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Biomedical subjects

C E Wade

Publications and source records attributed to C E Wade.

At least 109 records · Page 6Linked to original sources

Orthostatic responses following 30-day bed rest deconditioning with isotonic and isokinetic exercise training.

To determine if intensive isotonic or isokinetic exercise training during 30 d of -6 degrees head-down bed rest (BR) would accentuate orthostatic intolerance, 19 men (32-42 years) were divided into a no-exercise control group (N = 5), and isotonic (Quinton ergometer, N = 7) and isokinetic (Lido ergometer, N = 7) exercise groups. Training was two 30-min periods per day for 5 days per week. Changes (* = p less than 0.05) in peak VO2 uptake (L/min) from control day 2 to BR day 29 were: isotonic +1.4%, isokinetic -10.2%*, no exercise -20.1%*. Changes in resting plasma volume (ml) from control day 1 to BR day 30 were: isotonic -3.7%, isokinetic -18.0%*, and no exercise -17.2%*. A 60 degrees head-up tilt test was administered on control day 1 and BR day 30; the test was terminated at 60 min or when presyncopal signs and/or symptoms occurred. Changes in means tilt tolerance were: isotonic, 42 to 34 min (delta = -8 min*); isokinetic, 53 to 30 min (delta = -23 min*); and no exercise, 46 to 30 min (delta = -16 min*). Mean day 30 group tolerances were all significantly lower than day 1 tolerances, but the reductions were not different between groups. Because there was no obvious relationship between type of exercise, exercise energy expenditure, change in peak VO2, or change in resting plasma volume and the consistent reduction in post-BR tilt tolerances, it appears that the orthostatic intolerance was due mainly to the reduction in body hydrostatic pressure from the -6 degrees head-down body position, and was not related to the level of physical fitness. Thus, factors other than training status are probably involved.

Adult↗

Hemodynamic response to abdominal aortotomy in the anesthetized swine.

This study was conducted to determine the hemodynamic response to uncontrolled hemorrhage following aortotomy in anesthetized swine. Eight Yorkshire swine underwent splenectomy and stainless steel wire placement in the anterior infrarenal aorta and were instrumented with Swan-Ganz and carotid artery catheters. Following an equilibration period, the wire was pulled. This produced a 5 mm aortotomy and spontaneous intraperitoneal hemorrhage. Serial measurements of mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), and cardiac output (CO) were obtained. From baseline to 5 min after aortotomy, there was a profound decrease in MAP in conjunction with a significant decrease in CO and MPAP. After the initial 5 min period, there was a progressive elevation in MAP, CO, and MPAP. Peripheral vascular resistance (PVR) was significantly decreased after aortotomy and returned to baseline after 60 min. From these data, we conclude that aortotomy produces a rapid depression and spontaneous recovery in MAP, CO, and MPAP. Aortotomy also produces a significant decrease in PVR, which is not generally associated with hemorrhagic hypotension.

Animals↗

Laser angioplasty: an atherosclerotic swine model.

Rapid production of occlusive, atherosclerotic iliac artery lesions was achieved in 25 of 27 (93%) Yucatan miniature swine, using a combination of high cholesterol diet and mechanical endothelial denudation. Animals were fed a diet with 2% of their calories as raw cholesterol 2 weeks prior to balloon denudation of iliac arteries, which resulted in atherosclerotic lesions within 8 weeks. Early after denudation we have demonstrated total occlusion of arteries by fibrin thrombi, which in time organize and ultimately result in fibrotic occlusive disease. The arterial walls and intima show varying degrees of foam cell infiltration with destruction of the internal elastic lamina and calcification. Totally occluded lesions show fibrointimal proliferation, fibrosis, and multiluminal channels, which are probably secondary to organized thrombus. Our model of occlusive iliac artery disease involving vessels of 1 to 3 mm in diameter allows the development of catheter systems suitable for use in human peripheral and coronary arteries. This model is useful for the study of angioplasty, whether mechanical, balloon, or laser-mediated.

Angioplasty, Balloon↗

Effects of the antiglucocorticoid RU 486 on adrenal function in dogs.

