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Biomedical subjects

L Coppola

Publications and source records attributed to L Coppola.

At least 37 records · Page 2Linked to original sources
PubMed1999

Out-patient management of acute myeloid leukemia after consolidation chemotherapy. Role of a hematologic emergency unit.

BACKGROUND AND OBJECTIVE: Increasing attention to quality of life and to health care costs has recently induced several cancer centers to change in-patient management into an out-patient setting even during high risk phases of disease. The aim of this prospective study was to evaluate feasibility and safety, as well as clinical characteristics, of out-hospital management of AML patients during their post-consolidation phase. DESIGN AND METHODS: All patients who were treated over a three year period by the three following protocols were included in the study: AML10 EORTC/GIMEMA for patients with AML, except for APL, aged </= 60 years; AML 13 EORTC/GIMEMA, for patients with AML, except for APL, aged >60 years; AIDA GIMEMA for APL patients. All patients submitted to the AML10 and AML13 protocols and those patients submitted to the AIDA protocol with difficult peripheral vein access had a central venous catheter (CVC) sited. Patients treated as in-patients were discharged at the end of consolidation chemotherapy provided they were in a good clinical condition. They were routinely evaluated on an out-patient basis twice weekly. In the event of any complication they were referred to the Emergency Unit of our Department dedicated to out-patients with hematologic diseases. RESULTS: One hundred and eleven patients with AML were eligible for intensive chemotherapy. After achievement of complete remission they received a total of 133 consolidation courses and in 127 instances they were followed on an out-patient basis during the aplastic phase. There were 69 cases (54%) of rehospitalization, 68 because of fever and only one because of severe anemia. Rehospitalization occurred in 90%,70% and 38% of courses in AML10, AML13 and AIDA protocols, respectively. Only one patient died: the cause of death was a brain hemorrhage. Coagulase negative staphylococci and viridans streptococci were the organisms most frequently isolated from blood. Most coagulase negative staphylococci were isolated in patients submitted to AML10 and AML13 protocols, who had an indwelling CVC. Empiric once-a-day antibacterial therapy with ceftriaxone and amikacin was effective in 75% of the cases and made early discharge possible in 28% of the cases with antibiotic therapy continued in an out-patient setting. Overall, patients were managed out of the hospital for 66% of the period of post-consolidation neutropenia (77%, 48% and 50% of the post-consolidation neutropenia period in patients treated with AIDA, AML10 and AML13 protocols, respectively). INTERPRETATION AND CONCLUSIONS: Thanks to the availability of an emergency unit specifically dedicated to out-patients with hematologic diseases, selected out-hospital management of AML patients during post-consolidation cytopenia is a feasible, well accepted and cost-saving option, and can contribute to lower the risk of developing severe nosocomial infections. The empiric therapy with once-a-day ceftriaxone plus amikacin was effective, with the exception of staphylococcal infections, and made it possible to discharge patients early to continue treatment in an out-patient setting.

Adult↗
PubMed1998

Effects of perindopril and carvedilol on endothelium-dependent vascular functions in patients with diabetes and hypertension.

OBJECTIVE: To compare the effects of the ACE inhibitor perindopril and the beta-blocker carvedilol on blood pressure and endothelial functions in NIDDM patients with hypertension. RESEARCH DESIGN AND METHODS: We conducted a double-blind randomized trial in 26 patients with NIDDM and mild hypertension. A 4-week run-in placebo period preceded the active 12-week treatment with perindopril (4-8 mg daily) or carvedilol (25-50 mg daily). Endothelial functions were assessed by evaluating the hemodynamic (mean blood pressure, leg blood flow) and rheological (platelet aggregation, blood viscosity, and blood filterability) responses to an intravenous bolus of 3 g L-arginine, the natural precursor of nitric oxide. RESULTS: Both perindopril and carvedilol significantly reduced mean blood pressure (P < 0.001) and increased leg blood flow (P < 0.05) to the same extent; blood filterability remained unchanged in both perindopril- and carvedilol-treated groups. Carvedilol reduced platelet aggregation and blood viscosity significantly (P < 0.05) but perindopril did not. Before treatment, the hemodynamic and rheologic responses to L-arginine were significantly lower in patients (P < 0.05-0.01) than in 20 nondiabetic nonhypertensive control subjects. After 12 weeks of treatment, both drugs normalized the hemodynamic responses to L-arginine. Platelet aggregation response to L-arginine was ameliorated by carvedilol and remained unchanged in the perindopril group. CONCLUSIONS: At the doses used, both drugs effectively reduce blood pressure and normalize the hemodynamic responses to L-arginine. The implications of the ameliorated endothelial function for the poor cardiovascular outlook of the NIDDM hypertensive patient need further assessment.

