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Biomedical subjects

A Iacono

Publications and source records attributed to A Iacono.

At least 37 records · Page 2Linked to original sources

In the lung aerosol cyclosporine provides a regional concentration advantage over intramuscular cyclosporine.

BACKGROUND: Acute rejection remains an almost universal complication among lung transplant recipients. Refractory rejection as well as chronic systemic immunosuppression is associated with significant morbidity and mortality. Recent studies suggest that aerosol cyclosporine may address these issues by effectively preventing acute cellular rejection while maintaining low systemic drug concentrations. This study was designed to evaluate the concentrations of cyclosporine in blood and lung tissue after aerosol and intramuscular administration. METHODS: Lewis rats were divided into 4 experimental groups: Groups A (n = 33) and B (n = 30) received aerosol cyclosporine 3 and 5 mg/kg, respectively; Groups C (n = 33) and D (n = 30) received systemic cyclosporine 5 and 15 mg/kg, respectively. We used high-performance liquid chromatography to quantitate blood and lung tissue cyclosporine levels at timed intervals. We used the trapezoidal rule to approximate area under the concentration vs time curve (AUC). RESULTS: Aerosol delivery of cyclosporine resulted in higher and more rapid peak drug levels in lung tissue samples than did systemic delivery. At an equivalent 5 mg/kg dose, the cyclosporine AUC was 3 times higher with aerosol delivery than with intramuscular delivery in lung tissue (477,965 vs 157,706 ng x hour/g, respectively). The lung tissue: blood AUC ratio was highest in the aerosol groups (27.3:1 and 17.4:1) compared with the intramuscular groups (8.1:1 and 9.4:1). CONCLUSION: Local aerosol inhalation delivery of cyclosporine provides a regional advantage over systemic intramuscular therapy by providing higher peak concentrations and greater lung tissue exposure.

Administration, Inhalation↗

Efficacy of carvedilol on complex ventricular arrhythmias in dilated cardiomyopathy: double-blind, randomized, placebo-controlled study.

AIMS: The aim of the present study was to investigate whether the addition of carvedilol to conventional therapy in dilated cardiomyopathy patients is associated with further benefits in the treatment of complex non-sustained ventricular arrhythmias (Lown class III, IV or V). METHODS AND RESULTS: We recruited 168 patients with ischaemic or idiopathic dilated cardiomyopathy, with complex ventricular arrhythmias. Patients able to tolerate low doses of carvedilol were randomized to treatment with carvedilol or placebo for 6 months. Carvedilol treatment improved ventricular function and reduced the incidence of arrhythmic episodes. Notably, by the end of the first month of treatment, the antiarrhythmic efficacy of the drug was significantly greater in patients with ischaemic than in those with idiopathic dilated cardiomyopathy, an effect that could probably be attributed to the anti-ischaemic properties of carvedilol. After 3 months, at a time when ejection fraction was significantly improved in all treated patients, the antiarrhythmic efficacy of carvedilol was similar in the two study groups. CONCLUSIONS: Carvedilol antiarrhythmic efficacy was paralleled by the improvement in ejection fraction, independent of the aetiology of heart failure. The possibility of adding to an already 'optimized' conventional therapy a drug able to reduce the incidence of complex non-sustained ventricular arrhythmias is a therapeutic option that should be considered in the treatment of these patients.

Administration, Oral↗

Noninvasive evaluation of arterial abnormalities in young patients with neurofibromatosis type 1.

