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Biomedical subjects

R Ferrari

Publications and source records attributed to R Ferrari.

At least 217 records · Page 12Linked to original sources
PubMed1995

Tumor necrosis factor soluble receptors in patients with various degrees of congestive heart failure.

BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) increases in patients with severe congestive heart failure (CHF) and cachexia. Two naturally occurring modulators of TNF-alpha activity have been identified in human serum. These two soluble proteins are the extracellular domains of the TNF receptors (sTNF-RI and sTNF-RII, respectively). The determination of circulating sTNF-Rs could provide us with some additional information about the activation of this cytokine in CHF. METHODS AND RESULTS: This study was undertaken to examine the concentration of sTNF-Rs and of bioactive and antigenic TNF-alpha in 37 consecutive patients with various degrees of CHF compared with that of 26 age-matched healthy subjects. Antigenic TNF-alpha increased (from 14.3 +/- 7.08 to 33.5 +/- 13.1 pg/mL, P < .001) in preterminal patients with severe CHF (New York Heart Association [NYHA] class IV). In these patients, sTNF-Rs were also increased (sTNF-RI from 1.17 +/- 0.43 to 4.43 +/- 2.14 ng/mL and sTNF-RII from 2.2 +/- 0.44 to 7.55 +/- 2.28 ng/mL, P < .001). When measured by cytolytic bioassay, TNF-alpha was undetectable (< 100 pg/mL). Addition of 625 pg/mL recombinant human TNF-alpha (rhTNF-alpha), corresponding in the bioassay to 60% of the lethal dose, to the serum of healthy subjects resulted in a significant increase of the expected cytotoxicity (from 625 to 1290 +/- 411 pg/mL, P < .001). Addition of the same dose of rhTNF-alpha to the serum of patients with mild to moderate CHF (NYHA classes II and III) increased the cytotoxicity from 625 to 877 +/- 132 pg/mL, P < .001. In 4 patients with severe CHF (class IV), the expected cytotoxicity was completely inhibited, whereas it was reduced from 625 to 263 +/- 198 pg/mL, P < .001, in the remaining 8 patients. Ten patients died within 1 month of entry into the study. They had the highest level of sTNF-RII (8.18 +/- 1.92 ng/mL). sTNF-RII was a more powerful independent indicator of mortality than TNF-alpha, sTNF-RI, NYHA class, norepinephrine, and atrial natriuretic peptide. CONCLUSIONS: Measurement of sTNF-Rs, in addition to antigenic and bioactive TNF-alpha, is essential for evaluation of the activation of this cytokine in CHF. Both sTNF-Rs increase in preterminal patients with severe CHF and might inhibit the in vitro cytotoxicity of TNF-alpha. Antigenic TNF-alpha also increases in severe CHF. The increased levels of sTNF-RII independently correlate with poor short-term prognosis.

Adult↗
PubMed1995

Metabolic disturbances during myocardial ischemia and reperfusion.

Myocardial ischemia is defined as an imbalance between fractional uptake of oxygen and the rate of cellular oxidation in the heart. This condition may have several potential outcomes: (1) when ischemia is brief, a transient post-ischemic ventricular dysfunction occurs on reperfusion, a condition termed "stunned myocardium"; (2) when it is prolonged and severe, irreversible damage occurs, with no recovery in contractile function upon reperfusion; (3) when ischemia is less severe, but still prolonged, the myocytes may remain viable but exhibit depressed contractile function. Under this condition, named "hibernating myocardium," the reperfusion is able to restore contractility. During these different ischemic conditions many biochemical changes happen; initially they represent a defensive and protective reaction against ischemic insults such as cellular acidosis and increase of inorganic phosphate levels that rapidly abolish the contractile activity. But with the prolongation of ischemia or restoration of the coronary flow, alterations in ions and overall Ca2+ homeostasis occur, together with an oxidative stress mediated by oxygen free radicals, which are not adequately counteracted by the cellular antioxidant defenses. All these biochemical alterations lead to membrane damage, mitochondrial swelling, and irreversible deterioration of contractile function.

