On the value of the activated clotting time for monitoring heparin therapy in acute coronary syndromes.
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Angina, Unstable↗
Biomedical subjects
A Branzi
Publications and source records attributed to A Branzi.
Evidence of a partial escape of renin-angiotensin-aldosterone blockade in patients with acute myocardial infarction treated with ACE inhibitors.
Angiotensin-converting enzyme (ACE) inhibitors have been designed to block the renin-angiotensin system and can represent an effective therapeutic approach in those settings where such a system is active, such as myocardial infarction. In a randomized placebo-controlled study, 10 patients with acute myocardial infarction allocated to treatment with increasing doses of zofenopril calcium and 10 patients allocated to placebo were studied in hospital, within 24 hours from symptoms, during 11 sampling periods to assess the time course of ACE inhibition and renin-angiotensin-aldosterone blockade. Zofenopril administration was followed by a dose-dependent inhibition of in vitro ACE activity (7.5 mg, 65%; 15 mg, 89%; 30 mg, 94.5%) and a progressive increase in plasma active renin. Conversely, plasma aldosterone decreased during the first 3 days of treatment and then returned toward baseline values, as did blood pressure, despite a persistent inhibition of ACE. The present data suggest the existence of an interesting dissociation between the time-course of ACE inhibition and that of blockade of the renin-angiotensin system in patients with acute myocardial infarction. This discrepancy could arise from the combination of an only partial in vivo ACE inhibition and the compensatory increase in plasma renin that occurs during treatment with ACE inhibitors. A better understanding of this relationship would seem to be useful in addressing the correct use of ACE inhibitors in patients with acute myocardial injury.
Aldosterone↗
Effect of enoximone alone and in combination with metoprolol on myocardial function and energetics in severe congestive heart failure: improvement in hemodynamic and metabolic profile.
The hemodynamic and myocardial metabolic effects of enoximone (phosphodiesterase III inhibitor), alone or in combination with metoprolol (beta-adrenergic blocker), were studied in patients with congestive heart failure. Ten patients (New York Heart Association Class III-IV) underwent right heart and coronary sinus catheterization, and parameters were assessed at basal condition, at peak enoximone response (mean intravenous loading dose = 2.2 mg/kg), and after the combination with metoprolol (mean intravenous dose = 8.5 mg). Heart rate tended to increase during enoximone administration (from 102 +/- 16 to 107 +/- 16 min-1, ns) and was reduced during enoximone plus metoprolol (to 88 +/- 15 min-1, p < 0.05 vs. basal). Cardiac index was increased during enoximone (from 2.2 +/- 0.2 to 3.8 +/- 0.5 1/min/m2, p < 0.05) and decreased during enoximone plus metoprolol (to 2.8 +/- 0.5 1/min/m2, p < 0.05 vs. enoximone). Mean pulmonary wedge pressure fell during enoximone and remained reduced during enoximone plus metoprolol (from 27 +/- 9 to 9 +/- 3 and to 13 +/- 4 mmHg, respectively, both p < 0.05). Myocardial oxygen consumption did not change during enoximone (from 27 +/- 8 to 25 +/- 13 ml/min, ns) and was reduced during enoximone plus metoprolol (to 19 +/- 8 ml/min, p < 0.05 vs. basal). Myocardial lactate extraction tended to be lower during enoximone and during enoximone plus metoprolol conditions (from 38 +/- 17% to 26 +/- 20% and to 29 +/- 24%, respectively), but no statistical significance was found. Myocardial efficiency was increased during enoximone and during enoximone plus metoprolol (from 9 +/- 3% to 15 +/- 6% and to 14 +/- 6%, respectively, both p < 0.05). Thus in patients with congestive heart failure enoximone improves hemodynamics and, in most cases, it does not influence energetics. The addition of metoprolol to enoximone reduces heart rate, cardiac index, and myocardial oxygen consumption without any other major changes, producing a more physiologic hemodynamic and metabolic profile.
Adult↗
Benefit of adding low molecular weight heparin to the conventional treatment of stable angina pectoris. A double-blind, randomized, placebo-controlled trial.
