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Biomedical subjects

G Guardigli

Publications and source records attributed to G Guardigli.

15 recordsLinked to original sources
PubMed2004

Oxidative stress during myocardial ischaemia and heart failure.

Oxidative stress is a condition in which oxidant metabolites exert their toxic effect because of an increased production or an altered cellular mechanism of protection. The heart needs oxygen avidly and, although it has powerful defence mechanisms, it is susceptible to oxidative stress, which occurs, for instance, during post-ischaemic reperfusion. Ischaemia causes alterations in the defence mechanisms against oxygen free radicals, mainly a reduction in the activity of mitochondrial superoxide dismutase and a depauperation of tissue content of reduced glutathione. At the same time, production of oxygen free radicals increases in the mitochondria and leukocytes and toxic oxygen metabolite production is exacerbated by re-admission of oxygen during reperfusion. Oxidative stress, in turn, causes oxidation of thiol groups and lipid peroxidation leading first to reversible damage, and eventually to necrosis. In man, there is evidence of oxidative stress (determined by release of oxidised glutathione in the coronary sinus) during surgical reperfusion of the whole heart, or after thrombolysis, and it is related to transient left ventricular dysfunction or stunning. Data on oxidative stress in the failing heart are scant. It is not clear whether the defence mechanisms of the myocyte are altered or whether the production of oxygen free radicals is increased, or both. Recent data have shown a close link between oxidative stress and apoptosis. Relevant to heart failure is the finding that tumour necrosis factor, which is found increased in failing patients, induces a rapid rise in intracellular reactive oxygen intermediates and apoptosis. This series of events is not confined to the myocytes, but occurs also at the level of endothelium, where tumour necrosis factor causes expression of inducible nitric oxide synthase, production of the reactive radical nitric oxide, oxidative stress and apoptosis. It is therefore, possible that the immunological response to heart failure results in endothelial and myocyte dysfunction through oxidative stress mediated apoptosis. Clarification of these mechanisms may lead to novel therapeutic strategies.

Animals↗
PubMed2003

Metabolic modulation and optimization of energy consumption in heart failure.

Chronic heart failure (CHF) is a common and disabling syndrome with a poor prognosis. It is a major and increasing public health problem. Angiotensin-converting enzyme inhibitors, diuretics, and digitalis are the standards treatments for CHF. Other drugs, such as beta-blockers, spironolactone, calcium antagonists, vasodilators, and antiarrhythmic agents are used to counteract the progression of the syndrome or to improve the hemodynamic profile. Despite optimum treatment with neurohumoral antagonists, prognosis of CHF remains poor; the patients complain of persistent reductions in their exercise capacity and quality of life. Fatigue and shortness of breath, two common and disabling symptoms in patient with CHF, are relatively independent from hemodynamic and neuroendocrine changes, although they seem to be related to the impairment of peripheral muscle metabolism and energetic phosphate production. Therefore, CHF is a complex metabolic syndrome in which the metabolism of cardiac and peripheral muscles is impaired and novel therapeutic strategies have been aimed at positive modulation with compounds such as carnitine, trimetazidine, and ranolazine.

Acetanilides↗
PubMed2000

Clinical feasibility of low energy internal atrial cardioversion with a three-electrode configuration in patients with unsuccessful conventional configurations.

Low energy internal cardioversion is a safe and highly effective method for atrial fibrillation termination. We will describe 6 patients in whom the conventional 2-electrode systems with the defibrillation leads positioned in the right atrium and in the coronary sinus or left pulmonary artery failed to terminate the arrhythmia despite the use of maximal available energies. A 3-electrode configuration including right atrium, coronary sinus and left pulmonary artery was used in order to encompass as much atrial mass as possible between the cathode and the anode. The atrial fibrillation was successfully interrupted in 4 out of 6 patients. The creation of a 3-electrode configuration may be a further technical expedient in order to increase the success rate of internal cardioversion when usual manoeuvres like lead repositioning, reversion of polarity, or addition of antiarrhythmic drugs are ineffective.

