Biomedical subjects

R Raddino

Publications and source records attributed to R Raddino.

At least 37 records · Page 2Linked to original sources

PubMed1990

Effects of anipamil on myocardial sarcolemmal and mitochondrial calcium transport, comparison with verapamil and nifedipine.

The calcium antagonists anipamil, verapamil and nifedipine inhibited, dose dependently, passive and ATP-driven 45Ca2(+)-uptake in purified rabbit ventricular sarcolemmal vesicles exposed to a wide range of free calcium concentration (from 0 to 200 microM). The IC50 values for passive binding were virtually identical for all calcium antagonists and the inhibition was relatively independent of the amount of free calcium employed. On the contrary, the order of potency for inhibition of the ATP-driven calcium uptake was: anipamil greater than verapamil greater than nifedipine. The inhibition of nifedipine, at free calcium concentrations lower than 80 microM, was preceded by a slight stimulation. The inhibitory effects of anipamil and verapamil, but not those of nifedipine, on the ATP-driven calcium uptake were more evident with increasing external calcium concentration. Verapamil and nifedipine failed to modify the initial rate of mitochondrial calcium transport either in the presence or in the absence of ADP; on the contrary, anipamil induced a dose-dependent inhibition of mitochondrial calcium transport. The inhibition occurred over the whole range of calcium concentrations tested, independent of the presence of ADP. The effects of anipamil, but not those of verapamil and nifedipine, on sarcolemmal and mitochondrial calcium transport were long lasting and survived membrane isolation.

Adenosine Triphosphate↗

PubMed1990

Assessment of peak oxygen consumption, lactate and ventilatory thresholds and correlation with resting and exercise hemodynamic data in chronic congestive heart failure.

To determine the clinical value of respiratory gas analysis during exercise, oxygen consumption (VO2) at peak exercise and at lactate and ventilatory threshold was assessed in 34 patients with chronic heart failure who underwent maximal exercise testing with expiratory gas monitoring and serial determinations of mixed venous lactate and hemodynamics by Swan-Ganz catheterization. A lactate threshold, defined as the point of abrupt increment of blood lactate, could be identified in every patient; the ventilatory threshold, detected on the basis of the respiratory changes, was found in 26 patients (77%). Lactate and ventilatory thresholds were significantly related to each other (r = 0.94; p less than 0.001) and to peak VO2 (r = 0.89; p less than 0.001 in both). Among the resting hemodynamic measurements, peak VO2 was significantly related only to total pulmonary resistances (r = -0.35). Among the parameters at maximal exercise, it was positively related to cardiac index, stroke work, stroke volume index and mean arterial pressure (r = 0.89, 0.74, 0.74 and 0.56, respectively) and inversely related to systemic vascular and total pulmonary resistances (r = -0.74 and -0.63). Using multivariate stepwise regression analysis only maximal cardiac index and, to a lesser degree, total pulmonary resistance were related to peak VO2. Similar correlations were found between the hemodynamics and the lactate and ventilatory threshold. Thus, peak VO2, lactate and ventilatory thresholds can be detected in most patients with chronic heart failure. These parameters are highly correlated to each other and bear similar relations to the hemodynamic response to exercise. The cardiac index is the main central hemodynamic determinant of exercise capacity.

Adult↗

PubMed1990

Beta 1- and beta 2-receptors are differentially desensitized in an experimental model of heart failure.

