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Biomedical subjects

C E Wade

Publications and source records attributed to C E Wade.

At least 91 records · Page 5Linked to original sources

Influences of traumatic brain injury on the outcomes of delayed and repeated hemorrhages.

Effects of traumatic brain injury (fluid percussion) on outcomes of hemorrhage, either delayed (70.5 min after the injury) or repeated (0.5 min after injury, then followed by a delayed hemorrhage), were examined in 4 groups of 10 anesthetized rats. Comparisons were made for delayed hemorrhage following sham injury (A1) vs. injury (A2) and for repeated hemorrhage following sham injury (B1) vs. injury (B2). No significant differences were observed in MAP, Cl, HR, SVI, SVRI, and CVP between groups A1 and A2. Hemodynamic recovery was significantly better in B1 than B2 at 70 min after the initial hemorrhage. The respective values of MAP and Cl for the groups B1 and B2 at 70 min were 65 +/- 3 vs. 56 +/- 4 mmHg and 220 +/- 15 vs. 182 +/- 15 ml/min/kg. Brain trauma did not affect survival rate (90 vs. 100%) following delayed hemorrhage, but significantly worsened the outcome of repeated hemorrhage. The 130 min survival rates for groups B1 and B2 were 50% and 10% (P = 0.08), respectively; their survival curves were significantly different (P = 0.02). Our data indicate that brain trauma has greater impact on responses to immediate hemorrhage than delayed hemorrhage, suggesting that traumatic brain injury may have a time-dependent effect on the response to hemorrhage.

Animals↗

The detrimental effects of intravenous crystalloid after aortotomy in swine.

We tested the hypothesis that, after aortotomy, rapidly replacing three times the blood volume deficit with intravenous crystalloid will increase hemorrhage and decrease survival. Sixteen anesthetized Yorkshire swine underwent splenectomy and stainless steel wire placement in the infrarenal aorta and were instrumented with pulmonary artery and carotid artery catheters. The wire was pulled, producing a 5 mm aortotomy and spontaneous intraperitoneal hemorrhage. The animals had been alternately assigned to either an untreated control group (n = 8) or a treatment group (n = 8), which received 80 ml/kg lactated Ringer's solution intravenously. The volume of hemorrhage and the mortality rate were significantly increased (p less than 0.05) in the treatment group receiving lactated Ringer's solution relative to the control animals (2142 +/- 178 ml versus 783 +/- 85 ml, and eight of eight animals versus zero of eight animals, respectively). From these data we conclude that, in this model of uncontrolled arterial hemorrhage resulting from abdominal aortotomy, rapidly administering lactated Ringer's solution intravenously significantly increases hemorrhage and death.

Acid-Base Equilibrium↗

Effects of a 15-d race on plasma steroid levels and leg muscle fitness in runners.

Effects of increased training distance on resting plasma testosterone and adrenal steroid levels, serum markers of protein catabolism and muscle fiber damage, and field tests of leg muscle fitness were studied in 19 male marathon runners. Data were collected 1-2 d before and 1 d after a 400-km road race over 15 d. The runners maintained their usual training speeds even though the race distance was twice their regular mileage. Testosterone levels decreased 31% (P less than 0.01), from 23.5 +/- 1.7 to 16.2 +/- 1.0 nmol.l-1. The ratio of cortisol to testosterone increased 83% (P less than 0.01). Blood urea nitrogen (BUN) concentration increased from 16.7 +/- 0.7 to 21.8 +/- 1.0 mg.dl-1 (P less than 0.05) and serum total protein decreased from 7.09 +/- 0.10 to 6.88 +/- 0.08 g.dl-1 (P less than 0.05). Serum creatine kinase (CK) activity increased 380%, from 152 +/- 11 to 731 +/- 74 U.l-1 (P less than 0.001) and was associated with persistent leg muscle soreness. There were no significant changes in body weight, estimated lean body weight, hematocrit, or plasma cortisol, aldosterone, progesterone, androstenedione, and DHEA sulfate levels. Test scores for leg power (vertical jump), strength (dead lift), flexibility (sit-and-reach), and speed (timed stands) did not change significantly. The decrease in plasma testosterone did not correlate with the changes in either BUN, total protein, or CK. The results indicate that existent leg muscle fitness was unaltered despite the suppression of circulating testosterone and the development of early protein catabolism and muscular damage.

Adrenal Cortex Hormones↗

Furosemide-induced disturbances of renal function in patients undergoing TURP.