Aged↗
PubMed1994

Long-term reliability of single lead atrial synchronous pacing systems using closely spaced atrial dipoles: five-year experience.

To assess the long-term capability of single atrioventricular (AV) lead VDD pacing systems using close atrial dipoles to assure reliable atrial guided pacing, the safety and efficacy of 86 VDD units implanted in 73 patients at a single center since November 1988 was reviewed. All patients suffered from advanced AV block with normal sinoatrial function. Sixty five patients received a LEM/CCS Twinal 30/30S system, four patients received a Vitatron-Saphir system, and four patients received a Medtronic Thera VDR 8348 system. All patients underwent provocative tests in search of myopotential interference, and Holter recordings; in a group of patients who underwent pacemaker replacement a comparison was made between implant and replacement measurements. The mean follow-up duration was 27.3 months. A high percentage of successfully VDD paced patients and a low incidence of pacemaker malfunction, regularly solved by pacemaker reprogramming, was reported. Atrial signal amplitudes comparable to those measured at implant were found at replacement in all patients. These data support the long-term reliability of single AV lead VDD pacing systems with closely spaced atrial dipoles, as well as stable atrial sensing by floating bipolar atrial electrodes and effective atrial synchronous ventricular pacing over time.

Aged↗
PubMed1994

AV delay optimization and management of DDD paced patients with dilated cardiomyopathy.

Ten DDD paced patients, suffering from dilated cardiomyopathy in the NYHA functional classes III or IV were studied by means of Doppler echocardiography at different programmed values of atrioventricular (AV) delay (200, 150, 120, 100, and 80 msec). The following variables were evaluated: LV diameter, ejection fraction, mitral and aortic flow velocity integrals, and stroke volume. During VDD pacing, a resting AV delay associated with the best diastolic filling and systolic function was identified and programmed individually. Shortening of the AV delay to about 100 msec was associated with a gradual and progressive improvement. Further decrease caused an impairment of systolic function. The patients were clinically and hemodynamically reevaluated after 2 months of follow-up. A reduction of NYHA class and an improvement of LV function were consistently found. The reported data suggest that programming of an optimal AV delay may improve myocardial function in DDD paced patients with congestive heart failure. This result may be the consequence of an optimization of left ventricular filling and a better use of the Frank-Starling law.

Aged↗
PubMed1993

Direct and autonomically mediated effects of oral quinidine on RR/QT relation after an abrupt increase in heart rate.

OBJECTIVES: This study evaluates the direct and autonomically mediated effects of oral quinidine on ventricular repolarization in humans. BACKGROUND: Interactions between quinidine-related vagolytic properties and autonomic modulation on ventricular repolarization are unknown. The relative role of the two components, if present, might improve our understanding of the therapeutic and proarrhythmic mechanisms of quinidine on the ventricular tissue. METHODS: Rate-related changes in the QT interval were investigated after an abrupt increase in heart rate in 15 patients during atrial pacing. In the control study, the QT interval was measured at six paced cycle lengths (600, 540, 500, 460, 430 and 400 ms) both in the basal state and after autonomic blockade (intravenous propranolol, 0.2 mg/kg, and intravenous atropine, 0.04 mg/kg); oral quinidine was then administered at a daily dosage of 1,200 mg for 3 to 4 days, after which the QT duration was reassessed using the same method in a second study. RESULTS: During the control study, the mean slope of the regression curve estimating the correlation between pacing cycle length and QT duration was significantly lower after autonomic blockade (0.14 +/- 0.05) than in the basal state (0.27 +/- 0.10, p < 0.05). Quinidine exhibited a prominent but opposite effect on the mean slope of the regression curves in basal conditions (from 0.27 +/- 0.10 to 0.20 +/- 0.07, p < 0.05) and after withdrawal of autonomic modulation (from 0.14 +/- 0.05 to 0.19 +/- 0.05, p < 0.05), thus annulling the differences observed between the two states in the control study. CONCLUSIONS: A quinidine-induced increase in QT duration as cycle length is prolonged is consistent with a reverse use dependence effect on ventricular repolarization. This effect is not evident in the basal state owing to interaction of quinidine-related vagolytic effect with the autonomic tone. Reverse use dependence and vagolytic activity on ventricular tissue indicate two potentially undesirable effects that could play a role in the lack of efficacy or proarrhythmic effect of quinidine.