Animals↗
PubMed1995

Heat shock protein 72 in cardiac and skeletal muscles during hypertension.

In order to elucidate the relationship between hypertension and hypertrophy in the production of heat shock proteins, we studied the induction of the HSP72 synthesis by the heart and gracilis muscles of normo (WKY) and hypertensive (SHR) rats subjected to hyperthermia (42 degrees C +/- 0.5 for 15 min). Two age groups were investigated in each strain: young (2 months, with developing cardiac hypertrophy) and old (18 months, with fully developed chronic cardiac hypertrophy). The gracilis muscle never developed hypertrophy, independently of hypertension or aging. 72 kDa inducible protein was determined by Western blot analysis using a specific monoclonal antibody. We also used a commercial standard, loaded on each blot, to quantitate densitometrically the signal. The heart of young SHR responds to heat shock more than their normotensive age-matched control (298.8 +/- 24.7% vs 88.3 +/- 8.5%, p < 0.001). This response is not maintained during aging as we did not find any significant difference between normo- and hypertensive old rats after exposure to hyperthermia (43.6 +/- 5.3% vs 65.3 +/- 10.4%). Unlike the heart, the gracilis muscle shows a basal spontaneous HSP72 synthesis in both the SHR (71.4 +/- 10.8%) and WKY (40.6 +/- 11.7%) animals. There was a significant increase in HSP72 synthesis in the gracilis muscle of young SHR with respect to their control (186.2 +/- 18.7% vs 115.8 +/- 9.9%, p < 0.02) which was maintained also during aging (171.9 +/- 17.3% vs 95.2 +/- 10.5%, p < 0.01). In conclusion, these data show that hypertension results in an increased synthesis of HSP72 both in cardiac and gracilis muscle in response to heat shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Calcium antagonists and left ventricular dysfunction.

Calcium antagonists are used in the management of a variety of cardiovascular disorders. Ischemia leads to left ventricular dysfunction, which is the clinical entity on which the calcium antagonists are expected to have their effect as a result of their anti-ischemic action. This article reviews the efficacy of calcium antagonists in several different settings of left ventricular dysfunction due to ischemia and reperfusion.

Calcium Channel Blockers↗
PubMed1995

In vitro administration of ergothioneine failed to protect isolated ischaemic and reperfused rabbit heart.

Ergothioneine, a natural thiol-containing molecule, has recently been proposed to protect the heart against damage caused by ischaemia and reperfusion. We investigated the possibility that ergothioneine can have a role in maintaining the myocardial thiol/disulfide balance and consequently also a protective effect against ischaemic and reperfusion injury. We used isolated Langendorff-perfused rabbit hearts subjected to 45 min global and total ischaemia followed by 30 min reperfusion at baseline coronary flow (22 ml/min). Ergothioneine was delivered at 10(-5) M and 10(-4) M 60 min before ischaemia and during reperfusion. Myocardial damage was determined in terms of mechanical function, creatine kinase (CK) and lactate release, energy phosphate stores and the occurrence of oxidative stress. In our experimental conditions the treatment was unable to prevent myocardial damage. Ergothioneine, independently from the dosage used, failed to: (i) increase recovery of developed pressure upon reperfusion (14.4 +/- 2.3 mmHg in control hearts vs. 10.3 +/- 2.9 and 12.5 +/- 2.3 mmHg in 10(-5) M and 10(-4) M ergothioneine treated hearts, respectively); (ii) decrease the rise in diastolic pressure (44.3 +/- 4.4 mmHg in control hearts vs. 49.8 +/- 5.8 and 48.0 +/- 7.7 mmHg in treated hearts); (iii) decrease the release of CK and lactate; (iv) increase the levels of adenosine triphosphate (ATP) and creatine phosphate (CP) in tissue upon reperfusion; (v) maintain ratio between oxidized and reduced forms of adenine nucleotide coenzyme, as index of aerobic metabolism; (vi) prevent the decline of reduced glutathione (GSH), or the accumulation of oxidized glutathione (GSSG) as an index of oxidative stress.

