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Biomedical subjects

S Goldman

Publications and source records attributed to S Goldman.

At least 325 records · Page 18Linked to original sources

Effects of 10- to 12-day treatment with L-thyroxine in rats with myocardial infarction.

The effects of treatment with L-thyroxine (T4) for 10-12 days on left ventricular (LV) function and myosin isoenzyme content in rats with LV dysfunction after myocardial infarction were studied. Electrocardiogram (ECG) criteria were used to select animals with large myocardial infarctions. These animals were divided into six groups: control and five treatment groups that received daily subcutaneous injections of T4 (1.5, 3, 6, 10, or 15 micrograms/100 g body wt) for 10-12 days. Intravascular pressures were then measured with micromanometer-tipped catheters, and the hearts were analyzed for myosin isoenzyme distribution. The lowest dose of T4 (1.5 micrograms) produced no changes in heart rate, LV pressure or aortic pressure (AoP), myosin isoenzyme composition, or serum T4 levels. Larger doses of T4 (3, 6, 10, and 15 micrograms) produced increases in LV rate of pressure development (dP/dt), heart rate, and T4 levels but did not change LV pressure or AoP. Myosin isoenzyme composition in the control group showed increases in the proportion of the V3 form and decreases in the V1 form compared with the normal pattern. T4 administration produced dose-dependent increases in the V1 myosin isoform and corresponding decreases in the amount of the V2 and V3 forms. Heart rate increases observed with larger doses of T4 could be prevented by addition of propranolol (500 mg/l) to the drinking water. However, in rats treated with T4 and propranolol, LV pressure, AoP, LV dP/dt, and myosin isoenzyme composition were unchanged compared with T4-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Improvement in early saphenous vein graft patency after coronary artery bypass surgery with antiplatelet therapy: results of a Veterans Administration Cooperative Study.

To determine whether specific antiplatelet therapies improved vein graft patency after coronary artery bypass grafting (CABG) we compared (1) aspirin, 325 mg daily, (2) aspirin, 325 mg three times daily, (3) aspirin plus dipyridamole (325 mg and 75 mg, respectively, three times daily), (4) sulfinpyrazone (267 mg three times daily), and (5) placebo (three times daily). Therapy, except aspirin, was started 48 hr before CABG. When aspirin was a treatment, one 325 mg dose was given 12 hr before surgery and therapy was maintained thereafter according to the assigned regimen. Angiographic graft patency data were obtained within 60 days of surgery. Analysis of early graft patency in 555 patients (1781 grafts), revealed the following graft patency rates: aspirin daily, 93.5%; aspirin three times daily, 92.3%; aspirin and dipyridamole, 91.9%; and sulfinpyrazone, 90.2%. All aspirin-containing therapeutic regimens improved (p less than .05) graft patency compared with placebo (85.2%). Chest tube drainage measured within the first 35 hr after CABG revealed that the median loss with aspirin daily (965 ml), aspirin three times daily (1175 ml), and aspirin plus dipyridamole (1000 ml) exceeded (p less than .02) that with placebo (805 ml), while median loss with sulfinpyrazone (775 ml) did not. The reoperation rate was greater (p less than .01) in all the treatment groups that received aspirin (6.5%) compared with the two nonaspirin groups (1.7%). Overall operative mortality was 2.3%, without significant differences among treatment groups. Transient renal insufficiency occurred in 5.3% of patients taking sulfinpyrazone. Thus, early vein graft patency was improved after CABG with all aspirin-containing drug regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗

Serial changes in left ventricular relaxation and chamber stiffness after large myocardial infarction in rats.

