Biomedical subjects

M Pahor

Publications and source records attributed to M Pahor.

At least 127 records · Page 7Linked to original sources

PubMed1991

Lack of correlation between the antiarrhythmic effect of L-propionylcarnitine on reoxygenation-induced arrhythmias and its electrophysiological properties.

1. The antiarrhythmic effect of L-propionylcarnitine (L-PC) was evaluated in the guinea-pig isolated heart; arrhythmias were induced with hypoxia followed by reoxygenation and by digitalis intoxication. 2. L-PC 1 microM, was found to be the minimal but effective antiarrhythmic concentration against reoxygenation-induced ventricular fibrillation. No antiarrhythmic effect was observed against digitalis-induced arrhythmias. D-Propionylcarnitine, L-carnitine and propionic acid did not exert antiarrhythmic effects. 3. During hypoxia and reoxygenation L-PC consistently prevented the rise of the diastolic left ventricular pressure, and significantly reduced the release of the cardiac enzymes creatine kinase (CK) and lactic dehydrogenase (LDH). 4. The electrophysiological effects of L-PC were then studied on either normal sheep cardiac Purkinje fibres or those manifesting oscillatory after potentials induced by barium or strophanthidin. 5. L-PC (1 and 10 microM) did not significantly modify action potential characteristics and contractility of normal Purkinje fibres, or the amplitude of OAP induced by strophanthidin or barium. 6. It is concluded that the antiarrhythmic action of L-PC on reoxygenation-induced arrhythmias is not correlated with its direct electrophysiological effects studied on normoxic preparations.

Animals↗

PubMed1991

Is age an independent risk factor of adverse drug reactions in hospitalized medical patients?

OBJECTIVE: To study the incidence and the risk factors of adverse drug reactions. DESIGN: Multicenter survey. SETTING: Hospitalized care: 22 internal medicine and 19 geriatric wards. PATIENTS: All patients (n = 9,148) consecutively admitted during two observation periods of 2 months. MAIN OUTCOME MEASURE: Incidence of adverse drug reactions. RESULTS: The mean age was 67.1 +/- 0.17 years (median 72); the mean duration of hospital stay was 18.1 +/- 0.19 days (median 14). Each patient was administered 5.1 +/- 0.03 (median 5) drug prescriptions. The incidence of probable or definite adverse drug reactions was 5.8% (532/9,148). In univariate analysis, the incidence of adverse drug reactions increased from 3.3% at under age 50 to 6.5% at age 70-79 and decreased over age 80 (5.8%). In multivariate logistic regression, taking more than four drugs (OR = 2.94, CI = 2.38-3.62), staying in hospital more than 14 days (OR = 2.82, CI = 2.26-3.52), having more than 4 active medical problems (OR = 1.78, CI = 1.29-2.45), staying in a medical ward instead of geriatric ward (OR = 1.33, CI = 1.09-1.63), and drinking alcohol (OR = 1.28, CI = 1.03-1.58) were positively correlated with adverse drug reactions occurrence (P less than 0.05). Age, gender, and smoking cigarettes were not significant predictors of adverse drug reactions. CONCLUSION: Age is not an independent risk factor of adverse drug reactions, and good geriatric care can reduce the incidence of adverse drug reactions.

Age Factors↗

PubMed1991

Enalapril prevents cardiac fibrosis and arrhythmias in hypertensive rats.

