publications and source records attributed to L Martinelli.

At least 73 records · Page 4Linked to original sources
PubMed1994

Non-respiratory components of heart rate variability in heart transplant recipients: evidence of autonomic reinnervation?

1. Although the high-frequency fluctuations in R-R interval (respiratory sinus arrhythmia) observed in heart transplant recipients are not a reliable marker of reinnervation because of a previously shown direct mechanical effect of breathing, the presence of a non-respiration-related low-frequency oscillation reflects rhythms generated outside the heart, and thus could be neurally mediated. 2. To evaluate the presence of reinnervation, the spontaneous variability in R-R interval was investigated, supine and after passive tilting, in 23 heart transplant recipients (age 43 years, range 23-64 years) and in 25 normotensive control subjects by autoregressive spectral analysis of low- and high-frequency spontaneous fluctuations in R-R interval and respiration. The response of R-R interval to amyl nitrite inhalation was also evaluated in five heart transplant recipients and eight control subjects. 3. Detectable low-frequency oscillations, unrelated to respiration, were present in 13/23 heart transplant recipients, particularly in those who were transplanted at least 20 months earlier (11/14). The natural logarithm of the power of low-frequency fluctuations was markedly lower than in control subjects (0.75 +/- 0.21 versus 5.62 +/- 0.20 ms2, P < 0.001). The low-frequency but not the high-frequency fluctuations correlated with time since transplantation (r = 0.44, P < 0.05). The subjects with low-frequency fluctuations showed a sudden decrease in R-R interval with amyl nitrite linearly related to the decrease in mean blood pressure (r > or = 0.94). The slopes obtained in these heart transplant recipients were comparable (although of lower values) with those obtained in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Can power spectral analysis of heart rate variability identify a high risk subgroup of congestive heart failure patients with excessive sympathetic activation? A pilot study before and after heart transplantation.

BACKGROUND AND OBJECTIVES: Autonomic dysfunction seems to be involved in the progression and prognosis of severe congestive heart failure. Parasympathetic activity can still be abnormal 4-8 weeks after haemodynamic improvement by heart transplantation. To identify patients in heart failure with a more pronounced neural derangement and to analyse the changes in sympathetic and parasympathetic activity soon after heart transplantation, spectral indices of heart rate variability were assessed in 30 patients in severe heart failure and in 13 patients after heart transplantation; a group of 15 age-matched subjects served as controls. METHODS AND RESULTS: Heart rate variability was assessed by standard electrocardiography (ECG) in patients in heart failure and by oesophageal ECG in patients after heart transplantation. Compared with controls, the mean RR interval and total power were reduced in heart failure. The 30 patients showed two different patterns of heart rate variability: in 14 no power was detected in the low frequency band (0.03-0.15 Hz) (LF) and total power was mainly concentrated in the high frequency band (0.15-0.45 Hz) (HF), whereas in the remaining 16 patients power in the LF band was increased and power in HF band was reduced compared with the controls. Patients with undetectable LF had a lower mean RR interval and total power (745(25) v 864(36) ms, p < 0.05; 118(16) v 902(202) ms2, p < 0.001), higher concentration of plasma noradrenaline (635(75) v 329(54) pg/ml, p < 0.05), and worse clinical status and prognosis (4 deaths v no deaths at 6 month follow up) than patients with a dominant LF band. In the post-transplant patients both the mean PP interval of the remnant atrium and total power resembled results in the patients with heart failure; in 7 of the 13 post-transplant patients no power was detectable in the LF band: when both HF and LF power were present the results resembled those in the 16 patients in heart failure. CONCLUSIONS: These data suggest that in more advanced stages of congestive heart failure, power spectral analysis of heart rate variability allows identification of a subgroup of patients with higher sympathetic activation and poorer clinical status who are at major risk of adverse events. In the short term after cardiac transplantation the spectral profile of the rhythm variability of the remnant atrium was not improved, suggesting that parasympathetic withdrawal and sympathetic hyperactivity persist, despite the restoration of ventricular function.

Echocardiography, Transesophageal↗
PubMed1994

[The noninvasive demonstration of functional reinnervation after heart transplantation].