To determine the time course of changes in left ventricular diastolic properties after a large myocardial infarction, we serially measured left ventricular relaxation, chamber stiffness, and the ratio of left ventricular cavity to wall volume (V/VW) after coronary artery ligation in rats. Left ventricular relaxation was measured during the occlusion and then both relaxation and chamber stiffness were measured at 3 hr, 24 hr, and 3, 5, and more than 22 days after infarction. Left ventricular pressures and left ventricular dP/dt were recorded with micromanometer-tipped catheters. Left ventricular relaxation was measured by computer digitization of the left ventricular pressure tracings and averaged over 100 to 150 cardiac cycles. Five chamber stiffness constants were calculated from pressure-volume curves that were obtained ex vivo. We found ventricular relaxation prolonged for the first hour after coronary occlusion; relaxation was maximally prolonged at 10 to 15 min after onset of occlusion. After 1 hr relaxation returned to normal. However, by 5 days ventricular relaxation was again prolonged. Left ventricular stiffness constants were increased at 3 and 24 hr, resulting in a shift of the left ventricular pressure-volume relation to the left. At 3 days after coronary artery ligation, all stiffness constants and the pressure-volume relation returned to normal. At more than 22 days the pressure-volume relation was shifted to the right and the stiffness constant for low filling pressures was decreased. V/VW was significantly decreased from 0.603 +/- 0.021 at 3 and 24 hr to 0.379 +/- 0.024 and 0.362 +/- 0.032, respectively. V/VW was significantly increased at more than 22 days (0.921 +/- 0.094).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cardiac and peripheral circulatory responses to angiotension and vasopressin in dogs.

To determine the cardiac and peripheral circulatory responses to changes in afterload with angiotension and vasopressin, we increased mean aortic pressure 25% and 50% above control in splenectomized and ganglion-blocked dogs. We compared these responses to similar mechanical increases in aortic pressure produced by partial balloon occlusion of the descending aorta. With 25% or 50% increases in aortic pressure, angiotensin, vasopressin, and balloon inflation produced no changes in heart rate, right atrial, and mean pulmonary artery pressures. At 25% increase in aortic pressure, cardiac output was maintained with angiotensin and balloon occlusion but decreased with vasopressin. At 50% increase in aortic pressure, cardiac output was maintained with only balloon occlusion and decreased with both angiotensin and vasopressin. Whenever cardiac output fell, central blood volume did not increase as after-load increased. These changes in preload can be explained by alterations in the venous circulation. Vasopressin did not alter venous compliance or unstressed vascular volume but increased resistance to venous return. Angiotensin also increased resistance to venous return but decreased venous compliance and did not change unstressed vascular volume. Balloon occlusion had no effects on these parameters. We conclude that: (a) angiotensin caused significant venoconstriction resulting in maintenance of cardiac output at 25% but not 50% increase in aortic pressure; (b) vasopressin increased the resistance to venous return without venoconstriction; this resulted in a fall in cardiac output even with a 25% increase in aortic pressure; and (c) the effects of the agents on the venous circulation were independent of the mechanical effects of a pressure increase in the arterial circulation.

Angiotensin II↗

Management of epidermoid carcinoma of the anus.

In two unselected, consecutive and population-based patient materials from two regions in Sweden, different treatment modalities in patients with epidermoid carcinoma of the anus have been evaluated. By using a primary radiotherapeutic approach, combined with surgery in patients with large and/or less radiosensitive tumours, considerably more surviving patients can be disease-free in the long term compared with a primarily surgical approach. In addition, several patients will have preserved anal function. Based upon these data together with the experience described in the literature, we conclude that surgery is no longer the primary treatment of choice in patients with anal carcinoma.

Adult↗

Atrial natriuretic peptide levels during development of chronic heart failure after myocardial infarction in rats.

Serum levels of atrial natriuretic peptide (ANP) are elevated in chronic heart failure presumably due to dilatation of the left atrium resulting from increases in intracardiac pressures. To define the time course of changes in serum ANP levels and to determine the relationship to left ventricular end-diastolic pressure, rats were subjected to coronary artery ligation to produce myocardial infarction and left ventricular failure. Atrial natriuretic peptide levels were measured weekly for four weeks thereafter. In rats with myocardial infarction and elevation of left ventricular end-diastolic pressure there was no change in ANP levels at 7 and 14 days. However, at day 21 and 28, ANP levels were elevated more than 3 fold. There was a correlation between ANP levels and left ventricular end-diastolic pressures. There was no correlation between ANP levels and right atrial pressures or serum sodium concentrations. We conclude that the chronic elevation of left ventricular end-diastolic pressure is required to produce an increase in ANP after myocardial infarction which results in chronic heart failure.