To evaluate the effects of hypertension on cardiac hypertrophy, on myocardial structure, and on ventricular arrhythmias, 27 3-month-old spontaneously hypertensive rats were treated with enalapril (10 mg/kg) daily for 11 months and compared with 26 untreated control rats. Systolic arterial pressure was significantly decreased in treated rats, and at the end of the experiment, it was 199 +/- 3 mm Hg (treated) versus 237 +/- 3 mm Hg (controls) (p less than 0.001). At this time, spontaneous arrhythmias and induced arrhythmias either by programmed electrical stimulation (train of stimuli +1 or 2 extrastimuli) or by trains of eight stimuli at decreasing coupling intervals were observed in isolated heart preparations. Comparing enalapril-treated and control rats, spontaneous arrhythmias (9 of 27 versus 20 of 26, respectively; p less than 0.01), programmed stimulation-induced arrhythmias (3 of 26 versus 12 of 23, respectively; p less than 0.01), and trains of stimuli-induced arrhythmias (4 of 26 versus 14 of 19, respectively, p less than 0.001) were less frequent in the enalapril group. Left ventricular weight was decreased in treated rats by 18% (p less than 0.001). Enalapril administration diminished the fraction of myocardium occupied by foci of replacement fibrosis normally occurring in control rats by 59% (p less than 0.001). Finally, a significant correlation was found between left ventricular weight, the extent of myocardial fibrosis, and the occurrence of ventricular fibrillation. It was concluded that chronic treatment with enalapril, which resulted in attenuation of systemic arterial pressure by limiting cardiac hypertrophy and myocardial fibrosis, decreases the propensity of the heart of hypertensive rats to arrhythmogenesis.

Analysis of Variance↗

PubMed1991

[Cardiovascular therapy problems in the elderly patient].

The therapeutic management of elderly patients should be extremely careful, particularly in those over 75 years of age. As a matter of fact, in such patients a steep increase of the risk of comorbidity and of dependence has been evidenced. This implies a more complex therapeutic management, that must be oriented to the amelioration of quality of life more than to the resolution of the single pathologies. However, all the intervention trials so far conducted excluded such patients. Therefore, they cannot be considered representative of the geriatric epidemiological reality. As a result, there is virtually no useful information on the efficacy and safety of cardiovascular drugs in patients over 75 years of age. However, the following items should be pointed out: only drugs whose efficacy has been proved should be used, and only after a thorough diagnosis; a multidimensional evaluation should be performed, also addressing psychological, social, environmental and economical factors that could affect the clinical course; the risks and benefits of any therapy should be considered, particularly in the presence of comorbidity, as the number of assumed drugs directly correlates with the risk of developing adverse reactions; drugs should be dosed according to renal function and body weight, possibly starting with half the dosage of younger patients; after starting the therapy, patients should be kept under strict clinical control, and every new symptom should be considered an adverse reaction, unless it will not disappear after withdrawal of the drug; serum drug concentration should be monitored whenever possible, given its larger variability in advanced age.

Aged↗

PubMed1991

Antiarrhythmic effect of L-propionylcarnitine in isolated cardiac preparations.

The effects of L-propionylcarnitine on reperfusion-induced ventricular arrhythmias were studied in isolated hearts from spontaneously hypertensive rats. During reperfusion, 60% (n = 15) of the hearts from control spontaneously hypertensive rats hearts developed irreversible ventricular fibrillation. In contrast, irreversible ventricular fibrillation did not occur in hearts from normotensive Wistar Kyoto rats (n = 11, p less than 0.01). In a second group of spontaneously hypertensive rats, the addition of 10(-6) M L-propionylcarnitine to the medium during ischemia and reperfusion reduced the incidence of irreversible ventricular fibrillation to 14% (n = 14, p less than 0.05 versus control spontaneously hypertensive rats, NS versus Wistar Kyoto rats). Concentrations of L-propionylcarnitine from 10(-6) to 10(-2) M were tested on isolated guinea pig papillary muscles using microelectrodes. Resting potential, action potential amplitude, action potential duration and active tension were not modified by L-propionylcarnitine; and 10(-3) M L-propionylcarnitine did not influence the oscillatory afterpotentials induced by digitalis. We conclude that reperfusion ventricular arrhythmias are more severe in spontaneously hypertensive rats than in Wistar Kyoto rats and that the antiarrhythmic effect of L-propionylcarnitine in spontaneously hypertensive rats is mediated by myocardial protection from damage induced by reperfusion.

Animals↗

PubMed1990

Cardiac aging, calcium overload, and arrhythmias.