Although RR interval variability appears to be an ideal method for assessing reinnervation after heart transplantation, it has been shown that respiratory sinus arrhythmia is caused by the mechanical effect of respiration on the right atrium. The neck-suction induces heart rate changes only by means of nervous reflex and its hemodynamic effect is local and hence appears as a useful method for assessing reinnervation. We tested the presence of autonomic reinnervation in 18 heart transplant recipients, compared to 12 donor-age-matched controls. We measured the power of RR interval low- (LF, around 0.1 Hz) and respiratory fluctuations (HF) before and during rhythmic neck-suction stimulation at 0.1 Hz and at a frequency (0.20 Hz) similar to, but distinct from, that of respiration (controlled at 0.25 Hz), before and during 0.04 mg/kg atropine infusion, using autoregressive spectral analysis of RR interval, respiration and neck pressure signals. The relationship between pairs of signals at each frequency was quantitatively assessed by bivariate coherence function. All transplanted subjects showed low-amplitude HF, related to respiration. Detectable LF (whose power was lower than in controls: 1.15 +/- 0.39 versus 6.08 +/- 0.27 1n-ms2, p < 0.001), non coherent with respiration, were present in 11/18 transplanted subjects, and correlated with months since transplantation (r = +0.59, p < 0.05). HF neck suction induced the presence of a 0.20 Hz fluctuation in 12/12 controls, distinct from and greater than the 0.25 Hz respiratory component (7.28 +/- 0.26 versus 6.69 +/- 0.74 1n-ms2, p < 0.01); this was not seen in any of the transplanted subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Aortic dissection. Prevalence, cause, and results of late reoperations.

From January 1977 to September 1992, 143 patients underwent an emergency operation for type A acute aortic dissection. Because of the location of the intimal tear, the replacement of the ascending aorta was extended to the transverse arch in 42 patients (29.3%). One hundred ten patients (78%) survived the operation. During the same period, 32 patients had to be reoperated on once (n = 24) twice (n = 6), or three times (n = 2) for a total of 42 reoperations. Nineteen patients had had the initial repair in our institution, and 13 had been operated on elsewhere. Reoperation was indicated for aortic valve disease (n = 4), recurring dissection (n = 7) threatening aneurysmal evolution of a persisting dissection (n = 28), or false aneurysm (n = 3). The redo procedure involved the aortic root and/or ascending aorta in 15 cases (group I), the transverse arch alone in 7 cases (group II), the transverse arch and the descending aorta or the descending aorta alone in 10 cases (group III), or the thoracoabdominal aorta in 10 cases (group IV). The risk factors for reoperation have been analyzed in the 110 survivors initially operated on in our institution. Seven of 18 patients with Marfan's syndrome (38.8%) versus 12 of 92 without Marfan's syndrome (13%) were reoperated on (p = 0.023). None of the 30 patients surviving arch replacement at initial repair required a reoperation, versus 19 of 80 (23.7%) patients surviving a replacement limited to the ascending aorta (p = 0.013). The overall mortality rate of reoperation was 21.8% (7/32) with a risk of 16.6% (7/42) at each procedure (group I, 13.3%; group II, 0%; group III, 20%; group IV, 30%). Hospital mortality was influenced by emergency operation (5/10) (p < 0.005) and thoracoabdominal replacement (3/10) (p < 0.035). The late survivals after reoperation are 65.1% +/- 17.6% at 1 year and 55% +/- 19.63% at 5 years (Kaplan-Meier, confidence interval 95%). The late survivals, after the initial repair, of the patients undergoing reoperation are 89.6% +/- 11.0%, 79.3% +/- 14.7%, 53.9% +/- 18.1%, and 35.9% +/- 21.8% at 1, 5, 10, and 12 years, respectively. In conclusion, aortic dissection is an evolving process that may require one or several reoperations after the initial repair. At initial emergency operation, the resection of the entry site, when located on or extending to the transverse arch, has reduced the risk of reoperation, in our experience. Elective reoperation must be considered before the occurrence of complications, especially in patients with Marfan's syndrome.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1994

Coexpression of aspartic proteinases and human leukocyte antigen-DR in human transplanted lung.

