Biomedical subjects

G C Kramer

Publications and source records attributed to G C Kramer.

At least 73 records · Page 4Linked to original sources

PubMed1989

Use of a 7.5% NaCl/6% Dextran 70 solution in the resuscitation of injured patients in the emergency room.

Animal studies and preliminary field patient trials suggest that hypertonic saline solutions can achieve resuscitation of hypovolemic shock with extremely small volumes. In the study reported here, we evaluated the effects of a hypertonic 7.5% NaCl/6% Dextran 70 (HSD) solution in the resuscitation of patients in the emergency room. Thirty-two patients were randomized into a prospective, randomized, placebo-controlled, double-blinded trial in which 250 ml of either HSD or, as a control, lactated Ringers (LR) was used as the initial fluid for resuscitation of patients with systolic blood pressures of 80 mmHg or less. The test solution was given intravenously, usually through a saphenous vein cut-down, over a period of 2-5 minutes. Conventional isotonic solutions were then given as necessary with an average of 2500 ml of fluid being given over the first 30 minutes of resuscitation. Survival was not improved, and the trial proved to be of most interest with regard to measurement of physiological quantities, which might have been expected to have been substantially abnormal because, in many cases, the measurements were made shortly after the infusion ran in. Very few abnormalities, however, were in fact detected. With the exception of one patient, the highest sodium concentration was 156 mEq/l, the highest chloride concentration was 126 mEq/1, and the highest osmolality was 401 mOsm/kg, and this value was obtained in a patient in the control LR group. Osmolality correlated far better with blood alcohol levels (Spearman's rank correlation coefficient = 0.81) than with any other variable, including sodium and chloride concentrations. The HSD solution was safe to use.(ABSTRACT TRUNCATED AT 250 WORDS)

Dextrans↗

PubMed1989

Comparison of hypertonic saline/dextran versus hypertonic saline/hetastarch for resuscitation of hypovolemia.

In the present study, we compare resuscitation of bled sheep with hypertonic saline/dextran or hypertonic saline/hetastarch. Unanesthetized sheep were subjected to 2 h of hemorrhagic hypotension and then resuscitated with 200 ml of 7.5% NaCl solution made up to include either 6% dextran 70 (Macrodex) or 6% hetastarch (Hespan). Both solutions provided an immediate and sustained improvement in arterial pressure and cardiac output. The hypertonic saline/dextran provided a slightly better overall response as mean arterial pressure, cardiac output and central venous pressure were higher in the dextran group at all times post resuscitation. However, only the differences in arterial pressure and initial plasma volume expansion were statistically significant. The somewhat better response to hypertonic saline/dextran may be explained by the higher oncotic pressures generated by dextran compared to equal concentrations of hetastarch.

Animals↗

PubMed1989

Resuscitation of hemorrhage with intraosseous infusion of hypertonic saline/dextran.

We resuscitated unanesthetized bled sheep (bled volume = 1.2-1.7 liters) with 200 ml of hypertonic saline/dextran 70 infused either through a peripheral vein (n = 6) or directly into the red marrow of the sternum (n = 6). Intraosseous infusion of the viscous 7.5% NaCl/6% dextran solution required 2-4 min. Plasma sodium was rapidly increased to the same level in both groups demonstrating equally rapid entry into the vascular space. Both regimens provide rapid and sustained normalization of arterial pressure and cardiac output. No significant differences between the two groups were apparent for any measured variable. Intraosseous infusion of hypertonic resuscitation fluids merits further research to evaluate the safety and efficacy for prehospital treatment of hypovolemia and trauma.

Animals↗

PubMed1989

Perspectives on clinical trials for hypertonic saline/dextran solutions for the treatment of traumatic shock.

Animal studies with hypertonic solutions suggest that they can achieve resuscitation of hypovolemic shock with extremely small volumes. Such small volume resuscitation might be ideal in the field treatment of injured patients. Our studies to date, with 60 patients entered into a prospective, randomized, placebo-controlled, and double-blind clinical trial, suggest that the use of a 7.5% NaCl/Dextran 70 solution increases blood pressures during transport. The solutions have been safe, and we have encountered no adverse side effects from their use. Survival rates to date favor use of the solutions, but we do not have convincing statistical significance yet in that regard.

Clinical Trials as Topic↗

PubMed1989

Cardiac performance following hypertonic saline.

