Effect of captopril on prostacyclin and nitric oxide formation in healthy human subjects: Interaction with low dose acetylsalicylic acid

1Angiotensin converting enzyme inhibitors have been suggested to act in part by potentiating the stimulatory effect of bradykinin on endothelial prostacyclin and/or nitric oxide (NO) formation. This may give rise to interaction with cyclo-oxygenase inhibiting drugs like acetylsalicylic acid, which is most often used in low doses in patients with cardiovascular diseases. 2We investigated the effects of captopril (2×25 mg day⁻¹), or ASA (1×100 mg day⁻¹), or the combination of both drugs for 7 days, on blood pressure, prostanoid and NO formation rates in a double-blind, double dummy, randomized crossover study in 13 healthy female subjects. The urinary metabolites of thromboxane A₂ (2,3-dinor-TXB₂) and prostacyclin (2,3-dinor-6-keto-PGF_1α), and PGE₂ were measured by gas chromatography/tandem mass spectrometry in urine on days 1, 6 and 7 of each medication. NO formation was assessed using urinary NO3− and cyclic GMP as indicators. 3Urinary 2,3-dinor-6-keto-PGF_1α excretion was not significantly changed by either captopril, ASA, or their combination. Urinary 2,3-dinor-TXB₂ excretion was inhibited by >80% by ASA alone or in combination with captopril (each P<0.05), but was not affected by captopril alone. Urinary PGE₂ excretion was not significantly changed by either of the treatments. Urinary NO3− and cyclic GMP excretion rates were not significantly changed by captopril, ASA, or their combination. 4Blood pressure was slightly reduced by captopril. ASA had no effect on blood pressure when given alone, nor did it modulate the effect of captopril on blood pressure during co-administration. Angiotensin II/angiotensin I ratio (index of ACE activity) was significantly decreased by captopril alone or in combination with ASA, but was unaffected by ASA alone. 5Captopril does not stimulate prostacyclin formation in healthy human subjects in a dose sufficient to substantially inhibit ACE activity. Co-administration of ASA significantly inhibits 2,3-dinor-TXB₂ excretion, but does not interfere with the blood pressure lowering effect of captopril in healthy human subjects.     

Linear Ablation with Duty‐Cycled Radiofrequency Energy at the Cavotricuspid Isthmus

Background: Multielectrode catheters using duty‐cycled radiofrequency (RF) have been developed to treat atrial fibrillation (AF). Many of these patients also have atrial flutter. Therefore, a linear multielectrode has been developed using the same RF energy. Objective: The concept and acute results of linear ablation using duty‐cycled RF were tested in the cavotricuspid isthmus (CTI). Methods: The CTI was targeted in 75 patients, in 68 (90%) among them as an adjunct to AF ablation with the same technology. A linear electrode catheter with a 4‐mm tip and five 2‐mm ring electrodes was connected to a generator titrating duty‐cycled RF at 20–45 W up to a target temperature of 70°C in 1:1 unipolar/bipolar mode. Results: During a mean procedure time of 20 ± 12 minutes, complete CTI block was achieved by 4 ± 3 applications of duty‐cycled RF in 69 (92%) patients. No more than three RF applications were necessary in 60% of patients. During the initial learning curve, standard RF had to be used in five (7%) patients. Complete block was not achieved in one patient with frequent episodes of AF. Char was observed in five (7%) patients with poor electrode cooling; consequently, the temperature ramp‐up was slowed and manually turned off in the event of low‐power delivery. Two groin hematomas occurred; otherwise, no clinical complications were observed. Conclusion: Multielectrode catheters delivering duty‐cycled RF can effectively ablate the CTI with few RF applications with promising acute results. Further modifications are necessary to improve catheter steering and prevent char formation. (PACE 2010; 444–450)     

