Recreational use of aminorex and pulmonary hypertension.

Pulmonary hypertension has been associated with ingestion of the appetite suppressant aminorex. A similar compound, 4-methyl-aminorex (street names, "U-4-E-uh" [pronounced euphoria] or "ice"), is a "designer" drug with central stimulant activity. This drug was discovered on the property of three individuals with diagnoses of pulmonary hypertension. The association between "recreational" aminorex manufacture and ingestion and the development of pulmonary hypertension is described.

Effect of postural changes and isometric exercise on Doppler-derived measurements of diastolic function in normal subjects.

To determine if simple maneuvers that occur in daily life, such as changes in body position and isometric handgrip exercise, affect Doppler-derived measurements of diastolic function, we studied 22 normal male subjects in the supine position at rest and during several postural manipulations and during handgrip exercise. Comparison of values obtained in the 80 degrees upright tilt position with those obtained in the standard supine position revealed significant decreases in early diastolic flow velocity (peak E) (-25 +/- 3 percent; p less than 0.001), late diastolic flow velocity (peak A) (-9 +/- 3 percent; p less than 0.01), and the ratio of early to late flow velocities (E/A ratio) (-17 +/- 4 percent; significant increases in deceleration time (+55 +/- 10 percent; p less than 0.001) and isovolumic relaxation time (+38 +/- 4 percent; p less than 0.001). Comparison of values obtained with supine isometric exercise with those obtained during the preceding supine resting state revealed significant decreases in peak E (-12 +/- 3 percent; p less than 0.001) and the E/A ratio (-21 +/- 4 percent; p less than 0.001) and significant increases in peak A (+15 +/- 4 percent; p less than 0.001) and isovolumic relaxation time (+16 +/- 3 percent; p less than 0.001). The response of Doppler-derived measurements of diastolic function to postural changes and isometric exercise is complex and multifactorial. Interpretation of these measurements must take into account changes in loading conditions.

Effect of autonomic blockade, postural changes and isometric exercise on Doppler indexes of diastolic left ventricular function.

Previous studies have demonstrated substantial changes in Doppler-derived indexes of left ventricular (LV) diastolic function in response to changes in loading conditions. To assess the influence of autonomic reflexes on these indexes, 2-dimensional and Doppler echophonocardiography were performed in 8 normal male subjects before and during autonomic blockade (0.2 mg/kg of propranolol and 0.04 mg/kg of atropine, intravenously) in the supine, passive upright 80 degree tilt and passive leg-raised positions, and during supine isometric exercise. During autonomic blockade in the supine position, there were significant increases in transmitral peak late filling velocity (A) (mean +/- standard error of the mean +34 +/- 7%) and isovolumic relaxation time (+18 +/- 9%), and significant decreases in transmitral peak early filling velocity (E) (-20 +/- 7%), deceleration time (-35 +/- 7%) and E/A ratio (-40 +/- 5%). E/A ratio decreased from 2.0 +/- 0.1 to 1.2 +/- 0.1 with autonomic blockade. When either upright tilt or isometric handgrip exercise was combined with autonomic blockade, the pattern of diastolic filling became distinctly "abnormal," with E/A ratio decreasing to 0.9 +/- 0.1. The effect of volume loading (increased end-diastolic volume and increased peak E) was seen in the legs-raised position only during autonomic blockade. It is concluded that autonomic blockade substantially alters the Doppler indexes of LV diastolic filling and modifies both hemodynamic response and Doppler indexes produced by positional changes and by isometric exercise.

Reevaluation of the role of atrial systole to cardiac hemodynamics: evidence for pulmonary venous regurgitation during abnormal atrioventricular sequencing.

Twenty open-chest dogs with experimental AV heart block were evaluated hemodynamically, angiographically, and by M-mode echocardiography to further elucidate mechanisms whereby abnormal AV sequencing results in decreased cardiac hemodynamics. During fixed-rate AV pacing, there was a consistent decrease in cardiac output, left ventricular and aortic pressures, and left ventricular dimensions with an increase in left atrial pressure as the AV interval was decreased from 100 to 0 msec, and there were further changes when the AV interval was set at -50 and -100 msec. The hemodynamic consequences of atrial fibrillation with regular ventricular rhythms were similar to the effects of an AV interval of 0 msec. It is important to note that retrograde blood flow into the pulmonary venous system (pulmonary venous regurgitation) was demonstrated by left atrial angiography at AV intervals of both -50 and -100 msec. However, left ventricular angiography failed to reveal mitral regurgitation during fixed-rate pacing at any AV interval or during atrial fibrillation with regular ventricular rates. Thus, during tachyarrhythmias characterized by abnormal AV sequencing, not only is there the loss of active atrial contribution to ventricular filling but there is also evidence for a retrograde or "negative atrial kick" further compromising cardiac hemodynamics.