The effect of aging was tested on experimental ventricular arrhythmias in isolated heart preparations from normal Wistar rats (NWR), Wistar Kyoto rats (WKY), and spontaneously hypertensive rats (SHR). Delayed afterdepolarizations and triggered activity induced by high-calcium perfusion (16 mM) in isolated papillary muscles were more frequent in the 24-month-old than in 6-month-old NWR. Reperfusion-VA were more severe in 14-month-old SHR than in WKY. The authors have previously shown that: (1) reperfusion- and reoxygenation-induced VA, in the isolated Langendorff perfused heart, were significantly more severe and frequent in 24-month-old than in 6-month-old NWR; (2) no age-related difference in the incidence of programmed electrical stimulation (PES, train of stimuli + 1 or 2 extrastimuli)-induced VA was observed in isolated NWR hearts during control perfusion, after coronary artery ligation or during hypoxia; (3) on the contrary, the incidence of PES-induced VA was significantly higher in isolated hearts from 14-month-old SHR than from 3-month-old SHR, and 3-month-old and 14-month-old WKY. It was concluded that "physiological" aging is associated with a higher propensity to calcium-related VA, while "pathological" aging characterized by hypertension of long duration increases the incidence of PES-induced VA, probably caused by myocardial fibrosis, which could facilitate reentry.

Aging↗

PubMed1989

Age-related increase in the incidence of ventricular arrhythmias in isolated hearts from spontaneously hypertensive rats.

In order to test the effect of arterial hypertension on cardiac electrical activity, isolated Langendorff perfused hearts from spontaneously hypertensive (SHR) and normotensive (WKY) rats were studied. The incidence of spontaneous ventricular arrhythmias occurring during the control perfusion was 0% (n = 28) in WKY, 31% in SHR (n = 29, p less than 0.01), 7% (n = 14) in 3-month-old SHR, and 53% in 14-month-old SHR (n = 15, p less than 0.05). The incidence of ventricular arrhythmias induced by programmed electrical stimulation (PES = stimulus train + two extrastimuli) was 18% in WKY (n = 28), 48% in SHR (n = 27, p less than 0.05), 29% (n = 14) in 3-month-old SHR, and 69% (n = 13) in 14-month-old SHR (p less than 0.05). The incidence of PES-induced irreversible ventricular fibrillation was 0% in WKY and in 3-month-old SHR (n = 42), whereas it was 38% (n = 13) in 14-month-old SHR (p less than 0.001). Myocardial norepinephrine was significantly reduced in SHR with respect to WKY, but no significant difference was observed between 3-month-old SHR and 14-month-old SHR. Thus, no correlation between myocardial norepinephrine and ventricular arrhythmias could be found. It was concluded that the duration of hypertension was the most important factor in the development of severe ventricular arrhythmias.

Aging↗

PubMed1989

Effects of verapamil on reoxygenation and programmed electrical stimulation-induced ventricular arrhythmias in the isolated heart.

The antiarrhythmic effect of verapamil was tested on spontaneous ventricular arrhythmias during reoxygenation after 15 min of glucose-free hypoxia and on programmed electrical stimulation-(8 stimuli + 1 or 2 extrastimuli) induced ventricular fibrillation in isolated Langendorff perfused guinea pig hearts. Verapamil (1 mg/l) added during hypoxia and reoxygenation significantly reduced, during reoxygenation, the incidence of arrhythmias (46%, N = 13 vs. controls 87%, N = 30; P less than 0.01), of ventricular fibrillation (0%, N = 13 vs. controls 70%, N = 30; P less than 0.001) and of programmed stimulation-induced ventricular fibrillation (0%, N = 10 vs. controls 100%, N = 16). No effect was observed on programmed stimulation-induced ventricular fibrillation during hypoxia (90%, N = 10 vs. controls 100%, N = 10). Verapamil added during reoxygenation reduced the incidence of reoxygenation arrhythmias and ventricular fibrillation (47% and 29%, N = 17, P less than 0.01 and P less than 0.05 vs. controls, respectively) but it had no effect on programmed stimulation-induced ventricular fibrillation (100%, N = 10). It is likely that verapamil exerts its antiarrhythmic effect by preventing cellular calcium overload during hypoxia and reoxygenation.

