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1.
Int J Cardiol ; 409: 132202, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38795975

ABSTRACT

BACKGROUND: In patients with Hypertrophic Cardiomyopathy (HCM) S-ICD is usually the preferred option as pacing is generally not indicated. However, limited data are available on its current practice adoption and long-term follow-up. METHODS: Consecutive HCM patients with S-ICD implanted between 2013 and 2021 in 3 international centers were enrolled in this observational study. Baseline, procedural and follow-up data were regularly collected. Efficacy and safety were compared with a cohort of HCM patients implanted with a tv-ICD. RESULTS: Seventy patients (64% males) were implanted with S-ICD at 41 ± 15 years, whereas 168 patients with tv-ICD at 49 ± 16 years. For S-ICD patients, mean ESC SCD risk score was 4,5 ± 1.9%: 25 (40%) at low-risk, 17 (27%) at intermediate and 20 (33%) at high-risk. Patients were followed-up for 5.1 ± 2.3 years. Two patients (0.6 per 100-person-years, vs 0.4 per 100 person-years with tv-ICD, p = 0.45) received an appropriate shock on VF, 17 (24%) were diagnosed with de-novo AF. Inappropriate shocks occurred in 4 patients (1.2 per 100-person-years, vs 0.9 per 100 person-years with tv-ICD, p = 0.74), all before Smart-Pass algorithm implementation. Four patients experienced device-related adverse events (1.2 per 100-person-years, vs 1 per 100 person-years with tv-ICD, p = 0.35%). CONCLUSIONS: S-ICDs were often implanted in patients with an overall low-intermediate ESC SCD risk, reflecting both the inclusion of additional risk markers and a lower decision threshold. S-ICDs in HCM patients followed for over 5 years showed to be effective in conversion of VF and safe. Greater scrutiny may be required to avoid overtreatment in patients with milder risk profiles.


Subject(s)
Cardiomyopathy, Hypertrophic , Defibrillators, Implantable , Humans , Cardiomyopathy, Hypertrophic/therapy , Male , Female , Middle Aged , Adult , Follow-Up Studies , Treatment Outcome , Time Factors , Aged , Patient Selection , Death, Sudden, Cardiac/prevention & control , Death, Sudden, Cardiac/epidemiology
2.
Clin Transl Oncol ; 22(6): 900-907, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31555967

ABSTRACT

BACKGROUD: Synergistic combinations between BRAF and MEK inhibitors, such as dabrafenib plus trametinib, vemurafenib plus cobimetinib or encorafenib plus binimetinib, represent the current standard of care in metastatic or locally advanced BRAF V600 mutated malignant melanomas (MM). However, no studies explored the direct head-to-head comparison between the three different combinations. In this paper, we performed a network meta-analysis to evaluate their efficacy in terms of overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and safety profile. METHOD: We performed a systematic review of the literature about published first line trials of BRAF and MEK inhibitors doublets in advanced mutated malignant melanoma. We compared then the results with an adjusted indirect analysis of randomized-controlled trials. Our primary survival outcome was OS. Secondary endpoints were PFS, ORR, G3-4 toxicities described in at least 5% of patients in experimental arms. RESULTS: We identified three phase-3 trials: coBRIM (vemurafenib and cobimetinib), COMBI-v (dabrafenib and trametinib) and Columbus study (encorafenib and binimetinib) for a total of 1230 included patients. The control arm was vemurafenib in all studies. The indirect comparison revealed no statistically differences for OS, PFS and ORR across trials, while safety profile differed between the three couples of agents. CONCLUSION: This indirect adjusted meta-analysis suggests a similar efficacy and a slightly different safety profile, related to specific molecular properties of the three different BRAF and MEK inhibitors currently approved in the management of advanced MM.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Melanoma/drug therapy , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Antineoplastic Agents/therapeutic use , Humans , Melanoma/genetics , Melanoma/pathology , Mutation , Network Meta-Analysis , Proto-Oncogene Proteins B-raf/genetics , Treatment Outcome
5.
Eur J Heart Fail ; 3(2): 197-202, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11246057