Recent reports suggested that a complex alteration in beta-receptor function occurs in failing human myocardium. We evaluated beta-receptor-subtype activity in an experimental model of monocrotaline (MCT)-induced cardiomyopathy in the rat. Through pulmonary hypertension, MCT causes right ventricular hypertrophy (RVH), either associated with heart failure or not, beta-Receptor function was evaluated in both failing-hypertrophic and hypertrophic hearts in binding studies with [125I]iodocyanopindolol (ICYP) and by measuring adenylate cyclase (AC) activity. In the right failing ventricle, beta 1- but not beta 2-receptor density was decreased. Lesion-associated modifications in the adenylate cyclase system were also observed: isoproterenol- and guanosine 5' [beta, gamma-imido]triphosphate [Gpp(NH)p]-stimulated cyclic AMP formation was reduced in the right failing ventricle, while the cyclic AMP responses to NaF and forskolin were unchanged. On the other hand, no changes in either beta-receptor density or function were found in hypertrophic ventricles. MCT-induced heart failure in the rat is thus associated with a selective decrease of beta 1-receptor density and function. These results suggest that MCT-induced cardiac failure may be an appropriate model in which to investigate heart insufficiency further.

Adenylyl Cyclases↗

PubMed1990

[The adrenergic beta system in an experimental model of heart failure].

Reports in the literature have suggested that a complex alteration in beta-receptor pathway takes place in failing human myocardium. The purpose of our study was to evaluate the beta-adrenergic receptor system in an experimental model of heart failure induced by monocrotaline in rats. Monocrotaline, administered with a single intraperitoneal injection (50 mg/Kg), causes pulmonary hypertension and right ventricular hypertrophy, associated with congestive heart failure. beta 1 and beta 2-receptors were characterized in the right ventricle by direct radioligand binding utilizing [125I] Iodocyanopindolol and selective beta 1-(CGP 20712A) and beta 2-(ICI 118551) antagonists. Adenylate cyclase was measured in basal condition and in the presence of different stimulators as isoproterenol with ICI 118551 (beta 1-receptor-stimulated activity), isoproterenol with CGP 20712A (beta 2-receptor-stimulated activity), Gpp(NH)p, NaF and forskolin. In the right ventricle of the failing hearts the beta 1-receptor density decreased selectively (-55.8%) while the beta 2-receptor density was unchanged. Modifications in the adenylate cyclase system were demonstrated: a reduction in the basal and beta 1- and beta 2-stimulated adenylate cyclase activity; a decrease in adenylate cyclase activation elicited by Gpp(NH)p, but not by forskolin and NaF. In conclusion, these data suggest that in monocrotaline-induced heart failure in the rat there is a selective beta 1-receptor down-regulation and an impaired coupling efficiency of G proteins. These results are in line with biochemical changes found in patients with heart failure.

Adenylyl Cyclases↗

PubMed1990

Alterations of calcium metabolism in spontaneously hypertensive rats.

We have examined the femurs of eight male spontaneously hypertensive rats and eight male Wistar Kyoto rats, aged 24 weeks. The mineral density of the bones was determined at the mid-point of the femurs by dual photon absorptiometry and the calcium content was estimated on bone ash by atomic absorption spectrophotometry. The data show that spontaneously hypertensive rats have lower bone density and calcium content than do age-matched Wistar Kyoto rats.

Absorptiometry, Photon↗

PubMed1990

Effects of temperature on myocardial calcium homeostasis and mitochondrial function during ischemia and reperfusion.