Adenine Nucleotides↗
PubMed1995

Biochemical evaluations in skeletal muscles of primates with MPTP Parkinson-like syndrome.

The toxic effects of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in primates can be exploited for investigating the physiopathology of Parkinson's disease which may also cause functional alterations of skeletal muscles, whose biochemical modifications have been studied very little. Some enzyme activities related to energy transduction in skeletal muscles were evaluated (gastrocnemius, soleus and biceps) from MPTP-treated monkeys. Systemically administered MPTP altered the enzyme activities related to: (i) the anaerobic glycolytic pathway (decrease in hexokinase and phosphofructokinase activities; increase in lactate dehydrogenase activity); (ii) the tricarboxylic acid cycle (decrease in malate dehydrogenase activity); (iii) the electron transfer chain (decrease in cytochrome oxidase activity related to complex IV). No alteration in mitochondrial Complex I was observed. Treatment with an ergot alkaloid derivative (dihydroergocryptine) modified some alterations in the muscle enzyme activities and reduced the rigidity and some autonomic dysfunction.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

Intermittent v continuous ischemia decelerates adenylate breakdown and prevents norepinephrine release in reperfused rabbit heart.

Myocardium tolerates intermittent ischemia followed by short reperfusions better than continuous ischemia of the same duration. We attempted to delineate the differential mechanism(s) involved in intermittent v continuous ischemia. Isolated, paced rabbit hearts were perfused at 22 ml/min. Coronary flow was stopped intermittently 12 x for 2 or 4 min, with 3-min reperfusions (total reperfusion period: 36 min). In two other groups, flow was stopped continuously for 24 or 36 min followed by a flat 36-min reperfusion. Following the first intermittent 2-min ischemia, adenosine efflux increased ninefold; in all subsequent ischemia/reperfusion cycles, adenosine and total purine releases were substantially less despite identical heart rates, coronary flows and ischemic periods. The rate-pressure product prior to the intermittent ischemias exhibited exponential correlations with total purine efflux during the 3 min of reperfusion. When intermittent ischemia was extended to 4 min, the initial attenuation of ATP breakdown during the prior 2-min occlusions was overcome, but during subsequent 4-min ischemia/reperfusion cycles, ATP breakdown was again attenuated relative to the first 4-min ischemia. After the prolonged continuous ischemias, purine efflux was up to 6 x higher than with intermittent ischemias of the same total time of zero flow. Lactate release and hence cellular H+ export after intermittent ischemias remained consistently elevated, but following the continuous ischemia of 36 min, release of lactate, and thus H+, was subsequentially decreased. Glycogen mobilization occurred regardless of the ischemia's nature, but it was markedly enhanced during continuous ischemias, where no fall in proglycogen levels occurred. Similarly, myocardial norepinephrine release increased substantially only during the prolonged continuous ischemias. Thus short intermittent ischemia attenuates cardiac adenylate degradation and glycogen mobilization; such ischemic insult also provides for better lactate and H+ washouts immediately upon reperfusion. Another beneficial effect of intermittent ischemia was the near-complete absence of free interstitial norepinephrine, which exacerbates myocardial ischemic insults. In addition, the exponential correlations between preischemic rate-pressure product and postischemic purine release suggest that preischemic energy demand may determine ATP breakdown in ischemic rabbit myocardium.

Adenine Nucleotides↗
PubMed1995

Activation of ANP synthesis during congestive heart failure in rats treated with monocrotaline.