THE RELATIONSHIP OF ANTICARDIOLIPIN ANTIBODIES TO DISEASE ACTIVITY IN SYSTEMIC LUPUS ERYTHEMATOSUS

Sera from 124 blood donors, 60 rheumatoid arthritis (RA) and57 SLE patients were measured for anticardiolipin antibodiesby ELISA. Significantly raised IgG (aCLG) and IgM (aCLM) anticardiolipinantibody levels were found in RA and SLE (p<0.0005). However,in SLE, both aCLG and aCLM levels were significantly higherthan in RA (p<0.0025). We then conducted a transectionalstudy to evaluate aCL levels and disease activity in SLE. Therewas a good positive predictive value (70%) between aCL and overalldisease activity, but not for individual systems. A strong associationbetween aCL and renal involvement irrespective of activity wasalso found (80%). Nine SLE patients fulfilled both the clinicaland serological criteria for the antiphospholipid syndrome (APS)and a further 18 patients fulfilled the serological criteriafor APS. Results indicate that aCL levels are of value in predictingoverall disease activity in SLE and in monitoring those patientswho fulfil or partially fulfil the criteria for APS. KEY WORDS: Anticardiolipin antibodies, Systemic lupus erythematosus, Disease activity     

Collagen Plug Vascular Closure Devices and Reduced Risk of Bleeding with Bivalirudin Versus Heparin Plus Abciximab in Patients Undergoing Percutaneous Coronary Intervention for Non ST‐Segment Elevation Myocardial Infarction

Introduction

In ISAR‐REACT‐4 (abciximab and heparin vs. bivalirudin for non‐ST‐elevation myocardial infarction [NSTEMI]), bivalirudin reduced the risk of bleeding after percutaneous coronary intervention (PCI) compared with unfractionated heparin plus abciximab (UFH + abciximab). Vascular closure devices (VCDs) may also prevent bleeding complications, and thus attenuate the benefit of bivalirudin. This analysis examined whether there exists an interaction on bleeding between VCDs and bivalirudin versus UFH + abciximab after PCI.

Methods

Patients with NSTEMI were randomly assigned to either receive UFH + abciximab or bivalirudin for PCI. The use of a VCD after femoral access was left to the operator's discretion. The effect of randomized treatment in patients who received a VCD was compared to that in patients with manual compression of the femoral access site. The primary end‐point of this analysis was the 30‐day incidence of ISAR‐REACT‐4 major bleeding.

Results

A total of 1,711 patients were enrolled in this analysis. Among the 365 (21.3%) patients receiving a VCD, 188 (51.5%) were treated with UFH + abciximab and 177 (48.5%) with bivalirudin. ISAR‐ REACT‐4 major bleeding was higher with UFH + abciximab than with bivalirudin, independent of whether a VCD was used (4.8% vs. 2.3% with VCD and 4.6% vs. 2.7% without VCD, Pint = 0.76). There were also no interactions between randomized treatment and VCDs with respect to any of the ischemic end‐points or net clinical outcome (Pint > 0.56).

Conclusions

In patients undergoing PCI for NSTEMI, the reduction of major bleeding by bivalirudin compared with UFH + abciximab was not affected whether a VCD was used.

     

Chemoreflexsensitivity in Patients with Survived Sudden Cardiac Arrest and Prior Myocardial Infarction

For evaluation of patients with an increased risk of sudden cardiac death, the analyses of ventricular late potentials, heart rate variability, and baroreflexsensitivity are helpful. But so far, the prediction of a malignant arrhythmic event is not possible with sufficient accuracy, For a better risk stratification other methods are necessary. In this study the importance of the ChRS for the identification of patients at risk for ventricular tachyarrhythmic events should be investigated. Of 41 patients included in the study, 26 were survivors of sudden cardiac arrest. Fifteen patients were not resuscitated, of whom 6 patients had documented monomorphic ventricular tachycardia and 9 had no ventricular tachyarrhythmias in their prior history. All patients had a history of an old myocardial infarction (> 1 year ago). For determination of the ChRS the ratio between the difference of the RR intervals in the ECG and the venous pO₂ before and after a 5-minute oxygen inhalation via a nose mask was measured (ms/mmHg). The 26 patients with survived sudden cardiac death showed a significantly decreased ChRS compared to those patients without a tachyarrhythmic event (1.74 ± 1.02 vs 6.97 ± 7.14 ms/mmHg, P < 0.0001). The sensitivity concerning a survived sudden cardiac death amounted to 88% for a ChRS below 3.0 ms/mmHg. During a 12-month follow-up period, the ChRS was significantly different between patients with and without an arrhythmic event (1.64 ± 1.06 vs 4.82 ± 5.83 ms/mmHg, P < 0.01). As a further method for evaluation of patients with increased risk of sudden cardiac death after myocardial infarction the analysis of ChRS seems to be suitable and predicts arrhythmias possibly more sensitive than other tests of neurovegetative imbalance. The predictive importance has to be examined by prospective investigations in larger patient populations.