Animals↗

Cardiac catheterization for patients with postinfarction angina.

A retrospective review was conducted to determine the incidence of cardiac catheterization for postinfarction angina, the associated coronary anatomy, and the subsequent clinical course. Over one year, 30 of 178 myocardial infarctions were complicated by postinfarction angina resulting in cardiac catheterization. This was 18% of cardiac catheterizations for evaluation of coronary artery disease. Among the 30 patients, 3 had left main disease, 3 had triple-vessel disease, 11 had double-vessel disease, 11 had single-vessel disease, and 2 had no significant disease. Nine patients had proximal left anterior descending disease without left main disease. In contrast to previous autopsy or surgical series, the extent of coronary artery involvement was less severe and followed a distribution similar to that found in uncomplicated myocardial infarctions. Nevertheless, 17 of the 30 patients underwent revascularization with angioplasty or bypass surgery compared with 41 of 137 without postinfarction angina (p = 0.01). Clinical characteristics of the patients with postinfarction angina did not predict who would ultimately require revascularization. Cardiac catheterization is necessary for management of patients with postinfarction angina, because a majority of them will require revascularization.

Angina Pectoris↗

Hydrophobic adherence and phase variation in Bordetella pertussis.

The hydrophobicity of Bordetella pertussis was assayed by measuring the ability of cells in suspension to adhere to a polystyrene surface. The quantity of adhered bacteria was measured by the binding of enzyme-conjugated anti B. pertussis antibodies. Hydrophobic adherence of non-pathogenic variant strains was about 20% of that exhibited by pathogenic strains. Hydrophobicity was a stable trait as it did not change with passaging or storage. Assays of a series of characterized stable variants suggested that the Filamentous Hemagglutinin (FHA) is the cell surface moiety responsible for hydrophobic adherence in B. pertussis.

Bacterial Adhesion↗

Prognostic significance of clinical stage, histologic grade, and nuclear DNA content in squamous-cell carcinoma of the anus.

Specimens from 47 cases of anal squamous-cell carcinoma were examined in Stockholm county (1978 to 1981) with respect to clinical stage (43 cases), histologic grade (41 cases), and DNA content of the tumor cells (31 cases). Follow-up ranged from four to seven years (median, 5.5 years). The increased mortality in advanced stage and high-grade lesions was significant. Analysis of DNA content showed that most tumors were aneuploid. No statistically significant effect of DNA content on survival could be demonstrated. Thus, histologic grade and clinical stage seem to be the best predictors of patient outcome in squamous-cell carcinoma of the anus.

Adult↗

Phase variation in Bordetella pertussis is accompanied by changes in DNA modification.

Pathogenic strains of Bordetella pertussis tend to undergo a phase variation process when propagated in vitro. The phase variants do not express part or all of the virulence factors of the pathogenic strain and are phenotypically stable. We have previously shown that variation involves a non-reversible, non-random process. In an attempt to characterize the molecular changes accompanying phase variation, chromosomal DNA, isolated from B. pertussis and its variants, was digested with a variety of restriction enzymes followed by agarose gel electrophoresis. While variant DNA was digested by all tested enzymes, pathogenic strain DNA was not digested by part of the enzymes, thus suggesting modification of the DNA at specific sites. DNA isolated from reversible, growth medium induced variants, demonstrated sensitivity to digestion identical to that of spontaneous, stable variants. Analysis of the restriction sequences of all the enzymes, which did not digest DNA from pathogenic strains, failed to reveal any common sequence known to be affected by methylation. HPLC and nearest-neighbor analysis showed a 2-fold increase in the level of DNA methylation in the pathogenic strain. It was concluded that (a) the chromosomal DNA in virulent strains of B. pertussis is protected against enzymatic digestion by an as yet unknown modification and (b) variation in B. pertussis may be caused by changes in the modification of the DNA rather than by mutation.