Adrenergic beta-Antagonists↗
PubMed1998

Density and localization of calcium channels of the L-type in human pulmonary artery.

The pharmacological profile and the anatomical localization of Ca2+ channels of the L-type were investigated in the human pulmonary artery to identify possible mechanisms involved in the regulation of the pulmonary vascular tone. Analysis was performed on slide-mounted frozen sections of human pulmonary artery using radioligand binding assay techniques associated with light microscope autoradiography. [3H]-Nicardipine was used as ligand. Human renal and right coronary arteries also were used as systemic reference arteries. Binding of [3H]-nicardipine to sections of human pulmonary artery was time-, temperature- and concentration-dependent, saturable and reversible. In the human pulmonary artery, the apparent equilibrium dissociation constant (Kd) was 0.12+/-0.02 nM and the maximum density of binding sites (Bmax) was 38.15+/-2.25 fmol/mg tissue. Kd values were 0.3+/-0.01 nM and 0.5+/-0.02 in the human renal artery and right coronary artery respectively. Bmax values were 248+/-16 fmol/mg tissue and 173+/-9.5 fmol/mg tissue in the human renal artery and right coronary artery respectively. The pharmacological profile of [3H]-nicardipine binding to sections of human pulmonary artery was consistent with the labeling of Ca2+ channels of the L-type. It was similar in the pulmonary artery and in the human renal and right coronary arteries. Light microscope autoradiography revealed a high density of [3H]-nicardipine binding sites within smooth muscle of the tunica media of human pulmonary artery as well as of human renal and right coronary arteries. A lower accumulation of the radioligand occurred in the tunica adventitia. No specific binding was noticeable in the tunica intima. Our data suggest that human pulmonary artery expresses Ca2+ channels of the L-type sensitive to dihydropyridines. These sites have similar affinity and lower density than those expressed by systemic arteries. The presence of Ca2+ channels of the L-type in human pulmonary artery suggests that their pharmacological manipulation may be considered in the treatment of pulmonary hypertension.

Aged↗
PubMed1997

Vascular effects of acute hyperglycemia in humans are reversed by L-arginine. Evidence for reduced availability of nitric oxide during hyperglycemia.

BACKGROUND: Acute hyperglycemia may increase vascular tone in normal humans via a glutathione-sensitive, presumably free radical-mediated pathway. The objective of this study was to investigate whether or not the vascular effects of hyperglycemia are related to reduced availability of nitric oxide. METHODS AND RESULTS: Acute hyperglycemia (15 mmol/L, 270 mg/dL) was induced in 12 healthy subjects with an artificial pancreas. Systolic and diastolic blood pressures, heart rate, and plasma catecholamines showed significant increases (P < .05) starting after 30 minutes of hyperglycemia; leg blood flow decreased significantly (15%; P < .05) at 60 and 90 minutes. Platelet aggregation to ADP and blood viscosity also showed significant increments (P < .05). The infusion of L-arginine (n = 7, 1 g/min) but not D-arginine (n = 5, 1 g/min) or L-lysine (n = 5, 1 g/min) in the last 30 minutes of the hyperglycemic clamp completely reversed all hemodynamic and rheological changes brought about by hyperglycemia. Infusion of NG-monomethyl-L-arginine (L-NMMA; 2 mg/min) to inhibit endogenous nitric oxide synthesis in 8 normal subjects produced vascular effects qualitatively similar to those of hyperglycemia but quantitatively higher (P < .05); however, heart rate and plasma catecholamine levels decreased during L-NMMA infusion, presumably as a consequence of baroreflex activation. Infusion of L-NMMA during hyperglycemia produced changes not different from those obtained during infusion of L-NMMA alone. CONCLUSIONS: The results show that acute hyperglycemia in normal subjects causes significant hemodynamic and rheological changes that are reversed by L-arginine. Moreover, the effects of hyperglycemia are mimicked to a large extent, but not entirely, by infusion of L-NMMA. This suggests that hyperglycemia may reduce nitric oxide availability in humans.

Acute Disease↗
PubMed1997

The vascular effects of L-Arginine in humans. The role of endogenous insulin.