We studied the antiglucocorticoid effects of RU 486 given orally in doses of 5 (low), 20 (intermediate), and 50 mg/kg (high) daily for 10 days to seven female mongrel dogs. No changes in plasma ACTH or cortisol levels were produced by the 5 mg/kg dose. Plasma ACTH levels increased 3-fold with both intermediate and high dosages. Plasma cortisol levels rose 4-fold (P less than 0.05) within 2 days of commencing the high dose schedule and within 3 days with the intermediate dosage. Plasma aldosterone concentrations increased significantly only with the highest dose schedule. Plasma RU 486 levels rose progressively during the 10 days of RU 486 administration and with the highest dose remained elevated for 7 days after it was stopped. Plasma RU 486 levels measured by RIA and high pressure liquid chromatography were comparable. The monodemethylated metabolite of RU 486 changed in parallel to the parent compound. During the high dose of RU 486, there was a 4% increase in body weight, with a reduction in hematocrit and plasma protein concentration. Plasma electrolyte levels and osmolality did not change. We conclude that in dogs a daily RU 486 dose of 5 mg/kg does not alter adrenal function, whereas higher doses (20 and 50 mg/kg) induce increases in plasma ACTH and cortisol concentrations. Despite the blockade of glucocorticoid receptors by RU 486, the presence of isotonic hypervolemia suggests that there was no functional deficiency of cortisol at the renal tubule or it was overshadowed by augmented mineralocorticoid production and action.

Administration, Oral↗

Upon-admission adrenal steroidogenesis is adapted to the degree of illness in intensive care unit patients.

Adrenal function was studied in 2 groups of intensive care unit (ICU) patients with varying degrees of illness, as determined by Acute Physiological and Chronic Health Evaluation (APACHE). The 15 seriously ill patients with high APACHE scores (greater than or equal to 25) had elevated Therapeutic Intervention Scores and increased mortality compared to the 15 ill patients (APACHE, less than or equal to 10; 67% vs. 27%). Plasma cortisol, aldosterone, and androstenedione concentrations were increased in the ICU patients compared to those in normal subjects (n = 23), being greater in the seriously ill patients. Plasma dehydroepiandrosterone sulfate (DHEAS) concentrations were low in both groups of ICU patients. The ratios of aldosterone or androstenedione to cortisol were not altered, whereas the DHEAS to cortisol ratios were reduced in the ICU patients. ACTH injection elicited increases in plasma cortisol, aldosterone, and androstenedione concentrations in both groups of ICU patients, and the ratios of aldosterone and androstenedione to cortisol did not change. In the seriously ill patients, plasma DHEAS increased, so that the DHEAS to cortisol ratio did not change, whereas in less ill patients plasma DHEAS did not increase, so that the DHEAS to cortisol ratio was reduced. In this study of patients admitted to an ICU, impairment of adrenal steroid secretion appears to be specific for DHEAS. Although plasma cortisol was elevated in ill patients proportional to the degree of illness, the contribution of the concomitant decrease in DHEAS to this increase is not clear.

Adrenal Glands↗

Effects of exercise on atrial natriuretic factor. Release mechanisms and implications for fluid homeostasis.

Atrial natriuretic factor is reported to be elevated during and immediately following exercise and is thought to play a role in fluid homeostasis and cardiovascular regulation. The predominant stimuli for atrial natriuretic factor release during exercise appear to be increases in atrial pressures or atrial distension, both of which are reported to increase with exercise. The intensity and perhaps duration of exercise also influence the magnitude of the atrial natriuretic factor response. It is not clear if the rise in plasma atrial natriuretic factor during exercise plays any role in altering renal function since high intensity exercise is typically associated with an antidiuresis. However, elevations in plasma atrial natriuretic factor may in part be responsible for the increase in urine flow reported when exercise is performed at low or moderate intensities. Atrial natriuretic factor also has vascular effects which may be important in buffering or moderating the blood pressure response to exercise. The atrial natriuretic factor response to exercise and basal levels of the hormone are greatly elevated in patients who suffer from a variety of cardiovascular and pulmonary disease conditions. These elevated plasma atrial natriuretic factor values are associated with increases in atrial pressure and appear to be related to the severity of disease. Although much controversy exists regarding the renal and vascular effects of atrial natriuretic factor, the measurement of this hormone, particularly during exercise, may be of clinical value by providing an additional tool to evaluate patients and determine the effectiveness of various treatment regimens.

Atrial Natriuretic Factor↗

Confounding factors in the hemorrhage of conscious swine: a retrospective study of physical restraint, splenectomy, and hyperthermia.