Animals↗

PubMed1989

Programmed electrical stimulation-induced arrhythmias in isolated hearts from adult and senescent rats.

In isolated hearts from normal rats, we previously demonstrated an age-related increase of spontaneous ventricular arrhythmias. The aim of the present experiments was to test the possible effect of aging on ventricular arrhythmias induced by programmed electrical stimulation. Experiments were performed in isolated cardiac preparations of 6- and 24-month-old normal Wistar rat hearts. Programmed electrical stimulation (single or double premature stimuli following a stimuli train) was tested in isolated Langendorff perfused hearts during control perfusion, after left anterior descending coronary artery ligature and during global hypoxia. No significant differences were observed between adult and senescent hearts in the incidence of programmed electrical stimulation-induced ventricular arrhythmias during these three different situations. These experiments demonstrate that the cardiac "physiological" aging process is not associated with a greater propensity to programmed electrical stimulation-induced arrhythmias.

Aging↗

PubMed1988

Electrophysiological mechanism for the antiarrhythmic action of propafenone: a comparison with mexiletine.

1. The antiarrhythmic potency of propafenone was evaluated in the guinea-pig isolated heart; arrhythmias were induced with (a) digitalis intoxication and (b) hypoxia followed by reoxygenation. 2. Propafenone, 0.5 microM, was found to be the minimal but effective antiarrhythmic concentration. The antiarrhythmic activity of propafenone developed slower than that of 10 microM mexiletine, which was the lowest effective concentration under the same experimental conditions. 3. The electrophysiological effects of propafenone were then studied on sheep cardiac Purkinje fibres (manifesting oscillatory afterpotentials and triggered automaticity induced by barium or strophanthidin) and compared with those of 10 microM mexiletine. 4. Both 0.5 microM propafenone and 10 microM mexiletine consistently blocked triggered activity in sheep Purkinje fibres. The onset of the effect of propafenone was slower than that of mexiletine. 5. Unlike mexiletine, propafenone did not reduce the amplitude of oscillatory afterpotentials. 6. In contrast, propafenone significantly reduced Vmax in barium- and strophanthidin-treated preparations. 7. It is concluded that the antiarrhythmic action of propafenone on digitalis- and reoxygenation-induced arrhythmias is probably due to an electrophysiological mechanism different from that of mexiletine. Mexiletine, by reducing the amplitude of oscillatory afterpotentials, prevents the attainment of the threshold; propafenone, by reducing the excitability of the cell, increases the threshold and consequently an oscillatory afterpotential of the same amplitude will not generate arrhythmias.

Animals↗

PubMed1986

Autopsy rate in younger and older hospitalized patients.

A retrospective study of the autopsy rate of the clinico-pathological correlations was made in a group of inpatients. The trend of autopsy rate was observed in all inpatients died in a university hospital during a nine year period (from 1975 to 1983). The agreement between the clinical and pathological death diagnosis was retrospectively controlled in 294 consecutive patients died and submitted to autopsy in the same hospital during a 6 month period (from January to June 1983). The results show that: In the oldest (greater than 60 yrs) patients, the autopsy rate trend was significantly reduced from 1975 to 1983, whereas the hospital admissions and the mortality rate increased. In the youngest subjects (less than 60 yrs), the autopsy rate trend, the hospital admissions and the mortality rate did not significantly change from 1975 to 1983. In all the years considered, the autopsy rate was significantly reduced in the oldest class (p less than 0.001). The agreement between the clinical and pathological diagnosis was observed in 83% of cases in the less than 60 years class and in 63% of cases in the greater than 60 yrs class (p less than 0.001). The association of main disease with other diseases was significantly more frequent in the greater than 60 yrs class with respect to the less than 60 yrs class (p less than 0.01). It has been concluded that the autopsy, especially in the elderly, is absolutely necessary for a better quality control of the clinical diagnosis and of the medical care.