This study aimed at evaluating whether increased availability of the natural precursor of nitric oxide, L-arginine, could influence systemic hemodynamic and rheologic parameters in humans and whether the effects of L-arginine are mediated by endogenous insulin. 10 healthy young subjects participated in the following studies: study I, infusion of L-arginine (1 g/min for 30 min); study II, infusion of L-arginine plus octreotide (25 microg as i.v. bolus + 0.5 microg/min) to block endogenous insulin and glucagon secretion, plus replacement of basal insulin and glucagon; study III, infusion of L-arginine plus octreotide plus basal glucagon plus an insulin infusion designed to mimic the insulin response of study I. L-Arginine infusion significantly reduced systolic (11+/-3, mean+/-SE) and diastolic (8+/-2 mmHg, P < 0.001) blood pressure, platelet aggregation (20+/-4%), and blood viscosity (1.6+/-0.2 centipois, P < 0.01), and increased leg blood flow (97+/-16 ml/min), heart rate, and plasma catecholamine levels (P < 0.01). In study II, plasma insulin levels remained suppressed at baseline; in this condition, the vascular responses to L-arginine were significantly reduced, except for plasma catecholamines which did not change significantly. In study III, the plasma insulin response to L-arginine was reestablished; this was associated with hemodynamic and rheologic changes following L-arginine not significantly different from those recorded in study I. These findings show that systemic infusion of L-arginine in healthy subjects induces vasodilation and inhibits platelet aggregation and blood viscosity. These effects are mediated, in part, by endogenous released insulin.

Adult↗
PubMed1997

Effect of insulin on blood rheology in non-diabetic subjects and in patients with Type 2 diabetes mellitus.

We evaluated the effect of insulin on platelet function, blood viscosity, and filterability in healthy subjects and in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Fifteen diabetic patients were free from cardiovascular complications (group A), while the other 15 patients had both clinical and measured evidence of coronary or peripheral vascular disease (group B); 15 non-diabetic subjects served as controls. On blood samples taken without stasis, maximal platelet aggregation to 1.25 micromol l(-1) ADP, blood and plasma viscosity, and blood filterability were measured in basal conditions, and after incubation of blood, plasma or platelet-rich plasma with insulin at two physiological concentrations (120 and 480 pmol l(-1)). Compared with healthy subjects, the diabetic patients of group B had higher values of blood (p < 0.01) and plasma (p < 0.05) viscosity, and platelet aggregation response to ADP (p < 0.01), as well as lower values of blood filterability (p < 0.01). The diabetic patients of group A had values intermediate between normal subjects and the patients of group B. In non-diabetic subjects, insulin significantly decreased platelet aggregation and blood viscosity at low shear rates (22.5 s(-1)) (p < 0.01 for both), and had no significant effects on other parameters. In the diabetic patients of group A, insulin decreased blood viscosity at high (225 s(-1)) rates of shear (p < 0.01) and increased blood filterability (p < 0.01). The effects of insulin were not dose-related. In the diabetic patients of group B, none of the parameters evaluated was significantly influenced by insulin. Type 2 diabetic patients present many abnormalities of the rheologic properties of blood. The beneficial effects of insulin on platelet aggregation and blood viscosity are not evident in Type 2 diabetic patients, especially those with vascular complications and this may be relevant to the development of those complications.

Adenosine Diphosphate↗
PubMed1997

L-arginine for testing endothelium-dependent vascular functions in health and disease.

The objective of this study was to assess the role of L-arginine, the natural precursor of nitric oxide, for testing endothelial function in physiological and pathophysiological conditions. In an initial study of 20 healthy subjects, mean blood pressure decreases in response to increasing doses of L-arginine (1, 2, 3, and 5 g) were 1.1 +/- 1.3, 2.6 +/- 1.5, 7.6 +/- 1.3, and 7.7 +/- 2 mmHg, respectively, P < 0.01. The enantiomer D-arginine (3 g) did not produce any change in mean blood pressure and platelet aggregation (n = 10), whereas the infusion of the L-arginine analog NG-monomethyl-L-arginine (6 mg/min) reduced by 70% the vascular effects of L-arginine. In the whole population of 52 healthy subjects, there was an inverse correlation between age and blood pressure or platelet aggregation changes after L-arginine. Compared with matched controls (n = 20), the changes in mean blood pressure and platelet aggregation after L-arginine were significantly lower in non-insulin-dependent diabetic (n = 20) and hypercholesterolemic (n = 16), but not in hypertensive (n = 20), subjects. Changes in blood viscosity were significantly lower only in hypercholesterolemic subjects. Our findings suggest that an intravenous bolus of 3 g L-arginine may be a simple and useful tool to assess the endothelial control of blood pressure and platelet activity in health and disease.

