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R Latini

Publications and source records attributed to R Latini.

At least 19 recordsLinked to original sources
PubMed2006

Murine models of myocardial and limb ischemia: diagnostic end-points and relevance to clinical problems.

Ischemic disease represents the new epidemic worldwide. Animal models of ischemic disease are useful because they can help us to understand the underlying pathogenetic mechanisms and develop new therapies. The present review article summarizes the results of a consensus conference on the status and future development of experimentation in the field of cardiovascular medicine using murine models of peripheral and myocardial ischemia. The starting point was to recognize the limits of the approach, which mainly derive from species- and disease-related differences in cardiovascular physiology. For instance, the mouse heart beats at a rate 10 times faster than the human heart. Furthermore, healing processes are more rapid in animals, as they rely on mechanisms that may have lost relevance in man. The main objective of the authors was to propose general guidelines, diagnostic end points and relevance to clinical problems.

Animal Experimentation↗
PubMed2005

Starc II, a multicenter randomized placebo-controlled double-blind clinical trial of trapidil for 1-year clinical events and angiographic restenosis reduction after coronary angioplasty and stenting.

The objective of this study was to investigate the effect of trapidil 200 mg t.i.d. in preventing the occurrence of death, of myocardial infarction and the need for repeat revascularization at 12 months after balloon PTCA with or without stenting. Coronary restenosis after stenting is still a major drawback of percutaneous coronary interventions (PCI) for 30-40% of patients. Trapidil has been shown to prevent restenosis after PTCA. Eligible patients were randomized to placebo or oral trapidil 200 mg t.i.d. at least 48 hr before PCI and continuing 6 months after a successful balloon angioplasty or stent implantation. Aspirin was given to all patients, and ticlopidine 250 mg b.i.d. to those who received a stent for 4 weeks. In a randomized subgroup of 216 patients, quantitative coronary angiography was performed also at 6-month follow-up. Out of the 933 patients enrolled, primary endpoint incidence was 20.3% in trapidil and 18.0% in placebo (P = 0.37). When recurrence or deterioration of angina was added to the combined endpoint, incidence was 27.4% in trapidil and 23.0% in placebo (P = 0.12). Restenosis rate in patients with 6-month angiography was 25.0% in trapidil arm vs. 30.1% in placebo (P = 0.43). Stent restenosis rate was similar in patients randomized to trapidil or placebo (30.2% vs. 23.8%, respectively; P = 0.44), while in patients treated with balloon angioplasty, it was lower in trapidil (17.1%) than in placebo (40.0%; P = 0.03). Oral trapidil 200 mg t.i.d. for 6 months in addition to aspirin did not influence the occurrence of major cardiac events after coronary angioplasty with or without stenting. In a prespecified subgroup of 191 patients treated with balloon angioplasty only, trapidil reduced angiographic restenosis.

Angioplasty, Balloon, Coronary↗
PubMed2002

Prediction of 6 months left ventricular dilatation after myocardial infarction in relation to cardiac morbidity and mortality. Application of a new dilatation model to GISSI-3 data.

AIMS: To predict the long-term left ventricular volume index early after myocardial infarction and to investigate the relationship between long-term left ventricular dilatation risk and clinical outcome. METHODS AND RESULTS: By applying a previously developed dilatation model, we predicted the 6-month left ventricular volume index early after myocardial infarction (median 9 days) in 13,679 GISSI-3 patients, to identify patients at high risk of long-term left ventricular dilatation. The left ventricular systolic and diastolic volume indexes at 6 months were predicted with r=0.72 and r=0.68, respectively, in the subgroup of patients in whom a pre-discharge echo was available (n=7842). Patients predicted to be at risk for long-term left ventricular dilatation had an increased risk of mortality (RR 1.87, 95% CI: 1.48 to 2.36) and heart failure at 6 months (RR 2.59, 95% CI:2.04 to 3.28), but no increased risk of reinfarction at 6 months (RR 1.12, 95% CI: 0.87 to 1.45) or of angina pectoris (RR 1.07, 95% CI: 0.95 to 1.20). CONCLUSION: Our prediction of long-term left ventricular dilatation, obtained by applying our new dilatation model in over 13,000 GISSI-3 patients, correlated well with mortality and heart failure after myocardial infarction. Therefore, our new dilatation model may contribute to more efficient risk stratification early after myocardial infarction.

Dilatation, Pathologic↗
PubMed2001

Effect of prone positioning on the survival of patients with acute respiratory failure.

