Responses of coronary vessels to adrenergic stimuli

Coronary responses to adrenergic stimuli were determined in the intact beating heart before and after administration of practolol, 4-(2-hydroxy-3-isopropylaminoproproxy) acetanilide, which in low doses blocks myocardial but not vascular beta receptors. The left circumflex coronary artery of dogs was perfused with arterial blood at constant flow, and coronary perfusion pressure was measured.Before practolol, intracoronary injections of isoproterenol and norepinephrine and electrical stimulation of left cardiac sympathetic nerves caused reductions in perfusion pressure or vasodilatation associated with increases in left ventricular dp/dt, heart rate, and systolic pressure.After practolol, the coronary vasodilator response to isoproterenol was reduced by about 30% and occurred without significant changes in dp/dt, heart rate, and pressures. The addition of propranolol blocked completely the coronary responses to isoproterenol. Vascular responses to isoproterenol in the paw were not altered by practolol.Practolol antagonized the increases in dp/dt, heart rate, and systolic pressure and reversed coronary responses to norepinephrine and nerve stimulation from dilatation to constriction. The constriction, in turn, was reduced or reversed by phentolamine, an alpha receptor antagonist. Propranolol did not augment the constriction seen in response to norepinephrine and nerve stimulation after practolol.These results indicate that the coronary vasodilator action of norepinephrine and sympathetic nerve stimulation is indirect and caused by stimulation of myocardial beta receptors. The direct effect of these two stimuli on coronary vessels is minimal and is mediated through stimulation of alpha (vasoconstrictor) receptors. In contrast, the coronary vasodilator response to isoproterenol is both direct and indirect, resulting from stimulation of vascular and myocardial beta receptors; the direct vascular effect predominated in this study.     

Effect of smoking on plasma neutrophil elastase levels

Plasma elastase is considered to indicate neutrophil elastase that has been released in vivo and has complexed with plasma inhibitors. Because smoking may play a pathogenetic role in emphysema by inducing elastase release in the lung, which may be reflected in the plasma elastase level, we evaluated the effect of smoking on plasma elastase in healthy men by using an enzyme-linked immunosorbent assay. No significant difference was found in plasma elastase levels between 30 smokers and 29 nonsmokers (103 +/- 23 [SD] ng/ml vs. 97 +/- 23 ng/ml). We found no significant change in plasma elastase level in eight heavy smokers when we compared morning with afternoon plasma samples taken about 7 hours later, while the subjects continued to smoke ad libitum in the interval. However, we found a significant rise in plasma elastase level in 12 healthy smokers who were tested after 8 hours of abstinence from smoking and then immediately and 1/2, 1, and 2 hours after intense smoking (eight cigarettes smoked over a period of 2 hours). Neutrophil count increased from a baseline of 3.8 +/- 0.7 X 10(3)/mm3 to 8.0 +/- 2.5 X 10(3)/mm3 at 1 hour, and 8.8 +/- 3.1 X 10(3)/mm3 at 2 hours. Plasma elastase level increased significantly (P less than 0.02) from a baseline of 111 +/- 30 ng/ml to 141 +/- 24 ng/ml at 1 hour after completion of smoking, but was not significantly different from baseline 2 hours after smoking (130 +/- 34 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantification of erythroid and granulocytic precursor cells in plateletpheresis residues

Mononuclear cell fractions of human blood and plateletpheresis residues were compared for their content of hemopoietic precursor cells. Erythroid burst-forming units (BFU-E) averaged 560 ± 130 per ml of blood and granulocyte-monocyte colony forming units (CFU-C) averaged 240 ± 90 per ml blood. Estimates based on a blood volume of 7 per cent of body weight indicate that the total blood pools of BFU-E and CFU-C are about 3.5 × 10⁶ and 1.5 × 10⁶ cells respectively. Plateletpheresis residues prepared after a mean of 3.4 liters of blood had been processed contained 1.3±0.22× 10⁶ BFU-E and 0.50 ± 0.13 × 10⁶ CFU-C. These values represent a 68 and 63 per cent recovery respectively of BFU-E and CFU-C from the processed 3.4 liters of blood. Sequential studies were performed over three days following one plateletpheresis in four donors. CFU-C and BFU-E approximately doubled between 48 and 72 hours after a plateletpheresis. During this time there was no significant alteration in the per cent of null, T- or B-lymphocytes in blood. Thus, plateletpheresis appears to lead to a mobilization of precursor cells, which results in a transient increase in their concentration in blood. Therefore, cytapheresis 48 to 72 hours after an initial short-term procedure could harvest much larger numbers of precursor cells. Moreover, such techniques would put blood precursor cell content of plateletpheresis residues within reach of the precursor cell content in the volume of human marrow used for transplantation.     