Neurofibromatosis regroups at least two different autosomal dominant genetic disorders: neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). Vascular disease is an underestimated complication of NF1. Few studies are available on this, all based on case reports. Neurofibromin, NF1 protein product, has also been detected in aortic smooth muscle. The purpose of this study was to evaluate the physical properties of the vessels, by measuring the carotid-femoral pulse wave velocity (PWV). This parameter was assessed by the Complior, a new noninvasive, validated device, used to screen a large population. The authors studied 64 neurofibromatosis patients (34 boys and 30 girls) with a mean age of 12 years (range 5-25 years). To investigate the presence of vascular lesions, aortic stiffness was evaluated by carotid-femoral PWV by using an automatic processor (Complior). They compared data from the PWV with a control group (30 healthy children, 17 boys and 13 girls, mean age 11 years, range 5-23 years). The calculated mean PWV in the control group was 6.5 +/- 1.15 m/s. The mean PWV of the 64 young patients with NF1 was 6.3 +/- 1.02 m/s. There was no difference between the two groups (p=0.39). Nevertheless, analysis of the linear regression has shown a linear relationship between systolic blood pressure (SBP) and PWV in the control group, while in NF1 patients this relationship is not present. The authors suggest that the coexistence of different factors, such as intimal proliferation, thinning media, fragmentation of the elastic tissue, irregularity, stenosis and tortuosity of the vessels, dysplasia of the small vessels, that counterbalance PWV, normalize the mean value. They emphasize the importance of a careful vascular evaluation, using noninvasive method, such as Complior. This device is well accepted by NF1 patients.

Adolescent↗

[TNF alpha and heart failure].

Tumor necrosis factor alpha (TNF alpha) is a cytokine with proinflammatory properties which produces negative inotropic effects on the heart. It is produced in a variety of conditions such as septic shock, acute myocarditis, reperfusion injury, and congestive hear failure (CHF). This production is probably due to activation of immune elements localized in the heart or periphery, or both. TNF alpha acts by binding to two specific receptors: TNF-R1 and TNF-R2. These two proteins have different effects. TNF-R1 has cytotoxic and antiviral activity, induces fibroblast proliferation, and mediates apoptosis. TNF-R2 is involved in septic shock and in lymphocyte proliferation. They both have negative inotropic effect on the heart. It has been showed that these receptors are down-regulated in congestive heart failure, while their soluble forms (sTNF-R1 and sTNF-R2) increase with the severity of symptoms. However the significance of this increase is still unclear. The role of Fas, a receptor protein that induces apoptosis, is also examined. Fas and its ligand have homologies respectively with TNF alpha and TNF-R. Also the soluble form of Fas (sFas) increases in relation to heart failure and is related to soluble forms of the similar receptor family, therefore it is possible that the same stimuli lead the three receptors to act together. SFas, as well as sTNF receptors, may play an important role in CHF.

Heart Failure↗

Arrhythmogenic substrate in young patients with repaired tetralogy of Fallot: role of an abnormal ventricular repolarization.

Ventricular repolarization analysis has been shown to be effective in the identification of electrical myocardial instability leading to ventricular arrhythmias. The aim of the present study was to examine ventricular repolarization time indexes, in terms of both absolute measures and dispersion across the myocardium, in young patients with repaired tetralogy of Fallot (41 pts; 28M/13F, age 11.7+/-3.6 years), assessing, furthermore, the possible influence of known negative prognostic factors relative to the surgical operation and residual haemodynamic abnormalities. The data of the study group were compared with those of 33 aged-matched asymptomatic control subjects (22M/11F, age 11.7+/-2.3 years). Ventricular depolarisation, as expressed by QRS duration, resulted significantly longer in total Fallot group than in the Control group (P<0.0001). Particularly, patients operated through a right ventricular approach showed higher values of QRS interval (P<0.0001) than those operated through a combined transatrial-transpulmonary approach. All the patients operated on for tetralogy of Fallot exhibit, with respect to control subjects, an inhomogeneous prolongation of ventricular repolarization across the myocardium, as showed by the significant increase in the absolute indexes of ventricular repolarization, JTc (P<0.001), QT (P<0.0001) and QTc (P<0.0001) with a concomitant prolongation of the indexes of dispersion of ventricular recovery time, QTcD (P<0.0001), JTcD (P<0.0001), 'adjusted' QTcD (P<0.001) and Tp-Te interval (P<0.0001). A temporal and regional variation in the ventricular repolarization across the myocardium in patients with repaired tetralogy of Fallot, could create the pathophysiological substrate for an increased cardiac electrical instability. The presence of negative prognostic factors, relative to the surgical intervention or residual haemodynamic abnormalities, even if not influencing the arrhythmic substrate, invariably present, could determine 'trigger' conditions essential for the development of ventricular arrhythmias.

Adolescent↗

The significance of bronchus-associated lymphoid tissue in human lung transplantation: is there an association with acute and chronic rejection?

