Comparison of efficacy of low molecular weight heparin (parnaparin) with that of unfractionated heparin in the presence of activated platelets in healthy subjects.

Arterial thrombosis is typically platelet-rich. In this study, it is shown that heparin levels resulting in the usual activated partial thromboplastin time therapeutic range provide only a small anticoagulant effect in the presence of activated platelets. Thrombin inhibition is also negligible when heparin is added to platelet-rich plasma. Aspirin improves the anticoagulant effect of heparin in these circumstances, but the degree of anticoagulation is still considerably lower than that observed in platelet-poor plasma. A low molecular weight heparin (parnaparin) is more active in the presence of activated platelets (such as may occur in acute coronary syndromes) regardless of whether aspirin is used concomitantly.

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.

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.

Electrophysiologic properties of prenalterol.

We assessed the electrophysiological properties of prenalterol, a new beta-selective agonist, in 10 patients with normal and 10 patients with delayed atrioventricular (A-V) conduction times. We evaluated sinus node function, A-V conduction times, refractory periods, atrial or ventricular arrhythmias, spontaneous or induced by the single extrastimulus technique during basal conditions, 5 minutes after a first dose of 20 micrograms/kg of prenalterol, and 5, 15 and 30 minutes after a second injection of the same dose. Prenalterol increased heart rate about 20%, with statistically significant shortening of right atrial refractory periods, A-V nodal functional and effective refractory periods and A-H interval in both groups after the first dose. In the 6 patients with sick sinus syndrome, prenalterol increased heart rate significantly and decreased maximum sinus node recovery time which reached a statistically significant value (P less than 0.05) 5 and 30 minutes after the second dose. At the highest dose, prenalterol seemed to increase the number of ventricular and/or atrial arrhythmias only in those patients with the arrhythmias before treatment. Prenalterol increases heart rate and decreases A-V node conduction times. The shortening of maximum sinus node recovery time in patients with the sick sinus syndrome, especially if confirmed after oral administration, could indicate a specific use of this drug in patients with sinus bradycardia or atrial fibrillation with a slow ventricular response.

Effects of coronary artery revascularization and perioperative myocardial infarction on left ventricular wall motion.

The effects of coronary artery revascularization and perioperative myocardial infarction on left ventricular wall motion are still controversial. In this study perioperative myocardial infarction was quantitatively estimated with the cumulative activity of the CK-MB isoenzyme in the perioperative period in a group of 77 consecutive patients undergoing coronary artery bypass surgery. After the operation (on average 9 +/- 1.8 months) all the patients were submitted to left ventricular and coronary angiography. Overall the global left ventricular ejection fraction was unchanged after the operation. The subgroup of patients with all patent grafts showed an improvement of both regional wall motion (P less than 0.05) and ejection fraction (from 58 +/- 13 to 64 +/- 13%, P less than 0.005); the number of angiographically abnormal left ventricular segments decreased from 28.5 to 16.6% (P less than 0.001). The cumulative activity of CK-MB enzyme was significantly correlated with the pre- and postoperative changes of ejection fraction (r = -0.51, P less than 0.01). Thus coronary artery bypass surgery can improve regional wall motion, but the likely benefit is observed in the absence of a perioperative myocardial ischemic damage.

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.

Long-term arterial patency after coronary reperfusion.

Coronary reocclusion is a frequent event after reperfusion and may be responsible for the deterioration of left ventricular function. It may occur early as well as in the chronic phase after hospital discharge. Current, evidence based, strategies to prevent reocclusion include antiplatelet and anticoagulant agents as well as the use of intracoronary stenting in those patients who are treated by PTCA. The combination of aspirin and ticlopidine adds on the results of stenting. Further treatments are currently investigated and may significantly improve the long-term coronary patency.

Performance of fineneedle aspiration cytology of the breast. Clinical experience in Ravenna (Italy).

AIMS AND BACKGROUND: Fineneedle aspiration cytology (FNAC) is a routine test in the evaluation of breast lesions. We assessed the diagnostic accuracy of mammography (MG), physical examination (PE), ultrasonography (US) and FNAC in 1064 histologically confirmed breast lesions (638 malignant, 426 benign) observed consecutively at the Cancer Prevention Center of Ravenna (Italy). METHODS: The performance of each test and the additional contribution of FNAC were determined. RESULTS: FNAC was done in 69.6% of cancers and 39.7% of benign lesions (P = 0.00000), the frequency of aspiration being significantly associated with severity at MG, PE, and US. For FNAC, the true positive rate was 95.1% and the true negative rate 67.4%. Only one breast cancer case was detected by FNAC alone (additional true positive rate 0.2%). The positive predictive value of FNAC in the absence of other abnormalities was 5%. The negative predictive value of a benign report at MG, PE, US and FNAC was 100%. CONCLUSIONS: All breast lesions should be evaluated by all available techniques, especially FNAC, and open biopsy should be avoided for those reported as benign at all tests.

Pharmacodynamic characteristics of low-molecular-weight dermatan sulphate after subcutaneous administration in acute myocardial infarction.

Sixteen patients (5 female and 11 male, mean age 59.1 years) who had had an acute myocardial infarction within the previous 7 days, were enrolled in an open pharmacodynamic study. Patients were randomly allocated to two treatment groups and given a single subcutaneous dose of 100 or 200 mg of a new low-molecular-weight dermatan sulphate. The drug pharmacodynamic profile was determined 1, 2, 4, 6, 8, 12 and 24 h after administration. The following coagulation and fibrinolysis tests were performed: activated partial thromboplastin time, thrombin time, activated factor X inhibition, Heptest (global clotting time), heparin cofactor II affinity, functional and antigenic plasminogen activator inhibitor and fibrin plate assay. Both Heptest and heparin cofactor II affinity were significantly increased (P < 0.001) in a dose-dependent manner. The XaI was enhanced, though to a lesser extent. None of the other coagulation or fibrinolysis tests showed significant changes at either dose. Systemic and local tolerance were always very good.