We studied plasma concentration, content, and mRNA for atrial natriuretic peptide (ANP-mRNA) in heart chambers of monocrotaline-treated rats. Three distinct groups emerged: group 1, with moderate congestive heart failure (CHF; pleural effusion < 1 ml; no peritoneal effusion); group 2, with severe CHF (pleural and peritoneal effusion > 1 ml); and group 3, with right hypertrophy and no CHF. Group 1 and 2 rats had right atrial and ventricular hypertrophy, raised plasma ANP (from 16.31 +/- 11.32 to 98.50 +/- 22.50 and 124.09 +/- 57.29 pg/ml, respectively; P < 0.001), and depletion of right atrial ANP (from 143.23 +/- 29.79 to 21.70 +/- 17.70 and 18.12 +/- 14.64 nmol/g, respectively; P < 0.001). Ventricular ANP concentration was unchanged. ANP-mRNA rose in the right atrium [10.6 (P < 0.02) and 7.9 (P < 0.01) times] and right ventricle (53.0 and 46.6 times; P < 0.01). In left unhypertrophied chambers it also increased, although to a smaller extent. Group 3 rats had isolated right ventricular hypertrophy, normal ANP levels in plasma and tissues, and no activation of synthesis. These data suggest that 1) plasma concentration and ANP synthesis are increased only in animals with CHF, 2) activation of ANP synthesis is maximal in early stages of CHF and is not related to the degree of hypertrophy, and 3) ANP-mRNA is also expressed in unhypertrophied heart chambers of rats with CHF but is not expressed in hypertrophied chambers of animals without CHF.

Animals↗
PubMed1994

Extraction and assay of creatine phosphate, purine, and pyridine nucleotides in cardiac tissue by reversed-phase high-performance liquid chromatography.

The levels of creatine phosphate, purine, and pyridine nucleotides in tissues provide important information on energetic and oxidative cellular states. Nevertheless, technical, theoretical, and methodological difficulties in extraction and quantification procedures have so far limited our understanding of the exact role that these substances play in metabolic processes which take place in cells. The objective of our study was to find an easy and rapid method for extracting, separating, and quantifying creatine phosphate, purine, and pyridine nucleotides in solid tissues. We adapted the classic acid-extraction procedure with HClO4 for purine and oxidized pyridine nucleotides and then developed a new alkaline extraction with phenol in a phosphate buffer solution (pH 7.8) for reduced pyridine nucleotides. Biopsies of myocardial tissue were frozen and ground at -180 degrees C using the appropriate extraction procedure. The separation and quantification of the metabolites were performed using a reversed-phase 3-microns Supelchem C18 column, with the addition of tetrabutylammonium as an ion-pair agent to the buffer solution, by ultraviolet detection. The recovery of the external and internal standards always exceeded 90%. The autooxidation or interconversion processes were almost insignificant for each reduced form. This technique allowed us to avoid complex enzymatic procedures and difficulties in the selective assay of pyridine nucleotides with chemiluminescence and surface spectroscopy.

Chromatography, High Pressure Liquid↗
PubMed1994

Echocardiography during infusion of dobutamine for identification of reversibly dysfunction in patients with chronic coronary artery disease.

