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R Ferrari

Publications and source records attributed to R Ferrari.

At least 361 records · Page 20Linked to original sources

Improved radioimmunoassay of atrial natriuretic peptide in plasma.

We describe a radioimmunoassay (RIA) for measurement of atrial natriuretic peptide (ANP), based on one-step incubation and a simplified extraction procedure. The extraction was performed on a "Supelclean LC 18" column, with 2-mL plasma samples. Use of a diiodinated tracer improved the sensitivity of the RIA method. The minimal detectable value was 5 ng/L. Simplification of the extraction procedure and simultaneous incubation of the reagents provide a method more suitable for routine standard assay of ANP than those currently available. Intra- and interassay CVs were 6% (n = 12) and 11% (n = 10), respectively. The mean concentration of ANP in plasma of 32 healthy volunteers was 33 (SEM 4) ng/L. The ANP values for plasma after one-step incubation correlated well with those determined by a commercial RIA kit: r = 0.971, slope = 1.099, intercept = 1.949 ng/L (n = 25).

Atrial Natriuretic Factor↗

Protective effects of gallopamil against ischemia and reperfusion damage.

To establish if the administration of gallopamil, a derivative of verapamil, protects heart muscle against the deleterious effect of ischemia and subsequent reperfusion, rabbits were injected subcutaneously twice daily with 2 mg/kg of Gallopamil for 5-6 days. The hearts were isolated and perfused with aerobic Krebs-Henseleit buffer solution by the Langendorff method. The hearts were paced (180 b/min) and wall temperature was controlled. Ischemia was induced by reducing coronary flow from 25 ml/min to 1 ml/min for 90 min and then the hearts were reperfused for 30 min. At the end of either the ischemic period or reperfusion, the hearts were assayed for ATP, CP, and calcium. Others were homogenized, their mitochondria harvested and monitored for oxidative phosphorylating and ATP generating activity as well as calcium content and uptake. The mechanical function of the hearts and noradrenaline release was also measured. Hearts that were made ischemic gained calcium, their endogenous stores of ATP and CP were depleted, their mitochondria had reduced RCI and state 3 respiration and increased calcium concentrations. During reperfusion tissue and mitochondrial calcium was significantly increased, the capacity of mitochondria to use oxygen for state 3 respiration was further impaired and their ATP generating capacity reduced. Diastolic pressure increased and there was no recovery of developed pressure and important noradrenaline release. Pretreatment with gallopamil protected the mitochondria against the ischemically induced changes in RCI, state 3 respiration. There was also a less marked rise in tissue and mitochondrial calcium and a reduced increase of diastolic pressure. Gallopamil also diminished the effect of reperfusion on the calcium accumulating activity of mitochondria and on the decline in the ATP generating and oxygen utilizing capacity of the mitochondria. The tissue levels of ATP and CP were better maintained, and noradrenaline release was reduced, the systolic pressure generating capacity was enhanced by the treatment with gallopamil. These results are discussed in accordance with the hypothesis that this drug protects heart muscle against the deleterious effects of ischemia and reperfusion by ensuring that sufficient ATP remains available to maintain homeostasis with respect to calcium.

Adenosine Triphosphate↗

Pulmonary endocrine cells in various species in the Himalaya.

The numbers, morphology and distribution of pulmonary endocrine cells in goats, sheep and the yak and its interbreeds with cattle, dzos and stols, were studied after their demonstration by means of the peroxidase-antiperoxidase technique with a polyclonal antiserum raised in the rabbit to human neuron-specific enolase, a marker for neuroendocrine cells. The numbers, morphology and distribution were related to species and not to residence at high altitude. Pulmonary endocrine cells were common and mainly distributed as solitary cells in the epithelium of the bronchial tree in sheep. They were much less common and found mainly as clusters in the alveolar capillary walls in goats and in the yak and its interbreeds with cattle.

Altitude↗

Metabolic changes during post-ischaemic reperfusion.

