Hemodynamic effects of an oral dopamine receptor agonist (fenoldopam) in patients with congestive heart failure

Dopamine receptor stimulation causes vascular and neurohumoral responses that may be beneficial in patients with heart failure. Oral inactivity, emesis and adrenergic-induced arrhythmias have limited the use of currently available compounds. Fenoldopam (SKF-82526-J) is a new, orally available, selective, dopamine-receptor agonist with potent renal vasodilating properties (six times that of dopamine) without positive inotropic or adrenergic activity. Drug efficacy was clinically evaluated in 10 patients with heart failure after single oral doses of placebo and 50, 100 and 200 mg of medication. Placebo produced no changes. Peak efficacy was noted 30 minutes to 1 hour after the 200 mg dose with mean blood pressure decreasing from 96 +/- 15 (mean +/- SD) to 83 +/- 8 mm Hg (p less than 0.05), pulmonary capillary wedge pressure decreasing from 23 +/- 6 to 20 +/- 8 mm Hg (p less than 0.05) and mean pulmonary artery pressure decreasing from 32 +/- 9 to 29 +/- 8 mm Hg (p less than 0.05). Systemic vascular resistance decreased from 1,987 +/- 887 to 1,191 +/- 559 dynes.s.cm-5 (p less than 0.05) with a subsequent 55% increase in cardiac index from 2.2 +/- 1.1 to 3.1 +/- 1.3 liters/min per m2 (p less than 0.05). Heart rate and right atrial pressure did not change (p greater than 0.05). No emesis or new tachycardia was noted at any dose. Baseline hemodynamics generally returned within 3 to 4 hours. Fenoldopam, therefore, is a short-acting, orally effective drug that decreases systemic vascular resistance and increases cardiac index in patients with heart failure and represents a new class of oral compounds that may be useful in treating such patients.     

Immediate and short-term benefit of multilesion coronary angioplasty: influence of degree of revascularization

The safety and short-term therapeutic benefit of multilesion percutaneous transluminal coronary angioplasty was assessed in 135 patients, 66 of whom had a minimum of 6 months of follow-up study. Primary success, defined as successful dilation of the most critical lesion or all lesions attempted without major in-hospital complications was obtained in 117 (87%) of the 135 patients. Cardiac complications associated with the procedure were uncommon; prolonged angina occurred in 5% and myocardial infarction in 3%; emergency coronary bypass surgery was performed in 4% of the patients. There were no deaths. Complete revascularization was achieved in 46% of the 117 patients with a primary success. Of the 66 patients eligible for 6 month follow-up, 80% had an uncomplicated course and required no further procedures. Clinical improvement by at least one angina functional class was observed in 90% of the patients. Cardiac events such as the need for a second revascularization procedure were significantly more common in patients who had incomplete versus complete revascularization (35 versus 9%; p = 0.018). Repeat coronary angiography performed an average of 5 months after angioplasty revealed restenosis in 18 of 22 symptomatic patients and 3 of 9 asymptomatic patients. Restenosis occurred at the site of a single dilation in 12 patients, at two sites in 8 patients and at three sites in 1 patient. Thus, multilesion coronary angioplasty is an important therapeutic option for selected patients with multivessel disease and can be performed with relatively low risk. Improvement in angina status can be expected even in patients who have incomplete revascularization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diabetic lipoprotein deficient serum: Its effect in low density lipoprotein (LDL) uptake and degradation by fibroblasts

Low density lipoproteins (LDL) isolated from poorly controlled diabetic patients are known to be taken up and degraded by fibroblasts at a lower rate than LDL isolated from normal subjects. This aberrant metabolic behavior has been attributed to a diabetic-related abnormality in LDL composition yet to be characterized. The studies reported in this article show that the decrease in uptake and intracellular degradation of LDL from diabetic patients is further enhanced when the cells are exposed to lipoprotein deficient serum (LPDS) isolated from the same poorly controlled diabetic patients. Comparative studies of the composition of LPDS obtained from normal donors and poorly controlled diabetic patients showed an increase in saturated and total unesterified fatty acids (UFA), lecithin, apolipoprotein A1, and immunoreactive insulin in the LPDS from diabetic patients. We postulate that exposure of cells to LPDS obtained from poorly controlled diabetic patients may induce changes in the composition of the fibroblast membrane and alter its fluidity, leading to further decrease in the uptake and degradation of LDL. During poor diabetic control, cell membrane changes, and modification of LDL composition are likely to act either additively or synergistically to induce an abnormal LDL-cell interaction. This abnormal interaction may be a relevant factor to explain the greater incidence of arteriosclerosis in diabetes mellitus.     