Adenosine Diphosphate↗
PubMed1996

Autologous bone marrow transplantation in 44 patients with aggressive non-Hodgkin's lymphoma at University "La Sapienza" of Rome.

High dose therapy followed by infusion of autologous bone marrow has become a major treatment option for an increasing number of poor prognosis non-Hodgkin's lymphoma (NHL) patients. In our study we analyzed the outcome of autologous bone marrow transplantation (ABMT) in 44 high grade NHL patients transplanted at our institution between 1985 and 1992. Median age was 31 years (range 12-61); nineteen were in partial remission (PR) after first line chemotherapy and 25 in sensitive relapse (SR). Of the 25 patients transplanted in SR, 14 relapsed after a median time of 5.5 months (range 1-26), 8 are in complete remission after a median follow up of 41.5 months and three died from toxicity. Of the 19 patients grafted in PR, 11 are alive and progression free after a median follow up of 52 months, while 8 relapsed at a median time of 5 months. The overall progression free survival (PFS) projected at 6 years is 35% with a 47% PFS for patients transplanted in PR and 28% for patients in SR. In conclusion, high dose therapy and ABMT has achieved widespread use as salvage therapy for patients with relapsed/refractory high grade NHL. In particular, our experience confirms that myeloablative treatment is a safe and well tolerated procedure for patients in PR, that may be easily applied as early salvage therapy without major toxicities.

Adolescent↗
PubMed1995

Abnormal rheologic effects of glyceryl trinitrate in patients with non-insulin-dependent diabetes mellitus and reversal by antioxidants.

OBJECTIVE: To evaluate 1) the hemorrheologic and hemodynamic effects of glyceryl trinitrate in patients with non-insulin-dependent diabetes mellitus and 2) the influence of antioxidants on these effects. DESIGN: Case-control study. SETTING: University hospital clinic. PATIENTS: 40 patients with diabetes and no evidence of cardiovascular complications and 40 controls matched for demographic variables and body habitus. INTERVENTIONS: Sublingual glyceryl trinitrate (0.3 mg) and transdermal glyceryl trinitrate patches (10 mg/d). Vitamin E, 300 mg/d orally for 7 days, and glutathione, 600 mg intravenously or intramuscularly, were given to test the effects of antioxidant supplementation. MEASUREMENTS: Systolic, diastolic, and mean arterial pressure and heart rate; left ventricular ejection fraction; platelet aggregation, blood viscosity, and blood filterability in vitro and ex vivo. RESULTS: Compared with controls, patients with diabetes had increased platelet aggregation to adenosine diphosphate (P < 0.005), increased blood viscosity (P < 0.001), and decreased blood filterability (P = 0.041) at baseline; blood pressure, heart rate, and ejection fraction were similar in the two groups. In controls, both sublingual glyceryl trinitrate and transdermal glyceryl trinitrate patches significantly reduced platelet aggregation (-38%; 95% CI, -49% to -27%) and blood viscosity (-8%; CI, -11% to -5%) and increased blood filterability (10%; CI, 7.0% to 13.1%). Slight but significant decreases in blood pressure and ejection fraction and an increase in heart rate were also seen in controls after administration of glyceryl trinitrate (both preparations). In patients with diabetes, glyceryl trinitrate paradoxically increased platelet aggregation (24%; CI, 15% to 33%) and blood viscosity (6%; CI, 2.9% to 8.8%) and decreased blood filterability (-7%; CI, -9.5% to -4.4%); hemodynamic values did not change significantly. In both groups, rheologic responses to glyceryl trinitrate (end concentration, 100 and 200 ng/mL) in vitro were similar to those seen in ex vivo studies. Vitamin E and glutathione normalized rheologic responses to glyceryl trinitrate in patients with diabetes. CONCLUSIONS: Organic nitrates have beneficial effects on blood rheology in controls but not in patients with diabetes, in whom a paradoxical deterioration is seen. Antioxidant supplementation can normalize primary tolerance to the rheologic effects of nitrates in diabetes.

Adult↗
PubMed1995

Hyperbaric oxygen, oxygen-ozone therapy, and rheologic parameters of blood in patients with peripheral occlusive arterial disease.