BACKGROUND: Patients with chronic coronary artery disease exhibit a dysfunctioning endothelium, which may be responsible for exercise-induced platelet activation and expression of a procoagulant moiety. In this study, we evaluated the therapeutic efficacy of a low molecular weight heparin (Parnaparin) in patients with stable angina pectoris. METHODS AND RESULTS: According to a double-blind, randomized, placebo-controlled trial, 29 patients with stable exercise-induced angina pectoris and angiographically proven coronary artery disease received a single daily subcutaneous injection of Parnaparin or placebo on top of aspirin and conventional antianginal medication over 3 months. Patients randomized to Parnaparin showed a significant decrease in the fibrinogen level (P = .035) and an improvement in both the time to 1-mm ST segment depression (P = .008) and the peak ST segment depression (P = .015). The Canadian Cardiovascular Society class for angina pectoris was also improved by Parnaparin (P = .016). Parnaparin did not affect ADP and collagen-induced platelet aggregation, whereas thrombin-induced aggregation was reduced (P = .0001). The bleeding time was slightly prolonged, but this was not associated with any significant bleeding. CONCLUSIONS: Patients with stable angina pectoris may be treated with Parnaparin in addition to aspirin and conventional antianginal medication. Side effects are negligible, and compliance is excellent.
Adult↗
[Role of transesophageal echography in the diagnosis of aortic dissection and in therapy programming].
The diagnostic accuracy of transesophageal echocardiography and its relevance on the decision making process were evaluated in 80 patients with suspected aortic dissection during a 37-month period. The diagnosis was proven by aortography and/or magnetic resonance and/or computerized tomography and/or surgery and/or autopsy in each case. Transesophageal echocardiography had no serious complication. A correct diagnosis of aortic dissection was made in 39 of 40 patients (sensitivity, 97.5%; specificity, 100%) and the type of dissection was correctly demonstrated in each case. Thrombi in the false lumen were detected in 16 patients. The primary entry site was correctly identified in 33 patients (85%). Aortic regurgitation was detected in 25 cases (severe in 9) and pericardial effusion in 14 (with tamponade in 2). Transesophageal echocardiography was more accurate than aortography in the diagnosis of noncommunicating intramural dissection (2 cases) and identified more precisely the retrograde extension of the dissection in DeBakey type III patients (4 cases). In 9 cases surgical indication was based on clinical data and transesophageal echocardiography alone. We conclude that transesophageal echocardiography allows a bedside, safe and accurate diagnosis of aortic dissection. In the majority of the patients it provides the minimal diagnostic information necessary to the therapeutical decision making.
Acute Disease↗
[Vasodilator agents: the lesson from large clinical trials].
The results of trials of vasodilators in patients with chronic heart failure showed improved survival by adding ACE-inhibitors or a combination of isosorbide dinitrate and hydralazine to the usual therapy with digoxin and diuretics. However, the mean prolongation of life is unsatisfactory (10-17 months) and very small effects are observed on the various measures of quality of life. In patients with asymptomatic left ventricular dysfunction, the treatment with ACE-inhibitors reduces the progression to the clinical phase of heart failure but not in all patients. Therefore is attractive to evaluate new agents to improve the results of the present therapeutic strategies. The attempts to combine new vasodilators to regimens including ACE-inhibitors have been inconclusive or even deleterious. The identification of subgroups of patients with different clinical, hemodynamic and neurohormonal characteristics may allow a more appropriate use of the new therapeutic resources.
Clinical Trials as Topic↗
[Restrictive cardiomyopathies].
The restrictive cardiomyopathies are the least common of the 3 major categories of cardiomyopathic disorders seen in Western countries. According to the report of the WHO/ISFC Task Force the term restrictive cardiomyopathy applies to only 2 conditions: endomyocardial fibrosis and Loeffler endocarditis while many specific myocardial diseases can develop a restrictive pathophysiologic profile along their natural history. During the last decade this topic has received 2 main contributions: the identification of a common pathophysiologic ground linking Loeffler endocarditis and endomyocardial fibrosis and the identification of the so-called idiopathic restrictive cardiomyopathy. This condition, defined as a myocardial disease with restrictive physiology, unknown etiology and without histological evidence of infiltrative or storage diseases, appears to be the single most frequent type of restrictive cardiomyopathy in Western countries. A revision of the current classification of cardiomyopathies and particularly of restrictive myocardial disease is necessary.