Failure of antiarrhythmic drugs to affect epicardial delay during acute experimental coronary artery occlusion and reperfusion: correlation with lack of antiarrhythmic efficacy.

Five antiarrhythmic drug protocols were studied to evaluate their efficacy in reducing the incidence of coronary artery ligation and/or reperfusion ventricular arrhythmias and to determine whether their antiarrhythmic activity correlated with their effect on epicardial delay. Protocols were as follows: I) preligation lidocaine (N = 19); II) preligation amiodarone (N = 18); III) preligation procainamide (N = 19); IV) prereperfusion lidocaine (N = 19); V) prereperfusion verapamil (N = 18); and control (no drug, N = 61). A total of 50 (82%) of the 61 control animals developed ventricular arrhythmias during coronary artery ligation and 29 (68%) of the 53 control dogs that survived until reperfusion developed ventricular arrhythmias upon reperfusion. None of these treatment protocols had a significant effect in reducing the incidence of either ventricular arrhythmias or ventricular fibrillation during coronary artery ligation or reperfusion compared with the control animals (P greater than .05). Correspondingly, the mean maximal epicardial delay during coronary artery ligation was also unchanged by each of these drug treatment protocols compared with the control group. Similarly, none of these treatment protocols demonstrated significant effect in preventing reperfusion ventricular arrhythmias or a consistent effect on the degree of mean maximal epicardial delay during reperfusion. Although the lack of antiarrhythmic efficacy of these agents precludes further speculation, further study is warranted to determine whether changes in epicardial delay can be used as markers for antiarrhythmic activity.

Failure of antiarrhythmic drugs to prevent experimental reperfusion ventricular fibrillation.

Ninety-nine adult mongrel dogs underwent acute ligation of the proximal left anterior descending coronary artery. Thirty minutes later, the occlusion was released to evaluate the effectiveness of five antiarrhythmic protocols in eliminating reperfusion ventricular fibrillation. The five protocols included: protocol 1 --i.v. lidocaine, preligation and prerelease (n = 19); protocol 2 -- i.v. lidocaine, prereperfusion only (n = 22); protocol 3 -- chronic, oral, daily amiodarone for 2 weeks preligation (n = 19); protocol 4 -- i.v. procainamide, preligation and prereperfusion (n = 21); and protocol 5 -- i.v. verapamil, prereperfusion (n = 18). Each regimen was evaluated with respect to the incidence of reperfusion ventricular fibrillation in dogs that survived to reperfusion, and the results were compared to 77 control dogs that underwent identical coronary artery occlusion and release procedures without drug therapy. The incidence of reperfusion ventricular fibrillation was as follows: protocol 1 -- seven of 15 dogs (47%); protocol 2 -- six of 18 (33%); protocol 3 -- 11 of 16 dogs (69%); protocol 4 -- eight of 17 dogs (47%); and protocol 5 -- 10 of 17 dogs (59%), compared with 36 of 60 (60%) in control dogs. Using chi-square analysis, protocol 2 was beneficial (p < 0.05). The dogs were then stratified into high- and low-risk subgroups based on the arrhythmic events of the antecedent coronary artery ligation periods, and predictive risk indexes for the occurrence of reperfusion ventricular fibrillation were developed. the Mantel-Haenszel method of statistical analysis revealed that none of these protocols resulted in a statistically significant reduction in the incidence of reperfusion ventricular fibrillation. Thus, use of these predictive indexes plus appropriate statistical methods has revealed, unexpectedly, limitations in the efficacy of a spectrum of antiarrhythmic agents in preventing reperfusion ventricular fibrillation.

Human platelet and fluorochemical interaction.

Since the fluorochemicals have become of interest for the development of artificial red blood cells, oxygenators, liquid breathing, and as a radiographic contrast medium, their interaction with biological substances is of importance. Fresh human platelets were placed in contact with four different fluorochemicals for a period of 50 min. The platelet function as measured by aggregation was determined before and after fluorochemical contact. Appropriate controls were also evaluated. No significant differences were found between the aggregation of platelets contacted with fluorochemicals and the aggregation of platelets from the same donor unexposed to fluorochemicals.