We attempted to identify the nature and time-course of metabolic changes occurring during ischaemia followed by reperfusion either in coronary artery disease patients undergoing intracoronary thrombolysis or in isolated and perfused rabbit hearts. Arterial and coronary sinus differences for oxygen, lactate, glucose, free fatty acid and creatine kinase were measured in patients undergoing successful intracoronary thrombolysis of left anterior descending occlusion. Early reperfusion (after 160 mins of ischaemia) restored aerobic metabolism and myocardial contractility. In contrast, reperfusion after more prolonged ischaemia (335 mins) did not restore mitochondrial function or contractile activity of the myocytes. Results obtained using isolated and perfused rabbit hearts also confirm that the likelihood of recovery during reperfusion depends on the rapidity of recanalization. Furthermore the data reported indicate that on reperfusion after prolonged ischaemia (90 mins) cell damage occurs, leading to a breakdown of the permeability barrier to ions and to larger molecules such as creatine phosphokinase. As a consequence, reperfusion produces a large increase of intracellular calcium, whilst the intracellular magnesium content is severely reduced. Under these conditions, with the observed loss of magnesium from the cell, mitochondrial calcium transport is highly stimulated and the equilibrium between ATP synthesis and calcium influx is shifted towards calcium influx. This sequence of events leads to mitochondrial calcium overload with subsequent damage of mitochondrial structure and loss of the ability to synthesize ATP. Reperfusion of the isolated rabbit hearts with solutions containing high magnesium and low calcium for 10 mins reduced mitochondrial calcium overload. This, in turn, resulted in maintenance of ATP synthesis and, on return to normal perfusate, in partial recovery of developed pressure and myocardial ATP content. These findings may be of importance in the restoration of blood flow to ischaemic heart muscle during thrombolysis.

Adenosine Triphosphate↗

Importance of early recanalization of the occluded coronary artery in acute myocardial infarction for preservation of left ventricular function.

Ninety-two patients with acute myocardial infarction, treated with intracoronary thrombolysis within 3 h from the onset of ischemic symptoms, were studied with coronary arteriography and left ventriculography. These examinations were repeated after 2 to 4 weeks to assess the importance of duration of ischemia on recovery of regional and global left ventricular pump function. Patency was achieved acutely and maintained at control angiography in 73 patients (87%), who were subdivided into three groups according to duration of ischemia before reperfusion: group 1 (29 patients): revascularized within 3 h; group 2 (22 patients): revascularized between 3 and 4 h; group 3 (22 patients): revascularized after 4 h. Patency was acutely achieved, but not maintained at control angiography in 11 patients (group 4), while thrombolysis was unsuccessful in eight patients (group 5). In group 1 there was a significant reduction in the number of hypokinetic segments (P less than 0.001) and a significant increase in mean percentual area change of hypokinetic segments (P less than 0.001) and in global ejection fraction (P less than 0.001). A still significant, but less evident improvement in these parameters was also seen in group 2 (P less than 0.05, P less than 0.01, P less than 0.01 respectively). Insignificant changes, with only occasional improvements were observed on group 3, while a tendency toward deterioration was found in group 4. A clear and significant (P less than 0.001) worsening of local and global ventricular function was detected in group 5. Our results indicate a significant inverse relationship between duration of ischemia and left ventricular functional improvement. Particularly, the first 3 to 4 h after onset of ischemic symptoms are critical for preservation of left ventricular function (group 1 and 2). Reperfusion after 4 h (group 3) is only rarely associated with improvement of ventricular motion. The importance of very early pharmacological thrombolysis and of maintenance of coronary patency is stressed.

Aged↗

Protective effect of a prostacyclin-mimetic on the ischaemic-reperfused rabbit myocardium.