Cardiomyopathy, Restrictive↗
[The prevalence, risk factors and clinical significance of atherosclerosis of the thoracic aorta: a transesophageal echocardiographic study].
Available information on atherosclerosis of thoracic aorta in man is scanty and mostly derived from pathological or surgical series. Transesophageal echocardiography makes a clear definition of the entire thoracic aorta possible and enables large, population based studies. In order to define prevalence, risk factors and clinical implications of aortic atherosclerosis, the echocardiographic recordings of 220 patients suitable for both evaluation of thoracic aorta and risk factors analysis were reviewed. Transesophageal echocardiography has been performed because of valvular diseases (78), suspected aortic aneurysm or trauma (43), evaluation of valve prosthesis (39), previous cerebral or peripheral embolic events (22), infective endocarditis (14), cardiac mass lesions (12) or other indications (12). Age ranged from 5 to 81 years (55 +/- 15), male to female ratio was 0.99. Simple and complex atherosclerotic plaques were identified in 33% and 10% respectively. Complex atheromas were more frequent among patients with previous embolic episodes (6/22, 27% versus 17/198, 8.5%; p = 0.019). The prevalence of any type of atherosclerosis progressively increased from the fourth (8%) to the eighth (88%) decade of age. By univariate analysis age (p < 0.001), history of hypertension (p < 0.001), systolic (p < 0.001) and diastolic (p < 0.05) pressure, type II diabetes mellitus (p < 0.01), HDL cholesterol (p < 0.01), HDL/total cholesterol (p < 0.01) and uricaemia (p < 0.05) were associated with aortic atherosclerosis. Discriminant analysis identified 5 independent variables associated with the presence and the extent of atherosclerosis (Wilk's Lambda = 0.43): number of cigarettes per day, age, history of hypertension, systolic pressure and type II diabetes mellitus. This model provided a 63% correct classification rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[The 24-hour hemodynamic changes after percutaneous mitral valvuloplasty].
Hemodynamic studies were performed immediately before, within 1/2 hour and 24 hours after percutaneous mitral valvuloplasty in 31 patients with severe mitral stenosis and pulmonary hypertension. Single rubber-nylon balloon (Inoue balloon) technique was used in all the procedures. Mean transmitral gradient fell from 12.7 +/- 5.4 mmHg to 6.1 +/- 3.1 mmHg (p < 0.001). Mitral valve area increased from 0.9 +/- 0.2 cm2 to 1.8 +/- 0.3 cm2 (p < 0.001). Mean pressure in the left atrium decreased from 21.8 +/- 7.1 mmHg to 16.9 +/- 5.1 mmHg (p < 0.001). After 24 hours there was a significant further drop in left atrial pressure (or pulmonary capillary wedge pressure), that decreased to 11.5 +/- 5 mmHg (p < 0.001). Mean cardiac output increased from 4.1 +/- 0.8 l/min to 4.5 +/- 0.9 l/min immediately after successful valvuloplasty and after 24 hours was significantly higher (5.4 +/- 1.2 l/min; p < 0.001). Mean pulmonary pressure immediately decreased from 29.2 +/- 9.7 mmHg to 26.5 +/- 6 mmHg (p < 0.05) and after 24 hours was 19.4 +/- 6 mmHg (p < 0.001). Left ventricular end-diastolic pressure increased from 9.9 +/- 3.8 mmHg to 13.8 +/- 5 mmHg (p < 0.001). In conclusion, pulmonary hemodynamic and cardiac output improve immediately after percutaneous mitral valvuloplasty and get progressively better up to 24 hours from the procedure.
Adult↗
Effects of two dosages of subcutaneous low molecular weight heparin (Parnaparin) and of unfractionated heparin on fibrin formation and lipolysis in acute myocardial infarction.