Age Factors↗

PubMed1986

On the mechanisms by which hypoxia eliminates digitalis-induced tachyarrhythmias.

The mechanism by which hypoxia abolishes the tachyarrhythmias induced by cardiac steroids was studied in cardiac Purkinje and ventricular muscle fibres. In muscle fibres, hypoxia reduces excitability markedly, reduces the size and increases the time to peak of the oscillatory potentials (Vos) and of the aftercontractions induced by cardiac steroids, thereby abolishing the tachyarrhythmias. In Purkinje fibres, hypoxia also decreases Vos and excitability but abolishes the tachyarrhythmias only if repeated or prolonged. In Purkinje-muscle preparations, hypoxia blocks impulse conduction from the fast discharging Purkinje fibres to the myocardial fibres when the latter are still little intoxicated. It is concluded that hypoxia affects promptly ventricular muscle fibres and (depending on the experimental conditions) Purkinje fibres also, and readily blocks impulse transmission to muscle fibres. Hypoxia abolishes arrhythmias by decreasing Vos size (probably through an impaired calcium uptake into the sarcoplasmic reticulum), by causing a conduction block at the Purkinje-muscle junction (probably through an increase in cytoplasmic calcium) and by reducing excitability.

Animals↗

PubMed1985

Electrophysiological mechanisms for the antiarrhythmic action of mexiletine on digitalis-, reperfusion- and reoxygenation-induced arrhythmias.

The antiarrhythmic potency of mexiletine was evaluated on three groups of guinea-pig isolated hearts. Arrhythmias were induced (a) with digitalis intoxication, (b) with hypoxia followed by reoxygenation and (c) with ischaemia followed by reperfusion. Mexiletine 10 microM was found to be very effective against all three types of arrhythmias in all three groups. The electrophysiological effects of mexiletine were then studied on sheep cardiac Purkinje fibres manifesting oscillatory afterpotentials and triggered automaticity induced by barium or strophanthidin. Mexiletine 10 microM consistently decreased the amplitude of oscillatory afterpotentials and blocked subsequent triggered activity in sheep Purkinje fibres. In contrast, mexiletine 10 microM had no significant effect on Vmax in normal, barium- and strophanthidin-treated preparations. The results are discussed in relation to the mechanisms of antiarrhythmic action of mexiletine.

Action Potentials↗

PubMed1985

Age-related incidence of reperfusion- and reoxygenation-induced ventricular tachyarrhythmias in the isolated rat heart.

Reperfusion- and reoxygenation-induced ventricular tachyarrhythmias were studied on 6-month-old (adult) and 24-month-old (senescent) Langendorff perfused rat hearts. The incidence of arrhythmias was significantly higher in the group of senescent hearts. Furthermore, the reperfusion- and reoxygenation-induced contracture was also more frequent in the group of senescent hearts. The interrelation between contracture and arrhythmias might represent an indirect evidence to suggest that alterations in cell calcium homeostasis have an important role in the origin of both phenomena and, possibly, in their increased incidence in the senescent heart.

Age Factors↗

PubMed1983

Abolition of digitalis tachyarrhythmias by caffeine.