Base Sequence↗

Development of tolerance to nitroglycerin in the arterial and venous circulation of dogs.

The purpose of this study was to define the effects of nitroglycerin on venous tone and to investigate the time course of nitroglycerin tolerance in the peripheral circulation. The changes in the arterial and venous circulation resulting from an intravenous infusion of nitroglycerin (5 micrograms/kg per min) after 5 minutes (acute infusion) were compared with those changes that occurred after 2 hours (chronic infusion) of the same infusion in six splenectomized, ganglion-blocked dogs. Hemodynamics, blood volume and venous and arterial compliance were measured during each infusion. Nitroglycerin initially decreased mean arterial pressure from 81.5 +/- 2.0 to 57.6 +/- 2.7 mm Hg (p less than 0.01). Central blood volume decreased from 21.1 +/- 1.4 to 15.9 +/- 1.1 ml/kg (p less than 0.01), while total blood volume and unstressed vascular volume did not change. In the acute study, nitroglycerin increased venous compliance 33% from 1.75 +/- 0.14 to 2.32 +/- 0.16 ml/mm Hg per kg (p less than 0.01) and arterial compliance 33% from 0.049 +/- 0.007 to 0.065 +/- 0.007 ml/mm Hg per kg (p less than 0.01). At the end of the 2 hour infusion, arterial pressure increased and was now unchanged from control. Central blood volume had returned to baseline, 17.8 +/- 0.9 ml/kg. Total blood volume and unstressed vascular volume remained unchanged. With the long-term infusion, both arterial and venous compliance decreased (p less than 0.02) to 0.050 +/- 0.006 and 1.50 +/- 0.06 ml/mm Hg per kg, respectively, such that neither value was different from control. Nitroglycerin levels remained constant throughout.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Right ventricular dysfunction and the exercise limitation of chronic obstructive pulmonary disease.

This study examined right ventricular function during exercise in patients with chronic obstructive pulmonary disease to answer the following questions: Is there a significant correlation between oxygen consumption at maximal exercise and exercise right ventricular ejection fraction? Does the right ventricular ejection fraction response to exercise correlate with exercise changes in pulmonary artery pressure, total pulmonary resistance or pulmonary vascular resistance? Which combinations of cardiac, ventilatory and blood gas variables are the best predictors of oxygen consumption at maximal exercise? Twenty-six patients with stable chronic obstructive pulmonary disease performed symptom-limited supine bicycle exercise with simultaneous hemodynamic and radionuclide ventriculographic measurements. The oxygen consumption at maximal exercise correlated with the exercise right ventricular ejection fraction (n = 21, r = 0.66; p less than 0.005), exercise stroke volume (r = 0.68; p less than 0.001), exercise cardiac output (r = 0.77; p less than 0.00005) and exercise ventilation (r = 0.85; p less than 0.00001). The change in right ventricular ejection fraction from rest to exercise correlated inversely with the change from rest to exercise in total pulmonary resistance (r = -0.51; p less than 0.05) but not with the change in mean pulmonary pressure (r = -0.37) or in pulmonary vascular resistance (r = 0.09). Multivariate analysis showed that the variables giving the highest combined correlation with oxygen consumption were ventilation and right ventricular ejection fraction (r = 0.95, adjusted r2 = 0.88). These results suggest that exercise oxygen consumption of patients with chronic obstructive pulmonary disease is related to right ventricular systolic function, exercise right ventricular dysfunction is related, in part, to abnormal exercise total pulmonary resistance, and exercise limitation in chronic obstructive pulmonary disease occurs as a result of the dynamic interaction between disordered right heart function and ventilation.

Adult↗

Atenolol for ventricular ectopy: a dose-response study.