Although low molecular weight heparins (LMWH) have been extensively investigated for the prophylaxis and treatment of venous thromboembolism in surgical environments, few data in acute myocardial infarction are available in the literature. In this study two dosages of a new LMWH, Parnaparin, and unfractionated heparin (UF) were investigated in 50 pts with acute myocardial infarction. 20 pts received UF (15.000 units, three subcutaneous injections, Group 1), 20 pts received Parnaparin (6.400 units, single injection, Group 2) and 10 pts received a higher dose of Parnaparin (12.800 units, single injection, Group 3). Similar fibrinopeptide A (FpA) levels were observed in Group 1 and Group 2. In Group 3 the dosage of Parnaparin resulted in a significant prolongation of the APTT and in lower FpA levels. Fibrin formation was decreased by Parnaparin in a concentration-dependent way, according to both the anti-Xa activity and the APTT ratio. Parnaparin did not result in a significant increase in free fatty acid concentration, in comparison with UF. Thus, Parnaparin may offer the advantage of a single subcutaneous injection in patients with acute myocardial infarction.
Aged↗
Spontaneous superoxide generation by polymorphonuclear leukocytes isolated from patients with stable angina after physical exercise.
The activation of circulating polymorphonuclear leukocytes was determined in terms of O2.- generation and elastase release in patients with stable angina (n = 12) and in control subjects (n = 8) after maximal physical exercise and after a 15-min recovery. There was no spontaneous O2.- formation under basal conditions in both groups of patients. On the contrary, there was significant formation of O2.- (p < 0.001) from patients with stable angina measured directly after exercise, along with a slight spontaneous O2.- formation in control subjects (p < 0.05). After recovery, the spontaneous polymorphonuclear leukocyte-O2.- formation decreased but was still present in the patients with stable angina, while in the healthy subjects these values returned to resting levels. The activation of polymorphonuclear leukocytes with phorbol 12-myristate 13-acetate enhanced O2.- formation both in healthy subjects and in patients with stable angina, with a lesser effect in the latter. Moreover, no differences were observed in polymorphonuclear leukocyte-stimulated O2.- formation during the protocol, both in the angina stable patients and healthy subjects. No changes were found in plasma elastase levels among stable angina patients nor in control subjects as a consequence of exercise or recovery. This study indicates there is an early activation of circulating polymorphonuclear leukocytes in terms of O2.- production in stable angina patients during maximal exercise, which is still present after a 15-min recovery. Such activation occurs without elastase release. However, in healthy subjects maximal exercise resulted in very little increase in neutrophil activation.
Angina Pectoris↗
[The effect of peripheral reflections on the left ventricle].
In order to evaluate the effect of modifications in reflections timing on the ventricular performance, 10 isolated rabbit hearts were connected to rubber tubes of different lengths (0.5, 0.8, 1.0, 2.5 m) with terminal stopper and 2 cylindric small tubes as constant hydraulic resistance. The terminal connection produced wide reflections which returned to the ventricle in early, mid, late systole and in the diastolic phase (2.5 m). Ventricular and aortic pressure, and aortic flow were continuously recorded, sampled and stored on a personal computer. Instantaneous and total systolic ventricular work and stroke volume were calculated using an automatic procedure. Mean coronary perfusion pressure was calculated as difference between aortic and ventricular pressure in diastolic phase. The results demonstrate an important modification of the ventricular performance related to the anticipation of the reflected pulse. The anticipation produces a decrease in the stroke volume (-14.5%), a decrease in the external work of the ventricle (-21%) and a decrease in mean coronary perfusion pressure (-28%). The first two parameters describe the performance of the pump with respect to the load, and the third evaluates the perfusion of the pump itself. Reported to the clinical situation, these results demonstrate that an increased stiffness of the aorta has a double negative effect, a decrease in cardiac output and in external ventricular work, and moreover a decrease in coronary pressure, which produces a reduction of coronary flow.
Animals↗
[Critical mitral stenosis in pregnancy: description of a case treated with percutaneous valvuloplasty].
We report the case of a 26-year-old woman who underwent mitral valvuloplasty during the 23rd week of gestation, following an episode of pulmonary edema. Dilation, performed without complications, increased mitral valve area from 0.9 to 1.8 cm2, cardiac output from 4.8 to 5.9 l/min, and decreased mean transvalvular gradient from 13.2 to 5 mmHg. The patient delivered spontaneously a full-term normal baby. Echocardiographic evaluation at 6 months confirmed the persistency of procedure's good outcome. According to some Authors and to our results it can be inferred that mitral valvuloplasty is a feasible and effective treatment for critical mitral stenosis during pregnancy.
