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Biomedical subjects

R Zucchi

Publications and source records attributed to R Zucchi.

At least 55 records · Page 3Linked to original sources
PubMed1992

Effects of verapamil, gallopamil, diltiazem and nifedipine on sarcoplasmic reticulum function in rat heart.

We investigated the effect of the calcium antagonists verapamil, gallopamil, diltiazem and nifedipine on cardiac sarcoplasmic reticulum function. In a cell-free homogenate from rat hearts, oxalate-supported Ca uptake was stimulated by verapamil, gallopamil and diltiazem at concentrations in the order of 10 nM to 100 nM, while higher concentrations were ineffective. Nifedipine was also ineffective. Peak stimulation of Ca uptake averaged 15-20% of control. Ca uptake is the difference between active Ca transport by Ca-ATPase and passive efflux through sarcoplasmic reticulum channels. In the presence of 300 microM ryanodine, which blocks sarcoplasmic reticulum channels, Ca uptake increased by 50%, but no further stimulation was produced by the addition of any calcium antagonist, at concentrations ranging from 1 nM to 100 microM. In a fraction enriched in sarcoplasmic reticulum, no drug affected the activity of Ca-ATPase at concentrations able to stimulate Ca uptake. We conclude that low concentrations of verapamil, gallopamil and diltiazem reduce Ca efflux through the Ca channels of the sarcoplasmic reticulum. Such an action might contribute to the clinical effect of these drugs.

Animals↗
PubMed1992

Adenosine and carnitine derivatives and calcium movements in rat heart sarcoplasmic reticulum.

Many researches indicate that some Ca antagonists modulate Ca fluxes not only at the level of the cytoplasmic membrane but also across the sarcoplasmic reticulum. The present study investigates whether certain compounds like propionylcarnitine or acetylcarnitine which have the capacity to influence cardiac activity might interfere with intracellular Ca movements. The results demonstrate that acetylcarnitine and propionylcarnitine do not affect the calcium intracellular movement in sarcoplasmic reticulum.

Acetylcarnitine↗
PubMed1991

Polyamines reduce heart injury caused by doxorubicin.

Isolated rat heart was perfused with 18 microM doxorubicin in the recirculating buffer. This treatment resulted in progressive contractile impairment. Aortic flow and minute work (i.e the product of cardiac output and peak systolic pressure) were reduced up to 20 and 29% of basal values, respectively. These parameters were partially restored in hearts perfused with 400 microM spermine, a naturally occurring polyamine, and 18 microM doxorubicin in the recirculating buffer. The results suggest the need for an investigation of the possible antagonistic role of polyamines against anthracycline cardiotoxicity.

Animals↗
PubMed1991

Effect of propionyl carnitine on cardiac energy metabolism evaluated by the release of purine catabolites.

The assessment of purine release in perfusion fluid is a new method (Zucchi et al.) which allows a continuous evaluation of energy metabolism in isolated perfused rat heart. Purine release in fact is related to the imbalance between ATP formed and utilized in myocytes. With this method we have investigated the effect of propionyl carnitine, carnitine and propionate on the working heart. The presence of millimolar concentrations of propionyl carnitine decreases purine release and improves cardiac performance as measured by cardiac output and double product (product of heart rate and aortic systolic pressure). Propionate has no effect, while carnitine slightly decreases purine release. The property shown by propionyl carnitine in decreasing the imbalance between ATP production and utilization and in improving cardiac performance is due to its ability to improve the energy metabolism of cardiomyocytes. This compound supplies oxidizable substrates and intermediates to the tricarboxylic acid cycle. In the presence of propionyl carnitine the myocardium therefore responds better to the sudden requirements of overwork and shows better functional efficiency for longer periods.

Adenosine Triphosphate↗
PubMed1990

Purine release from isolated rat heart: a new approach to the study of energy metabolism.

The rate of release of purines (adenosine, inosine, hypoxanthine, xanthine and uric acid) from isolated working rat hearts was measured and compared to tissue concentrations of high energy phosphate compounds. Hearts were subjected to different workloads, and perfusions were performed: with normal oxygen supply (group 1); with the addition of insulin to the standard perfusion buffer, which contained glucose as energy source (group 2); in hypoxic conditions (group 3). In each group purine release increased (P less than 0.01) at higher workload and was closely related to indices of mechanical performance such as cardiac output or minute work (r = 0.902 and 0.858 in group 1, r = 0.902 and 0.851 in group 2, r = 0.851 and 0.881 in group 3, P less than 0.001 in each case). Work had no effect on adenine nucleotides but produced a significant (P less than 0.01) reduction in phosphocreatine/creatine ratio. The comparison of different groups showed that at any level of heart performance purine release was higher (P less than 0.001) in group 3 vs. group 1, and lower (P less than 0.001) in group 2 vs. group 1. High energy phosphates were reduced in group 3 vs. group 1 but were unchanged in group 2 vs. group 1. We conclude that in the isolated heart purine release is directly related to the rate of energy consumption, and inversely related to the rate of energy production. Purine release provides a sensitive method to evaluate myocardial energy metabolism, which is more sensitive than measurement of high energy phosphates.