ABSTRACT

BACKGROUND: A profound autonomic unbalance is present in heart failure: its correlation with the etiology of the disease has never been investigated. AIMS: We characterized the sympatho-vagal balance and autonomic responsiveness of 42 patients (21 with ischemic heart failure, 21 with idiopathic dilated cardiomyopathy). Patients had comparable NYHA class, ejection fraction, exercise pVO(2), exercise ventilatory response, incidence of beta-blocking treatment. None showed periodic breathing or nocturnal arterial desaturation. METHODS: Heart rate variability was assessed in the time and frequency domain during: (1) 10 min of quiet supine resting and free breathing; (2) 10 min of regular breathing at a frequency of 20 acts/min (=parasympathetic stimulus); and (3) 10 min of active standing (=sympathetic stimulus). The ratio of the low- to high-frequency components of each autospectrum obtained in the frequency domain (LF/HF) was used as an index of sympathovagal balance. RESULTS: Patients with ischemic heart failure had a greater baseline sympathetic activation (higher LF/HF) than those with idiopathic dilated cardiomyopathy, maintaining some parasympathetic responsiveness as well (reduced LF/HF with regular breathing). CONCLUSIONS: There is a distinct autonomic control according to the etiology of heart failure, a finding that may help understanding its pathophysiology, and could be useful in the clinical management of patients.


Subject(s)
Autonomic Nervous System/physiopathology , Coronary Disease/physiopathology , Heart Failure/physiopathology , Heart/innervation , Sympathetic Nervous System/physiopathology , Vagus Nerve/physiopathology , Aged , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/physiopathology , Chronic Disease , Coronary Disease/diagnosis , Female , Heart Failure/diagnosis , Hemodynamics/physiology , Humans , Male , Middle Aged , Prognosis
6.
J Neurosci Res ; 63(2): 214-23, 2001 Jan 15.
Article in English | MEDLINE | ID: mdl-11169632

ABSTRACT

Recovery after peripheral nerve injury depends not only on the amount of reinnervation, but also on its accuracy. The rat sciatic nerve was subjected to an 8 mm long gap lesion repaired either by autograft (AG, n = 6) or tubulization with impermeable silicone tube (SIL, n = 6) or permeable tube of poly-L-lactide-epsilon-caprolactone (PLC, n = 8). Recordings of the compound muscle action potential (CMAP) from gastrocnemius (mGC), tibialis anterior (mTA) and plantar (mPL) muscles were performed 90 days after injury to assess the amount of muscle reinnervation. The CMAP amplitude achieved in mGC, mTA and mPL was similar in after nerve autograft (39%, 42%, 22% of control values) and PLC tube implantation (37%, 36%, 24%) but lower with SIL tube (29%, 30%, 14%). The nerve fascicles projecting into each of these muscles were then transected and retrograde tracers (Fluoro Gold, Fast Blue, DiI) were applied to quantify the percentage of motoneurons with single or multiple branches to different targets. The total number of labeled motoneurons for the three muscles did not differ in autografted rats (1186 +/- 56; mean +/- SEM) with respect to controls (1238 +/- 82), but was reduced with PLC tube (802 +/- 101) and SIL tube (935 +/- 213). The percentage of neurons with multiple projections was lower after autograft and PLC tube (6%) than with SIL tube (10%). Considering the higher CMAP amplitude and lower number of neurons with multiple projections, PLC nerve conduits seem superior to SIL tubes and a suitable alternative to autografts for the repair of long gaps.


Subject(s)
Muscle, Skeletal/innervation , Nerve Regeneration/physiology , Peripheral Nerves/transplantation , Prostheses and Implants , Recovery of Function/physiology , Animals , Anterior Horn Cells/pathology , Caproates/pharmacology , Cell Count , Female , Fluorescent Dyes/pharmacology , Lactones/pharmacology , Muscle, Skeletal/physiology , Peripheral Nerve Injuries , Peripheral Nerves/physiology , Polyesters/pharmacology , Rats , Rats, Wistar , Sciatic Nerve/injuries , Sciatic Nerve/physiology , Sciatic Nerve/transplantation , Silicones/pharmacology , Transplantation, Autologous
7.
Clin Sci (Lond) ; 98(5): 545-51, 2000 May.
Article in English | MEDLINE | ID: mdl-10781385