BACKGROUND: In animal models of acute rejection in lung allografts, bronchus-associated lymphoid tissue (BALT) plays a major role in the induction and persistence of the alloreactive response. We undertook a study of the clinical and histologic associations with BALT identified on transbronchial biopsy in human lung allograft recipients. METHODS: Transbronchial biopsies of patients receiving single lung, double lung, and combined heart-lung transplantation from 1984 to 1997 at the University of Pittsburgh Medical Center were reviewed. Seventy-seven patients had transbronchial biopsies demonstrating BALT. We examined all pathologic reports and slides, and graded rejection utilizing the Revised Working Formulation for the Classification of Pulmonary Allograft Rejection. Twenty-nine of 77 patients were selected at random to evaluate the distribution of BALT lymphocyte subsets immunohistochemically. RESULTS: There was no relationship between native disease or the transplant procedure and the identification of BALT. BALT was found from 9 days to 2431 days after transplant (average: 440 days; median: 157 days) in association with clinically insignificant acute cellular rejection (A0, A1) in 75% of cases. Bronchiolitis obliterans developed in 29% of patients with a BALT-positive biopsy, a percentage not different from that of our overall lung transplant population. Immunohistochemical examination of BALT showed helper T cells predominated over cytotoxic T cells in zones surrounding B cell-rich follicular center cells. CONCLUSIONS: The association of BALT with high-grade acute cellular rejection and with the development of bronchiolitis obliterans could not be confirmed in human lung allografts. BALT most often accompanied A0 or A1 rejection. This raises the possibility that the presence of BALT on transbronchial biopsy may be part of the evolution of immunologic tolerance in human pulmonary allografts.

Acute Disease↗

Perioperative correlates of malignant ventricular tachyarrhythmias complicating coronary surgery.

Sustained ventricular tachyarrhythmias (VT), such as monomorphic or polymorphic ventricular tachycardia, and ventricular fibrillation, represent the most serious arrhythmic events that can complicate the postoperative course of coronary artery bypass grafting (CABG). The perioperative factors potentially associated with post-CABG sustained VT onset have not been thoroughly investigated. As a consequence, the aim of our study was to identify which perioperative variables might predict post-CABG VT occurrence. One hundred and fifty-two consecutive patients who underwent CABG surgery at our Institute were included in the study. Post-CABG VT occurred in 13 out of 152 patients (8.5%, six cases of monomorphic ventricular tachycardia and seven cases of ventricular fibrillation). Univariate analysis revealed that VT patients were significantly younger (54.8 +/- 6.6 vs 60.1 +/- 8.8, P = 0.038), exhibited more severe coronary artery disease (CAD) (no. of diseased vessels, 2.92 +/- 0.3 vs 2.45 +/- 0.7, P = 0.023; and percentage of patients with three-vessel CAD, 91.7 vs 57.3%, P = 0.043), and received a greater number of CABGs than those remaining in sinus rhythm (SR) (percentage of patients receiving three or more CABGs, 76.9 vs 38.8%, P = 0.018) Moreover, VT patients more frequently developed intra- or postoperative myocardial infarction (total CK > 1,000, 76.9 vs 38%, P = 0.016; and MB-CK > normal range, 72.7 vs 30.7%, P = 0.014), electrolyte derangement (84.6 vs 45.6%, P = 0.017), and a severe hemodynamic impairment (need for intra-aortic balloon pump (IABP), 23 vs 2.9%, P = 0.009). On multivariate analysis, total CK > 1,000, postoperative electrolyte imbalance, the need for three or more CABGs, and for IABP all were independent correlates for VT. In conclusion, post-CABG VT seem to be related to the preexistence of a severe underlying coronary artery disease along with perioperative triggering factors, such as acute ischemia, electrolytic disorders, and sudden hemodynamic impairment.

Coronary Artery Bypass↗

Comparison of losartan and hydrochlorothiazide on cognitive function and quality of life in hypertensive patients.