Furosemide remains the drug of choice for patients with the transurethral resection syndrome. Furosemide is often used intraoperatively to treat patients suspected of having excessive irrigant absorption. To examine the efficacy of such therapy, a randomized study was performed in which furosemide was administered to patients undergoing routine transurethral resection of the prostate (TURP) to determine the effect of furosemide on electrolyte and fluid volume conservation in these patients. Seven patients treated with furosemide on completion of TURP had a statistically significant delayed drop in serum sodium values after normal initial values (139 mEq/L to 134 mEq/L). Seven untreated control patients did not have a similar drop in sodium values, and the difference between groups was significant. We suggest that furosemide be used with caution in patients undergoing routine TURP, and when given it should be accompanied by the infusion of an isotonic balanced salt solution.

Aged↗

Hypertonic saline/dextran improves renal function after hemorrhage in conscious swine.

This study was performed to determine whether resuscitation with a single bolus of 7.5% NaCl/6% Dextran 70 (hypertonic saline/Dextran, HSD) could restore renal function following hemorrhage. Chronically instrumented, conscious pigs were hemorrhaged 28 ml/kg. This level of hemorrhage reduced mean arterial pressure (MAP) and cardiac output (CO) to nearly half, renal blood flow (RBF) to approximately 25%, and glomerular filtration rate (GFR) and urine flow (V) to less than 10% of their initial values. A single, 4 ml/kg bolus injection of HSD increased MAP and RBF to approximately 80% of baseline values and restored CO and GFR to levels which were significantly different from control values. These improvements were sustained for 2 h with no further treatment. Urine flow transiently increased although not to pre-hemorrhage values, and then subsided. Plasma osmolality increased from 275 to 282 mOsm/kg H2O, and plasma sodium increased from 141 to 149 mEq/l. Recovery following administration of an equal volume of normal saline was significantly less for all variables. Euvolemic animals showed no response in MAP, CO, RBF, or GFR when treated with HSD although V, osmotic and sodium excretion increased. These results demonstrate that resuscitation with HSD following hemorrhage not only restores MAP and CO, but maintains renal function as well.

Acute Kidney Injury↗

Superiority of hypertonic saline/dextran over hypertonic saline during the first 30 min of resuscitation following hemorrhagic hypotension in conscious swine.

We compared the effectiveness of intravenously administering hypertonic saline/dextran (HSD; 7.5% NaCl in 6% Dextran-70, n = 6) to hypertonic saline (HS) alone (7.5% NaCl, n = 8) in rectifying detrimental effects of hemorrhage on cardiovascular function. Chronically instrumented conscious swine were hemorrhaged 37.5 ml/kg over 60 min. If untreated, this model is 100% lethal within 60 min. Swine received HSD or HS at 4 ml/kg. Functional variables were measured before and at 5, 15, and 30 min following treatment. HSD produced a significantly greater plasma volume expansion than HS alone (13.6 compared to 9.9 ml/kg). Over 30 min expansion was sustained in pigs receiving HSD but pigs receiving HS regressed. Cardiac index (CI) increased for both treatments, being greater with HSD, 104 ml/kg/min, compared to HS alone, 46 ml/kg/min. Neither group fully sustained these elevated values post-treatment, but remained consistently greater than values after hemorrhage; however, the difference in CI between treatments was maintained. Oxygen delivery showed a trend similar to that of CI. We conclude that resuscitation with HSD is superior to HS in improving cardiovascular function over the first 30 min after hemorrhage.

Animals↗

Traumatic brain injury creates biphasic systemic hemodynamic and organ blood flow responses in rats.

Traumatic brain injury affects systemic circulation as well as directly damages the brain. The present study examined the effects of fluid percussion brain injury on systemic hemodynamics and organ arterial blood flow in rats. Rats were prepared for fluid percussion injury under anesthesia. Twenty-four hours later, rats were anesthetized (1.0% halothane in N2O:O2) and prepared for radioactive microsphere measurement of cardiac output and organ blood flow. After baseline blood flow and physiological measurements were established, the rats were injured (2.47 +/- 0.02 atm, n = 17) or not injured (n = 20). Additional blood flow determinations were made at two of the following four time (T) points: 5, 15, 30, and 60 min after the injury or sham injury. Fluid percussion brain injury produced an immediate systemic hypertension followed by a hypotension and low cardiac output. Organ blood flows remained constant or increased for 30 min and then declined. Decreased blood flow was most pronounced in the kidneys and the spleen and was less severe in the liver. The reduced cardiac output was redistributed to favor blood flow through the heart and pancreas. These data suggest that traumatic brain injury creates a hyperdynamic period followed by a hypodynamic state with a heterogeneous hypoperfusion among organs.