Atrial level right to left intracardiac shunt associated with postoperative hypoxemia: demonstration with contrast two-dimensional echocardiography

Transient hypoxemia is not uncommon after major cardiac or thoracic surgery. The differential diagnosis includes atelectasis, pulmonary embolus, pneumonitis, congestive heart failure and several other diverse cardiovascular and pulmonary problems. Less well recognized is transient right to left intracardiac shunting through a patient foramen ovale or previously unsuspected atrial septal defect. Three cases of clinically important hypoxemia associated with right to left shunting after aortocoronary bypass surgery are presented. The right to left shunting was documented with contrast-enhanced echocardiography, which is a simple, inexpensive and accurate means of screening patients for intracardiac right to left shunts and may play a valuable role in the postoperative management of patients.     

Palliative dilation of esophageal carcinoma

The authors' experience with palliative dilation of 46 consecutive patients evaluated for squamous cell carcinoma of the esophagus was retrospectively reviewed. Thirty-nine of 46 patients (85%) underwent dilation in order to palliate symptoms, enable endoscopy and biopsy, or prepare for placement of an esophageal prosthesis. Thirty-two of the 46 patients (70%) were treated with radiation therapy and seven (15%) underwent placement of an esophageal prosthesis. Thirty-five of the 39 patients dilated (90%) noted improvement in swallowing, allowing resumption of a soft or regular diet. Complications were noted in three of the 39 patients dilated (8%). The authors conclude that peroral dilation is a safe, effective, and probably underutilized method of palliation in patients with squamous cell esophageal carcinoma.     

Discordance between ambulatory monitoring and programmed stimulation in assessing efficacy of class IA antiarrhythmic agents in patients with ventricular tachycardia

Concordance between programmed stimulation and 24 hour ambulatory electrocardiographic (Holter) monitoring was studied in 54 patients with sustained ventricular tachycardia during 84 therapeutic trials with class IA antiarrhythmic agents. During baseline studies before treatment, all patients had frequent (greater than or equal to 30/h) ventricular premature complexes on Holter recordings and sustained ventricular tachycardia inducible by one to three extrastimuli. During treatment, programmed stimulation and Holter monitoring were repeated. Efficacy of treatment determined by programmed stimulation (ventricular tachycardia no longer inducible or nonsustained) was compared with three Holter criteria of efficacy: I = 83% or more reduction of ventricular premature complexes and abolition of ventricular tachycardia; II = 50% or more reduction of ventricular premature complexes and 90% or more reduction of couplets and abolition of ventricular tachycardia; III = abolition of ventricular tachycardia in patients with ventricular tachycardia during a baseline Holter recording. Treatments were judged effective by programmed stimulation criteria in only 25% of cases but in 51, 63 and 75% of cases by Holter criterion I, II and III, respectively. Results of programmed stimulation and Holter monitor were discordant (effective by one criterion but ineffective by the other) in 50% of cases using Holter criterion I, in 54% using Holter criterion II and in 61% using Holter criterion III. In the majority of discordant results, treatments appeared efficacious by Holter criteria but ineffective by programmed stimulation criteria, suggesting insensitivity of efficacy by Holter criteria or nonspecificity of induced ventricular tachycardia during treatment, or both.     

Effect of the renin-angiotensin system on limb circulation and metabolism during exercise in patients with heart failure

The maximal aerobic exercise capacity of patients with chronic heart failure is frequently decreased because of inadequate blood flow to working skeletal muscle. To investigate whether this reduced flow is in part due to interference by angiotensin II with arteriolar dilation in working muscle, the effect of the angiotensin-converting enzyme inhibitor captopril on leg blood flow, leg vascular resistance, leg oxygen consumption (VO2) and leg lactate release during maximal upright bicycle exercise was examined in 12 patients with heart failure (maximal VO2 10.7 +/- 3.1 ml/min per kg). Captopril decreased leg resistance at rest (258 +/- 115 to 173 +/- 67 U, p less than 0.01) and maximal exercise (68 +/- 69 to 45 +/- 29 U, p less than 0.01) associated with proportionately similar decreases in systemic vascular resistance. However, maximal exercise duration and maximal VO2 were unchanged and, at identical peak exercise work times, there was no improvement in leg blood flow (2.0 +/- 0.9 to 2.0 +/- 1.1 liters/min, p = NS), leg VO2 (261 +/- 104 to 281 +/- 157 ml/min, p = NS) or leg lactate release (269 +/- 149 to 227 +/- 151 mg/min, p = NS). These data suggest that, during exercise in patients with heart failure, angiotensin II does not interfere with blood flow to working skeletal muscle.     