BACKGROUND: Although placing patients with acute respiratory failure in a prone (face down) position improves their oxygenation 60 to 70 percent of the time, the effect on survival is not known. METHODS: In a multicenter, randomized trial, we compared conventional treatment (in the supine position) of patients with acute lung injury or the acute respiratory distress syndrome with a predefined strategy of placing patients in a prone position for six or more hours daily for 10 days. We enrolled 304 patients, 152 in each group. RESULTS: The mortality rate was 23.0 percent during the 10-day study period, 49.3 percent at the time of discharge from the intensive care unit, and 60.5 percent at 6 months. The relative risk of death in the prone group as compared with the supine group was 0.84 at the end of the study period (95 percent confidence interval, 0.56 to 1.27), 1.05 at the time of discharge from the intensive care unit (95 percent confidence interval, 0.84 to 1.32), and 1.06 at six months (95 percent confidence interval, 0.88 to 1.28). During the study period the mean (+/-SD) increase in the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen, measured each morning while patients were supine, was greater in the prone than the supine group (63.0+/-66.8 vs. 44.6+/-68.2, P=0.02). The incidence of complications related to positioning (such as pressure sores and accidental extubation) was similar in the two groups. CONCLUSIONS: Although placing patients with acute respiratory failure in a prone position improves their oxygenation, it does not improve survival.

Female↗
PubMed2001

CHF-1024, a DA2/alpha2 agonist, blunts norepinephrine excretion and cardiac fibrosis in pressure overload.

We compared the effects of an ACE inhibitor, captopril, with those of a DA2-dopaminergic/alpha2-adrenergic receptor agonist (CHF-1024) on neuroendocrine activation and cardiac fibrosis in a model of pressure-overload hypertrophy. Interrenal aortic stenosis was performed in 89 rats, treated with CHF-1024 (0.33, 2 or 6 mg kg(-1) day(-1)), or captopril (1 g/L). Hemodynamic variables were recorded. Cardiac and renal weights, plasma aldosterone, renin activity and urinary catecholamine excretion were measured, as well as cardiac collagen. Blood pressure was lower in stenotic animals treated with CHF-1024 compared to vehicle (161 +/- 10 vs 219 +/- 10 mmHg, p < 0.01), but LV weight was similar. CHF-1024 elicited a marked dose-dependent attenuation of urinary norepinephrine excretion (1.80 +/- 0.18 in controls compared to 0.40 +/- 0.14 microg/24 h at the highest dose, p < 0.01) and of LV perivascular fibrosis. Captopril provoked a marked hypotension, reduced cardiac and body weights, plasma aldosterone concentration, dopamine excretion and perivascular collagen. The DA2/alpha2 agonist CHF-1024 effectively blunts adrenergic drive and cardiac fibrosis in a rat model of pressure overload.

Adrenergic alpha-Agonists↗
PubMed2001

Cardiac protection by pharmacological modulation of inflammation.

Inflammation is a reaction to primary injury of various kinds, such as infection and trauma, which has both beneficial and detrimental effects. Inflammation has been associated with major diseases of the heart and vessels. Research has focused not only on ischaemia but also on post-ischaemic reperfusion, which is known to activate and amplify the inflammatory response. Although reperfusion should always be attempted in the clinical environment, it has been shown experimentally that it can cause some cardiac damage, in addition to that caused by ischaemia. Therefore, it is reasonable to attempt to increase the benefit obtainable with reperfusion by modulating inflammatory processes triggered by reperfusion itself. In this field, different potential therapeutic targets have been identified and interventions have been tested over the last 30 years. With the exception of adenosine, which probably does not act merely through inhibition of the inflammatory response, no other compounds have yet proven successful in clinical trials. Active research is ongoing. Broadening the approach from the heart to the cardiovascular system, promising data is emerging on cardiovascular protection conferred by statins in patients with coronary heart disease (CHD) and high levels of C-reactive protein (CRP), a systemic marker of inflammation. Similarly, results of trials aimed at preventing cardiovascular events by eradicating chronic infections will be among the first to directly test whether such therapies will decrease risks of cardiovascular disease.

Adenosine↗
PubMed2000

PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans.

BACKGROUND: Inflammation is an important component of ischemic heart disease. PTX3 is a long pentraxin whose expression is induced by cytokines in endothelial cells, mononuclear phagocytes, and myocardium. The possibility that PTX3 is altered in patients with acute myocardial infarction (AMI) has not yet been tested. METHODS AND RESULTS: Blood samples were collected from 37 patients admitted to the coronary care unit (CCU) with symptoms of AMI. PTX3 plasma concentrations, as measured by ELISA, higher than the mean+2 SD of age-matched controls (2.01 ng/mL) were found in 27 patients within the first 24 hours of CCU admission. PTX3 peaked at 7.5 hours after CCU admission, and mean peak concentration was 6.94+/-11.26 ng/mL. Plasma concentrations of PTX3 returned to normal in all but 3 patients at hospital discharge and were unrelated to AMI site or extent, Killip class at entry, hours from symptom onset, and thrombolysis. C-reactive protein peaked in plasma at 24 hours after CCU admission, much later than PTX3 (P<0.001). Patients >64 years old and women had significantly higher PTX3 concentrations at 24 hours (P<0.05). PTX3 was detected by immunohistochemistry in normal but not in necrotic myocytes. CONCLUSIONS: PTX3 is present in the intact myocardium, increases in the blood of patients with AMI, and disappears from damaged myocytes. We suggest that PTX3 is an early indicator of myocyte irreversible injury in ischemic cardiomyopathy.