An isolated rabbit heart preparation was used to characterize the effects of hypothermia on the deterioration in mitochondrial respiratory function and on the calcium overload that occurs during ischemia and reperfusion. Hearts were perfused aerobically with an asanguineous solution for 120 minutes or made totally ischemic for 90 minutes at 37 degrees, 34 degrees, 28 degrees, 22 degrees C, respectively, and reperfused for 30 minutes at 37 degrees C. Mitochondrial function was assessed by measuring calcium content, yield, oxygen consumption, and adenosine triphosphate-producing capacities. In addition, the mechanical function of the hearts was measured together with tissue adenosine triphosphate, creatine phosphate, and calcium content. In a separate series of experiments, the effect of temperature on the initial rate of respiration-supported calcium accumulation of mitochondria from freshly excised, nonperfused rabbit hearts was determined. The hearts made ischemic at 37 degrees C were severely depleted of tissue adenosine triphosphate and creatine phosphate. Their mitochondria accumulated calcium and the oxidative phosphorylating activity was impaired. During reperfusion, tissue and mitochondrial calcium levels were substantially increased, state 3 of mitochondrial respiration was further impaired, and the adenosine triphosphate-generating capacities were severely reduced. Diastolic pressure increased and there was no recovery of developed pressure. Isolated mitochondrial function of hearts made ischemic at 28 degrees and 22 degrees C was protected. There was a less marked increase in tissue and mitochondrial calcium, and the initial rate and total production of adenosine triphosphate were maintained. In these hearts there was an almost complete recovery of mechanical performance at reperfusion, whereas the ischemia-induced depletion of tissue adenosine triphosphate and creatine phosphate was not significantly reduced by hypothermia. The hearts made ischemic at 34 degrees C were only partially protected. These data suggest that a decrease in temperature from 37 degrees to 22 degrees C during ischemia did not significantly prevent depletion of adenosine triphosphate at the end of ischemia but reduced tissue and mitochondrial calcium overload, maintaining mitochondrial function. Thus in our experiments the protective effect of hypothermia might be related to a direct reduction of tissue and mitochondrial calcium accumulation rather than to a slowing in rates of energy utilization. This possibility is supported by the finding that in freshly excised, nonperfused rabbit hearts, hypothermia significantly reduced the initial rate of mitochondrial calcium transport.

Animals↗

PubMed1989

Prolonged protective effect of the calcium antagonist anipamil on the ischemic reperfused rabbit myocardium: comparison with verapamil.

To assess whether pretreatment with the calcium antagonist anipamil protects the heart against ischemic and reperfusion damage and to establish how long the protection persists after cessation of the therapy, rabbits were injected subcutaneously twice daily for 5 days with 2 mg/kg body weight of this drug. The heart was then isolated 2, 6, or 12 hours after the last injection and was perfused by the Langendorff technique during a control period and 90 minutes of total ischemia (37 degrees C), followed by 30 minutes of reperfusion. Diastolic and developed pressure was monitored; coronary effluent was collected and assayed for creatine phosphokinase (CPK); mitochondria were harvested and assayed for respiratory activity, ATP production, and calcium content; and tissue concentration of adenosine triphosphate (ATP) and creatine phosphate were determined. The data obtained with anipamil were compared with those obtained with verapamil administered to the rabbit at the same dose and following the same procedure. Pretreatment with anipamil induced a negative inotropic effect under normoxic conditions; reduced the rate and extent of depletion of ATP and creatine phosphate during ischemia, with an incomplete restoration of the nucleotides after reperfusion; maintained mitochondrial function and calcium homeostasis during ischemia and reperfusion; reduced the rate of CPK release; and improved the recovery of ventricular function on reperfusion. The protective effects of anipamil persisted for as long as 12 hours after the last administration. In contrast, the protective and negative inotropic effects of verapamil were no longer apparent in heart isolated 6 or 12 hours after the last dose of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1989

Inhibitory actions of amiodarone on the isolated rabbit heart and aorta.

1. The inhibitory actions of amiodarone on the isolated rabbit heart and aorta have been studied. 2. Amiodarone inhibited vasopressin- and ergonovine-induced coronary spasm, starting from a concentration of 10(-7) M which did not affect myocardial contractility to 10(-4) M, which decreased myocardial contractility. 3. Sinus node activity was largely unaffected even when the highest dose of 10(-4) M was used. 4. Amiodarone did not modify the smooth muscle contraction in rabbit aorta strips precontracted with noradrenaline or potassium. 5. Comparison with other inhibitors of the cardiovascular system (alpha- and beta-blockers, nitrates, calcium entry blockers) points out a peculiar pharmacological profile of amiodarone and indicates some doubts about its presumed anti-adrenergic properties.

Amiodarone↗

PubMed1989

Action of steroid sex hormones on the isolated rabbit heart.