Administration, Oral↗
PubMed1992

Italian multicenter study on a single lead VDD pacing system using a narrow atrial dipole spacing.

Since November 1988, 514 patients with advanced atrioventricular (AV) block and normal sinoatrial function have received the single lead VDD pacing system Twinal 30 Lem/CCS in 30 Italian centers. At implantation, particular attention was paid to the correct positioning of the atrial dipole in the mid- to mid-high right atrium and to the atrial electrogram characteristics. The follow-up included a chest X ray, to be performed before discharge of the patient from the hospital, telemetric evaluations of the endoatrial potential, provocative tests for interferences by myopotentials, 24-hour ambulatory EGG recordings, and where possible, exercise stress tests. The mean follow-up duration was 15.2 months, ranging from 1 to 42 months. A very low percentage of chronic atrial fibrillation, loss of atrial sensing, and system replacement was reported, most of the patients (93.5%) being paced in VDD mode. All investigations indicated an excellent overall system performance, stable AV synchrony, and infrequent myopotential interference, and a low complication rate throughout the follow-up period.

Aged↗
PubMed1990

AV delay and exercise stress tests: behavior in normal subjects.

In normal subjects the atrioventricular (AV) conduction is accelerated during exertion. The relationship between heart rate and AV delay is usually described as "linear". Looking at the increasing importance given to an appropriate AV synchrony in permanent dual chamber and P synchronous pacing we present the results of an investigation performed to study the correlation between AV conduction time and heart rate under stress conditions, and disclose some new aspects of this matter, which will possibly be useful for a further improvement of pacemaker technology.

Adult↗
PubMed1990

A new single lead VDD pacing system.

In 24 patients with advanced heart block and normal sinus node function, a new single lead VDD pacing system was implanted. At implantation, the endoatrial, bipolar electrogram was recorded in all patients. The lead position was checked by means of chest X-ray. At discharge and after 1, 3, and 6 months, testing for myopotential inhibition, telemetric evaluation of the endoatrial potential, and Holter recordings were made. After discharge, 18 patients performed two cardiopulmonary exercise tests at two different rate-matched AV intervals. All investigations showed good AV synchrony and a lack of interferences by myopotentials. The maximum rate-matched AV interval provided a significantly improved exercise capacity, which was more evident in patients with signs of myocardial failure.

Aged↗
PubMed1989

[Changes in plasma myoglobin levels in ischemic heart disease].

The aim of the present study is to evaluate the real need and the sensitivity of serum myoglobin levels as an early index for the diagnosis of acute myocardial infarction. A total of 62 patients (38 suffering from acute myocardial infarction, 16 from "angina pectoris", 8 from heart failure) and 20 healthy volunteers were included in the study. The patients with acute myocardial infarction were divided in 3 subgroups according to the time passed between the beginning of the pain and their admittance to our Department (Coronary Care Unit), that was, less than 6 hours, between 6 and 12 hours, between 12 and 24 hours. Among the patients with "angina", 8 presented spontaneous crisis whereas 4 had crisis only during treadmill test. 8 of the healthy volunteers received intramuscular injections of physiological solution every 12 hours during the 3 days preceding the study. In all subjects serum myoglobin level were measured by radioimmunoassay; in patients with acute myocardial infarction serum CK and MBCK levels with enzymatic method were measured too. No variation of plasma myoglobin levels was seen in patients with angina, neither in healthy volunteers had they received or not intramuscular injections. The low increase in plasma myoglobin levels observed in patients with heart failure might be due to a deficit of renal function. Serum myoglobin levels were significantly elevated in all the patients with acute myocardial infarction, whereas plasma CK and MBCK levels were significantly high only 6 hours after the necrosis. In myocardial infarction the levels of myoglobin rise during the first hours, peak at 10 hours and return to normal in 20 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1989

Changes in prostaglandin renal synthesis in cardiovascular disease.