Animals↗

Effects of hypertonic saline (7.5%)/dextran 70 on human red cell typing, lysis, and metabolism in vitro.

The introduction of a 7.5% hypertonic saline/6% dextran 70 (HSD) solution into clinical trials for the treatment of hypovolemic states, and the past concerns regarding the possible interference of dextran with blood serology, prompted us to investigate the effects of HSD on human red-cell typing and stability. HSD was evaluated with fresh and 35-day stored CPDA-1 red cells from 12 healthy donors. A 1:5 mixture of HSD to blood in vitro had no effect on ABO, Rh, and MN typing in both fresh and stored blood. HSD produced no significant lysis with fresh cells and a minimal level with stored blood. No evidence of metabolic or morphologic changes was seen after HSD treatment. The results of this study suggest that the clinical use of HSD for the treatment of hemorrhagic shock will not affect blood group determinations or red-cell stability from stored blood which may be infused after the HSD-treated patient is transported to a hospital.

Blood Grouping and Crossmatching↗

Renal responses to graded hemorrhage in conscious pig.

We developed a conscious pig model with a chronically instrumented kidney to measure renal blood flow (RBF), glomerular filtration rate (GFR), and excretory functions during hemorrhage. Seven to 10 days before experimentation, pigs were splenectomized, arterial and venous catheters were implanted, an ultrasonic flow probe was placed on the renal artery, and a pyelostomy was performed for nonocclusively placing a ureteral catheter. Measurements were taken before hemorrhage, and at hemorrhage volumes of 7, 14, 21, and 28 ml/kg (equivalent to 10.5, 21, 31, and 42% of the estimated blood volume), or at corresponding time points for controls. RBF was decreased by 30% when 21% of the blood (14 mg/kg) was removed, before arterial pressure, GFR, or urine flow or excretion was changed. At volumes of hemorrhage greater than 14 ml/kg, there were progressive decreases in RBF, GFR, urine flow rate, osmotic and electrolyte excretion, and arterial pressure. Thus pigs, like humans, respond to hypovolemia with an early redistribution of blood flow away from the kidney.

Animals↗

Lysine vasopressin in the treatment of refractory hemodialysis-induced hypotension.

The etiology of hemodialysis-induced hypotension is multifactorial. We assessed the efficacy of intranasal lysine vasopressin (LV) in 6 patients with refractory hemodialysis-induced hypotension. Autonomic testing was abnormal in all. Intranasal LV and placebo were assessed in a double-blind crossover fashion. With LV, the mean number of hypotensive episodes was less (0.9 +/- 0.8 vs. 1.5 +/- 1; t = 3.95, p less than 0.05), as was the total volume of intravenous fluid administered because of hypotension (155 +/- 57 vs. 280 +/- 123 cm3; t = 2.98, p less than 0.05). Systolic, diastolic, and mean arterial blood pressures were significantly greater at 90 min of the dialysis session. Measured baseline epinephrine, norepinephrine, and antidiuretic hormone levels were elevated above normal levels and fell with hypotension despite the use of LV. The results from this study demonstrate the utility of LV in the treatment of refractory hemodialysis-induced hypotension.

Administration, Intranasal↗

Blood gas and acid-base status of conscious pigs subjected to fixed-volume hemorrhage and resuscitated with hypertonic saline dextran.

Conscious, chronically instrumented pigs were subjected to a progressive, fixed-volume hemorrhage (37.5 ml/kg over 1 h) and subsequent resuscitation with 7.5% hemorrhage (37.5 ml/kg over 1 h) and subsequent resuscitation with 7.5% NaCl/6% Dextran 70 (4 ml/kg). Hemorrhage led to increases in arterial PO2, HbO2, plasma lactate, base deficit, and mixed venous PCO2. It led to decreases in arterial PCO2, plasma bicarbonate, and buffer base, as well as mixed venous PO2, HbO2, and pH. These effects were attributable to reduced O2 delivery, lactacidemia, hyperventilation, and hemodilution. Resuscitation with hypertonic saline/dextran produced a transient increase in arterial PCO2 and base deficit and a transient decrease in pH, effects that were attributable to a transfer of venous blood attributes to the arterial circulation. Resuscitation also produced an immediate decrease in arterial buffer base, an effect attributable to hemodilution. Subsequently, over 4 h, most cardiopulmonary and metabolic variables gradually reverted toward control levels, thereby ameliorating the deleterious blood gas and acid-base disturbances produced by severe hemorrhage.

Acid-Base Imbalance↗

Normal physiological values for conscious pigs used in biomedical research.