The antiarrhythmic efficacy, safety, and tolerance of atenolol was evaluated in 32 patients with an average of at least 60 ventricular ectopic depolarizations/hr. Patients received, single-blind, the following treatments for 2 weeks each: placebo and atenolol, 50, 100, and 200 mg daily. A 24-hour ambulatory ECG recording was obtained each week. Reduction in ventricular ectopic frequency by at least 75% occurred in six of 32 patients receiving 50 mg daily, five of 30 patients receiving 100 mg daily, and three of 21 patients receiving 200 mg daily (P = not significant for any paired dose comparison). No patient who failed to respond to a lower dose responded to 200 mg daily. The frequency of ventricular tachycardia was reduced by at least 75% in eight of 17 patients receiving 50 mg daily, seven of 16 patients receiving 100 mg daily, and eight of 11 receiving 200 mg daily (P = not significant for any paired dose comparison). Atenolol was discontinued because of adverse effects in 12 patients. The results indicate that atenolol is more effective in suppressing ventricular tachycardia than in suppressing overall ventricular ectopy.

Adult↗

Control of cardiac function and venous return in thyrotoxic calves.

The mechanisms responsible for maintenance of the high-output state associated with thyrotoxicosis have been investigated by measurement of cardiac-function curves and venous compliance during ganglionic blockade with trimethaphan. Thirteen calves were injected daily with L-thyroxine (200 micrograms/kg) for 12-14 days. Thyroxine treatment increased heart rate (70%), left ventricular systolic pressure (22%), cardiac output (120%), left ventricular maximum rate of pressure development (dP/dt) (56%), and total blood volume (18%) and decreased systemic vascular resistance (39%). These hemodynamic changes persisted during ganglionic blockade or autonomic blockade with atropine and propranolol. Cardiac-function curves in conscious thyrotoxic calves were displaced upward and to the left. Mean circulatory filling pressure (MCFP), measured during anesthesia, was increased from 8 +/- 1 to 12 +/- 1 mmHg. During autonomic and ganglionic blockade MCFP remained elevated after treatment with thyroxine. Venous compliance decreased from 2.1 +/- 0.2 to 1.3 +/- 0.1 ml X mmHg-1 X kg-1 after thyroxine. Unstressed vascular volume was increased from 52.3 +/- 1.1 to 67.1 +/- 0.9 ml/kg. Thus the elevated cardiac output and new cardiac-function curve in thyrotoxicosis are associated with a combination of increased inotropic state, increased blood volume, and decreased venous compliance. These effects are not the result of autonomic influences and may represent direct actions of thyroid hormone on the heart and peripheral venous circulation.

Animals↗

Peripheral circulatory control of preload-afterload mismatch with angiotensin in dogs.

To determine whether changes in the venous circulation were responsible for preload-afterload mismatch with angiotensin, we examined the changes in the heart and the peripheral circulation in six splenectomized dogs after ganglion blockade during an angiotensin infusion to increase mean aortic pressure 25 and then 50%. The peripheral circulation was evaluated by measuring mean circulatory filling pressure (MCFP), arterial compliance, and venous compliance. A 25% increase in mean aortic pressure increased MCFP from 6.2 +/- 0.3 to 7.6 +/- 0.3 mmHg (P less than 0.001) but did not change cardiac output, heart rate, or stroke volume. Systemic vascular resistance increased (P less than 0.01) from 0.50 +/- 0.02 to 0.59 +/- 0.03 mmHg X min X kg X ml-1. Arterial and venous compliances decreased (P less than 0.01) from 0.08 +/- 0.03 to 0.06 +/- 0.03 ml X mmHg-1 X kg-1 and from 2.1 +/- 0.1 to 1.6 +/- 0.1 ml X mmHg-1 X kg-1, respectively. A 50% elevation in mean aortic pressure increased MCFP from 7.1 +/- 0.4 to 9.5 +/- 0.9 mmHg (P less than 0.001) but did not change heart rate. At this level of aortic pressure, cardiac output and stroke volume decreased (P less than 0.01) 12 and 19%, respectively, whereas systemic vascular resistance increased (P less than 0.001) from 0.48 +/- 0.03 to 0.83 +/- 0.05 mmHg X min X kg X ml-1. Arterial and venous compliances decreased (P less than 0.01) from 0.08 +/- 0.01 to 0.05 +/- 0.01 ml X mmHg-1 X kg-1 and from 2.1 +/- 0.1 to 1.4 +/- 0.1 ml X mmHg-1 X kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Effects of L-thyroxine in rats with chronic heart failure after myocardial infarction.