The present study was undertaken to examine cardiovascular function before and after either intravenous or intra-arterial infusion of hypertonic saline (7.5% NaCl) in halothane-anesthetized dogs. A high-fidelity micromanometer and ultrasonic dimension transducers were implanted to measure pressure and wall motion of the left ventricle (LV). Cardiac output (CO) was measured using an electromagnetic flowmeter and thermodilution. The slope (Ees) of the linear regression of the LV pressure-diameter relationship was used as an index of cardiac contractility. Intravenous infusion of hypertonic saline (3 ml/kg) increased mean arterial pressure (MAP, 104 +/- 6 to 116 +/- 6 mmHg), heart rate (HR, 124 +/- 21 to 140 +/- 13 bpm), CO (3.2 +/- 0.9 to 4.2 +/- 0.5 l/m) and Ees (11.6 +/- 2.1 to 14.8 +/- 1.9 mmHg/mm). Systemic vascular resistance (SVR) fell by 18%. The above responses were similar whether infusion was intravenous or intra-arterial into innervated or denervated hind limbs. While nerve blockade at T-4 (xylocaine) attenuated the changes in CO and SVR and completely prevented the tachycardia, the inotropic response remained intact. These studies suggest that the cardiac effects of hypertonic saline infusion are not mediated by pulmonary or peripheral osmoreceptors and the increased contractility may result from a direct myocardial effect of increased osmolality.

Animals↗

PubMed1988

NMR monitoring of phosphate metabolism of rat skeletal muscle during hemorrhage and resuscitation.

Phosphorus nuclear magnetic resonance (NMR) spectroscopy allows noninvasive monitoring of intracellular high-energy metabolites. In the present study we used topical NMR to monitor intracellular levels of ATP, creatine phosphate (CrP), inorganic phosphate (Pi), and pH in the biceps femoris muscle of rats during hemorrhagic shock and resuscitation. Twelve rats weighing 300-500 gm were anesthetized and bled to a mean arterial pressure (MAP) of 50-55 mm Hg for 90 minutes. Then they were resuscitated with lactated Ringers' until MAP returned to normal or resuscitation fluid equaled four times the shed blood volume. During resuscitation, the rats fell into one of two groups: survivor group (n = 5) which could be successfully resuscitated for 60 minutes or longer; or nonsurvivor group (n = 7) which died during resuscitation. In both groups, ATP levels were maintained during hemorrhage and resuscitation. Intramuscular pH dropped about 0.2 pH units in both groups at the end of hemorrhage; however, pH was restored back toward baseline in the survivor group. CrP levels were lower in the nonsurvivor group at the end of hemorrhage. After resuscitation, CrP returned to nearly baseline levels in the survivor group; in the nonsurvivor group, CrP was further depleted after resuscitation. Pi levels were increased in both groups at the end of hemorrhage, but in the survivor group Pi decreased during the first 15 minutes of resuscitation; in the nonsurvivor group Pi increased further to four times baseline levels. This study demonstrated that topical NMR can quantitate a metabolic deficit in skeletal muscle during hemorrhage and resuscitation. The results show that improvement of intracellular Pi and CrP levels correlated with survival.

Adenosine Triphosphate↗

PubMed1988

Measurement of bronchial blood flow with radioactive microspheres in awake sheep.

Distribution of bronchial blood flow was measured in unanesthetized sheep by the use of two modifications of the microsphere reference sample technique that correct for peripheral shunting of microspheres: 1) A double microsphere method in which simultaneous left and right atrial injections of 15-microns microspheres tagged with different isotopes allowed measurement of both pulmonary blood flow and shunt-corrected bronchial blood flow, and 2) a pulmonary arterial occlusion method in which left atrial injection and transient occlusion of the left pulmonary artery prevented delivery to the lung of microspheres shunted through the peripheral circulation and allowed systemic blood flow to the left lung to be measured. Both methods can be performed in unanesthetized sheep. The pulmonary arterial occlusion method is less costly and requires fewer calculations. The double microsphere method requires less surgical preparation and allows measurement without perturbation of pulmonary hemodynamics. There was no statistically significant difference between bronchial blood flow measured with the two methods. However, total bronchial blood flow measured during pulmonary arterial occlusion (1.52 +/- 0.98% of cardiac output, n = 9) was slightly higher than that measured with the double microsphere method (1.39 +/- 0.88% of cardiac output, n = 9). In another series of experiments in which sequential measurements of bronchial blood flow were made, there was a significant increase of 15% in left lung bronchial blood flow during the first minute of occlusion of the left pulmonary artery. Thus pulmonary arterial occlusion should be performed 5 s after microsphere injection as originally described by Baile et al. (1).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Airway blood flow distribution and lung edema after histamine infusion in awake sheep.