We examined long-term changes in cognitive function and quality of life (QL) in hypertensive patients by comparing the antihypertensive effect of hydrochlorothiazide (HCTZ) and losartan. We studied 69 patients (age range, 30 to 73 years) with mild-to-moderate hypertension. All patients, in a double-blind study, were randomly allocated to either treatment with 50 mg losartan once daily or 25 mg HCTZ once daily. The sample in each treatment group was divided by age (younger than 60 years or 60 years or older). At baseline and after 26 months, a QL questionnaire appropriate for the hypertensive patients was given. Cognitive function was evaluated, at baseline and after 26 months, by psychometric tests consisting of items from the Mini-Mental State Examination (MMSE) and the Sandoz Clinical Assessment Geriatric (SCAG). A score of less than 24 on the MMSE and more than 40 on the SCAG was predictive of cognitive impairment. The losartan group had a significant improvement in SCAG (P<.001) and MMSE (P<.001). No significant changes were observed in the HCTZ group (SCAG, P = .1; MMSE, P = .2). Sixty-five percent of the elderly had a MMSE score less than 24 and 70% had a SCAG score greater than 40, v. 35% and 48%, respectively, in younger patients. The health state index of QL improved significantly in both groups (losartan group, P<.01; HCTZ group, P<.02); the improvement in QL scores in patients using HCTZ was significant only in subjects aged 60 years and older (P<.04). These results suggest that losartan can have a positive effect not only on blood pressure but also on impaired cognitive function, reversing even minimal cognitive deficits induced by hypertension. The elderly patients in our sample had worse scores and cognitive performance was lower than in younger patients, even if in the losartan group the score improvement was the same at all ages. The same could not be said for HCTZ.

Adult↗

Clinical significance of cytomegalovirus-specific T helper responses and cytokine production in lung transplant recipients.

Cytomegalovirus (CMV) disease continues to be a major problem for lung transplant recipients. In CMV-seropositive individuals, we detected two types of CMV-specific responses: a self-restricted response stimulated by soluble CMV antigen (sCMV-Ag) and a non-self-restricted response induced by CMV-infected cells (cCMV-Ag). Lung transplant recipients who develop the CMV-specific self-restricted T helper response have a low risk of recurrent CMV disease. In contrast, during CMV disease, lung transplant recipients exhibit only the non-self-restricted T helper responses. We characterized the T cell activation and the kinetics of cytokine production of sorted CD4+ and CD8+ T cells from PBLs of CMV seropositive donors. The two types of CMV antigens induced cytokine production in both T cell subsets. We also performed competitive RT-PCR for Granzyme B (GB) in BAL cells of lung transplant recipients prior to, during and following CMV disease. CMV disease was associated with increase in GB gene expression when was accompanied by acute cellular rejection while it remained low in patients with CMV disease that did not have a complicated course. In summary, CMV-activated T cells within the allograft may produce inflammatory cytokines and effector molecules that may promote allograft rejection.

Antigens, CD↗

Unopposed neutrophil elastase in bronchoalveolar lavage from transplant recipients with cystic fibrosis.

Large numbers of neutrophils with unopposed neutrophil elastase (NE) proteolytic activity are found in lower respiratory tract secretions from most patients with advanced cystic fibrosis (CF). To determine whether antielastase defenses may be overwhelmed in epithelial lining fluid after lung transplantation, we measured NE activity (cleavage of the specific substrate, MeO-Suc-Ala-Ala-Pro-Val-pNA) in bronchoalveolar lavage fluids (BALF) obtained for surveillance or diagnostic purposes at various intervals (1 mo to 7 yr after transplantation) from 52 recipients who had undergone double or bilateral lung transplantation for end-stage CF. Unopposed NE activity was found in BALF from 14 recipients, most of whom also had >= 10(5) colony forming units (cfu) of Pseudomonas aeruginosa in BALF. Ten of the 14 recipients with unopposed NE in bronchoalveolar lavage (BAL) had developed obliterative bronchiolitis (OB), but only 8 of the 38 subjects without unopposed NE activity had OB (p = 0. 002; Fisher exact test). We conclude that antiprotease defenses in lower respiratory tract secretions of CF patients receiving lung allografts are sufficient in the majority of patients to prevent unopposed NE activity. However, the presence of unopposed NE activity in BAL from lung allografts of patients with CF is associated with progressive, irreversible OB and graft failure.

Adolescent↗

[Efficacy of diltiazem in uremic hemodialyzed patients with isolated diastolic dysfunction and dialysis hypotensive crisis].