ABSTRACT

The objective of the present study was to determine the variability of the arterio-venous O(2) concentration difference [C(a-v)O(2)] at anaerobic threshold and at peak oxygen uptake (VO(2)) during a progressively increasing cycle ergometer exercise test, with the purpose of assessing the possible error in estimating stroke volume from measurements of VO(2) alone. We sampled mixed venous and systemic arterial blood every 1 min during a progressively increasing cycle ergometer exercise test and measured, in each blood sample, haemoglobin concentration and blood gas data. Ventilation, VO(2) and CO(2) uptake were also measured continuously. We studied 40 patients with normal haemoglobin concentrations and with stable heart failure due to ischaemic or idiopathic cardiomyopathy. Mean values (+/-S.D.) for C(a-v)O(2) were 7.8+/-2.6, 13.0+/-2.4 and 15. 0+/-2.7 ml/100 ml at rest, anaerobic threshold and peak VO(2) respectively. The patients with heart failure were divided into classes according to their peak VO(2). Classes A, B and C contained patients with peak VO(2) values of>20, 15-20 and 10-15 ml.min(-1). kg(-1) respectively. At anaerobic threshold, C(a-v)O(2) was 12.3+/-1. 3, 13.1+/-2.7 and 13.5+/-2.6 ml/100 ml for classes A, B and C respectively (class A significantly different from classes B and C; P<0.05). At peak exercise C(a-v)O(2) was 13.6+/-1.4, 15.6+/-2.5 and 15.4+/-3.2 ml/100 ml for classes A, B and C respectively (class A significantly different from classes B and C; P<0.05). Stroke volume was estimated for each subject using the mean values of the measured C(a-v)O(2) in each functional class and individual values of VO(2) and heart rate using the Fick formulation. The average difference between the stroke volume estimated from mean C(a-v)O(2) and that obtained using the patient's actual C(a-v)O(2) value was 9.2+/-9.7, 1.0+/-8.8 and -0.2+/-6.1 ml at anaerobic threshold, and -1.9+/-11.3, 0.9+/-10.0 and -2.3+/-8.5 ml at peak exercise, in classes A, B and C respectively. Among the various classes, the most precise estimation of stroke volume was observed for class C patients. We conclude that stroke volume during exercise can be estimated with the accuracy needed for most purposes from measurement of VO(2) at the anaerobic threshold and at peak exercise, and from population-estimated mean values for C(a-v)O(2) in heart failure patients.


Subject(s)
Heart Failure/physiopathology , Stroke Volume/physiology , Adult , Aged , Anaerobic Threshold/physiology , Cardiac Output/physiology , Exercise/physiology , Exercise Test , Female , Heart Failure/blood , Humans , Lactic Acid/blood , Male , Middle Aged , Oxygen/blood , Oxygen Consumption/physiology
8.
J Clin Neurophysiol ; 16(6): 566-73, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10600024

ABSTRACT

This prospective study was planned to assess whether quantitative EEG (qEEG) can give an estimate of the timing of achievement of three endpoints (loss of activities of daily living, incontinence, and death) in 72 consecutive patients (53 females, 19 males; mean age, 70.8) affected with probable Alzheimer's disease, as defined according to the NINCDS-ADRDA criteria. Power-weighted, log-transformed relative values of the four conventional EEG bands were considered in a central-posterior temporal region for each hemisphere. The hypothesis was tested by the lifereg procedure of the Statistical Analysis System package (first significance level accepted, P < or = 0.01). Because patients were in different stages of the disease, the statistical analysis was performed in the entire group as well as in the subgroup of 41 patients (mean age, 69.6) with mild dementia (scoring 3 or 4 on the global deterioration scale). In the whole group, the loss of activities of daily living was predicted by delta power in either side (P = 0.01), incontinence was predicted by alpha power in the right side (P < 0.01), whereas the statistical significance was not reached for death (P < 0.05). In the subgroup of mild demented patients, the loss of activities of daily living was predicted by delta power in the left side (P = 0.01), incontinence by both delta (P < 0.01) and alpha (P < 0.001) power in the right side, and death was not significantly predicted (P = 0.08). Quantitative EEG is a low-cost, discomfort-free technique which may be used to obtain information on the timing of disease evolution. The results showed in mild Alzheimer's disease appear especially interesting to attempt a prediction of the future time course of the disease from its beginning.