The effects of thyroid hormone on left ventricular (LV) function and myosin isoenzyme distribution were evaluated in rats 3 wk after myocardial infarction. When compared with normal rats, animals selected for study had moderately severe LV dysfunction as judged by decreased aortic and LV systolic pressures and a 34% decrease in LV maximum rate of pressure development (dP/dt). Average LV end-diastolic pressure was increased to 26 +/- 1 mmHg from 5 +/- 1 mmHg. The infarcted rats were divided into saline-treated control (n = 10) and treatment (n = 13) groups. The latter group received thyroxine (T4, 1.5 micrograms/100 g body wt) immediately after the first determination of pressures and at 24 and 48 h. At 72 h, aortic and LV pressures and myosin isoenzyme composition were measured. In the thyroxine-treated group LV end-diastolic pressure decreased from 27 +/- 2 to 18 +/- 2 mmHg, and LV dP/dt increased from 5,627 +/- 249 to 6,064 +/- 355 mmHg/s. Heart rate and aortic pressure did not change. After saline injections, LV end-diastolic pressure remained elevated, and the other hemodynamic parameters were unchanged. Determination of ventricular myosin isoenzyme composition in the saline-treated group revealed an increase in the V3 myosin isoform and a decrease in the V1 isoform as compared with the normal values. This pattern was not altered by T4 treatment. A separate group (n = 7) of rats was treated with a 10 times larger dose of thyroxine (15 micrograms/100 g body wt) for the same period of time. In this group, there was neither hemodynamic improvement nor changes in myosin isoenzyme distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Beta-2 adrenoceptor control of the venous circulation in intact dogs.

The effects of beta-2 adrenoceptor stimulation on the peripheral circulation in 10 dogs were evaluated. All studies were done during ganglion blockade with hexamethonium. Venous capacitance was assessed by measuring mean circulatory filling pressure, venous compliance and unstressed vascular volume. Beta-2 stimulation was achieved with terbutaline (27 micrograms/min) after beta-1 blockade with metoprolol (0.75 mg/kg). At a dose of terbutaline that decreased mean aortic pressure from 80.4 +/- 3.5 to 58.9 +/- 1.9 mm Hg (P less than .01), there was no change in cardiac index (155.8 +/- 10.5 vs. 161.1 +/- 9.1 ml/kg/min) despite an increase in heart rate from 118.6 +/- 5.2 to 132.6 +/- 5.0 beats/min. Right atrial pressure, left ventricular end-diastolic pressure and dP/dt did not change. Systemic vascular resistance decreased from 0.52 +/- 0.02 to 0.39 +/- 0.03 mm Hg . min . kg . ml (P less than .01). Arterial compliance increased from 0.067 +/- 0.003 to 0.088 +/- 0.007 ml/mm Hg/kg and the volume of blood shifted out of the larger arteries was 1.8 +/- 0.4 ml/kg. Mean circulatory filling pressure did not change but venous compliance decreased from 1.90 +/- 0.04 to 1.47 +/- 0.06 ml/mm Hg/kg and unstressed vascular volume increased from -14.5 +/- 0.5 to -8.4 +/- 0.5 ml/kg. Central blood volume increased from 22.8 +/- 1.1 to 27.4 +/- 2.2 ml/kg. There was an increase in total blood volume from 81.1 +/- 2.7 to 90.5 +/- 3.7 ml/kg. To determine the extent to which changes in the spleen were responsible for these observations, five dogs were studied 2 weeks after splenectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