Adult↗
Biochemical correlates with myocardial aging.
Both contraction and relaxation times are prolonged in cardiac muscle of senescent animals. This is in part explained by an alteration of excitation-contraction coupling due to an increased duration of the action potential, reduced biosynthesis of the Ca(2+)-stimulated ATPase pump of sarcoplasmic reticulum, and prevalence of the V3 isoform of myosin with slow ATPase activity. The response to catecholamine decreases with aging because of a defective transmission of alpha and beta adrenergic stimulation mediated respectively by phosphoinositide hydrolysis and adenylate cyclase. Cardiac energetics is also impaired in the aged myocardium, since ATP and creatine phosphate levels are reduced by about 20%. This reduction seems in part the consequence of defective mitochondrial function, especially in fatty acid oxidation and ATP translocation to the cytoplasm. In this paper we have discussed the possibility that oxygen free radicals may be a cause of myocardial senescence, by damaging the nuclear and mitochondrial genomes as well as membranes and other cellular components.
Aging↗
Myocardial metabolic and hemodynamic effects of a sustained intravenous infusion of nifedipine with and without metoprolol in patients with unstable angina.
We tested the usefulness of a sustained intravenous infusion of nifedipine and a combination of nifedipine and metoprolol in the early management of 14 patients with unstable angina pectoris. After a 24-hour run-in period, nifedipine was titrated in a stepwise fashion (mean dose 27 +/- 7 micrograms/min). After nifedipine treatment coronary blood flow increased from 150 +/- 66 to 183 +/- 74 ml/min (p less than 0.05), whereas double product, myocardial oxygen consumption, and both arterial and coronary sinus (nor)epinephrine levels were unchanged. Myocardial lactate uptake increased from 3.4 +/- 26.1 to 31.3 +/- 26.6 mumol/min (p less than 0.005) and free fatty acid uptake from 7.2 +/- 22.1 to 34.5 +/- 33.7 mumol/min (p less than 0.05). A small nonsignificant improvement in amino acid metabolism was observed. Metoprolol was added in seven patients and led to a decrease in double product (-2.2 +/- 1.6 x 10(3); p less than 0.01) and myocardial oxygen consumption (-3.2 +/- 3.8 ml/min; p less than 0.05). The lactate uptake/oxygen uptake ratio increased by 18% after metoprolol (p = NS). The number of episodes of chest pain decreased from 2.4 +/- 1.1/24 hours to 0.1 +/- 0.2 in the nifedipine group and from 2.9 +/- 1.1/24 hours to 0.3 +/- 0.5 in the nifedipine plus metoprolol group (both p less than 0.01). We conclude that in the acute phase of unstable angina, intravenous nifedipine can be carefully titrated to improve coronary blood flow and oxidative metabolism. The addition of metoprolol is also associated with a reduction in myocardial oxygen demand. This treatment results in significant hemodynamic stability.
Adult↗
[Comparative effects of doxazosin and enalapril in patients with arterial hypertension and exercise-induced acute myocardial ischemia].
The effects of doxazosin (alpha-1-inhibitor) and enalapril (ACE-inhibitor) on blood pressure and exercise stress test were assessed in 10 hypertensive patients (8 M, 2 F, age 58 +/- 9 years) with coronary artery disease and exertional myocardial ischemia. A single blind, cross-over, placebo controlled trial was performed. Placebo was administered for 2 periods of 2 weeks, doxazosin and enalapril for at least 3 weeks. The sequence of the active drugs was randomized and the single daily dose, obtained by titration, was 7 +/- 5 mg for doxazosin and 18 +/- 13 mg for enalapril. Blood pressure measurements and treadmill tests (Bruce protocol) were performed at the end of each period. Rest systolic and diastolic pressures after placebo were respectively 173 +/- 15 and 106 +/- 9 mmHg and were reduced to 153 +/- 11 and 93 +/- 12 mmHg (p less than 0.05) after doxazosin and to 150 +/- 24 and 93 +/- 12 mmHg (p less than 0.05) after enalapril. Total exercise time was 473 +/- 91 s after placebo and increased to 545 +/- 84 s (p less than 0.05) after doxazosin and 529 +/- 100 s (p less than 0.05) after enalapril. Time to 1 mm ST depression (ST1) was 297 +/- 102 s after placebo and increased to 414 +/- 96 s (p less than 0.05) after doxazosin and to 396 +/- 133 s (p less than 0.05) after enalapril. Double product at peak exercise and at ST1 were respectively 26.3 +/- 2.8 and 22.1 +/- 2.8 x 10(3) and remained unchanged after enalapril and doxazosin. Peak exercise diastolic blood pressure was 107 +/- 5 mmHg after placebo, was reduced to 94 +/- 15 mmHg (p less than 0.05) after doxazosin and was unchanged after enalapril (101 +/- 10 mmHg, NS). Thus, doxazosin and enalapril induced a comparable decrease of rest blood pressure and a similar increase of exercise time in hypertensive patients with exertional myocardial ischemia. Doxazosin but not enalapril reduced exercise diastolic blood pressure.
