Bucindolol, a beta-adrenoceptor blocker with vasodilatory action: its effect in systemic hypertension

Bucindolol is a newly developed, nonselective beta-adrenergic blocking agent with intrinsic sympathomimetic activity and direct vasodilator properties. In 14 patients with mild to moderate essential hypertension, the effects of bucindolol, hydrochlorothiazide and their combination on blood pressure (BP), heart rate (HR) and parameters of the renin-aldosterone system were compared with those after placebo. Bucindolol's antihypertensive effect was evident within the first hour after drug administration, maximal at 2 to 3 hours, and lasted for as long as 12 hours. Compared with placebo values (108 +/- 5 mm Hg), both bucindolol (97 +/- 9 mm Hg) and hydrochlorothiazide (99 +/- 10 mm Hg) alone significantly and comparably reduced the 12-hour averaged standing diastolic BP, with the combination resulting in approximately additive effects (91 +/- 9 mm Hg). Although bucindolol alone did not affect HR, it attenuated the hydrochlorothiazide-induced increase in HR. There was a tendency for bucindolol to decrease plasma renin activity. Except for transient postural hypotension in 2 patients, bucindolol was well tolerated.     

Morphology of ventricular premature beats as an aid in the electrocardiographic diagnosis of myocardial infarction

To determine whether morphologic analysis of ventricular premature beats (VPBs) can aid in the electrocardiographic diagnosis of myocardial infarction (MI), 12-lead electrocardiograms were evaluated in 760 consecutive patients who underwent cardiac catheterization, and 2-minute multiple-lead rhythm strips were evaluated in 515 of these patients. VPBs occurred in 58 patients; 21 had prior MI diagnosed by regional akinesia or dyskinesia on left ventricular cineangiography. Standard criteria were used to diagnose prior MI from the sinus beats of the electrocardiogram. Infarction was diagnosed from the morphology of a VPB when it had a QR or QRS pattern with Q wave greater than or equal to 0.04 second. Morphologic analysis of VPBs had a low sensitivity (29%) but high specificity (97%) and high predictive value (86%) for the diagnosis of MI. Sinus beats diagnosed MI with higher sensitivity (52%, and 69% if patients with left bundle branch block and left ventricular hypertrophy were excluded from analysis) than VPB morphologic analysis (p less than 0.05), but with similar specificity (97%) and predictive value (92%). Two patients with angiographic MI had no MI according to standard electrocardiographic criteria, but did have an MI manifest by VPB morphologic analysis. Despite low sensitivity, analysis of the morphology of VPBs may be useful for the diagnosis of MI when the morphology of sinus beats is not diagnostic. Therefore, VPB analysis is complementary to the standard electrocardiographic diagnosis of MI.     

Lyme disease—A review of the literature

It appears that a tick introduces an agent—presumably a spirochete—into the skin (see Fig. 1). Immune complexes form and become systemic during the rash. Some patients (identified by the presence of cryoglobulins containing IgM, Clq-reactive material, and depressed IgG and IgA levels) then alter their immune response and may develop neurologic, cardiovascular, or joint involvement. Despite systemic clearing in some patients, the immune complexes localize to the joints where a chronic synovitis develops, similar to rheumatoid arthritis. Why the immune complexes localize to the joints is an enigma. It is tempting to postulate that this localization occurs because of an altered immune response in a genetically predisposed group. However, three of 10 patients with chronic arthritis did not have the B-cell alloantigen DRw2.     

Anterior ST segment depression during acute inferior myocardial infarction: evidence for the reciprocal change theory

We evaluated the recently proposed concern that ECG anterior ST segment depression in patients with acute inferior wall myocardial infarction represents an additional area of ischemia and therefore implies worsened prognosis. We studied patients enrolled in the Aspirin Myocardial Infarction Study (AMIS), ages 30 to 69 years, who sustained an inferior myocardial infarction within 6 months from the start of the study. Two hundred nineteen patients who met those criteria were followed for an average of 38.2 months. One hundred ten patients had significant anterior lead ST depression (greater than or equal to 0.1 mV) during their acute inferior infarction and their 3-year mortality rate was 9.1%. One hundred nine patients had no anterior ST abnormality and a mortality rate of 10.1% (p = ns). Only one patient with significant depression had a subsequent anterior wall myocardial infarction. Anterior ST depression correlated closely with the magnitude of inferior ST segment elevation. Since ST depression does not alter long-term mortality but relates to magnitude of ST elevation, it probably represents a reciprocal change.     

