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Biomedical subjects

M Di Gennaro

Publications and source records attributed to M Di Gennaro.

At least 19 recordsLinked to original sources
PubMed1991

Possible sources of iron for lipid peroxidation.

Possible sources of iron for lipid peroxidation are described and discussed. In particular, evidence is presented that microsomes contain ferric nonheme iron which may participate in formation of lipid oxidants, provided reductants are available to favor its mobilization from membrane binding sites. Aging- and tumor-associated changes of this microsomal pool of nonheme iron are also described and discussed from biochemical and biomedical viewpoints.

Animals↗
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

Microsomal iron-dependent NADPH oxidation: evidence for the involvement of membrane-bound nonheme iron in NADPH oxidation by rat heart microsomes.

Rat heart microsomes were found to contain nonheme iron and two lines of evidence suggested that this iron was involved in NADPH oxidation. As first evidence, pretreatment of rats with iron gluconate increased microsomal iron content and NADPH oxidation. As second evidence, treatment of microsomes with nonionic detergent Triton N-101 decreased membrane iron content and NADPH oxidation. Triton N-101-solubilized nonheme iron was nondialyzable and ammonium sulfate-precipitable, indicative of association with protein(s). This protein-bound iron per se did not oxidize NADPH but its addition to detergent-treated microsomes restored very high rates of NADPH oxidation, that were abolished by inhibiting NADPH-cytochrome P450 reductase with p-hydroxymercuribenzoate. Since heart microsomes did not contain cytochrome P450, these results suggested that stimulation of NADPH oxidation was mediated by direct electron transfer from reductase to iron. Purified rat heart ferritin and hemosiderin did not stimulate NADPH oxidation and the stimulation observed with detergent-solubilized microsomal iron was much higher than that observed with EDTA-Fe3+, a very effective electron acceptor for the reductase. This suggested that (i) microsomal iron was different from other intracellular iron-storage proteins, and (ii) microsomal iron was unusually permissive to one-electron transfer from reductase.

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

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

An outbreak of cholera in a refugee camp in Africa.

A total of 541 cases of cholera were observed between May 7 and July 19, 1985 among the 9,929 displaced persons present in a refugee camp in Africa. In spite of malnutrition and other diseases affecting this population, only 12 deaths occurred. Antiepidemic measures consisted of preparation of isolation-wards, treatment of contaminated materials, training of refugees and patient care. Mass prophylaxis, initially considered, was dropped before the end of the epidemic.

Adolescent↗
PubMed1988

Induction of overdrive excitation in the sinoatrial node in the presence of caffeine.

The induction of spontaneous repetitive activity by a drive ('overdrive excitation') was studied in the sinoatrial node of the guinea pig by recording electrical and mechanical activity in sinoatrial preparations made quiescent by exposure to 20 mM caffeine of caffeine plus high [Ca]0. Electrical drive induced action potentials that were followed by oscillatory potentials and simultaneous aftercontractions. The oscillatory potentials (and the associated aftercontractions) increased in magnitude with successive action potentials, thereby initiating spontaneous beats during slow drives or after fast drives. The repetitive activity eventually slowed and ceased abruptly as the oscillatory potential failed to attain the threshold. Overdrive induced oscillatory potential and aftercontractions even when it did not initiate spontaneous activity. These results suggest that in the presence of caffeine calcium overload can occur in the sinoatrial node and result in oscillatory potentials and abnormal automaticity.

Action Potentials↗
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

Relationship between caffeine effects and calcium in canine cardiac Purkinje fibers.

The actions of caffeine (1-9 mM) on electrical and mechanical events were studied under conditions known to change the intracellular calcium in canine cardiac Purkinje fibers perfused in vitro. It was found that caffeine in a dose-dependent manner 1) shifts the early repolarization to more positive values, 2) shifts the plateau to more negative values, 3) prolongs the terminal phase 3 (induction of a "tail"), 4) transiently increases and then decreases the force of contraction with respect to control values, 5) causes a smaller tail in the presence of agents (local anesthetics, tetrodotoxin, high potassium) that have been shown to diminish the force of contraction, presumably by decreasing cellular calcium, 6) causes the oscillatory potentials in high calcium to peak sooner after the action potential and eventually to disappear as the tail develops, 7) induces a tail at lower concentrations when cellular calcium is enhanced by lowering the external sodium concentration or in the presence of veratridine, and 8) fails to induce a marked tail in the presence of metabolic inhibitors. It is concluded that in Purkinje fibers caffeine induces a marked delay in the final repolarization through a process modulated by calcium. This process may be related to an electrogenic sodium-calcium exchange.

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↗