Aspartic proteinases have recently been shown to be implicated in antigen processing. We explored the expression of two aspartic proteinases, cathepsins E and D, and of human leukocyte antigen-DR (HLA-DR) molecules in a consecutive series of 80 transbronchial biopsies from transplanted lungs. For controls, we studied five normal donor lungs (not suitable for transplantation on account of thoracic trauma) and macroscopically normal areas of three cancer-affected lungs. Two of the five unsuitable donor lungs showed minimal inflammatory changes. Macroscopically normal samples from the three cancerous lungs showed mild and focal inflammatory infiltrates. In histologically normal lungs, HLA-DR expression was limited to professional antigen-presenting cells. Macroscopically normal lung samples with minimal inflammatory changes from both donor and cancer lungs showed variable HLA-DR expression by alveolar and bronchial epithelial cells and by endothelial cells. All transplanted lung biopsies showed HLA-DR expression by epithelial (alveolar and bronchial) and endothelial cells, with a trend for increased positivity in acute rejection. Cathepsin E was restricted to Clara and to rare bronchus-associated lymphoid tissue-related epithelial cells in histologically normal lung samples, whereas minimal de novo cathepsin E expression by rare alveolar pneumocytes was noted in control lung samples exhibiting minimal inflammatory changes. In all transplanted lung biopsies, cathepsin E was diffusely expressed de novo by hyperplastic alveolar epithelial cells, regardless of the presence or degree of rejection. Cathepsin D was expressed only by alveolar macrophages and by ciliated bronchial cells of normal, minimally inflamed, and transplanted lungs. In transplanted lung, Clara cells and several hyperplastic alveolar pneumocytes coexpressed HLA-DR and cathepsin E, whereas all alveolar macrophages and a few ciliated cells coexpressed cathepsin D and HLA-DR. The present investigation suggests that the de novo expression of cathepsin E and HLA-DR by hyperplastic alveolar pneumocytes of transplanted lung may be crucial for antigen processing and presentation to recipient competent T cells, and thus for the triggering of the immune-inflammatory cascade that leads to rejection.

Acute Disease↗
PubMed1994

[The ergometric test after a heart transplant: its usefulness and limits].

Aim of this study was to analyze the cardiovascular response to graded physical exercise in patients who have undergone cardiac transplantation and to assess the ability of exercise stress testing in early detection of coronary artery disease. We studied 114 transplanted subjects (100 men and 14 women, mean age 46.6 +/- 11.3 years), who performed exercise stress testing 6 months after bypass and then every 6 (+/- 1) months during a 5-year follow-up. Variations of hearth rate (HR), systolic blood pressure (SBP), heart rate-pressure product (RPP) values and exercise stress tolerance were studied both in basal and maximum workload conditions. Mean HR values at basal conditions (103.9 +/- 11.3 b/min at 6 months and 89 +/- 12.7 b/min at 60 months, p < 0.05) and maximum workload tolerance (67.7 +/- 20.4 W at 6 months and 100 +/- 17 W at 60 months, p < 0.05) were significantly different at the beginning and at the end of follow-up. SBP values both at basal conditions and at peak exercise had always been constant. Exercise was stopped for leg muscle fatigue in 92% and dyspnea in 7% of the subjects; isolated T-wave and ST segment changes were found in 29.8% and in 10.5% of the patients respectively, whereas 11.4% exhibited both ST-T variations. Angiographic examination (performed in 80/114 patients) showed significant coronary disease (stenosis > 50%) in 8, coronary atherosclerosis (CAD) of minor degree in 4 and provoked spasm in 2 subjects. In this subgroup exercise stress testing induced ischemic ECG changes (ST segment depression > or = 1 mm) without angina in 1 patient, ST-T segment variations only in 5 and no electrocardiographic alterations (negative tests) in 2 patients. Four subjects with CAD and 1 with coronary spasm induced by angiography showed isolated ST segment and T-wave changes. Our work demonstrated that exercise stress testing plays a relevant role in the study of the denervated heart response to dynamic exercise. The rise in workload tolerated, observed in our population, seems to be related to time elapsed from surgery, improvement in clinical conditions, psychological stability and patient's confidence in his own abilities. The tolerance to exercise 6 months after graft seems to predict the quality of performance in the following tests. Our angiographic results reveal a low sensitivity of the exercise stress test in detecting CAD in this population according to traditional electrocardiographic criteria for myocardial ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Expression of proliferating cell markers in normal and diseased human hearts.