A retrospective study showed that variability in the responses of heart rate and mean arterial pressure to hemorrhage in conscious swine can be induced by handling procedures, hyperthermia, and splenectomy. All animals were hemorrhaged 38.5 ml/kg over 1 hour. Physical restraint caused tachycardia prior to hemorrhage, an effect that was enhanced during hemorrhage; hemorrhage had no effect on the heart rate of unrestrained animals. Animals restrained in a sling also had an attenuated fall in mean arterial pressures throughout the experiment compared to normothermic swine. Splenectomized swine had elevated heart rates compared to sham-operated animals, with the difference persisting throughout hemorrhage. No difference in mean arterial pressure was noted due to splenectomy. These sources (handling, hyperthermia, and splenectomy) of experimental variability should be considered in the design and interpretation of experiments using conscious swine.

Animals↗

Hormonal and renal responses to converting enzyme inhibition during maximal exercise.

The role of angiotensin II in the hormonal and renal responses to maximal exercise was investigated by using the angiotensin-converting enzyme inhibitor captopril. Nine male subjects performed a standardized maximal treadmill test with and without acute captopril treatment (25 mg orally). At rest, captopril elevated plasma renin activity and lowered aldosterone levels. With maximal exercise, captopril treatment reduced the increase in mean arterial blood pressure by 8 mmHg and the increase in plasma renin activity by 3.0 ng ANG I.ml-1.h-1. The responses of adrenocorticotropin (ACTH), cortisol, and vasopressin to maximal exercise were not altered by captopril treatment. Although aldosterone levels were reduced at rest with captopril, during maximal exercise no difference was noted between treatments. Captopril treatment had no effects on the renal handling of salts or water during exercise. In conclusion, angiotensin II plays a role in the increase in mean blood pressure during maximal exercise in normal subjects but has no effect on the exercise responses of ACTH, vasopressin, and aldosterone or on the renal handling of salts and water.

Adrenocorticotropic Hormone↗

Simple method for bleeding the unanaesthetized rat by tail venipuncture.

A technique is described for the intermittent collection of blood from the rat tail. By using commonly available equipment, blood samples can easily be obtained from rats without the need for anaesthesia. The development of this technique makes the rat more readily available as an animal model for repeated withdrawals of small blood samples for pharmacokinetic or bioavailability evaluations.

Animals↗

Spectrum of serum cortisol response to ACTH in ICU patients. Correlation with degree of illness and mortality.

Recent reports suggest adrenal insufficiency in critically ill patients is common. We found only one case of de novo adrenal insufficiency using admission ACTH injection in 70 selected intensive care unit (ICU) patients. Random serum cortisol levels correlated positively with illness severity in ICU patients using proven methods for assessing illness severity. Those with the highest random serum cortisol levels (greater than 60 micrograms/dl) had the greatest mortality, while those with lower random cortisol levels which stimulated to more than 18 micrograms/dl after ACTH injection had improved outcomes. Based on our results, routine screening for adrenal insufficiency in ICU patients is not warranted. If it is suspected, the cosyntropin test should be performed since low random cortisol levels (even to 5 micrograms/dl) are not diagnostic of adrenal insufficiency.

Adrenal Insufficiency↗

Plasma volume and endocrine responses to water immersion with intermittent positive-pressure breathing in men.

The effect of intermittent positive-pressure breathing (PB), induced by expiring against a resistance of 12.5 mm Hg, on plasma volume and endocrine responses to standing water immersion, was studied in seven male subjects, 28-49 years of age. The men were immersed to the neck (35 +/- 0.5 degrees C) for 90 min with PB from 30 to 60 min. Compared to control values, the hematocrit and hemoglobin concentration decreased (p less than 0.001) during immersion while plasma osmolality was unchanged, indicating an isotonic increase in plasma volume (hemodilution) which peaked after 75 min at +15.5% of the preimmersion plasma volume. This hemodilution was not significantly affected by PB. Plasma renin activity and vasopressin and aldosterone concentrations decreased progressively throughout immersion (p less than 0.001) and were unaffected by PB. The magnitude of these hormonal decreases was accentuated by preexisting, presyncopal symptoms in four subjects. It is concluded that intermittent PB as 12.5 mm Hg failed to compensate for the negative-pressure breathing of standing subjects immersed in water to the neck.

Adult↗

A new look at pericardial substitutes.

