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U Limbruno

Publications and source records attributed to U Limbruno.

29 records · Page 2Linked 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↗
PubMed1991

Evaluation of pulmonary vascular pressures in cardiac patients: the role of the chest roentgenogram.

In 77 patients (34 with left heart valvulopathy, 17 with dilated cardiomyopathy, and 26 with chronic coronary artery disease) pulmonary vascular pressures were estimated from the chest film by means of a new scoring system. Standard chest x-ray films taken immediately before diagnostic right and left cardiac catheterization were analyzed independently by three readers without knowledge of the hemodynamic findings. The radiographic signs were subdivided into three groups as follows, and to each one a score derived from a retrospective statistical analysis was attributed: (A) signs of interstitial edema, (B) patterns of pulmonary blood flow distribution, and (C) alterations in the pulmonary arteries. The sum of the scores of groups A and B x-ray findings correlated well with pulmonary wedge pressure, and the sum of the scores of groups A, B, and C correlated more strongly with the mean pulmonary artery pressure. These results confirm that it is possible, in patients with chronic heart disease, to assess accurately the pulmonary artery and wedge pressures by means of the noninvasive and easily performed chest roentgenogram.

Blood Pressure↗
PubMed1991

[Coronary disease in patients operated on for valvulopathy].

In order to evaluate the influence of a significant coronary artery disease in patients with valvular heart disease or with prosthetic valves, we reviewed literature and our own experience. The incidence of coronary artery disease in valvulopathies has been diffusely studied and reported and, in a consecutive series of our hemodynamic studies, resulted 11%. The influence of a coronary artery disease on early and late results of a surgical procedure is different whether the coronary artery disease is operated or not. In particular, the combined surgery shows a higher early mortality, but a much better long-term prognosis. In addition, sometimes surgery introduces rare causes of coronary artery disease. Finally, it seems that coronary artery disease arises very rarely in patients undergone valvular surgery or, at least, patients rarely complain anginal symptoms in the post-surgical follow-up. In our experience on 529 patients only 6 complained typical angina and only 2 showed a coronary artery disease not present at the time of operation.

Aortic Valve↗
PubMed1990

Cardiac alpha-crystallin. III. Involvement during heart ischemia.

Rat hearts were perfused in the working heart or Langendorff mode and then subjected to total normothermic ischemia. The content of alpha-crystallin in the water soluble protein fraction obtained from these hearts diminished in a time-dependent manner during ischemia. The protein was recovered in the low g pellet of the homogenate. The redistribution was dramatic, selective for alpha-crystallin and irreversible. Large crystallin clumps formed also when exposing the soluble protein fraction of control hearts to slightly acidic pH (6.5-7.0). Electron microscopic analysis showed that aggregation of the globular homo-oligomeric units of crystallin occurred. The aggregates probably represented denatured protein and were similar in appearance to lenticular alpha H-crystallin. In purified form, however, cardiac crystallin particles did not cluster at pH 6.5. Aggregation only occurred in the presence of other protein components (including, probably, cytosolic actin) of the soluble fraction. A direct and selective interaction between actin and cardiac crystallin could be demonstrated using actin-Sepharose affinity chromatography procedures. The results suggest that large aggregates of cardiac crystallin form very early during ischemia, due to acidification of the cytosol. Cardiac crystallin is highly homologous to stress proteins and is localized on the Z-disks, where it plays probably a structural or protective role. Its rapid and complete denaturation could be involved in the genesis of the irreversible structural damages occurring during ischemia.

Animals↗
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↗
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↗