Proliferating cell nuclear antigen (PCNA) myocyte expression and histopathologic features related to its occurrence were investigated in normal and diseased hearts of adult humans using both immunohistochemical and Western blotting techniques. Ki67 Western blotting was also performed in the same samples used for PCNA blotting. Two hundred seventy-one endomyocardial biopsies, and 15 adult, 1 embryonic and 2 fetal hearts were studied. The biopsies were from normal donor hearts (n = 71), patients with cardiomyopathy and myocarditis (n = 64), and patients with transplantation with (n = 106) and without (n = 30) acute rejection of any grade. The 15 hearts were from 1 heart donor, and from patients with cardiomyopathy (n = 5), valvular heart disease (n = 2), ischemic heart disease (n = 4), amyloidosis (n = 1) and transplantation with acute rejection (n = 2). The PCNA labeling index was plotted against myocyte hypertrophy, inflammatory infiltrates and binucleation index. The PCNA labeling index ranged from 2 to 9% in embryonic and fetal hearts. PCNA was expressed by 1 to 2% of myocyte nuclei in 12% of normal heart biopsies, 1 to 5% of myocyte nuclei in 28% of cardiomyopathy and myocarditis biopsies, and by up to 8% of myocyte nuclei in 53% of biopsies of patients with transplantation, independently of the presence and degree of acute rejection. In the latter biopsies and in myocarditis, some inflammatory cells also showed PCNA expression. PCNA positive myocytes were both mono- and binucleated, and there was no correlation between binucleation and PCNA labeling indexes. Ki67 and PCNA blotting confirmed immunohistochemical results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Morphologic changes induced by acetylcholine infusion in normal and atherosclerotic coronary arteries.

Low doses of acetylcholine induce "endothelium-dependent" dilatation in normal coronary arteries and constriction of diseased vessels. This study investigated morphologic changes induced by perfusion of normal and diseased coronary arteries with low and high doses of acetylcholine. Vessels were excised from a series of beating hearts explanted at transplantation for idiopathic dilated cardiomyopathy and coronary artery disease. Coronary arteries from other explanted hearts, perfused with saline solution under similar conditions were taken as controls. Samples were studied using conventional histopathologic and immunohistochemical methods. Coronary arteries were grouped according to presence or absence of histologically detectable structural modifications of any type and extent. Low doses of acetylcholine induced changes in all but 1 structurally diseased coronary artery, whereas no change was induced in any but 1 histologically normal coronary artery. High doses of acetylcholine induced contraction changes in both normal and diseased vessels. Changes observed in the wall of the contracted vessels were: (1) endothelial cell contraction with protruding nuclei and detachment of their intercellular junctions with exposure of subjacent collagen to flow, (2) contraction of plaque smooth muscle cells, (3) formation of cushions protruding into vessel lumens causing blunt microchannels. Contraction in both intimal and plaque cells occurred even in diseased vessel segments with intimal denudation. These effects seemed to be dose-dependent in structurally normal vessels because low doses of acetylcholine did not produce any morphologically detectable changes in histologically normal coronary arteries, while low doses of acetylcholine induced similar reactions in vessels affected by both atherosclerosis and subintimal fibrocellular thickening.

Acetylcholine↗
PubMed1993

Emergency and elective cardiac retransplantation.

Among 265 patients transplanted at our Institution, 7 underwent cardiac retransplantation. There were five emergency retransplantations, the indication being graft failure in one case and acute rejection in four cases. Two patients, retransplanted because of acute rejection, had a positive panel reactivity antibody and a negative donor crossmatch. In the rejection cases immunosuppression was enhanced by perioperative plasmapheresis and a postoperative 1-month course of cyclophosphamide. In two cases emergency retransplantations were successfully performed despite a highly positive prospective crossmatch. Two patients underwent elective retransplantations for chronic rejection 12 and 41 months, respectively, after the primary transplants. The overall early and late survival rates are 71% and 57%, respectively, with a mean follow-up of 48.5 months. The early and late mortality for elective retransplantation is zero. Our experience confirms both the high operative risk for emergency retransplantation and the excellent results for elective retransplantation. The use of plasmapheresis and cyclophosphamide allowed us to undertake retransplantation successfully in 2 cases with positive donor crossmatch. Both hyperimmunized patients in our series were retransplanted because of irreversible acute rejection despite a negative crossmatch with the primary donor. The meaning of negative crossmatch in patients with preformed cytotoxic antibodies is therefore questionable.

Adult↗
PubMed1993

Creatine-kinase isoenzyme pattern in colonic infarction consequent to acute aortic dissection. A case report.

Bowel infarction can complicate acute aortic dissection (AAD); in that case early diagnosis, which decreases the high mortality, is often difficult. We report the case of one patient who underwent surgery for AAD and developed a colonic infarction, which was clinically manifest on the 4th postoperative day. However, bowel ischemia was suspected already 48 hours after surgery, on the basis of the suggestive CK pattern and the absence of myoglobin in plasma. Total CK activity reached the highest level only 48 hours after surgery (92,800 U/l); the peak was coincident with LDH, which increased proportionally less; CK-MM constituted 100% of total CK activity. The absence of myoglobin in plasma excluded the presence of rhabdomyolysis. We conclude that such laboratory findings suggest the occurrence of severe bowel ischemia.