The presence of pericardial adhesions may increase morbidity and mortality during reoperation for cardiac disease. Pericardial substitutes (patches) are commercially available, and reportedly they reduce or prevent adhesions. We implanted five (1984 to 1985) newer pericardial substitutes in dogs. A new polytetrafluoroethylene surgical membrane, two types of glutaraldehyde-stabilized bovine pericardium, formaldehyde-preserved bovine pericardium, and glutaraldehyde-stabilized equine pericardial patches were each implanted in six adult dogs (total 30 dogs) with two dogs from each of the five groups killed at 3, 9, and 18 months. At autopsy the condition of each patch was recorded photographically, and specimens were substituted for histologic examination. Adhesions and epicardial reactions were graded as none, minimal, moderate, or severe. None of the materials produced severe pericardial adhesions, and no adhesions were detected in nine dogs. Eleven dogs had no epicardial reaction and only one showed a severe reaction. Adhesions to portions of the suture line required sharp dissection in 11 dogs. If there is concern over the possibility of calcification in heterologous tissue, polytetrafluoroethylene may be chosen. Patch type did not significantly alter patch behavior.

Animals↗

Increased vertebral bone mineral in response to reduced exercise in amenorrheic runners.

Seven female runners found to have exercise-induced amenorrhea and decreased bone mineral were reevaluated after 15 months. During the 15-month period, four runners took supplemental calcium and reduced their weekly running distance by 43%, resulting in an average 5% increase in body weight, increased estradiol levels and eumenorrhea. Bone mineral content increased from 1.003+/-0.097 to 1.070+/-0.089 grams per cm.(2) Three runners continued to have amenorrhea, with no change in running distance or body weight. Estradiol levels remained abnormally low and there was no significant change in the bone mineral content, although all three took supplemental calcium. We found that early osteopenia associated with exercise-induced menstrual dysfunction improved when runners reduced their running distance, gained weight and became eumenorrheic.

Adult↗

Drinking and subsequent suppression of vasopressin is unaltered by naloxone in dogs.

The effect of the opioid antagonist naloxone on drinking and the subsequent suppression of plasma vasopressin were evaluated in seven dogs following 24 hr of water deprivation. Each animal underwent an intravenous injection of vehicle as a control and a low (0.05 mg/kg) and high (1 mg/kg) dose of naloxone. Plasma vasopressin was significantly (p less than 0.05) increased from a control value of 4.6 +/- 1.9 microU/ml to 9.9 +/- 3.1 microU/ml after the high dose of naloxone. Fluid intake was not altered by naloxone; 42 +/- 6 ml/kg for the control, 45 +/- 8 ml/kg at the low dose, and 49 +/- 7 ml/kg for the high dose. Six minutes after the onset of drinking vasopressin was reduced by 48% for the control, 41% for the low dose and 45% for the high dose, with no significant difference among treatments. Thus, in dehydrated dogs naloxone presumably blocks endogenous opioids, elevates vasopressin following dehydration, but does not affect drinking behavior or the subsequent suppression of vasopressin after drinking.

Animals↗

Effects of sodium depletion and angiotensin II on osmotic regulation of vasopressin.

After alterations in sodium balance, osmotic reactivity of vasopressin (AVP) release was evaluated in seven conscious dogs during bilateral intracarotid infusions of hypertonic saline. A low-sodium diet reduced plasma sodium concentration by 3%; deoxycorticosterone acetate (30 mg/day for 2 days) elevated the concentration by 1%. Neither treatment altered resting plasma AVP. Hypertonic intracarotid infusions increased jugular plasma osmolality by 20 +/- 2 mosmol/kg independent of manipulations. Plasma AVP values were significantly increased (P less than 0.05) in sodium-depleted dogs compared with values of the control animals. In addition, the osmotic reactivity of AVP release was evaluated during exogenous administration of angiotensin II (ANG II). Intravenous infusion of ANG II (5 ng . kg-1 . min-1) increased plasma concentration of ANG II but did not alter concentration of plasma AVP. The slope for the relationship of jugular plasma osmolality to plasma AVP during hypertonic intracarotid infusions was significantly increased with intravenous infusion of ANG II. Sodium depletion and intravenous ANG II potentiate the relationship of plasma osmolality and plasma AVP when evaluated with intracarotid hypertonic saline infusions in dogs.

Angiotensin II↗