Animals↗
PubMed1990

Adenine nucleotide depletion and contractile dysfunction in the "stunned" myocardium.

STUDY OBJECTIVE: The aim of the study was to assess the contribution of adenine nucleotide depletion to postischaemic myocardial dysfunction ("stunned" myocardium). DESIGN: Isolated perfused hearts release purine catabolites even in the absence of ischaemia, and undergo spontaneous reduction of adenine nucleotide pool. A comparison was therefore made between mechanical function, purine release and tissue adenine nucleotides in working rat hearts reperfused after short term ischaemia or subjected to prolonged perfusion (up to 180 min). EXPERIMENTAL MATERIAL: 49 Sprague-Dawley rats of 250-300 g body weight were used. The animals were anaesthetised and the hearts quickly excised and perfused with the working heart technique. MEASUREMENTS AND MAIN RESULTS: Reperfusion after 10 min ischaemia provided a good model of "stunned" myocardium: aortic flow and minute work decreased by 15(SEM 2)% and 20(3)%, no enzyme leakage was observed, and the adenine nucleotide pool decreased by 3.5(0.4) mumols.g-1. During prolonged perfusion no change was observed in any haemodynamic variable until the adenine nucleotide pool was depleted by over 8.5 mumols.g-1. Adenylate energy charge and the phosphocreatine-creatine pool were unchanged in all cases. CONCLUSIONS: Depletion of adenine nucleotides does not account for contractile dysfunction in our model of "stunned" myocardium.

Adenine Nucleotides↗
PubMed1990

Effect of amrinone in the working rat heart: influence of ischaemic damage, adenosine and calcium.

The action of amrinone on the isolated working rat heart was studied. In basal conditions up to 400 mg/l amrinone behaved as a pure chronotropic agent, raising the heart rate by 23%. In ischaemia-damaged hearts 100 mg/l amrinone had a true inotropic action, provoking significant increases in cardiac output (11%), aortic flow (10%) and double product (9%). The addition of 10 microM adenosine, which inhibits the inotropic action of catecholamines, did not modify the response to amrinone. However, when calcium was reduced from 2.5 to 1.25 mM, the inotropy of ischaemia-damaged hearts was not significantly affected by amrinone, and its chronotropic action was reduced. It is concluded that after acute ischaemic damage amrinone increases heart performance even in a poorly responsive species in which no inotropic effect can be produced under basal conditions. In this model its action is resistant to adenosine but depends on the availability of a sufficient amount of extracellular calcium.

Adenosine↗
PubMed1989

Sarcoplasmic reticulum function in the "stunned" myocardium.

Transient ischemia does not induce myocardial necrosis but may be associated with prolonged contractile dysfunction ("stunned" myocardium). It has been suggested that alteration of the excitation-contraction coupling system (sarcoplasmic reticulum) could be responsible for this phenomenon. We tested this hypothesis by characterizing sarcoplasmic reticulum (SR) function in an isolated rat heart model of "stunned" myocardium (hearts reperfused after 10 min of normothermic global ischemia). At the end of the ischemic period oxalate-supported Ca-uptake was depressed either in the whole homogenate or in isolated SR (to 47% and 22% of control values, respectively). During reperfusion Ca-uptake of the whole heart homogenate recovered almost completely whereas slight but significant depression persisted in isolated SR (48 +/- 2 vs 67 +/- 4 nmol/min x mg, P less than 0.01). In the presence of ruthenium red or ryanodine, two inhibitors of SR Ca-release channels, Ca-uptake was stimulated. Both in the whole heart homogenate and in isolated SR, such stimulation was remarkably smaller after reperfusion than in control conditions (P less than 0.001) suggesting reduced conductivity state of the SR Ca-release channels. Ca-stimulated, magnesium-dependent ATPase activity was remarkably reduced during ischemia and postischemic reperfusion induced only incomplete recovery (93 +/- 18 vs 169 +/- 14 nmol ATP/min x mg protein, P less than 0.05). We conclude that complex modifications of SR function occur in the "stunned" myocardium and could contribute to the contractile impairment found in this condition.

Animals↗
PubMed1989

Protection of isolated rat heart from oxidative stress by exogenous creatine phosphate.