The effect of dietary sodium chloride on blood pressure, body fluids, electrolytes, renal function, and serum lipids of normotensive man.

Eight normotensive white middle-aged men were given low, moderate, and high salt diets with constant potassium intakes each for periods of at least 4 weeks. There was a tendency for body weight, serum sodium, exchangeable sodium, and inulin space to increase. Indirect blood pressure measurements revealed no change in blood pressure, either supine or upright measurements, during the 3 study intervals. Inulin clearance (and presumably glomerular filtration rate) rose with increase in dietary salt. Urinary potassium excretion rose progressively as salt intake increased. Total body potassium tended to decrease with increase in dietary salt. There was no changes in the excretion of calcium, magnesium, phosphorus, nor were there changes in the blood level of potassium. There was no change in total body water. The serum cholesterol and triglyceride levels were not appreciably affected by the different dietary sodium intakes. Plasma renin activity and urinary aldosterone excretion rose progressively with the two levels of sodium restriction. These studies indicate that normal man is able to compensate for large differences in sodium intake with minor metabolic changes. These changes do not necessarily lead to hypertension over a one-month period. Nevertheless, many hemodynamic and hormonal compensatory mechanisms come into play. It is evident that hypertension might result should the sodium load not be excreted, the circulating volume become too great for the excretory capacity, or if neural or endocrine adjustments be inadequate.     

Regulation of blood flow in Paget's disease of bone.

Previous studies have demonstrated an increase in blood flow to extremities involved by Paget's disease of bone. It has been assumed that the increase in blood flow is through bone, but warmth of skin overlying Pagetic bone suggests that cutaneous blood flow might be increased. In three patients with Paget's disease involving one extremity, we compared blood flow in "Pagetic" extremities with flow in the contralateral normal extremities. Resting blood flow (measured with water plethysmographs) was 14.2plus or minus2.9 (meanplus or minusSE) ml/min times 100 ml extremity in the Pagetic limbs. The contribution of cutaneous flow to the increase in extremity blood flow was evaluated with epinephrine iontophoresis, which suppresses flow to skin but not to underlying tissue. Epinephrine iontophoresis of the Pagetic extremities decreased blood flow from 14.2plus or minus2.9 to 3.6plus or minus1.5 ml/min. Local heating (which increases cutaneous flow only) failed to increase blood flow in the Pagetic extremities as much as it did in the normal extremities. This suggests that cutaneous vessels in the Pagetic extremities were already dilated. During heating, blood flow in the normal extremities was similar to resting flow in the Pagetic extremities; this indicates that increases in cutaneous flow could account for most of the increase in total blood flow in the Pagetic extremities. Adrenergic control of blood flow to the Pagetic extremities was compared with that of the normal extremities. Vasoconstrictor responses to reflex stimuli in the Pagetic extremities were reduced; when vasoconstriction occurred it was gradual and sustained after termination of the stimuli, which suggests an exaggerated humoral response but reduced neural response to the stimuli. Intravenous epinephrine produced vasoconstriction in the Pagetic extremities and vasodilatation in the normal extremities. In summary, responses to epinephrine iontophoresis and heating suggest that the increase in blood flow in Pagetic extremities is primarily the result of cutaneous vasodilatation.     

Effects of thrombolysis on the 12-lead signal-averaged ECG in the early postinfarction period

Signal-averaged ECG has been used to identify patients at risk for ventricular tachycardia and sudden death after myocardial infarction. The goals of this prospective study were to examine the effects of reperfusion achieved with thrombolytic therapy on the 12-lead signal-averaged ECG and on ventricular arrhythmias in the early period after acute myocardial infarction (AMI). A total of 190 consecutive patients with AMI who fulfilled the inclusion criteria were enrolled. Thrombolysis was attempted in 80 patients and was considered successful in 57 (group I) and unsuccessful in 23 (group II); 110 patients were not treated with thrombolytic agents (group III). Signal averaging of 12 ECG leads was performed within 2 days in all patients and between 7 and 10 days after admission in 163 patients. The filtered QRS complex duration (QRSD) was significantly shorter in group I compared to group III in 7 of 12 ECG leads at 2 days and in 10 of 12 leads at 7 to 10 days. The root mean square voltage of the terminal 40 msec of the QRS complex (RMS40) did not change between the two signal-averaged ECG recordings in group I, whereas it became lower in three ECG leads in group II and in seven ECG leads in group III. There was no correlation between infarct site and significant changes in infarct-related signal-averaged ECG leads. The occurrence of complex ventricular arrhythmias was not significantly different among the three groups. We conclude that successful reperfusion, compared with failed and nonattempted reperfusion, is associated with fewer abnormalities in the 12-lead signal-averaged ECG in the early period after AMI.(ABSTRACT TRUNCATED AT 250 WORDS)     

The exceptional responsiveness of certain human myeloid leukemia cells to colony-stimulating activity.