Adrenergic alpha-Antagonists↗
[The management of postthrombolysis patients].
Early reperfusion with thrombolytic therapy in acute myocardial infarction results in myocardial salvage. However, it is apparent that patients remain at substantial risk for vascular reocclusion and residual ischemia (either peri-infarct or at a distance). Vascular reocclusion is promoted by local factors (residual thrombus, high shear rate, exposure of deep arterial tissues) as well as by systemic factors (activation of platelets and coagulation factors). Reocclusion after thrombolysis is significantly prevented by aspirin and intravenous heparin but not by coronary angioplasty. Neither recurrent myocardial infarction nor left ventricular dysfunction are favourably affected by coronary angioplasty which, together with coronary by-pass surgery, should be considered only in case of documented recurrent ischemia. The well-acknowledged role of beta-blockers after myocardial infarction holds true even after thrombolytic therapy, since this treatment decreases the occurrence of new ischemic events. The process of left ventricular remodeling after myocardial infarction is presently investigated and a positive effect has been shown in patients with large myocardial infarction being treated with converting-enzyme inhibitors and/or nitrates. The results of large-scale clinical trials currently underway are eagerly awaited.
Adrenergic beta-Antagonists↗
[Restenosis after coronary angioplasty: its pathogenesis and prevention].
Restenosis after coronary angioplasty is due to a proliferation of smooth muscle cells growing in the vascular lumen, beneath the residual fragments of the atherosclerotic plaque, as seen in necropsy studies and examination of the specimens removed by atherectomy. At the histological analysis thrombi or their fibrocellular organization are not usually detectable. Smooth muscle cell proliferation leading to restenosis is very similar to the one observed in the experimental models of response-to-injury, so that these models are used to investigate into the pathogenetic mechanisms of restenosis. The main stimulus to the loss of the contractile phenotype and to the start of the smooth muscle cell proliferation is represented by the growth factors delivered by platelets adhered to the disendothelialized wall and by the smooth muscle cells themselves, stretched during the dilatation. Other stimuli can be growth factors delivered by monocytes and fibroblasts, by thrombin, endothelin, angiotensin and interleukin 1. The elastic recoil of the vessel wall, the plaque debris and the regional wall shear stress can also contribute to restenosis. The restenosis tissue is different from the atheromatous plaque in that it is almost only constituted by smooth muscle cells and intercellular matrix, while atheroma is much more complex due to the presence of various kinds of cells, of necrotic debris and lipid substances. The smooth muscle cells proliferation also contributes to the pathogenesis of atherosclerosis, but the stimuli starting this process have not been clarified yet; moreover this process is much slower than restenosis, interacting with several factors. Encouraging results have been achieved in the prevention of restenosis after angioplasty in experimental models, but not in man. In order to reduce the incidence of restenosis one should improve the results of angioplasty, even by the use of atherectomy and intracoronary stents. Among pharmacologic approaches anticoagulants, heparin, antiplatelet agents, calcium-channel blockers, corticosteroids all proved ineffective. Studies are in progress evaluating the effect of inhibitors of platelet-derived growth factor (PDGF), antitumor agents and radiation therapy, hirudin, angiotensin-converting enzyme inhibitors and HMG-CoA reductase inhibitors.
Angioplasty, Balloon, Coronary↗