Subject(s)
Alzheimer Disease/physiopathology , Electroencephalography , Activities of Daily Living , Aged , Aged, 80 and over , Alzheimer Disease/complications , Alzheimer Disease/mortality , Disease Progression , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Statistical Distributions , Surveys and Questionnaires , Urinary Incontinence/etiology
9.
Clin Neurophysiol ; 110(10): 1831-7, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10574298

ABSTRACT

OBJECTIVE: The present study was undertaken to investigate whether a synoptic parameter of quantitative EEG (qEEG), such as the power spectral profile, may be used as a simple marker to stage Alzheimer's disease (AD) in the clinical setting. METHODS: To this purpose, the qEEG spectral profile was examined in 48 patients (mean age: 73 years) with probable (NINCDS-ADRDA criteria) AD, who were divided into 4 groups, according to the Global Deterioration Scale (GDS; score: 3-6). The spectral profile of each patient was expressed by the relative power of seven frequency bands (2-3.5, 4-5.5, 6-7.5, 8-9.5, 10-11.5, 12-13.5, 14-22.5 Hz). Mean values in each of the four GDS groups as well as in a control group of 18 healthy elderly subjects underwent multivariate analysis of variance. RESULTS: A normally shaped but shifted-to-the left spectral profile was found in GDS 3 group, whereas a reduced background rhythm with various increase in slow activity power characterized both GDS 4 and 5 groups. Finally, an 'exponential asymptotic' profile with the highest power in the lowest frequencies was the hallmark of GDS 6 group. Overall, the 4-5.5 Hz and the 10-11.5 Hz band powers showed the highest statistical significance in differentiating the patient groups between one another and from controls (P < 0.0001). CONCLUSIONS: These data show that spectral profile is a very simple parameter which can be used to stage the disease on a pathophysiological basis.


Subject(s)
Alzheimer Disease/diagnosis , Alzheimer Disease/physiopathology , Electroencephalography , Aged , Aged, 80 and over , Disease Progression , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Severity of Illness Index
10.
Biomaterials ; 20(16): 1489-500, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10458562

ABSTRACT

We compared regeneration and functional reinnervation after sciatic nerve resection and tubulization repair with bioresorbable guides of poly(L-lactide-co-epsilon-caprolactone) (PLC) and permanent guides of polysulfone (POS) with different degrees of permeability, leaving a 6 mm gap in different groups of mice. Functional reinnervation was assessed to determine recovery of motor, sensory and sweating functions in the hindpaw during four months postoperation. Highly permeable PLC guides allowed for faster and higher levels of reinnervation for the four functions tested than impermeable or low-permeable PLC guides, while semipermeable 30 and 100 kDa POS tubes yielded very low levels of reinnervation. The regeneration success rate was higher with PLC than with POS tubes. Morphometrical analysis of cross-sectional nerves under light microscopy showed the highest number of regenerated myelinated fibers at mid tube and distal nerve in high-permeable PLC guides. Impermeable PLC guides allowed slightly worse levels of regeneration, while low-permeable PLC guides promoted neuroma and limited distal regeneration. The lowest number of regenerated fibers were found in POS tubes. In summary, highly permeable bioresorbable PLC guides offer a suitable alternative for repairing long gaps in injured nerves, approaching the success of autologous nerve grafts.


Subject(s)
Biocompatible Materials/pharmacology , Nerve Regeneration/drug effects , Polyesters/pharmacology , Polymers/pharmacology , Sulfones/pharmacology , Absorbable Implants , Animals , Biopolymers/pharmacology , Female , Materials Testing , Mice , Microscopy, Electron, Scanning , Sciatic Nerve/pathology , Sciatic Nerve/physiology
11.
Biophys Chem ; 76(3): 185-98, 1999 Feb 22.
Article in English | MEDLINE | ID: mdl-17027464

ABSTRACT

We present a model to describe the physics of chemoreception in processes determined by competitive ligand binding. Our model describes the competition between various populations, such as ligands vs. blockers and receptors vs. decoys, in protein activation when diffusion is rate-determining. Full spatio-temporal solutions can be obtained numerically. The model structure is kept simple enough as to permit its easy generalization to describe a large subset of the manifold of possible situations occurring in nature. The power and simplicity of the proposed method are exhibited through the solution of several examples which are discussed in detail.

12.
Am Heart J ; 135(3): 503-9, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9506337

ABSTRACT

BACKGROUND: Mechanisms of restenosis after percutaneous transluminal coronary angioplasty (PTCA) have not been defined yet. Experimental studies have shown that thrombin, by stimulating platelet growth factor secretion and smooth muscle cell proliferation, can play a major role. METHODS AND RESULTS: In 34 patients with single-vessel coronary disease undergoing PTCA, thrombin activity was evaluated through serial fibrinopeptide A (FPA) plasma determinations. Samples were performed before PTCA, immediately after and 24 hours, 72 hours, and 6 months later. Patients were grouped according to the development (group 1, n = 13) or nondevelopment (group 2, n = 21 ) of restenosis at a 6-month angiographic control. No difference in the two groups was found concerning baseline FPA values. In patients in group 1, soon after PTCA higher FPA levels (27.3 +/- 13.7 ng/ml) than those in group 2 (9.2 +/- 5.6 ng/ml; p < 0.05 vs pre-PTCA, and p < 0.01 between the two groups) were observed. No differences in FPA levels were detected at the other steps between the two groups. CONCLUSION: Our data suggest that thrombin plays a role in the process of restenosis after PTCA; acute FPA response to the procedure seems to have a predictive value.