We have studied the marrow cells from a patient with acute myeloid leukemia (AML) for their responsiveness to colony-stimulating activity (CSA) in vitro. The AML cells were stimulated by CSA to rapid and extended growth in liquid culture. In the absence of CSA, the majority of cells died. CSA also stimulated the clonal growth of AML cells, and the minimum requirement for CSA was one-tenth to one-fiftieth that required to stimulate the growth of normal marrow CFU-C. CSA for AML cells was eluted from Sephacryl S-200 columns in fractions that represented an apparent molecular weight of 45,000 daltons. This fraction also produced optimal stimulation of normal human marrow. During remission, the patient's marrow cells did not grow in liquid culture and produced normal numbers of granulocytic and erythroid colonies in response to CSA and erythropoietin. Extended culture of the AML cells resulted in cell differentiation evidenced by decreasing proliferative capacity and by morphological and histochemical changes. These studies indicate that certain AML cells are extraordinarily responsive to CSA, an in vitro mediator of normal granulopoiesis.     

Stimulation of renin by acute selective chloride depletion in the rat.

To determine whether acute chloride depletion per se stimulates renin, we produced selective chloride depletion without sodium depletion in rats by peritoneal dialysis (PD) against 0.15 M NaHCO3 or 0.15 M NaNO3. Control rats were dialyzed against 0.15 M NaCl. Plasma renin activity (PRA) was measured before (PRA1) and 105 minutes after (PRA2) PD. Plasma volume was expanded after PD by infusion of salt-free albumin and was measured immediately after PRA2 by [131I]albumin. In experiment 1, rats were prepared on a normal diet. PRA2 (7.0 +/- 1.0 ng/ml per hr, mean +/- SEM) was increased (P less than 0.05) over PRA1 (4.7 +/- 0.7 ng/ml per hr) in Cl-depleted but not in control rats (PRA1 = 5.3 +/- 0.7, PRA2 = 6.1 +/- 0.7, P = NS). In experiment 2, to produce greater chloride depletion, all rats were prepared for 2 weeks on a low salt diet. PRA2 (47 +/- 5 ng/ml per hr) was increased as compared to PRA1 (24 +/- 2 ng/ml per hr, P less than 0.005) in the Cl-depleted group but not in the control group (PRA1 = 24 +/- 3, PRA2 = 27 +/- 6 ng/ml per hr, P = NS). Serum potassium and final plasma volume were slightly but not significantly lower than controls in these Cl-depleted rats. To exclude an additive effect of these two stimuli for renin, in experiment 2a we infused chloride-depleted rats with three times as much albumin as controls and with KHCO3, 100 mEq/liter. Despite volume expansion and potassium loading, PRA2 (41 +/- 6 ng/ml per hr) was significantly elevated as compared to PRA1 (25 +/- 4 ng/ml per hr, P less than 0.01). Since acute metabolic alkalosis also was present in all Cl-depleted renin-stimulated rats, an additional group (2b) was dialyzed against 0.15 M NaNO3; final plasma arterial pH (7.43) was not different from controls (7.42). Nevertheless, PRA2 levels again were higher (36 +/- 6 ng/ml per hr, P less than 0.05) as compared to PRA1 (23 +/- 4 ng/ml per hr). In all experiments, arterial blood pressure, glomerular filtration rate, and filtered sodium load were not different. Free water reabsorption was lower in Cl-depleted than in control rats. We conclude that acute selective chloride depletion per se is a potent stimulus for renin release.     

Elevated serum and bronchoalveolar lavage fluid levels of interleukin 8 and granulocyte colony-stimulating factor associated with the acute chest syndrome in patients with sickle cell disease

The role of cytokines in the development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD) was studied. Serum interleukin 8 (IL-8) levels were elevated in 14 episodes and undetectable in six out of 20 episodes of ACS in 19 patients with SCD. In contrast, IL-8 levels were undetectable in the sera of 29 control patients with SCD studied during routine clinic visits or hospitalization for vaso-occlusive crises. The differences in mean IL-8 levels and the proportion of patients with detectable levels between the two groups were highly significant (P < 0.0001 and 0.04 respectively). The mean IL-8 level in bronchial fluid samples from children with ACS was also significantly higher than that in sickle cell patients undergoing elective surgery (5500 +/- 1400 pg/ml vs. 1900 +/- 470 pg/ml, P = 0.03). Granulocyte colony-stimulating factor (G-CSF) (2000 +/- 1700 pg/ml) was present in five out of six samples of bronchial fluid, but not serum, from children with ACS. All but one of the patients with ACS studied were negative for the Duffy red cell antigen, which is a receptor that binds and inactivates IL-8 and other chemokines. These findings suggest that IL-8 and G-CSF may play a role in the development of the ACS and the complications associated with it.