To assess whether the administration of the stable prostacyclin-mimetic ZK 36374 (iloprost) protects the myocardium in a dose-dependent manner against ischaemia and reperfusion, isolated rabbit hearts were infused with three different concentrations of iloprost: 2.7, 27 and 270 nM. Diastolic and developed pressures were monitored; coronary effluent was collected and assayed for creatine phosphokinase (CPK) activity and for noradrenaline concentration; mitochondria were harvested and assayed for respiratory activity; ATP production and calcium content and tissue concentration of adenosine triphosphate (ATP) and creatine phosphate (CP) were determined. Treatment with iloprost altered neither developed pressure under normoxic conditions nor the rate and extent of depletion of ATP and CP during ischaemia. The ischaemic-induced deterioration of mitochondrial function, however, was attenuated. On reperfusion, hearts treated with iloprost recovered better than the untreated hearts with respect to left ventricular performance, replenishment of ATP and CP stores and mitochondrial function. The reperfusion-induced mitochondrial calcium overload and release of CPK and of noradrenaline were also significantly reduced. The effect of iloprost was dose-dependent. The lower concentration (2.7 nM) failed to modify ischaemic and reperfusion damage. The best protective effect was found at 27 nM. An increase of the dose to 270 nM did not result in further protection. It is concluded that iloprost infusion provides a dose-dependent protection of the heart against some of the deleterious effects of ischaemia and reperfusion and, in particular, prevents mitochondrial calcium overload and maintains mitochondrial function. Because this protection occurred in the absence of negative inotropic effect during normoxia or of a coronary dilatory effect during ischaemia, it cannot be attributed to an energy sparing effect or to improvement of oxygen delivery. Therefore, alternative mechanisms of action are to be considered.

Adenosine Triphosphate↗

The role of glutathione status in the protection against ischaemic and reperfusion damage: effects of N-acetyl cysteine.

It is known that myocardial ischaemia causes a marked decline of cellular thiol pool and of protein sulphydryl groups content. Reperfusion under these conditions results in oxydative damage which is concomitant with poor recovery of mechanical function. We have evaluated the role of glutathione status in the protection against ischaemic and reperfusion damage by treating the isolated rabbit hearts with N-acetylcysteine (10(-6) M), a sulphydryl group donor. Ischaemic and reperfusion damage was determined in terms of mechanical function, rate of lactate and creatine kinase (CPK) release, mitochondrial function and tissue content of reduced (GSH) and oxidized (GSSG) glutathione and of protein sulphydryl groups (SH). After 60 mins of ischaemia (induced by reducing coronary flow from 24 to 1 ml/min) followed by 30 mins of reperfusion there was an increase of diastolic pressure to 51.6 +/- 3.5 mmHg with only a 22% recovery of systolic pressure, massive CPK release and a deterioration in mitochondrial function. Tissue contents of GSH and of protein SH were severely decreased, while those of GSSG were increased. The GSH/GSSG ratio was reduced from the aerobic value of 50 to 13.4, suggesting that an oxidative stress has occurred. N-acetylcysteine infused for 60 mins before ischaemia determined a 38% increase in tissue content of GSH with no major changes of GSSG or protein SH. The ischaemic-induced decrease of GSH and protein SH was also limited by pretreatment with N-acetylcysteine and there was no accumulation of GSSG after reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗

Effect of L-carnitine derivatives on heart mitochondrial damage induced by lipid peroxidation.

We have incubated heart mitochondria with ferrous ions as catalyst of lipid peroxidation. Ferrous ions induced an increase of malondialdehyde formation and a reduction of mitochondrial oxygen consuming and calcium transporting capacities. L-Carnitine and Acetyl-L-Carnitine failed to prevent mitochondrial damage. Propionyl-L-Carnitine significantly improved mitochondrial function, but failed to reduce malondialdehyde formation. This protective effect was specific for Propionyl-L-Carnitine as propionic acid and L-Carnitine did not modify mitochondrial damage.

Acetylcarnitine↗

[Postoperative external biliary fistulas: personal case series].

Over the period 1974-1986, five patients with external biliary fistulas were admitted to our clinic. The fistulas set in as complications of surgical operations due in 3 cases to a Kehr drainage of the common bile duct, in 1 case to drainage of a subhepatic abscess and in 1 case to pancreatic hydatid cyst. The causes of onset of the fistulas are reported as well as the therapy adopted in each case.

Biliary Fistula↗

Immunoreactivity to various peptides in the human carotid body.

Human carotid bodies, removed at routine necropsies, have been subjected to radioimmunoassay for various peptides. Average levels of immunoreactivity, expressed in pm/g, were: met-enkephalin 612, leu-enkephalin 162, bombesin 73, neurotensin 67, VIP 9 and substance P 16. No alpha-hANP immunoreactivity could be detected.

Carotid Body↗