MDL 17,043: short- and long-term cardiopulmonary and clinical effects in patients with heart failure

MDL 17,043, an inotropic and vasodilator drug, is believed to have beneficial effects in patients with heart failure. Its short- and long-term hemodynamic and cardiopulmonary effects were studied in 10 patients with New York Heart Association functional class III heart failure who were maintained on digitalis and diuretic drugs. Hemodynamics at baseline study and after 24 hours of oral therapy (four doses of 6 mg/kg) showed increased cardiac output (3.9 +/- 0.7 to 6.1 +/- 1.1 liters/min, p less than 0.05), increased stroke volume (42 +/- 12 to 60 +/- 15 ml, p less than 0.05), decreased systemic vascular resistance (1,564 +/- 326 to 1,009 +/- 296 dynes X s X cm-5, p less than 0.05) but no change in pulmonary capillary wedge pressure (31 +/- 6 to 25 +/- 13 mm Hg, p = NS). Only systemic vascular resistance and arteriovenous oxygen difference were significantly decreased during exercise. When restudied after 5 weeks of therapy, neither cardiac output nor stroke volume showed a sustained increase at rest or during exercise, and effects on systemic vascular resistance and arteriovenous oxygen difference were not sustained at exercise (p = NS). Peak oxygen uptake during exercise was 8.1 +/- 2.5 ml/kg per min at baseline and was not significantly increased either acutely (9.2 +/- 2.4 ml/kg per min, p = NS) or chronically (8.9 +/- 2.2 ml/kg per min, p = NS). Problems of increased ventricular arrhythmias and diarrhea were noted after therapy was begun.(ABSTRACT TRUNCATED AT 250 WORDS)     

Altered erythrocyte Na-K pump in anorectic patients

The status of the erythrocyte sodium pump was evaluated in a group of patients suffering from anorexia nervosa and a group of healthy female control subjects. Anorectic patients showed significantly higher mean values of digoxin-binding sites/cell (ie, the number of Na-K-ATPase units) with respect to control subjects while no differences were found in the specific 86Rb uptake (which reflects the Na-K-ATPase activity) between the two groups. A significant correlation was found between relative weight and the number of Na-K-ATPase pump units (r = -0.66; P less than 0.0001). Anorectic patients showed lower serum T3 concentrations (71.3 +/- 53 ng/dL) with respect to control subjects (100.8 +/- 4.7 ng/dL; P less than 0.0005) and a significant negative correlation between T3 levels and the number of pump units (r = -0.52; P less than 0.003) was found. Our study therefore shows that the erythrocyte Na-K pump may be altered in several anorectic patients. We suggest that this feature could be interrelated with the degree of underweight and/or malnutrition.     

Instability of fasting blood glucose values in noninsulin-dependent diabetic patients with long-term insulin treatment

We studied serum free C-peptide immunoreactivity (CPR) and the coefficient of variation (CV) of fasting blood glucose values (FBG) in 26 insulin-treated patients with non-insulin-dependent diabetes mellitus (NIDDM) in relation to the duration of insulin treatment. Serum free CPR responses during 100 g oral glucose tolerance test (OGTT) were significantly lower in patients with insulin treatment for five years or more than in those with insulin treatment for less than five years although their previous immunoreactive insulin (IRI) responses during OGTT before insulin treatment showed no significant difference. CV of FBG was found to be significantly higher at the time of this study (20.6 +/- 7.8%, mean +/- SD) than at the second year of insulin treatment (15.3 +/- 7.7%, P less than 0.05) in the patients with insulin treatment for five or more years but did not show any significant difference in patients with insulin treatment for less than five years at the corresponding times. Thus we measured CV of the FBG in NIDDM patients at various intervals during the long-term insulin or oral hypoglycemic agent treatment in another study. In 20 patients with insulin treatment, CV of FBG was found to be significantly different among the various intervals during insulin treatment (P less than 0.0025). It was significantly higher at the eight year (22.2 +/- 8.6%) and 12th year (21.9 +/- 9.1%) than at the second year (14.9 +/- 6.1%) and fifth year (15.0 +/- 6.7%) of insulin treatment (P less than 0.025, P less than 0.025; P less than 0.05, P less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)