OBJECTIVES: The aim of this study was to test whether the contractile response of akinetic myocardium to low dose dobutamine is useful for detecting myocardial viability in patients with coronary artery disease and persistent left ventricular dysfunction. BACKGROUND: In some patients with chronic coronary artery disease, persistent abnormalities of left ventricular wall motion can be reversed by successful coronary artery bypass surgery. Thus, identification of potentially reversible dysfunction has important therapeutic and prognostic implications. Echocardiography during infusion of low dose dobutamine can detect viable myocardium in patients after thrombolytic therapy. However, there is no detailed information on the use of this method in patients with chronic left ventricular dysfunction without reperfusion. METHODS: We studied 33 selected patients with angiographically proved coronary artery disease and persistent left ventricular dysfunction. The effect of dobutamine infusion (5 micrograms/kg body weight per min, followed by 10 micrograms/kg per min) on left ventricular wall motion was evaluated by transthoracic echocardiography before coronary artery bypass grafting and compared with that obtained immediately after the operation (evaluated by intraoperative epicardial echocardiography) and both 2 weeks and 3 months later. Left ventricular wall motion was analyzed qualitatively by dividing the left ventricle into 16 segments, and a score was assigned to each region. RESULTS: Before coronary artery bypass surgery, 314 segments were akinetic. Of these, 183 became normokinetic immediately after revascularization, and 15 became hypokinetic. Dobutamine infusion was able to predict improvement in 178 of the 205 segments that recovered function after revascularization (sensitivity 86.8%) and to identify 89 of the 109 segments that did not recover postoperatively (specificity 81.6%). Mean (+/- SD) segment scores were 2.24 +/- 0.35 at baseline, 1.49 +/- 0.34 (p < 0.001) after dobutamine infusion, 1.51 +/- 0.38 (p < 0.001) immediately after and 1.51 +/- 0.38 (p < 0.001) 2 weeks after coronary artery bypass and 1.55 +/- 0.37 (p < 0.001) at 3-month follow-up. CONCLUSIONS: Echocardiography during infusion of low dose dobutamine is a safe and accurate method for identifying reversible dysfunctioning myocardium and predicts early reversibility of wall motion after surgical revascularization in selected patients with coronary artery disease with chronic left ventricular dysfunction.

Coronary Artery Bypass↗
PubMed1994

Effect of angiotensin converting enzyme inhibition with quinaprilat on the ischaemic and reperfused myocardium.

We assessed whether the local inhibition of myocardial converting enzyme by quinaprilat and captopril reduces the functional and metabolic damage caused by ischaemia and reperfusion. Quinaprilat and captopril were either subcutaneously injected (0.3 mg/kg once daily for 5-6 days) in the rabbit before isolation of the heart or delivered to the isolated hearts in the perfusate (10(-6) M) 60 min before ischaemia. Cardiac protection was evaluated in terms of left ventricular pressure recovery during reperfusion, creatine phosphokinase (CPK) release, mitochondrial function, ATP and CP tissue contents, calcium homeostasis and the occurrence of oxidative stress, established by measuring content and release of reduced and oxidized glutathione. Both drugs exerted cardioprotection. Optimal myocardial preservation is achieved when quinaprilat is prophylactically administered to the rabbit. Recovery of developed pressure on reperfusion improved from 11.3 +/- 2.7 (S.E.) to 25.4 +/- 5.4 mmHg, P < 0.01 and the release of CPK was reduced from 665.8 +/- 101.4 to 231.8 +/- 81.4 mU/min/g wet wt, P < 0.01. Peak of noradrenaline release was also attenuated, from 5.253 ng/min/g wet wt to 1.764 ng/min/g wet wt. The accumulation of tissue and mitochondrial calcium was reduced from 52.3 +/- 7.5 and 44.1 +/- 5.6 to 20.5 +/- 3.2 and 27.3 +/- 4.6 nmol/kg dry wt, respectively, P < 0.01. This resulted in significant (P < 0.01) improvement of left ventricular diastolic dysfunction during ischaemia and reperfusion and in a preservation of all indices of mitochondrial function, allowing a higher recovery of ATP and CP after reperfusion (from 4.1 +/- 0.5 and 5.2 +/- 0.5 to 11.1 +/- 1.1 and 24.8 +/- 1.0 mumol/g dry wt, respectively, P < 0.01). Reperfusion-induced myocardial accumulation and release of oxidized glutathione were reduced from 0.301 +/- 0.056 and 0.318 +/- 0.083 to 0.138 +/- 0.025 nmol/mg protein and 0.076 +/- 0.012 nmol/min/g wet wt, respectively, P < 0.01. Similar results were obtained when quinaprilat was administered to the isolated heart. These data suggest that the cardioprotective effect of quinaprilat is independent from haemodynamic changes or direct reduction of toxicity due to oxygen free-radicals but it is likely to be related to a reduction in the release of noradrenaline, maintenance of high energy phosphates and membrane integrity.

Adenosine Triphosphate↗