Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation: II. Dense spontaneous echocardiographic contrast (The Stroke Prevention in Atrial Fibrillation [SPAF-III] study).

We analyzed transesophageal echocardiograms from 772 participants in the Stroke Prevention in Atrial Fibrillation (SPAF-III) study, characterizing spontaneous echocardiographic contrast (SEC) in the left atrium or appendage as faint or dense. The association of dense SEC with stroke risk factors and anatomic, hemodynamic, and hemostatic parameters related to specific thromboembolic mechanisms was evaluated by multivariate analysis. Spontaneous echocardiographic contrast was present in 55% of patients and was dense in 13%. Age (odds ratio [OR] 2.4/decade, P <.001), constant atrial fibrillation (OR 6.9, P <.001), history of hypertension (OR 3. 2, P <.001), and current tobacco smoking (OR 2.6, P =.04) were independent clinical predictors of dense SEC. Multivariate analysis of clinical, echocardiographic, and hemostatic parameters yielded age as the sole independent clinical predictor of dense SEC (OR 2. 4/decade, P <.001). Other independent predictors were measures of left atrial/appendage flow dynamics, left atrial size (OR 2.4/cm diameter, M-mode, P <.001), atherosclerotic aortic plaque (OR 2.8, P =.002), and plasma fibrinogen >350 mg/dL (P <.001). Results were similar when SEC of any density was analyzed. In conclusion, SEC occurred in more than half of these patients with prospectively defined nonvalvular atrial fibrillation but was usually faint. Dense SEC was strongly associated with previously reported clinical predictors of stroke, linking them to thromboembolism through atrial stasis. Diverse pathophysiologic factors including atrial stasis, fibrinogen level, and aortic plaque influence SEC.

Cardiovascular effects of sevoflurane compared with those of isoflurane in volunteers.

BACKGROUND: Sevoflurane is a new inhalational anesthetic with desirable clinical properties. In some clinical situations, an understanding of the detailed cardiovascular properties of an anesthetic is important, so the authors evaluated the hemodynamic effects of sevoflurane in healthy volunteers not undergoing surgery. METHODS: Twenty-one subjects were randomized to receive sevoflurane, isoflurane, or sevoflurane: 60% N2O. Anesthesia was induced and maintained by inhalation of the designated anesthetic. Hemodynamic measurements were performed before anesthesia, during controlled ventilation, during spontaneous ventilation, and again during controlled ventilation after 5.5 h of anesthesia. RESULTS: A few subjects became excessively hypotensive at high anesthetic concentrations (2.0 minimum alveolar concentration [MAC] sevoflurane, 1.5 and 2.0 MAC isoflurane), preventing data collection. Sevoflurane did not alter heart rate, but decreased mean arterial pressure and mean pulmonary artery pressure. Cardiac index decreased at 1.0 and 1.5 MAC, but in subjects with mean arterial pressure > or = 50 mmHg returned to baseline values at 2.0 MAC when systemic vascular resistance decreased. Sevoflurane did not alter echocardiographic indices of ventricular function, but did decrease an index of afterload. Sevoflurane caused a greater decrease in mean pulmonary artery pressure than did isoflurane, but the cardiovascular effects were otherwise similar. Administration of sevoflurane with 60% N2O, prolonged administration or spontaneous ventilation resulted in diminished cardiovascular depression. CONCLUSIONS: At 1.0 and 1.5 MAC, sevoflurane was well tolerated by healthy volunteers. At 2.0 MAC, in subjects with mean arterial pressure > or = 50 mmHg, no adverse cardiovascular properties were noted. Similar to other contemporary anesthetics, sevoflurane caused evidence of myocardial depression. Hemodynamic instability was noted in some subjects at high anesthetic concentrations in the absence of surgical stimulation. The incidence was similar to that with isoflurane. The cardiovascular effects of sevoflurane were similar to those of isoflurane, an anesthetic commonly used in clinical practice since 1981.

Antiplatelet effects of oral diltiazem, propranolol, and their combination.

1. The antiplatelet effects of a single oral dose of the calcium entry blocker diltiazem (60 mg), the beta-adrenoceptor blocker propranolol (40 mg), and their combination were studied in five healthy subjects. 2. Platelet aggregation and ATP release induced by adrenaline and ADP and ADP induced platelet thromboxane A2 generation were significantly inhibited (P less than 0.05) by either diltiazem or propranolol, although propranolol tended to have greater inhibitory effects on platelet function than diltiazem that did not reach statistical significance. 3. Combination therapy resulted in additive antiplatelet effects that were significantly (P less than 0.05) greater than either drug alone. 4. These data indicate that combined administration of a calcium entry blocker and a beta-adrenoceptor blocker results in additive inhibitory effects on platelet function. These effects may mediate part of the therapeutic efficacy of combination therapy in patients with coronary artery disease.

Effects of oral diltiazem on platelet function: alone and in combination with "low dose" aspirin.

The effects of 3 days of oral diltiazem, "low dose" aspirin (40 mg/day), and their combination on platelet function was studied in 5 normal subjects. Both drugs inhibited platelet aggregation and ATP release induced by collagen, epinephrine and threshold concentrations of ADP. Aspirin and diltiazem decreased thromboxane A2 generation during ADP induced aggregation by 94 percent and 53 percent respectively, however both agents inhibited aggregation similarly, which suggests that diltiazem's anti-platelet effect was due to mechanisms other than inhibition of thromboxane metabolism alone. Combination therapy resulted in a partially additive inhibitory effect on ADP induced aggregation and thromboxane A2 generation. Two subjects had bleeding times over 15 minutes after receiving combination therapy.

Management of patients after thrombolytic therapy for acute myocardial infarction.

The coronary artery thrombus that causes acute myocardial infarction can be lysed, and reperfusion can be achieved, in the first few hours after infarction. However, the infarct vessel will reocclude in 15-30% of patients, and this event is frequently associated with pain, reinfarction, arrhythmias, or death. The risk of reocclusion is greatest in patients with high-grade residual stenosis after thrombolysis. Percutaneous coronary angioplasty may be performed safely after thrombolytic therapy. Angioplasty effectively decreases the degree of residual stenosis, and may thereby reduce the risk of reocclusion and consequent ischemic events. However, a substantial proportion of patients with acute infarction are not suitable candidates for angioplasty. Coronary artery bypass surgery has also been safely performed within several days after thrombolytic therapy. Further studies are needed to determine which patients will benefit most from this aggressive approach to acute myocardial infarction.

Effect of mitral regurgitation on the murmur of pulmonic regurgitation.

We evaluated auscultatory findings in a 67-year-old man with acquired pulmonic and mitral regurgitation. During inspiration, the murmur of pulmonic regurgitation decreased in intensity prior to surgery, but increased in intensity after mitral valve replacement. Inspiration reduces the volume of mitral regurgitation, thereby reducing the volume and murmur of pulmonic regurgitation.