The influence of exogenous creatine phosphate (CP) on peroxidative heart injury was investigated in two experimental models: isolated working rat hearts and myocardial membrane preparations. In the first model the addition of 190 microM hydrogen peroxide to the perfusion buffer caused a marked decrease of aortic flow, minute work and peak aortic pressure, and leakage of intracellular enzymes. In the presence of 10 mM CP the hemodynamic damage produced by the same concentration of hydrogen peroxide was significantly lower and enzyme release was also remarkably reduced. The protection was concentration-dependent and the whole structure of the molecule was required since creatine was found to be ineffective. In the absence of hydrogen peroxide, CP and creatine did not affect heart performance. In microsomal membrane preparations CP decreased the formation of thiobarbituric acid-reactive material (malonaldehyde) induced by hydrogen peroxide in the presence of ferrous ions. This protection was concentration-dependent and occurred at physiological concentrations of CP. Also in this experimental model creatine had no effect and creatine plus inorganic phosphate was much less active than CP. The influence of CP on oxidative heart stress could account for the beneficial effect of this substance in different models of ischemic injury.

Animals↗
PubMed1989

The adenosine hypothesis revisited: relationship between purine release and coronary flow in isolated rat heart.

We evaluated the adenosine hypothesis through a new approach, based on the study of the relationship between coronary flow or resistance and purine release, which is an accurate index of myocardial adenosine release. Isolated rat hearts were perfused at different work loads, in hypoxic conditions and after a short period of global ischaemia. When the results of all experiments were considered together, purine release was significantly but weakly related to coronary flow and coronary resistance (r = 0.416 v coronary flow, r = 0.378 v the reciprocal of coronary resistance, p less than 0.01). Closer relationships were obtained within the three subgroups: the correlation coefficients increased to 0.819 and 0.835 (p less than 0.001) in the hearts perfused at different work loads with normal oxygen supply, to 0.701 and 0.757 (p less than 0.02 and p less than 0.01) in the hypoxic hearts, and to 0.897 and 0.978 (p less than 0.02 and p less than 0.01) in the hearts recovering from ischaemia. The relationships between purine release and coronary flow or resistance were significantly different in the three subgroups (p less than 0.001): at any value of purine release coronary resistance was highest during hypoxia and lowest after ischaemia, while the opposite was true for coronary flow. We suggest that the adenosine hypothesis is converted into a "weaker" statement: adenosine is involved in the adjustment between heart performance and coronary resistance but other factors contribute to the regulation of coronary flow, and/or affect the response to adenosine.

Adenosine↗
PubMed1988

Adenosine binding sites in pig ventricular sarcolemma and interaction with calcium channels.

Two classes of adenosine binding sites were identified in pig ventricular sarcolemma using 5'-N-[3H]ethylcarboxamideadenosine ([3H]NECA) as radioligand (Bmax = 88 fmol/mg protein, Kd = 28 nM; Bmax = 7100 fmol/mg protein, Kd = 730 nM). Competition experiments indicated that the higher affinity group had the pharmacological characteristics of the A2 adenosine receptors. The lower affinity binding sites may correspond to the A3 adenosine receptors demonstrated in rat brain. Results with the calcium antagonist [3H]nitrendipine suggest that adenosine exerts some of its effects on the heart also through a direct binding to specific calcium-channel subtypes.

Adenosine↗
PubMed1987

Asynergy and left ventricular performance in dilative cardiomyopathy.

The purpose of this work was to evaluate the presence and importance of asynergy in dilative cardiomyopathy. A semiautomatized analysis of left ventriculograms was performed in 18 cases, the morphology of longitudinal and transverse axes time-length curves was evaluated, and mathematical indices of asynchrony and hypokinesis were defined. Ten normal subjects and 9 patients affected by aortic regurgitation were used as controls. In dilative cardiomyopathy, anomalous (polyphasic) time-length curves were present in 55% of the cases, while they were absent in aortic regurgitation and in all normal subjects but one. In addition, the asynchrony index was slightly increased and the hypokinesis index significantly increased (28.8 +/- 7.2% vs. 17.8 +/- 7.1%, p less than 0.001). A negative correlation existed between the asynchrony index and the ejection fraction (r = -0.483, p less than 0.05) and both the ejection fraction and the maximum normalized velocity of contraction were reduced in the patients with the anomalous curves (29.7 +/- 6.9% vs. 46.0 +/- 11.5%, p less than 0.01; 1.66 +/- 0.52 s-1 vs. 2.86 +/- 1.33 s-1, p less than 0.02). It was concluded that asynergy, and especially asynchrony, is frequent in dilative cardiomyopathy and it is strongly associated with a major impairment of overall left ventricular function.

Adolescent↗