Subject(s)
Angioplasty, Balloon, Coronary , Coronary Disease/physiopathology , Coronary Disease/therapy , Thrombin/physiology , Aged , Angina, Unstable/physiopathology , Angina, Unstable/therapy , Coronary Angiography , Female , Fibrinopeptide A/analysis , Humans , Male , Middle Aged , Myocardial Ischemia/physiopathology , Myocardial Ischemia/therapy , Recurrence , Time Factors
13.
Cardiologia ; 42(7): 743-50, 1997 Jul.
Article in Italian | MEDLINE | ID: mdl-9270180

ABSTRACT

The aim of the study was to estimate the relative importance of the Bohr effect and redistribution of blood from the non-exercising tissues on the arterial-venous oxygen content differences across the exercising extremities and the central circulation in patients with chronic heart failure; the relationship among femoral vein, systemic and pulmonary artery oxygen partial pressure and hemoglobin saturation was determined. It has been reported that the maximal reduction in femoral vein pO2 precedes peak oxygen consumption and lactic acidosis threshold in patients with chronic heart failure and normal subjects during exercise. The increase in oxygen consumption at work rates above lactic acidosis threshold, therefore, must be accounted for by increase in blood flow in the exercising muscles and right-ward shift on the oxyhemoglobin dissociation curve. Since the total cardiac output increase is blunted in patients with chronic heart failure, diversion of blood flow from non-exercising to exercising tissues may account for some of the increase in muscle blood flow. Ten patients with chronic heart failure performed a progressively increasing leg cycle ergometer exercise test up to maximal effort while measuring ventilation and gas concentration for computation of oxygen uptake and carbon dioxide production, breath-by-breath. Blood samples were obtained, simultaneously, from systemic and pulmonary arteries and femoral vein at rest and every minute during exercise to peak oxygen consumption. At comparable levels of exercise, femoral vein pO2, hemoglobin saturation and oxygen content were lower than in the pulmonary artery. PCO2 and lactate concentration increased steeply in femoral vein and pulmonary artery blood above lactic acidosis threshold (due to lactic acid build-up and buffering), but more steeply in femoral vein blood. These increases allowed femoral vein oxyhemoglobin to dissociate without a further decrease in femoral vein pO2 (Bohr effect). The lowest femoral vein pO2 (16.6 +/- 3.9 mmHg) was measured at 66 +/- 22% of peak VO2 and before the lowest oxyhemoglobin saturation was reached. Artero-venous oxygen content difference was higher in the femoral vein than in the pulmonary artery; this difference became progressively smaller as oxygen consumption increased. "Ideal" oxygen consumption for a given cardiac output (oxygen consumption expected if all body tissues had maximized oxygen extraction) was always higher than the measured oxygen consumption; however the difference between the two was lost at peak exercise. This difference positively correlated with peak oxygen consumption and cardiac output increments at submaximal but not at maximal exercise. In conclusion, femoral vein pO2 reached its lowest value at a level of exercise at or below the lactic acidosis threshold. Further extraction of oxygen above the lactic acidosis threshold was accounted for by a right shift of the oxyhemoglobin dissociation curve. The positive correlation between increments of cardiac output vs "ideal" and measured oxygen consumption suggests a redistribution of blood flow from non-exercising to exercising regions of the body. Furthermore the positive correlation between exercise capacity and the difference between "ideal" and measured oxygen consumption suggests that patients with the poorer function have the greater capability to optimize blood flow redistribution during exercise.


Subject(s)
Exercise , Heart Failure/metabolism , Oxygen/blood , Aged , Female , Humans , Male , Middle Aged
14.
Am J Cardiol ; 79(8): 1120-4, 1997 Apr 15.
Article in English | MEDLINE | ID: mdl-9114779

ABSTRACT

In chronic heart failure, oxygen delivery during exercise is impaired mainly because of failure of cardiac output to increase normally. Compensatory mechanisms are hemoglobin concentration increase, right-ward shift in the oxyhemoglobin dissociation curve, and blood flow redistribution from the nonexercising organs to the exercising muscles.