Aged↗
PubMed2000

Up-regulation of AT(1) and AT(2) receptors in postinfarcted hypertrophied myocytes and stretch-mediated apoptotic cell death.

To determine whether up-regulation of AT(1) and AT(2) receptors occurred in hypertrophied myocytes after infarction and whether AT(2) played a role in stretch-mediated apoptosis, left ventricular myocytes were dissociated from the surviving portion of the wall 8 days after coronary occlusion and cardiac failure in rats. Control cells were obtained from sham-operated animals. Myocytes were stretched in an equibiaxial stretch apparatus and angiotensin II (Ang II) formation and cell death were measured 3 and 12 hours later. AT(1) and AT(2) proteins were evaluated in freshly isolated myocytes and after stretch. The effects of AT(1) and AT(2) antagonists on stretch-induced Ang II synthesis and apoptosis were also established. Myocardial infarction increased AT(1) and AT(2) in myocytes and stretch further up-regulated these receptors. Ang II levels were higher in postinfarcted myocytes and this peptide increased with the duration of stretch in both groups of cells. Similarly, apoptosis increased with time in control and postinfarcted myocytes. Absolute values of Ang II and apoptosis were greater in myocytes from infarcted hearts at 3 and 12 hours after stretch. Addition of AT(1) blocker to cultures inhibited stretch-activated apoptosis in both myocyte populations as well as the generation of Ang II in postinfarcted myocytes. In contrast, AT(2) antagonists had no impact on these cellular events. In conclusion, Ang II stimulated cell death through AT(1) receptor activation, whereas ligand binding to AT(2) receptor did not alter Ang II concentration and apoptosis in normal and postinfarcted hypertrophied myocytes.

Angiotensin II↗
PubMed2000

Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96,712 randomized patients. Angiotensin-converting Enzyme Inhibitor Myocardial Infarction Collaborative Group.

OBJECTIVES: We sought to determine whether the clinical effects of early angiotensin-converting enzyme (ACE) inhibitor (ACEi) treatment for acute myocardial infarction (MI) are influenced by the concomitant use of aspirin (ASA). BACKGROUND: Aspirin and ACEi both reduce mortality when given early after MI. Aspirin inhibits the synthesis of vasodilating prostaglandins, and, in principle, this inhibition might antagonize some of the effects of ACEi. But it is uncertain whether, in practice, this influences the effects of ACEi on mortality and major morbidity after MI. METHODS: This overview sought individual patient data from all trials involving more than 1,000 patients randomly allocated to receive ACEi or control starting in the acute phase of MI (0-36 h from onset) and continuing for four to six weeks. Data on concomitant ASA use were available for 96,712 of 98,496 patients in four eligible trials (and for none of 1,556 patients in the one other eligible trial). RESULTS: Overall 30-day mortality was 7.1% among patients allocated to ACEi and 7.6% among those allocated to control, corresponding to a 7% (standard deviation [SD], 2%) proportional reduction (95% confidence interval 2% to 11%, p = 0.004). Angiotensin-converting enzyme inhibitor was associated with similar proportional reductions in 30-day mortality among the 86,484 patients who were taking ASA (6% [SD, 3%] reduction) and among the 10,228 patients who were not (10% [SD, 5%] reduction: chi-squared test of heterogeneity between these reductions = 0.4; p = 0.5). Angiotensin-converting enzyme inhibitor produced definite increases in the incidence of persistent hypotension (17.9% ACEi vs. 9.4% control) and of renal dysfunction (1.3% ACEi vs. 0.6% control), but there was no good evidence that these effects were different in the presence or absence of ASA (chi-squared for heterogeneity = 0.4 and 0.0, respectively; both not significant). Nor was there good evidence that the effects of ACEi on other clinical outcomes were changed by concomitant ASA use. CONCLUSIONS: Both ASA and ACEi are beneficial in acute MI. The present results support the early use of ACEi in acute MI, irrespective of whether or not ASA is being given.

Aged↗
PubMed2000

Myocyte death in streptozotocin-induced diabetes in rats in angiotensin II- dependent.