Although the domestic pig is rapidly becoming an animal of choice in certain areas of biomedical research requiring a large animal model, effective utilization of the species is often encumbered by a lack of reference values for common functional variables. To address this problem, normal data for over 100 physiologic or related variables were collected from conscious chronically instrumented animals that were maintained under near basal conditions. Included were measurements of body composition, fluid volumes, blood physical and biochemical characteristics, blood gas and acid-base status, plasma hormone levels, energy metabolism, renal function, hemodynamics and pulmonary function. Most porcine values were similar to those collected under comparable conditions from humans. Compared to adult man, however, pigs had higher values for extracellular space, plasma volume, arterial pH, plasma bicarbonate, cardiac output, arterial pressure, expired ventilation, heat production, and core temperature, and lower values for red cell volume, hemoglobin level, plasma osmotic and oncotic pressure, arterial O2 content, renal blood flow and glomerular filtration rate. Many of these deviations were due to immaturity. Nevertheless, we have found pigs to be an excellent large animal model for a variety of functional studies.

Acid-Base Equilibrium↗

Work capacity during 30 days of bed rest with isotonic and isokinetic exercise training.

The purpose was to test the hypothesis that twice daily, short-term, variable intensity isotonic and intermittent high-intensity isokinetic leg exercise would maintain peak O2 uptake (VO2) and muscular strength and endurance, respectively, at or near ambulatory control levels during 30 days of -6 degrees head-down bed rest (BR) deconditioning. Nineteen men (aged 32-42 yr) were divided into no exercise control (peak VO2 once/wk, n = 5), isokinetic (Lido ergometer, n = 7), and isotonic (Quinton ergometer, n = 7) groups. Exercise training was conducted in the supine position for two 30-min periods/day for 5 days/wk. Isotonic training was at 60-90% of peak VO2, and isokinetic training (knee flexion-extension) was at 100 degrees/s. Mean (+/- SE) changes (P less than 0.05) in peak VO2 (ml.m-1.kg-1) from ambulatory control to BR day 28 were 44 +/- 4 to 36 +/- 3, -18.2% (3.27-2.60 l/m) for no exercise, 39 +/- 4 to 40 +/- 3, +2.6% (3.13-3.14 l/min) for isotonic, and 44 +/- 3 to 40 +/- 2, -9.1% (3.24-2.90 l/min) for isokinetic. There were no significant changes in any groups in leg peak torque (right knee flexion or extension), leg mean total work, arm total peak torque, or arm mean total work. Mean energy costs for the isotonic and isokinetic exercise training were 446 kcal/h (18.8 +/- 1.6 ml.min-1.kg-1) and 214 kcal/h (8.9 +/- 0.5 ml.m-1.kg-1), respectively. Thus near-peak, variable intensity, isotonic leg exercise maintains peak VO2 during 30 days of BR, while this peak, intermittent, isokinetic leg exercise protocol does not.

Adult↗

Resuscitation of conscious pigs following hemorrhage: comparative efficacy of small-volume resuscitation.

Efficacy of small-volume resuscitation (4 ml/kg) with 7.5% NaCl in 6% Dextran 70 (HSD), 7.5% NaCl (HS), dextran (D), and 0.9% NaCl (NS) was evaluated in conscious swine bled 37.5 ml/kg over 60 min. Hemorrhage reduced cardiac index (CI), stroke volume (SV), and mean arterial pressure (MAP). Four-hour survival after HSD (67%) was significantly (P less than 0.05) greater than after HS (25%), D (17%), or NS (0%). The superior performance of HSD, and to a lesser extent HS, was associated with rapid plasma volume expansion, improved CI and SV, and decreased heart rate. The acute increases in cardiac index and stroke volume were greater following treatment with HSD and the improvement persisted for 4 hr. HSD also produced a transient increase in MAP. Plasma Na+ concentration and osmolality were increased to a similar extent with HSD and HS, while plasma K+ levels were initially decreased, returning to control levels within 60 min. HSD appears to be a superior small-volume resuscitation solution compared to the other treatments with no detrimental effects.

Animals↗

Oxygen delivery and demand in conscious pigs subjected to fixed-volume hemorrhage and resuscitated with 7.5% NaCl in 6% Dextran.

A conscious porcine model was used to investigate the adequacy of O2 delivery relative to O2 demand, initially during a fixed-volume hemorrhage (37.5 ml/kg over 1 hr) and subsequently after resuscitation with 7.5% NaCl/6% Dextran 70 (4 ml/kg). Hemorrhage produced a small increase in O2 consumption, severe lactacidemia, and a doubling of apparent O2 demand. These effects were attributable to a behavioral compensation (periodic bouts of muscle activity) which presumably served to improve venous return. Despite enhanced ventilatory function, arterial O2 delivery was markedly reduced by hemorrhage, an effect that was due entirely to decrements in cardiac output and hemoglobin level. The disparity between O2 delivery and O2 demand was lessened following resuscitation with 7.5% NaCl/6% Dextran 70, primarily by suppression of demand and secondarily by an augmentation of delivery.

