Vittorio Cervi

Benefit of adding low molecular weight heparin to the conventional treatment of stable angina pectoris. A double-blind, randomized, placebo-controlled trial.

BackgroundPatients 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 ResultsAccording 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. Conclsions. 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.

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.

On the value of the activated clotting time for monitoring heparin therapy in acute coronary syndromes.

Abstract Heparin therapy may be monitored at the bedside with new portable machines measuring the activated clotting time (ACT) of the whole blood and the activated partial thromboplastin time (aPTT). Although the ACT is usually believed to be a convenient substitute for the aPTT, the value of its measurement in patients with acute coronary syndromes has never been evaluated. This study prospectively compares the ACT and the aPTT for monitoring heparin therapy in the coronary care unit.

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 Xal 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.

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.

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.

Felodipine in severe chronic congestive heart failure: Acute effects on central hemodynamics and regional blood flow distribution

SummaryIn order to assess the effect of felodipine, a new calcium antagonist with vascular selectivity, on regional blood flow distribution at rest in chronic congestive heart failure, ten patients were studied during an acute test. Right heart catheterization allowed the evaluation of hemodynamic parameters; renal blood flow was calculated using paraamino-hippuric acid clearance; hepatic blood flow measurement was based on indocyanine green clearance; and limb blood flow was assessed with venous occlusion plethysmography. Blood samples were collected for the analysis of plasma catecholamines, renin, and aldosterone. All parameters were recorded in duplicate under basal conditions and after felodipine infusion.The infusion of felodipine induced a significant increase in cardiac index, stroke work index, and limb blood flow. Systemic and pulmonary arterial blood pressure, pulmonary wedge pressure, and systemic resistance underwent a significant decrease. The heart rate, pulmonary resistance, renal blood flow, and hepatic blood flow were not changed.In conclusion, felodipine was of benefit in congestive heart failure at rest in an acute test, acting through a marked decrease in vascular resistance and a consequent improvement in cardiac output and limb blood flow. No changes in renal and hepatic blood flow were observed.

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.

Acute Effects of Feliodipine on Regional Blood Flow in Chronic Heart Failure

Our study group consisted of 8 males (age 44-70, mean 55) with idiopathic (6 patients) or ischemic (2 patients) dilated cardiomyopathy in congestive heart failure (New York Heart Association 111-IV). They were on chronic digitalis and diuretic therapy. All the patients underwent hemodynamic monitoring with a Swan-Ganz catheter, The following parameters were measured under basal conditions (B) and during F infusion (0.01 5 mg/minute bolus; 0.0075 mg/minute infusion): heart rate (HR), mean blood pressure (MBP, arm cuff), pulmonary wedge pressure (PW), cardiac index (CI, thermodilution method), muscular blood flow (MBF, strain gauge plethysmography), renal blood flow (RBF, paraaminohippuric acid clearance), and hepatic blood flow (HBF, Cardiogreen clearance). Systemic vascular resistance (SVR) and sodium clearance (CNa) were also calculated.