Acute Disease↗
PubMed1992

Monitoring by two-dimensional electrophoresis somatic embryogenesis in leaf and petiole explants from Vitis.

A two-dimensional electrophoretic analysis of the total proteins was carried out in Vitis rupestris as model system in order to characterize the different developmental stages--from callus to plantlets--of somatic embryogenesis events in the grapevine. The patterns of callus, embryogenetic callus, somatic embryos and plantlets derived from leaf and petiole explants were compared. Each differentiation step was characterized by specific peptide spots.

Cells, Cultured↗
PubMed1992

Optimization of sampling time for cyclosporine monitoring in transplant patients.

Cyclosporine (CsA) dosing is based on CsA plasma or blood concentrations measured 12 to 24 hours after drug administration (trough levels). This study evaluated the relationship between the timing of CsA concentrations and subsequent pharmacokinetic parameters to predict an optimal sampling period. Plasma samples were obtained from 22 patients before their morning dose of CsA and at 2, 4, 6, 8, 10, and 12 hours after the dose on the 7th and on the 21st day after heart transplantation. The plasma samples were assayed by both HPLC and FPIA. The Cmax for CsA was achieved over a period ranging from 2 to 6 hours (mean/median = 4.7/4.0) during the day 7 and the day 21 studies. The mean (+/- SD) half-life was 3.2 (1.0) hours on day 7 and 2.9 (1.1) hours on day 21, (P > 0.05); the mean apparent oral clearance was 276 (117) L/hr on the day 7 and 269 (209) L/hr on day 21, (P > 0.05). When CsA plasma concentration by either FPIA and HPLC was monitored, the drug concentration best correlated with AUC was found to correspond to the plasma samples taken 4 to 8 hours after drug administration. The authors conclude that through blood sampling for therapeutic drug monitoring of CsA is not optimal, and that further studies are necessary to correlate concentration monitoring during the dosing interval with pharmacologic and toxicologic parameters.

Adolescent↗
PubMed1992

Right ventricular failure after heart transplantation: relationship with preoperative haemodynamic parameters.

The prevalence of right ventricular failure after orthotopic heart transplantation, evaluated in 196 patients, was 11.7%, as assessed by the presence during the first postoperative month of right atrial pressure > 10 mm Hg. Two deaths, related to refractory right ventricular failure, were observed within the first month, both in subjects with preoperative pulmonary arteriolar resistances > 5 Wood Units. The haemodynamic profile after heart transplantation showed a significant decrease (P < 0.01) and an early normalization of pulmonary arterial pressure, pulmonary wedge pressure and pulmonary arteriolar resistances, while right atrial pressure slowly decreased until the third month. In a long-term analysis of survival (death within 1 year) the probability of death was significantly related to the values of right atrial pressure and cardiac index during the first month after heart transplantation. Otherwise, the presence of elevated values of right atrial pressure did not show a significant correlation with the echocardiographic right ventricular end-diastolic diameter nor with the presence of right bundle branch block. The careful selection of patients referred for the cardiac transplantation (mean value of pulmonary arteriolar resistances in the evaluated subjects was 2.5 +/- 1.5 Wood Units) improves the probability of avoiding the appearance of severe right ventricular failure in the postoperative period in most cases. The best predictor of right ventricular failure remains to be clearly identified.

Blood Pressure↗
PubMed1992

Endomyocardial biopsy of normal donor hearts before cardiac transplantation. A morphological and morphometrical study in 97 cases.

Endomyocardial biopsies from 97 normal donor hearts were examined. Morphometric analysis showed: mean myocyte diameter 22.21 +/- 6.93 mu, mean nuclear dimension 7.32 +/- 2.33 mu, mean nuclear/sarcoplasmic ratio 0.33 +/- 0.02. 31 biopsies showed enlarged myocytes (mean diameter 31.65 +/- 3.98 mu) with increased nuclear size (mean 10.45 +/- 1.39 mu), but preserved nuclear/sarcoplasmic ratio (mean 0.33 +/- 0.01). The mean age of these latter subjects was significantly higher. Endocardial thickness mean value was 17.73 +/- 4.58 mu, but in 28 cases the value exceeded the considered upper normal limit of 20 mu. Interstitial mononuclear cells were rare and randomly present. Interstitial fibrosis was observed in 15% and focal fibrosis in 27% of cases. Our results show that histology of biopsies from clinically normal hearts can widely vary, sometime overriding the pathologic boundaries. These apparently "benign" abnormalities should be kept in mind when specific pathologic substrates of cardiac diseases have to be defined.

Adolescent↗