Animals↗

Dextran concentrations in plasma and urine following administration of 6% dextran-70/7.5% NaCl to hemorrhaged and euvolemic conscious swine.

Dextran metabolism was investigated in ten hemorrhaged and seven euvolemic conscious swine. Chronically instrumented, splenectomized swine were subjected to a progressive fixed-volume hemorrhage (27 ml/kg over 45 min). Resuscitation with 4 ml/kg of a 7.5% NaCl/6% dextran 70 (HSD) solution was begun 5 min later. Blood and urine samples were drawn before and during hemorrhage, and at 15, 60, and 120 min following intravenous HSD infusion. Hemorrhage significantly reduced cardiac output (CO) and mean arterial pressure (MAP) and eliminated urinary flow. HSD administration to hemorrhaged pigs returned CO and MAP to control values and improved urinary flow. Creatinine clearance returned to prehemorrhage values. These parameters were not affected by HSD in nonhemorrhaged animals. Plasma dextran concentrations were 20-30% higher in hemorrhaged pigs compared with euvolemic swine. In additional studies, plasma t1/2 for dextran was 9.4 hr in hemorrhaged pigs (n = 3) compared to 10.8 hr in euvolemic animals (n = 2). These data show that HSD ameliorates the effects of hemorrhage on cardiovascular and renal function and suggest that plasma clearance of dextran may be affected by hemorrhage.

Animals↗

Blood lactate as a prognosticator of survival following hemorrhage in conscious swine.

Arterial blood lactate concentration at the end of fixed volume hemorrhage was evaluated as a predictor of survival in unmedicated chronically instrumented immature swine. Compared to basal values, 8.4 +/- 4.5 mg/dl (means +/- SD, n = 52), hemorrhaged animals (n = 71) with a lactate of 43.9 +/- 37.1 mg/dl lived while animals (n = 65) with a lactate of 106.5 +/- 40.4 mg/dl died. Lactate concentration at the end of hemorrhage successfully predicted survival (81.0%). Prospective evaluation, using a blood lactate concentration of 125 mg/dl (n = 27), showed a predictive success of 81.0%. Arterial plasma lactate concentration at the end of hemorrhage thus may be used to predict survival in the conscious swine.

Animals↗

The influence of early surface thromboreactivity on long-term arterial graft patency.

The influence of early graft surface thromboreactivity on long-term arterial polyester (Dacron) graft patency was investigated with separate ex vivo and in vivo animal models. First, parallel, flow-regulated external aortocaval fistulae were created in five pigs with use of paired 8 mm X 35 cm crimped, warp-knitted, low-profile filamentous velour Dacron tubes: one tube preclotted with autologous blood, the other autoclaved after being soaked in human albumin. Autologous radiolabeled platelets, red cells, and radiolabeled human fibrinogen were injected at initiation of graft flow, with timed graft samples submitted for isotope gamma well-counting. Flow surface accumulation of radiolabeled blood elements was greater on the preclotted graft limb at-all time intervals studied, greatest after 5 minutes of flow initiation with RBC accumulation on the preclotted limb 5.19 +/- 0.84 (x +/- S.E.), platelet accumulation 5.57 +/- 1.00, and fibrinogen accumulation 1.82 +/- 0.14 times greater than that on the albumin-treated limb. Second, bilateral iliofemoral artery bypass grafts were placed in 12 mongrel dogs using 6 mm X 10 cm externally supported, noncrimped, warp-knitted, low-profile filamentous Dacron tubes. Before implant in each dog, one graft limb was clotted with autologous blood and the other was autoclaved after being soaked in 25% human albumin. Fresh autologous radiolabeled platelets were injected after wound closure in seven of these dogs. Postimplant graft imaging at 24 and 72 hours showed radiolabeled platelet accumulation to be 1.43 +/- 0.21 and 2.05 +/- 0.18 times greater on the preclotted graft limb. Six of 12 preclotted graft limbs and 7 of 12 albumin-treated graft limbs were patent when animals were killed 5 to 6 months after implant (not significant). Heat-denatured albumin-coated Dacron surfaces have a reduced early thromboreactivity but do not appear to greatly potentiate long-term arterial graft patency.

Albumins↗