We investigated the factors able to stimulate (hormones, drugs, fluid volume changes and prostaglandin precursors) or inhibit (NSAIDs) renal prostaglandin synthesis. We then assessed the effects of NSAIDs on: A) the efficacy of certain drugs (furosemide, ACE-inhibitors), whose action is mediated by a stimulation of prostaglandin synthesis; B) the physiopathology of cardiovascular diseases such as myocardial infarction and heart failure, in which renal and circulatory output is reduced; C) arterial hypertension.

Cardiovascular Diseases↗
PubMed1988

[Hemodynamic and renal effects of synthetic atrial natriuretic factor (alpha-h-ANF) in patients with congestive heart failure].

We studied the effects of alpha-human atrial natriuretic factor (alpha-h-ANF) on diuresis, glomerular filtration rate (GFR), natriuresis, atrial blood pressure (BP), heart rate (HR) and plasmatic levels of aldosterone, renin activity (PRA), antidiuretic hormone (ADH) in 21 patients with congestive heart failure (CHF), (NYHA, class IV) and 15 healthy volunteers. Three different doses (25, 50 and 100 micrograms) of alpha-h-ANF were administered; each subject received only one dose. Protocol was as follows: 2 periods of 30 minutes each before alpha-h-ANF administration; 2 periods of 15 minutes and 3 of 30 minutes each after it. Aldosterone, PRA, ADH and plasmatic level of ANF were measured by radioimmunoassay. In patients with CHF 25 and 50 micrograms of alpha-h-ANF produced a significant increase in diuresis, GFR, and natriuresis but no modification of BP. On the contrary BP decreased significantly after 100 micrograms of alpha-h-ANF, without changes in renal function. In healthy volunteers the effects of alpha-h-ANF appeared simultaneously and to same degree after each dose. Both in patients and healthy subjects alpha-h-ANF administration had little effect on aldosterone, renin and ADH secretion. The effects of alpha-h-ANF in patients with CHF may be caused by a lowered receptor sensitivity due to a high level of ANF and to their different haemodynamic status.

Aged↗
PubMed1987

Analysis of azide-insensitive Ca2+-dependent ATPase activity in atrial specimens from patients with coronary or valvular heart disease.

The activity of the azide-insensitive Ca2+-dependent ATPase (highly enriched in myofibrillar ATPase activity) was studied in specimens of both right and left atria which were taken from patients with ischemic and/or valvular heart disease during coronary by pass and/or valvular substitution. A significantly lower enzymatic activity was found in atrial specimens from patients with left ventricular heart failure in comparison to the atrial fragments obtained from the patients with normal heart function. Such an inhibition reflected a significant increase in the Km of the enzyme for ATP and was associated with a concomitant reduction in Vmax, both more evident in the left atrial fragments. Moreover, tissue homogenates of atrial specimens from failing hearts exhibited a lower protein SH group content when compared to the atrial homogenates from the heart with normal left ventricular heart function.

Azides↗
PubMed1987

Expression of major histocompatibility complex class II antigens on bile duct epithelium in patients with hepatic graft-versus-host disease after bone marrow transplantation.

We studied the expression of major histocompatibility complex (MHC) class II antigens in liver biopsies taken from ten patients with clinical and biochemical evidence of liver damage after bone marrow transplantation. In all six patients who had histologically confirmed graft-versus-host disease, MHC class II antigens were detected on intrahepatic bile ducts. In four patients with no histological features of graft-versus-host disease, MHC class II antigens were not detected. In controls, a positive reaction for bile duct MHC class II antigens was only detected in the patients with primary biliary cirrhosis. Characterisation of the lymphocytes surrounding the bile ducts showed a prevalence of Leu 3+ cells in graft-versus-host disease and primary biliary cirrhosis. We propose that the aberrant expression of class II antigens on bile duct epithelium cells may play a role in the pathogenesis of graft-versus-host disease. A similar pattern in primary biliary cirrhosis may suggest a common pathogenetic mechanism.

Adult↗