Subject(s)
Cardiomyopathy, Dilated/metabolism , Exercise , Heart Failure/metabolism , Muscle, Skeletal/metabolism , Oxygen Consumption , Aged , Cardiomyopathy, Dilated/complications , Chronic Disease , Heart Failure/etiology , Humans , Middle Aged
15.
Biomaterials ; 17(10): 959-62, 1996 May.
Article in English | MEDLINE | ID: mdl-8736729

ABSTRACT

A new conduit made with a bioabsorbable copolymer, poly (L-lactide-co-6-caprolactone), was evaluated in an animal model as a guide for nerve regeneration. The conduit had an inner diameter of 1.3 mm and a wall thickness of 175 microns. Segments of length 1.2 cm were interposed between the proximal and distal stumps of transected ischiatic nerves in Wistar rats, bridging a nerve gap of 1 cm. All of the procedure was performed under general anaesthesia using microsurgical techniques. Controls were performed at 1, 3 and 6 months and it was demonstrated that the conduit was still undamaged after 30 d. Progressive signs of degradation appeared at 90 and 180 d. Nerve regeneration in the lumen was effective as confirmed by histological and electron microscopical investigations. These preliminary results emphasize the interesting properties of the conduit with regard to the achievement of a neural prosthesis.


Subject(s)
Nerve Regeneration , Peripheral Nerves/physiology , Peripheral Nerves/surgery , Polyesters , Prostheses and Implants , Absorption , Animals , Biocompatible Materials , Evaluation Studies as Topic , Male , Rats , Rats, Wistar
16.
J Appl Physiol (1985) ; 80(2): 623-31, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8929607

ABSTRACT

Arteriovenous O2 content (a-vCO2) differences increase during exercise in normal subjects through several mechanisms including PO2, O2 pressure at which hemoglobin (Hb) is half saturated with O2 (P50), and Hb concentration changes. The present study was undertaken to evaluate how much these biochemical changes are relevant to a-vCO2 difference through exercise in patients with heart failure. Twenty-seven patients with congestive heart failure [10 patients in functional class A (peak exercise O2 uptake >20 ml x kg-1 x min-1), 9 in class B (20-15 ml x kg-1 x min-1), and 8 in class C (15-10 ml x kg-1 x min-1)] underwent a cardiopulmonary exercise test with once-per-minute simultaneous blood sampling from the pulmonary and systemic arteries for determination of Hb, PO2, PCO2, pH, O2 content (CO2), Hb saturation and lactic acid (pulmonary artery only), and calculation of P50. Analysis of data was done at six exercise stages: the first at rest, the last at peak exercise, and the second to the fifth at one-, two-, three-, and four-fifths of O2 consumption increase. a-vCO2 difference at peak exercise was 14.3 +/- 2.1, 16.9 +/- 2.4, and 14.7 +/- 2.1 (SD) ml/dl in class A, B, and C patients, respectively. The contribution of Hb, P50, and PO2 changes to the increments of a-vCO2 difference during exercise was 21, 17, and 63%, respectively; the only interclass difference observed was for P50, which plays a greater role in a-vCO2 difference in class A. Hb changes act mainly at the arterial site, whereas P50 and PO2 act at the venous site. Hb increase was constant through the test, venous P50 increase was greater above anaerobic threshold, and venous PO2 reduction was most remarkable at the onset of exercise; in class C patients, no venous PO2 change was recorded in the second half of exercise. Thus a-vCO2 difference increase during exercise is notable in patients with heart failure but unrelated to the severity of the syndrome. Hb, P50, and, to the greatest degree, PO2 changes participate in the increment of a-vCO2 difference. In class C patients, the lack of PO2 reduction in the second half of exercise suggests the achievement of a "whole body critical venous PO2."