The aim of our study was to assess the effects of diltiazem on diastolic function, left ventricular mass and intradialytic hypotension, in uremic patients on maintenance hemodialysis. Forty-eight uremic patients on maintenance hemodialysis (mean age 46 +/- 5 years) with diastolic heart failure and normal systolic function (ejection fraction > 40%), although hemodialysis had been correctly performed, were included in the study. All patients had left ventricular hypertrophy. Diltiazem was given at the dosage of 60 mg, twice a day, for 3 months. At the end of this period, significant improvement of Doppler echocardiographic filling pattern and clinical symptomatology were observed, but left ventricular mass index was unchanged. Episodes of intradialytic hypotension were significantly reduced. We conclude that diltiazem improves symptoms and left ventricular diastolic filling in uremic patients with diastolic heart failure, without modifying left ventricular mass index; impaired diastolic function has an important role in recurrent dialysis hypotension.

Adult↗

[Angiotensin-II receptor inhibitors in hemodialysed uremia patients with arterial hypertension: candesartan cilexitil versus losartan].

BACKGROUND: The aim of this study was to evaluate, in patients with chronic renal failure in hemodialysis and arterial hypertension, the effectiveness of a new angiotensin II receptor antagonist, the candesartan cilexitil, comparing it with losartan, the first of this new class of drugs. METHODS: We have selected 128 patients with chronic renal failure (92 males and 36 females, mean age 56 +/- 6 years) and arterial hypertension, subjected to hemodialysis 3 times a week, with hemodialytic seniority of 90 +/- 10 months. The inclusion criteria in the study were given from the presence, after 15 days of pharmacological wash-out, of values of diastolic blood pressure (DBP) > or = 95 mmHg and systolic blood pressure (SBP) > or = 150 mmHg, despite a hemodialysis correctly performed. Patients were divided into two groups whether they received single blind randomized candesartan cilexitil 16 mg or losartan 50 mg at hour 8.00 for a period of 8 weeks at the end of which, after a period of pharmacological wash-out of 15 days, the drugs were administered to inverted groups for other 8 weeks. After 4 and 8 weeks of treatment an evaluation of the anti-hypertensive effectiveness by means of medical complete visit and measurement of blood pressure were made. The statistical analysis was made by means of Student's t test for paired data. RESULTS: All the patients concluded the study. After 4 weeks of treatment SBP and DBP were reduced in the group with candesartan cilexitil with regard to baseline values (SBP 151.8 +/- 6.3 vs 159.8 +/- 5.1 mmHg, p < 0.05; DBP 93.6 +/- 4.5 vs 98.1 +/- 3.7 mmHg, p < 0.05). In the losartan group (SBP 151.8 +/- 6.3 vs 158.7 +/- 5.5 mmHg, p < 0.05; DBP 93.6 +/- 4.5 vs 97.5 +/- 3.8 mmHg, p < 0.05) no significant reduction in blood pressure values was observed compared with baseline values (SBP 158.7 +/- 5.5 vs 159.8 +/- 5.1 mmHg, NS; DBP 97.5 +/- 3.8 vs 98.1 +/- 3.7 mmHg, NS). After 8 weeks of treatment in the candesartan cilexitil group (SBP 128.3 +/- 5.9 vs 159.8 +/- 5.1 mmHg, p < 0.05; DBP 81.5 +/- 4.1 vs 98.1 +/- 3.7 mmHg, p < 0.05) and in the losartan group (SBP 151.7 +/- 5.1 vs 159.8 +/- 5.1 mmHg, p < 0.05; DBP 92.7 +/- 3.9 vs 98.1 +/- 3.7 mmHg, p < 0.05) blood pressure values were reduced in the same manner as at baseline. By comparing the two drugs, candesartan cilexitil proved to have a better antihypertensive effectiveness (SBP 128.3 +/- 5.9 vs 151.7 +/- 5.1 mmHg, p < 0.05; DBP 81.5 +/- 4.1 vs 92.7 +/- 3.9 mmHg, p < 0.05). CONCLUSIONS: Our experience suggests that angiotensin II receptor antagonists may be a therapeutic remarkable option in patients with chronic renal failure in hemodialysis and arterial hypertension; the antihypertensive effect seems to be class-specific. Nevertheless, at least for our data, a better and more rapid antihypertensive results was obtained with candesartan cilexitil.