To determine whether myocyte death and angiotensin II (AT II) formation are implicated in the development of diabetic cardiomyopathy, rats were injected with streptozotocin, and apoptosis and necrosis were measured at 3, 10, and 28 days. Expression of the components of the renin-angiotensin system (RAS) and AT II levels were assessed at 3 days. The percentage of AT II-labeled myocytes and the number and distribution of AT II sites in myocytes were measured at 3 and 10 days. The effects of AT1 blockade on local RAS and cell death were examined at 3 days. Diabetes was characterized by myocyte apoptosis that peaked at 3 days and decreased at 10 and 28 days, in spite of high concentrations of blood glucose. Cell necrosis was absent throughout. Angiotensinogen, renin, and AT1 receptor increased in myocytes from diabetic rat hearts, while angiotensin-converting enzyme and AT2 remained constant. AT II quantity increased severalfold, as did the fraction of AT II positive cells and the number of AT II sites per myocyte. However, AT II labeling decreased at 10 days, which paralleled the reduction in myocyte death. AT1 antagonist inhibited upregulation of this receptor and angiotensinogen, which prevented AT II synthesis and myocyte death at their peaks with diabetes. An aggregate 30% myocyte loss and a 14% increase in the volume of viable cells were found in diabetic rats at 28 days. Thus diabetic cardiomyopathy may be viewed as an AT II-dependent process in which that peptide plays a critical role in myocyte death and hypertrophy.

Angiotensin II↗
PubMed2000

Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure.

AIMS: In addition to diabetes mellitus, less severe abnormalities of glucose and insulin metabolism may be related to functional status in patients with heart failure. We examined the relationship of hyperglycaemia (> or =6.1 mmol. l(-1)) and hyperinsulinaemia (> or =11.2 mU. l(-1)) to functional status and cardiac function in patients with heart failure. METHODS AND RESULTS: Fasting plasma glucose and insulin levels were obtained in 663 heart failure patients. The average left ventricular ejection fraction was 0.28+/-0.07, 63% were in New York Heart Association Functional Class (NYHA-FC) I/II and 37% were in NYHA-FC III/IV. Twenty seven percent had diabetes mellitus, but an additional 8% had undiagnosed diabetes mellitus (glucose > or =7 mmol. l(-1)) and 9% had glucose levels between 6.1 and 7 mmol. l(-1), so that a total of 43% (287) of patients had elevated glucose levels (> or =6.1 mmol. l(-1)). In general, more diabetic patients had NYHA-FC III/IV symptoms, shorter 6 min walk distances, but similar left ventricular ejection fractions compared to non-diabetic patients. The non-diabetic patients in NYHA-FC III/IV had higher glucose and insulin levels than patients in NYHA-FC I/II (6.3+/-0.2 vs 5.6+/-0.1 mmol. l(-1), P<0.001 and 19.6+/-2.3 vs 10. 2+/-0.6 mU. l(-1), P<0.001). Non-diabetic patients with elevated glucose levels had shorter 6 min walk distances compared to those with normal glucose levels (368.2+/-8 m vs 389.+/-4 m, P=0.02), however, left ventricular ejection fraction was similar. CONCLUSION: Glucose abnormalities are extremely common in heart failure patients (43% of patients). Diabetes mellitus and hyperglycaemia or hyperlinsulinaemia in non-diabetic patients were related to worse symptomatic status but not worsening left ventricular ejection fraction compared to patients with normal glucose and insulin levels.

Biomarkers↗
PubMed2000

Left ventricular response to beta-adrenergic stimulation in aging rats.

The incidence of heart failure in the population increases steeply among older people. Overactivation of the sympathetic nervous system is associated to and responsible for worsening of heart failure. This study describes the influence of aging on short-term left ventricular (LV) adaptation to b-adrenergic stimulation in Wistar rats. In controls at 18 mo, interstitial fibrosis was increased with respect to 3-mo-old rats, whereas myocytes dimension and the messenger RNA (mRNA) abundance of atrial natriuretic peptide (ANP), a2(I) procollagen, transforming growth factor (TGF-b1, TGF-b3), and secreted protein, acidic and rich in cysteine (SPARC) were not different. To determine how aging affects LV adaptation to adrenergic stimulation, two groups of animals received isoproterenol (ISO, 1 mg/kg/d) for 3 days. There was no significant difference between young and older rats with respect to increase in LV weight, myocytes dimension, and mRNA abundance of all the genes considered, except a1(III) procollagen. These findings indicate that despite limited compensatory hypertrophy and higher fibrosis, LV from aged nonsenescent rats preserves the capacity to adapt to b-adrenergic stimulation through the upregulation of several genes encoding extracellular matrix-related proteins.

Adaptation, Physiological↗