For many years, clinical practice has consolidated the use of both hyperbaric oxygen and oxygen-ozone therapy in the treatment of peripheral occlusive arterial disease (POAD). We investigated the influence of these treatments on hemorrheologic parameters that play an important role in the pathogenesis and the clinical course of arteriosclerosis. Two groups of 15 patients suffering from POAD, assigned at random either to a cycle of HBO therapy or O2-O3 therapy, were evaluated for blood viscosity, erythrocyte filterability, hematocrit value, fibrinogen concentration, and thrombin time. The O2-O3 therapy caused a significant increase of erythrocyte filterability and a significant decrease of blood viscosity. By contrast, HBO therapy did not produce any significant change. The increase of lipid peri-oxidation, proved by raised malonyldialdehyde plasma levels, seems a likely mechanism involved in the hemorrheologic effects of O2-O3 therapy.

Aged↗
PubMed1995

Influence of ozone on haemoglobin oxygen affinity in type-2 diabetic patients with peripheral vascular disease: in vitro studies.

The use of ozone in the treatment of peripheral vascular disease (PVD) is increasing. The purpose of this study was to evaluate the effect of ozone on haemoglobin oxygen affinity in Type-2 diabetic patients with PVD. Twenty diabetic patients presenting with PVD (Clinical stage II-IV according to Fontaine) and 20 non-diabetic healthy matched subjects were studied. In both groups, aliquots of blood were ozonised with mixtures of oxygen-ozone (O2-O3) to reach end-concentrations of 6.5, 13, 26 and 78 micrograms O3 per ml of substrate. At baseline, diabetic patients presented significantly lower haemoglobin oxygen affinity values but higher plasma levels of free haemoglobin and malonyldialdehyde (MDA) than controls. In both diabetic patients and controls, exposure of blood to ozone reduced haemoglobin oxygen affinity in an "all-or-none" fashion, without changing 2-3, diphosphoglycerate concentrations in erythrocytes. Both free haemoglobin and MDA concentrations showed significant, dose-dependent increases after blood ozonisation. Thus, ozone caused a significant increase in oxygen unloading of haemoglobin in both normal subjects and Type-2 diabetic patients with PVD.

2,3-Diphosphoglycerate↗
PubMed1994

Hemorheological and cardiovascular responses to beta-endorphin and naloxone in healthy subjects and in patients with essential hypertension.

The purpose of the present study was to determine if opioid agonism (beta-endorphin) and antagonism (Naloxone) exert rheological and cardiovascular effects in normal humans and in patients with essential hypertension. Eight hypertensive patients were matched for age, sex, and body habitus (body mass index, waist to hip ratio) with eight normotensive healthy subjects. In all subjects, heart rate and blood pressure (continuous automatic recording), blood and plasma viscosity, fibrinogen, hematocrit, and platelet aggregation to ADP were evaluated during an infusion of human synthetic beta-endorphin (0.5 mg/h). On a different day and in randomized order, the subjects were submitted to another beta-endorphin infusion preceded by an i.v. naloxone bolus (5 mg in 5 min). beta-Endorphin and naloxone failed to significantly alter heart rate or blood pressure in both normotensive and hypertensive subjects. In hypertensive patients, beta-endorphin significantly increased blood viscosity and ADP-induced platelet aggregation, but only the former effect was naloxone-sensitive. In normotensive subjects, beta-endorphin caused a transient but significant decrease of platelet aggregation that was reversed by naloxone. These data suggest that beta-endorphin may play some role in the inhibitory control of platelet aggregation in normal subjects. An altered responsiveness of some rheological determinants to beta-endorphin seems to be present in human hypertension.

Adenosine Diphosphate↗
PubMed1993

Hyperinsulinemia in hypertension: increased secretion, reduced clearance or both?