Steroid sex hormones, testosterone, progesterone and diethylstilbestrol, have been tested on the isolated rabbit heart. These hormones produced a negative inotropic effect (1-10 mumol/l) and an inhibitory effect on the vasopressin- or ergonovine-induced coronary spasm (0.1-10 mumol/l). Basal coronary tone was increased by testosterone and progesterone, while diethylstilbestrol induced a slight reduction of coronary perfusion pressure. The negative inotropic effect was reversed by calcium and isoprenaline, thus resembling the calcium entry blocker activity. The activation of myocardial and coronary contractility by the calcium agonist, Bay K 8644, was antagonized by all these hormones. These observations demonstrated an influence of steroid sex hormones with calcium fluxes in the isolated rabbit heart.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1989

[Pharmacologic characterization of the internal mammary artery used in myocardial revascularization].

The aim of this study concerned the pharmacological investigation of the isolated internal mammary artery. Spirally-cut vascular segments were obtained from patients undergoing myocardial revascularization and set up in isolated baths under isometrical tension. Reactivity of internal mammary artery preparations to stimulatory and inhibitory agents was evaluated. KCl (90 mM), noradrenaline (10-8)-10(-5) M) and serotonine (10(-9)-10(-5) M) induced a tonic contraction lasting for more than 60 min. Angiotensin II (10(-6)-10(-5) M) and dopamine (10)-8)-10(4) M) resulted virtually uneffective. The serotonine-induced contractions were strongly inhibited by ketanserin (10-9)-10(-6) M), a selective S2-blocker, and also by verapamil (10(-3)-10(-6) M) and nitroglycerin (10(-7)-10(-5) M). These data suggest that internal mammary artery is sensitive to different contractile agents, in particular serotonine activates muscular contractions through S2 receptors. The knowledge of such a mechanism may be of clinical relevance.

Acetylcholine↗

PubMed1988

A randomized double-blind crossover study of nicardipine and nifedipine in patients with angina pectoris and concomitant essential hypertension.

The two dihydropyridine calcium antagonists, nicardipine and nifedipine, were compared in 12 patients with both stable angina pectoris and systemic hypertension using a double-blind, crossover protocol. After a 2-week placebo run-in period, each patient was randomized to either nicardipine or nifedipine; each drug was titrated up to either blood pressure normalization, appearance of adverse effects, or maximal dosage (40 mg, three times a day with nicardipine and 30 mg, three times a day with nifedipine) and then administered for 4 weeks. Maximal symptom-limited exercise tests were performed at the end of the placebo run-in and each treatment period, 3 and 8 hours after drug administration. Nicardipine and nifedipine were used at the mean doses of 100 +/- 20 mg/day and 57 +/- 20 mg/day, respectively. Both drugs reduced, significantly and similarly, standing and supine blood pressure, frequency of anginal episodes, and nitroglycerin consumption. At 3 hours after drug administration, exercise duration and time to 1-mm ST depression increased significantly from 402 +/- 84 and 306 +/- 108 seconds, respectively, with placebo; to 533 +/- 135 and 442 +/- 138 seconds during nicardipine; and to 518 +/- 118 and 437 +/- 133 seconds during nifedipine, with a concomitant reduction of peak ST depression. Both submaximal and maximal exercise diastolic blood pressure were significantly reduced by the two calcium antagonists whereas systolic blood pressure was decreased only at submaximal but not at maximal exercise; the heart rate was not significantly modified by the two drugs at any exercise stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Effects of calcium entry blockers not connected with calcium channels inhibition.

We tested the effects of calcium entry blockers (verapamil, nifedipine, diltiazem) in comparison with nitroglycerin to investigate their inhibitory mechanisms of smooth muscle contraction not connected with the calcium blockade through calcium channels. The experiments were carried out by using isolated rabbit aorta strips in both normal and Ca2+-free solutions. Our results indicate that nitroglycerin and calcium entry blockers act on different calcium pools; the differences observed among calcium entry blockers suggest that other factors, different from calcium channels blockade (alpha-adrenergic block, unspecific effects), may be responsible for their inhibitory effect when high doses are employed.

Angiotensins↗

PubMed1987