Subject(s)
Exercise/physiology , Heart Failure/metabolism , Hemoglobins/metabolism , Oxygen Consumption/physiology , Oxygen/blood , Anaerobic Threshold/physiology , Blood Gas Analysis , Carbon Dioxide/blood , Carboxyhemoglobin/metabolism , Exercise Test , Female , Heart Failure/blood , Heart Failure/physiopathology , Humans , Lactic Acid/blood , Male , Middle Aged
17.
Eur Heart J ; 17(2): 230-6, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8732376

ABSTRACT

Procoagulant activity, thrombin and fibrinolytic system activation have been demonstrated in the first 24-48 h after acute myocardial infarction treated with thrombolytic therapy. Little is known about what happens in the subsequent days, during which the incidence of ischaemic recurrence is high. In 21 patients treated with streptokinase and in 20 patients treated with urokinase we evaluated, with multiple plasma determinations, D-dimer and fibrinogen plasma levels in the first week after myocardial infarction. From the 2nd hour after the beginning of thrombolysis to the 4th day, all patients received intravenous heparin in doses sufficient to raise the partial thromboplastin time to twice its normal level; subcutaneous calcium heparin (12,000 U/day) was subsequently substituted for the intravenous route. Coronary angiography was performed 7 days after infarction. From the basal values 2.22 +/- 1.44 nmol.1(-1) in the streptokinase group and 3.28 +/- 3.05 nmol.1(-1) in the urokinase group, D-dimer rose consistently in the 1st hour after thrombolysis 269.4 +/- 206.7 nmol.1(-1) and 44.5 +/- 35.5 nmol.1(-1) in the streptokinase and urokinase groups, respectively; P < 0.001. After the peak value, which in both groups was reached after 5 h, D-dimer slowly decreased during the study period. It reverted to normal values only in 10/21 patients in the streptokinase group; in the urokinase group normalization was attained in 14/20 patients between the 3rd and 6th days. After withdrawal of i.v. heparin in patients of both groups with TIMI 0 or 1 grade of coronary patency, D-dimer rose to levels four to seven times greater than normal; in patients of both groups with TIMI 2 or 3 grade coronary flow, D-dimer showed a monophasic pattern of progressive normalization (P < 0.05 and P < 0.01 at the 6th and 7th days, respectively, for differences between TIMI 0-1 and TIMI 2-3 groups). After myocardial infarction, thrombolysis is followed by active and persistent fibrin degradation more marked and lasting after streptokinase than after urokinase. When occurring sooner, it is a consequence of plasmin activation induced by thrombolytic agents; later it seems to be related to intracoronary substrate, as suggested by the relationship of plasma elevation of D-dimer with the presence of occluded or suboccluded infarction-related vessels.


Subject(s)
Fibrinolysis/physiology , Myocardial Infarction/drug therapy , Myocardial Infarction/physiopathology , Thrombolytic Therapy , Aged , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Fibrinolytic Agents/therapeutic use , Humans , Male , Middle Aged , Myocardial Infarction/blood , Plasminogen Activators/therapeutic use , Streptokinase/therapeutic use , Time Factors , Urokinase-Type Plasminogen Activator/therapeutic use
18.
J Peripher Nerv Syst ; 1(1): 53-64, 1996.
Article in English | MEDLINE | ID: mdl-10970120

ABSTRACT

We compared reinnervation of target organs after sciatic nerve resection and repair by tubulization with biodurable tubes of silicone and teflon, or bioresorbable nerve guides of collagen and poly(L-lactide-co-6-caprolactone) (PLC) leaving a 6 mm gap in different groups of mice. All tubes were of 1 mm inside diameter and thin-walled (50 to 250 microm). Functional reinnervation was assessed by noninvasive methods to determine recovery of sweating, sensory and motor functions in the hindpaw repeatedly during 5 months postoperation. PLC guides allowed faster and higher levels of reinnervation for the four functions tested than collagen and silicone tubes, while teflon tubes gave the lowest levels of recovery. Regenerative reinnervation by thin nociceptive and sudomotor fibers was higher than by large sensory and alphamotor fibers in all groups. Resorbable tubes promoted regeneration in a higher proportion of mice than durable tubes. In cases with effective regeneration the nerve cable was multifascicular, with mild to moderate mononuclear cell infiltrates and a thin newly formed perineurium. The number of myelinated fibers was higher in PLC and silicone tubes than in collagen and teflon tubes. There was only minimal inflammatory reaction within the remnants of collagen tubes, but not in the other materials. PLC tubes of slow reabsorption rate seem useful for repairing long gaps in injured nerves.