Angiotensin Receptor Antagonists↗

Compared effects of sotalol, flecainide and propafenone on ventricular repolarization in patients free of underlying structural heart disease.

Antiarrhythmic drugs are known to affect the depolarization and repolarization time in a different fashion. The aim of the present study was to compare the effects of Sotalol, Flecainide and Propafenone on some common (QT, QTc, JT, JTc) or uncommon (QTc dispersion, T-peak to T-end interval) electrocardiographic parameters in order to evaluate the effects of these antiarrhythmic drugs on ventricular repolarization time both in terms of absolute values and of dispersion across the myocardium. The analysis of these antiarrhythmic drug effects was performed on the standard 12-lead electrocardiograms of 31 patients (17F and 14M, age 38.1+/-17 years, range 11-67 years) in the free-drug state and at the steady state after oral treatment with Sotalol (160 mg daily), Flecainide (200 mg daily) and Propafenone (450 mg daily). These drugs were prescribed, separately, to all the 31 patients, free of underlying structural heart disease, for the treatment of their atrio-ventricular nodal re-entry tachycardia. Data of the present study show that Sotalol, over the range prescribed, significantly prolongs ventricular repolarization index QT (P=0.001), JT (P=0.0001) and JTc (P=0.0001) values in an homogeneous fashion, as shown by the significant decrease in QTcD (P=0.019) and Tp-Te (P=0.01). On the contrary, Flecainide treatment was associated with an increase in QTcD (P=0.029), Tp-Te (0.0001), QT (P=0.001), QTc (P=0.0001) and QRS (P=0.0001), with no significant changes in JT and JTc. Propafenone, over the range prescribed, did not affect repolarization time, resulting only in a prolongation of depolarization time as expressed by the increase of QRS (P=0.0001).

Adolescent↗

Impact of heart rate and atrioventricular delay on left ventricular diastolic filling in patients with dual-chamber pacing for sick sinus syndrome or atrioventricular block.

We examined the effect of left ventricular filling on different combinations of programmable heart rate and atrioventricular delay in patients with dual-chamber pacemakers. Pacing mode with heart rates of 60 beats/min and 156 ms of atrioventricular delay induced a diastolic pattern that resembles more than others the one observed in healthy subjects in sinus rhythm.

Aged↗

Increased QT dispersion and other repolarization abnormalities as a possible cause of electrical instability in isolated aortic stenosis.

The aim of our study was to analyze the ventricular repolarization phase in patients with isolated aortic stenosis (AS) in order to search for possible abnormalities that might contribute to an explanation of the electrical instability peculiar to this valve disease. We selected a population of 39 patients with isolated AS (25 M and 14 F, mean age 60+/-16 yrs). As controls we considered a group of 31 age-matched healthy subjects 20 M and 11 F, mean age 55+/-14 yrs, P=NS. Disease severity was assessed by echocardiography, calculating the maximum and mean pressure gradients max and mean PG) and the functional valve orifice area. Various electrocardiographic intervals (QT, QT'c, JT, JTc) and indices (QT and QTc dispersion were adopted for a detailed non-invasive evaluation of the ventricular repolarization. In patients with AS, M-QT (391+/-45 ms vs 362+/-25 ms, P=0.002), M=QTc (431+/-29 ms vs 412+/-19 ms, P=0.003), M-JT (290+/-41 ms vs 265+/-26 ms, P=0.003, M-JTc 331+/-29 ms vs 302+/-19 ms, P<0.001, QTD (67+/-34 ms vs 40+/-15 ms, P<0.001), QTcD (77+/-36 ms vs 52+/-23 ms, P<0.001) all resulted significantly greater than in controls. QTD and QTcD both resulted linearly related either to max PCi (r=0.388, P=0.018 and r=0.357, P=0.03) or to mean PG (r=0.513, P=0.004 and r=0.438, P=0.015), while M-JT and M-JTc turned out to be directly related only to mean PG (r=0.436, P=0.016 and r=0.483, P=0.007). Our findings suggest a prolonged duration of ventricular recovery and a greater dispersion of ventricular repolarization in patients with AS and might account for the electrical instability proper to this valve dysfunction. Besides, the existence of a linear direct relation between the severity of AS and the degree of inhomogeneity of left ventricular recovery, together with the correlation found among mean PCr and the total duration of the repolarization phase, expressed by the intervals JT and JTc, strongly suggest the hypothesis that in AS arrhythmogenic substrates development parallels the worsening of the valve defect.