The present study was designed to evaluate the distribution of bronchial blood flow to major airways and peripheral lung and to quantitate lung edema during a 2-h histamine infusion (2 micrograms.kg-1.min-1) in unanesthetized sheep. By the use of radioactive microspheres, the blood flow to trachea and to tracheal cartilage, smooth muscle, and mucosa/submucosa was determined along with measurements of blood flow to different sized airway segments and the systemic blood flow to lung parenchyma. Histamine greatly increased blood flow to medium-sized (5- to 10-mm-diam) central airways in which blood flow increased 5-10 times base line, whereas in small (1- to 5-mm-diam) central airways the increase was 10-15 times. Blood flow in tracheal mucosa/submucosa increased six times base line, but in tracheal smooth muscle the increase was only three times base line, and in cartilage it remained at base line. Most of the systemic blood flow to the lung perfuses less than 1-mm-diam peripheral airways, and these airways demonstrated less vasodilation during histamine infusion. Mean blood flow to whole-lung parenchyma (whole lung minus trachea) was only two times base line during histamine infusion. Water content of trachea and main stem bronchi was significantly increased after histamine. Histopathologic findings after histamine infusions included congestion and edema of airways with only minor effects noted in alveoli. We conclude that histamine is a potent and selective vasodilator of bronchial vessels and particularly affects blood flow to central airways and to airway mucosal/submucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Comparison of peripheral and central infusions of 7.5% NaCl/6% dextran 70.

Although it had been known for several years that central venous injections of hypertonic salt solutions with added dextran could effectively resuscitate animals from hemorrhagic shock, it was not known whether peripheral injections could result in the same beneficial effects. Chronically instrumented, unrestrained, and unanesthetized sheep were subjected to a moderate degree of hemorrhagic shock and then resuscitated with a 2-minute infusion of 7.5% NaCl/6% dextran 70 in a volume of 5 ml/kg body weight. Infusions were made into the cephalic vein, the femoral artery, or, centrally, the superior vena cava. All three routes of injection promptly reestablished arterial pressure and cardiac output. All gave equivalently good restoration of plasma volume. None of the injections damaged the vessels, as determined either by gross inspection or by histologic examination. Thus the solution was safe and effective when given peripherally. It might be useful in the field resuscitation of hypovolemic patients.

Animals↗

PubMed1987

3% NaCl and 7.5% NaCl/dextran 70 in the resuscitation of severely injured patients.

Cardiovascular resuscitation of the severely injured patient in the field remains unsatisfactory because large volumes of intravenous fluid are needed to keep up with ongoing blood losses and because only small volumes of fluid can be given. In the first study reported here, small volumes (less than or equal to 12 mL/kg) of 3% NaCl were given to patients who were having surgery for severe injuries. The 3% NaCl restored blood pressure, pH, and urine output with approximately one half of the cumulative fluid requirement of patients who received isotonic fluids (p less than 0.05). In a second study, 7.5% NaCl/dextran 70, 250 mL, was given in a prospective, randomized, and double-blinded trial to injured patients in the field. Blood pressure in the hypertonic/hyperoncotic group increased 49 mmHg during transport (p less than 0.005); blood pressure in patients given lactated Ringer's solution increased 19 mmHg (NS). Survival favored the hypertonic/hyperoncotic group. The 7.5% NaCl/dextran 70 solution appears particularly promising for treatment of injured patients in the field.

Adult↗

PubMed1986

Wick sampling of interstitial fluid in rat skin: further analysis and modifications of the method.