Subject(s)
Absorbable Implants , Nerve Regeneration , Neurology/methods , Sciatic Nerve/physiopathology , Animals , Female , Mice , Sciatic Nerve/pathology
19.
J Card Fail ; 1(5): 401-8, 1995 Dec.
Article in English | MEDLINE | ID: mdl-12836715

ABSTRACT

Dead space/tidal volume ratio (VD/VT) evaluation is currently performed in patients with respiratory and cardiac disorders, and includes measurement of arterial CO2 partial pressure (PaCO2). PaCO2 is generally derived from either PETCO2 (end-expiratory CO2 pressure) or PJCO2 (calculated as PJCO2 = 5.5 + 0.9 PETCO2 - 2.1 VT). The applicability of these methods may be questionable in chronic heart failure due to its frequent association with lung dysfunction. In 63 patients with congestive heart failure, the authors compared PaCO2 versus PETCO2 and PJCO2 and VD/VT measured with PaCO2 versus VD/VT estimated with PETCO2 (estimation 1) or PJCO2 (estimation 2). Comparisons were made at rest, at submaximal exercise, and at peak exercise. Considering all 326 measurements, there was a strong correlation, but not an identity, between PaCO2 and PETCO2 (PaCO2 = 7.25 + 0.80 PETCO2, r = .84, P < .0001) and between PaCO2 and PJCO2 (PaCO2 = 6.18 + 0.84 PJCO2, r = .85, P < .0001). Results were comparable concerning PaCO2 versus PJCO2. Measured VD/VTs also strongly correlated with estimated VD/VTs (VD/VT measured = -0.03 + 1.11 VD/VT [estimation 1], r = .90, P < .0001, and VD/VT measured = 0.03 + 0.92 VD/VT [estimation 2], r = .90, P < .0001). However, only at rest and, solely for estimation 1, at submaximal exercise were the slopes and y intercepts of measured versus estimated VD/VT not different from 1 and 0, respectively; in this regard, lung dysfunction was more influential than the severity of cardiac failure. Although PaCO2 strongly correlates with PETCO2 and PJCO2, these measurements may not be reliable for a noninvasive calculation of VD/VT in chronic congestive heart failure.


Subject(s)
Heart Failure/physiopathology , Respiratory Dead Space/physiology , Tidal Volume/physiology , Carbon Dioxide/blood , Chronic Disease , Exercise Test , Female , Humans , Linear Models , Male , Middle Aged , Oxygen Consumption/physiology , Partial Pressure
20.
Am J Cardiol ; 76(11): 793-8, 1995 Oct 15.
Article in English | MEDLINE | ID: mdl-7572657

ABSTRACT

We investigated exercise capacity after fluid depletion in patients with moderate congestive heart failure (CHF). Twenty-one patients underwent ultrafiltration (mean volume +/- SEM: 1,770 +/- 135 ml). Echocardiography, tests of pulmonary function, and a cardiopulmonary exercise test with hemodynamic and esophageal pressure monitoring were performed before ultrafiltration and 3 months later. Tests without invasive measurements were repeated 4 and 30 days after ultrafiltration. Twenty-one control patients followed the same protocol but did not have ultrafiltration. Patients who underwent ultrafiltration and increased their oxygen consumption at peak exercise (peak VO2) by > 10% at the 3-month evaluation (group A1, n = 9) were separated from those who did not (group A2, n = 8); 3 patients did not complete the follow-up. Four days after the procedure, peak VO2 had risen from 17.3 +/- 0.8 to 19.3 +/- 0.9 ml/min/kg in group A1, and from 11.9 +/- 0.7 to 14.1 +/- 0.7 ml/min/kg in group A2 (p < 0.01). Plasma norepinephrine and pulmonary function were consistent with a greater severity of the syndrome in group A2. At 3 months in group A1, the relations of filling pressure to cardiac index of the right and left ventricles were shifted upward; the esophageal pressure swing (differences between end-expiratory and end-inspiratory pressure) for a given tidal volume was lower; the peak exercise dynamic lung compliance had increased from 0.10 +/- 0.05 to 0.14 +/- 0.03 L/mm Hg (p < 0.01). None of these changes were detected in group A2 and control patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Body Fluids/metabolism , Exercise Tolerance , Heart Failure/physiopathology , Heart/physiopathology , Lung/physiopathology , Aged , Analysis of Variance , Esophagus/physiopathology , Exercise Test , Follow-Up Studies , Heart Failure/metabolism , Hemodynamics , Humans , Lung Compliance , Middle Aged , Norepinephrine/blood , Oxygen Consumption , Pressure , Tidal Volume , Ultrafiltration , Ventricular Pressure
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