[Calcification of mitral anulus and mitral valve prolapse. Description of a case with severe mitral valve insufficiency]. / Calcificazione dell'anulus mitralico e prolasso valvolare mitralico. Descrizione di un caso con insufficienza metralica severa.

We report the case of a women, 40 years old, suffering from a severe mitral insufficiency caused by the simultaneous presence of three anatomical anomalies: mitral valve prolapse, mitral anulus dilation and calcification. Such degrees of calcification are generally found in older people and in association with a similar degeneration of all the fibrous skeleton of the heart. Whereas the association of mitral valve prolapse with mitral anulus dilation has been clearly remarked, a few cases (16 as a whole in our knowledge) with scanty details documented the possibility of an associated mitral anulus calcification.

[Late-appearing cholestatic icterus after a month of treatment with ticlopidine]. / Ittero colestatico a comparsa ritardata dopo trattamento per un mese con ticlopidina.

A 65-year-old man was submitted to coronary angioplasty and stent implantation for stable angina. The treatment included a 30-day therapy with ticlopidine (in addition to aspirin, metoprolol, ramipril, amlodipine and nitrates). One month after ticlopidine withdrawal a progressive cholestatic jaundice took place. Viral, immunogenic as well as nutritional causes were ruled out. The abdominal echography disclosed a normal biliary tree and the liver biopsy showed a centrolobular cholestasis pattern. Drug-induced cholestatic reaction was diagnosed and attributed to ticlopidine. There was a progressive improvement in clinical and laboratory findings 4 months after steroid treatment. The clinical picture was normalized after 6 months. When considering the option ticlopidine, even for a short time after coronary angioplasty, the possibility of drug-induced hepatotoxicity should be kept in mind. Consequently, markers of liver toxicity should be monitored carefully.

Periodontal health improves systemic inflammatory and haemostatic status in subjects with coronary heart disease.

OBJECTIVES: A relationship between poor oral health and coronary heart disease (CHD) and systemic inflammatory and haemostatic factors has been recently documented in an Italian population. The present study was performed to assess whether intensive dental care may produce a periodontal improvement along with a change in systemic inflammatory and haemostatic factors. MATERIAL AND METHODS: The study population consisted of 18 males aged 40-65 years with proven CHD and elevated values of systemic inflammatory and haemostatic factors. A detailed description of their oral status was given by using two different dental indices (clinical periodontal sum score and clinical and radiographic sum score). Blood samples were taken for measurement of the following systemic markers of inflammation [(C-reactive protein (CRP), leucocytes, fibrinogen)] and haemostatic factors [(von Willebrand factor, fibrin D-dimer and oxidized-low density lipoprotein (Ox-LDL)]. All parameters were determined in each subject at baseline, after 4 months as a control and 3 months after an intensive protocol of scaling and root planing. anova for repeated measures was used for the statistical analysis. RESULTS: No statistical difference was found between values at baseline and at the 4-month-control. All oral indexes showed a significant decrease (p< .01) 3 months after periodontal treatment. All systemic inflammatory indexes decreased but only the decrease in CRP reached statistical significance (p< .05). A significant decrease (p< .01) was also found as regards Ox-LDL among haemostatic factors. CONCLUSIONS: Preliminary results from the present study suggest an association between poor oral status and CHD, and provide evidence that the improvement of periodontal status may influence the systemic inflammatory and haemostatic situation.

The role of infarct size in early and late mortality.

To evaluate the impact of infarct size on morbidity and mortality, blood samples were drawn for CPK-MB determination in 144 consecutive patients with first acute myocardial infarction. Enzymatically estimated infarct size was significantly higher in patients who developed in-hospital arrhythmias, congestive heart failure or mechanical complications, or died. After hospital discharge, infarct size was correlated with the extension score of resting thallium-201 perfusion defects. However, infarct size did not predict the occurrence of long-term complications. Thus, infarct size affects the short-term prognosis. The long-term follow-up is determined by the complex interaction of left ventricular dysfunction, residual ischemia, and arrhythmogenic potential.

[The management of postthrombolysis patients]. / La gestione dei pazienti post-trombolisi.

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.

[Extension of necrosis in the acute phase of myocardial infarct. Clinical picture and prognosis]. / La estensione della necrosi nella fase acuta dell'infarto miocardico. Quadro clinico e prognosi.

In a consecutive series of 297 patients prospectively evaluated at the time of admission for an acute myocardial infarction, the extension of necrosis was found to occur in 16,4% of the cases. The electrocardiographic site of extension was the same as during the initial episode in over 75% of cases suggesting the possibility of a similar pathogenetic mechanism and the involvement of the same coronary district. Patients in Killip class I were respectively 61% and 45% before and after the extension, in class II 33% and 14%, in class III 6% and 14%, in class IV 0 and 27% (p less than 0,001). In-hospital mortality was 16,1% without and 38,8% with extension (p less than 0,001). The peak level of CPK-MB was an average of 110 +/- 45 U/1 before and 96 +/- 34 after the extension (p = N.S.). It was not possible to recognize the patients at risk of extension according to the traditional clinical parameters (age, sex, site of necrosis, transmural involvement, residual angina, Norris index and Killip class before the extension). It is concluded that the protection of the myocardium at risk is of primary importance in the setting of acute myocardial infarction, regardless of the possibility of saving areas already compromised at the time of admission or the hypothetical "border zone".