Adult↗

Left ventricular function and exercise tolerance in patients with type II diabetes mellitus.

BACKGROUND: Left ventricular (LV) preload changes may alter exercise tolerance (ET), probably lessening activation of the Maestrini-Starling mechanism. Reduced LV filling (pre-load) during the diastolic phase, usually impaired in diabetic patients, could affect ventricular function. HYPOTHESIS: To evaluate the relationship between some echocardiographic LV function indices and ET, 24 patients (age 43-75 years, mean 54 +/- 13 years, Group A) with type II diabetes mellitus (DM), not suffering from other pathologies, and for whom the ergometric stress test (EST) resulted in an early interruption because of muscular fatigue and/or dyspnea, and 14 patients (age 38-70 years, mean 53 +/- 12 years, Group B) with type II DM and maximal ergometric stress test, used as control group, were studied. METHODS: The EST was performed by increasing the load by 25 W every 2 min; its duration was used as an ET index and correlated with clinical parameters of LV function obtained with M-mode, two-dimensional, and Doppler echocardiography. RESULTS: No patients in either Group A or Group B showed a high systolic blood pressure value at rest and/or an LV hypertrophy and/or an alteration of systolic functional indices. In neither group was there significant correlation between ET and duration of DM, basal heart rate, basal and max systolic blood pressure, and EF values. Linear regression analysis showed a significant correlation between Doppler parameters of the diastolic function and ET index in Group A, while there was no significant correlation in Group B. CONCLUSION: From these data we can deduce that in absence of left systolic ventricular dysfunction the impairment of LV relaxation in DM can influence exercise tolerance, probably by limiting activation of the contractile reserve.

Case-Control Studies↗

Electrophysiologic significance of leftward QRS axis deviation in bifascicular and trifascicular blocks.

BACKGROUND: Intraventricular conduction disturbances determine complete impairment of impulse propagation along the right or left bundle branch or the two left fascicles. HYPOTHESIS: This study was undertaken to investigate the electrophysiologic significance of QRS axis (QRSA) orientation in bifascicular and trifascicular blocks. METHODS: A group of 76 subjects, 43 with right bundle-branch block (RBBB) and left anterior hemiblock (LAH) (Group A), and 33 with left bundle-branch block (LBBB) (Group B), was submitted to electrophysiologic evaluation. RESULTS: In Group A, QRSA was inversely related only to intraventricular conduction, while in Group B, QRSA inversely related to infrahisal conduction times. A value of < -60 degrees was considered the cut-off point for determining subjects with a considerable leftward QRSA deviation. Of the 27 Group A patients with a QRSA < -60 degrees, 38.5% developed an infrahisal second-degree atrioventricular (AV) block during incremental atrial stimulation (IAS) in comparison with 11.1% of those with QRSA > -60 degrees. Of the 9 Group B patients with a QRSA < -60 degrees, 44.4% exhibited severe impairment of infrahisal conduction at baseline and 66.6% developed an infrahisal second-degree AV block during IAS, whereas among the remaining 24 with a QRSA > -60 degrees, in only 8.3% were both infrahisal (HV1 and HV2) intervals dangerously prolonged, and 23.8% encountered an infrahisal second-degree AV block during IAS. In Group A, atrioventricular conduction time > 200 ms exhibited a better predictive accuracy than QRSA < -60 degrees for the development of an infrahisal second-degree AV block during IAS, whereas the latter appeared the best noninvasive predictor in Group B with a slightly lesser predictive accuracy than HV > 80 ms. CONCLUSION: The degree of leftward QRSA deviation seems to reflect the entity of intraventricular conduction delay in patients with RBBB + LAH, while it appears to be directly related to infrahisal conduction prolongation in those with LBBB.

Aged↗