Digitalis-induced ventricular tachyarrhythmias (VTAs) are believed to be due to oscillatory afterpotentials (OAPs) generated by an oscillatory release of calcium from the sarcoplasmic reticulum (SR). Caffeine blocks the calcium uptake into the SR and then may influence VTAs by depleting the SR stores of calcium. We studied the action of digitalis and caffeine, singly and in combination, in the isolated guinea pig heart perfused by means of a modified Langendorff apparatus. Digitalis (beta-methyldigoxin 1.27 X 10(-6) M) caused VTAs and ventricular fibrillation (VF) in all the hearts. Caffeine alone decreased heart rate but never caused VTAs. With the administration of digitalis and caffeine (1 mM), VTAs rarely developed and VF never occurs. With digitalis and higher concentration of caffeine (10 mM), neither VTAs nor VF were observed. In hearts with complete atrioventricular block, digitalis increased the ventricular rate from 143 +/- 10 to 270 +/- 13 beats/min (n = 8) in 12 +/- 1.9 min and provoked the appearance of multiple ventricular pacemakers. The addition of 10 mM caffeine to the digitalis-containing solution reduced the ventricular rate to 171 +/- 12 beats/min (P less than 0.001 vs. digitalis alone, not significant vs. control, n = 8) and abolished the digitalis-induced multiple pacemakers. Ventricular asystole was occasionally observed during the perfusion with digitalis + 10 mM caffeine. Caffeine alone did not modify the diastolic pressure, whereas caffeine and digitalis rapidly increase it. These results represent indirect evidence to support that SR plays an important role in the origin of the digitalis-induced VTAs.

Animals↗

PubMedDate not supplied

Increased propensity of the aged myocardium to develop calcium-related electrophysiological alterations.

The electrico-mechanical effects of calcium overload have been studied in cardiac papillary muscles of young adult and senescent Wistar rats driven at different rates. Action potential duration and contraction duration were found to be more prolonged in senescent than in younger animals during control conditions. Oscillatory afterpotentials and aftercontractions were more frequent in senescent than in younger rats during high calcium perfusion. Triggered activity was induced in senescent fibers but not in younger ones. Resting tension increased more in senescent fibers whereas the peak tension was not different in the two groups. It is concluded that aging is associated with a reduced capacity of the cardiac cells to handle an increased calcium load.

Journal Article↗

PubMedDate not supplied

Digitalis in the treatment of heart failure in the elderly. The GIFA study results.

Digitalis glycosides have played an important role in the treatment of patients with heart failure (HF) for more than two centuries. Despite the introduction of new therapeutic strategies in the treatment of HF, and controversies regarding the role of digitalis in HF in sinus rhythm and its effect on mortality, digoxin is one of the most commonly prescribed drugs in the community and in hospital settings, particularly in the elderly. The Italian Group of Pharmacosurveillance in the Elderly (GIFA) monitored 20,047 hospitalized patients in 1988, 1991 and 1993, and found that digoxin was the most frequently prescribed drug in the management of HF. Inappropriate prescriptions of digitalis, defined with standardized criteria, were uncommon, and the mean daily dosage was low. Compared to earlier studies the incidence rate of adverse drug reactions (ADRs) to digoxin, was also low. The reduction in ADRs incidence was probably due to a better understanding of digoxin pharmacokinetics and to a lower daily dosage in the elderly. Nevertheless, digoxin toxicity was significantly more frequent in patients aged >or= 80 years than in those aged < 65 and and 65-79 years. In a multidrug approach to the treatment of chronic HF, digoxin exerts clinical benefits also in patients with sinus rhythm, it is not costly, it is easy to administer, and toxic effects are not common.

Journal Article↗

PubMedDate not supplied

Assessment of physical function in aging rodents: a strategy for improving preclinical testing.

Geriatric medicine has recently focused on the biological mechanisms contributing to disability in the activities of daily living (ADLs), with special emphasis given to the study of sarcopenia, an age-related decline in muscle mass. Explaining the etiology of sarcopenia may provide useful information for the development of targeted interventions, especially those that are pharmacological in nature. However, exploratory studies aimed at evaluating the long-term effects of a particular intervention are costly and time consuming in a clinical setting. Therefore there is a need for preclinical testing of the efficacy of pharmacotherapies. This review provides (1) example of factors that contribute to the incidence of disability; (2) the conceptualization of a widely accepted human model of disability applied to an animal model; and (3) information on the potential advantages that may be realized from such translational research.

Activities of Daily Living↗