Contrasting effects of nifedipine and verapamil on myocardium and vascular smooth muscle at two levels of coronary occlusion in the dog

The calcium flux inhibitors nifedipine and verapamill have recently been used in the setting of both classical Heberden's and variant angina. It has also been suggested that these agents may preserve function and viability of threatened myocardium. The effects of these agents on the relationship between myocardial blood flow and contraction in the setting of partial coronary occlusion is unknown. Thus 39 open-chest dogs underwent partial coronary occlusion to diastolic perfusion pressures of 25 or 40 mm Hg. The dogs then received intracoronary infusions of 10 μg nifedipine or 100 μg verapamil. Myocardial blood flow was measured with tracer microspheres and myocardial shortening was assessed with ultrasonic crystals. At 25 mm Hg nifedipine improved myocardial shortening while blood flow did not change. In contrast, verapamil caused shortening to be abolished but also did not change blood flow. At 40 mm Hg nifedipine, while not affecting shortening, caused a “redistribution” of blood flow from endocardium; in contrast, verapamil again caused shortening to be abolished, but only increased epicardial blood flow leaving endocardial flow intact. Thus verapamil and nifedipine have differing effects. Nifedipine is a potent vasodilator at doses having no negative inotropic effects. In addition, nifedipine can cause a transmural “redistribution” of blood flow from endocardium to epicardium. In contrast, verapamil is also a potent vasodilator, but has profound negative inotropic effects.     

Determinants of circulatory response to intravenous hydralazine in congestive heart failure

To determine whether the circulatory response to hydralazine in heart failure is influenced by initial hemodynamic status or left ventricular (LV) chamber size, 28 patients with chronic LV dysfunction were studied. Hemodynamic measurements and echocardiographic LV end-diastolic dimension were correlated with the response to 20 mg of intravenous hydralazine and to a dose titrated in each patient to reduce systemic resistance by ≥ 20%. Hydralazine, 20 mg, decreased systemic resistance from 23 ± 8 to 18 ± 8 U(p < 0.01) and increased the cardiac index from 2.0 ± 0.5 to 2.5 ± 0.6 liters/min/m² (p < 0.01) and the stroke work index from 21 ± 11 to 24 ± 9 g · m/m² (p < 0.05). Titrating the dose to decrease systemic resistance by ≥ 20% increased the cardiac index further to 2.7 ± 0.6 liters/min/m² and the stroke work index to32 ± 9 g · m/m². The change in systemic resistance produced by 20 mg of hydralazine correlated only with initial systemic resistance (r = 0.53), suggesting that vascular response to hydralazine is a direct function of initial vascular resistance. The percentage change in stroke work index produced by 20 mg of hydralazine correlated directly with indexes of LV preloadend-diastolic wall stress (r = 0.69) and pulmonary wedge pressure (r = 0.43) and inversely with stroke work index (r = ?0.49), an index of ventricular work. Similar but less close correlations were observed when the dose of hydralazine was titrated. The hemodynamic response to hydralazine did not correlate with LV end-diastolic dimension or right atrial pressure. Thus, vascular response to moderate doses of hydralazine is related to initial systemic vascular resistance. LV pump response is related to the level of initial LV pump dysfunction but not to LV chamber size or right atrial pressure.     

Isolated ultrafiltration in the therapy of volume overload accompanying oliguric vascular shock states.

Isolated ultrafiltration (removal of plasma water and solute without dialysis) was used as a "last resort" therapy in three patients with diuretic and pressor resistant oliguria complicating severe volume overload and vascular shock. The improvement in clinical and hemodynamic parameters is reported and the possible mechanisms of action (decreased pulmonary capillary wedge pressure and increased colloid osmotic pressure) are discussed.