PubMed HealthSearch

Biomedical subjects

A Sgadari

Publications and source records attributed to A Sgadari.

7 recordsLinked to original sources

Temperature-dependence of the age-related difference in the inotropic effect of norepinephrine in the rat myocardium.

The influence of temperature on the myocardial inotropic response to norepinephrine was studied in rats of different ages. Right papillary muscles isolated from 3-, 12-, and 24-month-old rats were superfused at two temperatures (29 degrees C and 37 degrees C) with progressively larger doses of norepinephrine. At 29 degrees C, the contraction duration was longer and the inotropic effect of norepinephrine was significantly smaller in 24-month muscles than in 3- and 12-month preparations. In muscles superfused at 37 degrees C, these age-related differences in the contraction duration and in the response to norepinephrine disappeared. Analysis of variance and covariance showed that temperature, but not age, is responsible for the differences in the inotropic response to norepinephrine observed. These results show that experimental conditions, among which temperature may play a major role, deeply affect the responsiveness of cardiac preparations to beta-adrenergic agonists.

Aging

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

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

[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

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

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

Age-related differences in isolated rat sinus node function.

In order to rule out age-related differences in the sinus node (SN) function, the effects of different substances were tested in SN isolated preparations from adult (4-5-month-old) and old (24-25-month-old) rats. No difference was seen in the in vivo heart rate between adult and old rats, whereas sinus node rate (SNR) was significantly lower in the old rather than in the adult preparations. The effects of acetylcholine (10(-9)-10(-5) M) were similar between the two groups of preparations. The response to adenosine (10(-9)-10(-4) M) was significantly higher in the adult than in the old preparations (p less than 0.05). No significant difference was noted in the response to isoproterenol (10(-10)-10(-6) M). High calcium (5.4-8.1 mM) caused an increase of the SNR that was significantly greater in the old than in the adult preparations (p less than 0.005). In conclusion, our results show an age-related decrease in the isolated SNR that does not seem to be mediated by different responses to neuromediators but is probably due to an alteration of the intrinsic activity of the SN cells.

Acetylcholine