Peripheral hyperinsulinism is said to be associated and perhaps implicated in the pathogenesis of hypertension. There is however some inconsistency in the evidence of the relationship between insulin and blood pressure. We prospectively investigated glucose metabolism, insulin and C-peptide values and serum lipids in a large sample of hypertensive as compared with age and body habitus-matched normotensive subjects. As a group, the 145 hypertensives (blood pressure: 160/99 +/- 8.5/6.5 mmHg, mean +/- SD) had significantly elevated fasting plasma insulin (p < 0.02), total and LDL-cholesterol (p < 0.01) than 132 normotensive control subjects. The fasting HbA1c (glycated hemoglobin A1c)/insulin ratio, an estimate of insulin sensitivity, was significantly lower (5.15 +/- 1.45) in the hypertensives than normotensives (5.8 +/- 1.5, p < 0.001). Hypertensives had normal fasting C-peptide levels and lower C-peptide/insulin molar ratios, indicating low hepatic insulin extraction. There was no correlation between mean blood pressure (1/3 systolic + 2/3 diastolic) and fasting serum C-peptide (p = 0.14), insulin (p = 0.11), HbA1c/insulin ratio (p = 0.6), C-peptide/insulin ratio (p = 0.22) and HbA1c (p = 0.19), even after adjusting for age, BMI and family history of diabetes. The differences between hypertensives and normotensives persisted after dividing the subjects according to the presence/absence of either obesity or impaired glucose tolerance, but the significance was lost due to the smaller samples of the subgroups. The obese hypertensives with impaired glucose tolerance had the lowest values of insulin sensitivity and clearance in the fasting state.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Guidelines for continuous infusion medications in the neonatal intensive care unit.

OBJECTIVE: To present practical guidelines in tabular form for dosage, calculation, preparation, and monitoring of common medications administered by continuous infusion to neonatal intensive care patients. DATA SOURCES: Review articles and clinical trials were identified through a computer literature search with subsequent bibliography scanning. STUDY SELECTION: Articles selected for review were considered important contributions. DATA EXTRACTION: Data from human studies and review articles published in the English language were evaluated. DATA SYNTHESIS: In emergency situations, physicians and other healthcare providers caring for critically ill newborns often perform rapid calculations to determine the dosage and rate of continuous intravenous medication infusions. Because of the crisis situation, there is the potential for calculation errors. We compiled a concise table designed to provide a standardized method for the administration of emergency medications to neonatal intensive care patients. This table must be used in conjunction with clinical judgment and each medication infusion rate must be adjusted to the patient's clinical response and individual parameters. CONCLUSIONS: These guidelines help to minimize the volume of fluid needed for medication administration and facilitate the calculation, preparation, and timely administration of these medications, thus preventing errors that might occur in an emergency situation.

Critical Care↗
PubMed1992

Glutathione (GSH) improved haemostatic and haemorheological parameters in atherosclerotic subjects.

Blood samples from ten patients with clinically evident manifestations of atherosclerotic disease were used to evaluate in vitro the effects of exogenous glutathione (GSH) on platelet aggregation and on blood filtration and viscosity. In two groups, each of ten atherosclerotic patients, matched for sex, age, prevalent localization, duration and gravity of disease, the effects of GSH infusion (600 mg every day for seven days) on the haemocoagulative pattern, platelet aggregation and blood filtration and viscosity were evaluated in a double-blind, placebo cross-over trial. The GSH in vitro addition resulted in a significant increase in blood filtration and a significant decrease in blood viscosity and platelet aggregation. The venous GSH infusion both significantly decreased blood viscosity and increased blood filtration. Partial thromboplastin time was lengthened after GSH infusion even thought it remained in the normal range.

Aged↗
PubMed1991

Autoradiographic localization of beta-adrenergic receptors in human large coronary arteries.

The distribution of beta-adrenergic receptors in sections of the human right and left coronary arteries and of the anterior intraventricular branch was studied by the use of combined in vitro radioreceptor binding and autoradiographic techniques. [125I]Cyanopindolol was used as a ligand for beta-adrenergic receptors. Binding of the radioligand to sections of the three coronary arteries under study was saturable, stereoselective, reversible, and displaceable by antagonists and agonists with the rank order of potency expected for beta-adrenergic receptors. Analysis of binding isotherms indicated maximum binding capacities of 41.5 fmol/mg protein for the right coronary artery, 35.4 fmol/mg protein for the left coronary artery, and 25.7 fmol/mg protein for the anterior interventricular branch. Dissociation constants were approximately 35 pM in the arteries examined. The relative amounts of beta 1- and beta 2-receptor subtypes were as follows: 72% beta 1-receptors and 28% beta 2-receptors in the right coronary artery; 65% beta 1-receptors and 35% beta 2-receptors in the left coronary artery; 40% beta 1-receptors and 60% beta 2-receptors in the anterior interventricular branch. The results of autoradiographic analysis revealed a predominance of beta 1-receptors in the medial layer. beta 2-Receptors were localized primarily in the adventitia, in the adventitia-media border, and in the intimal layer. These results should lead to a better understanding of the mechanisms involved in the control of coronary circulation in humans.

Adolescent↗