UNLABELLED: We compared modifications of the wick technique for analysis of interstitial fluid in rat subcutis. Nylon wicks were implanted for 60 min in back skin of rats after anesthesia with pentobarbital or after sacrifice by potassium chloride injection. Wicks were implanted dry or loaded with saline or varied dilutions of rat serum. Implantation of dry wicks and wicks loaded with diluted serum in living, anesthetized animals produced similar results; the protein concentration of wick fluid averaged about 60% that of the plasma protein concentration. The saline loaded wicks produced wick fluid with a lower protein concentration, average about 45% that of plasma protein concentration. The lower concentrations apparently resulted from simple dilution. Wick fluid sampled from dead animals had similar total protein concentrations, but in the dead animals there was a lower concentration of the large plasma proteins and a relatively higher concentration of the smaller proteins. CONCLUSIONS: Wick implantation in living animals causes a transitory inflammatory reaction and a decrease in the size selectivity of macromolecular sieving, but local osmotic forces bring about a concentration equilibrium with undisturbed interstitium. Implantation of dry wicks in subcutis either in vivo or post mortem provides a simple, direct method for sampling the total protein concentration and colloid osmotic pressure of interstitial fluid. Implantation of dry wicks postmortem permits measurement of individual component protein concentrations and evaluation of molecular selectivity between plasma and interstitium.

Animals↗

PubMed1986

Small-volume resuscitation with hypertonic saline dextran solution.

Small-volume hypertonic resuscitation has been proposed as an effective means for restoration of cardiovascular function after hemorrhage at the scene of an accident. We evaluated the cardiovascular, metabolic, and neurohumoral response of resuscitation after hemorrhage using 200 ml of 2400 mosm sodium chloride, 6% dextran 70. Unanesthetized adult sheep were bled to maintain mean arterial pressure at 50 mm Hg for 3 hours, shed blood volume = 42 +/- 7 ml/kg. The sheep were then treated with a single bolus infusion of hypertonic saline dextran (n = 7) or normal saline solution (control group, n = 7) and then observed for a 30-minute period of simulated patient transport during which no additional fluid was given. Hypertonic saline dextran caused rapid restoration of blood pressure and cardiac output within 2 minutes of infusion. Cardiac output remained at or above baseline level, while both O2 consumption and urine output increased to above baseline level during the 30 minutes of simulated patient transport. By comparison 200 ml of normal saline solution caused only a small increase in blood pressure and no improvement in cardiac output or oxygen consumption. After this 30-minute period, both groups were given lactated Ringer's solution as needed to return and maintain cardiac output at its baseline value. The volume of lactated Ringer's solution required to maintain cardiac output was less in the hypertonic group, 371 +/- 168 ml, only one sixth that of the control group, 2200 +/- 814 ml. In summary after 3 hours of hypovolemia, a small volume of hypertonic saline dextran, about 4 ml/kg, fully restored cardiovascular and metabolic function for at least 30 minutes and significantly lowered the total volume requirements of resuscitation.

Animals↗

PubMed1985

Infusion of very hypertonic saline to bled rats: membrane potentials and fluid shifts.

Anesthetized rats were subjected to a moderate degree of hemorrhagic shock, lowering their mean arterial pressure to approximately 50 mm Hg for approximately 100 min. At the end of the shock period, resting skeletal muscle transmembrane potentials had depolarized from a baseline value of -82 mV to -65 mV; intracellular water had increased by 13%; and intracellular sodium and chloride contents had doubled. Eight rats were then given an infusion of very hypertonic saline (2400 mOsmole/kg, calculated osmolality) in a volume equal to only 10% of the volume of shed blood; another eight rats were given the equivalent amount of sodium and chloride in an isotonic solution (volume equal to 80% of shed blood). The mean arterial pressure in the rats that were given the very hypertonic saline returned to 81 mm Hg, compared to 55 mm Hg in the animals given normal saline. The membrane potentials in the hypertonic group polarized back to near normal- -78 mv--compared to no changes in the normal saline group. Intracellular water returned to preshock values in the hypertonic group as did intracellular sodium and chloride contents. Cellular contents in the normal saline group remained at shock levels. It was concluded that, in rats, infusion of small amounts of hypertonic saline can reverse some of the cellular abnormalities induced by hemorrhagic shock.

Animals↗

PubMed1985

A comparison of several hypertonic solutions for resuscitation of bled sheep.

Small volumes (4 ml/kg) of 2400 mOsm NaCl restore cardiac output and mean arterial pressure to 80% of baseline after hemorrhage (65% of blood volume) in unanesthetized sheep. An equal volume of normal saline is less effective. To identify an optimal hypertonic solution, we screened six 2400 mOsm solutions in 18 randomized experiments in 8 sheep: NaCl, NaHCO3, NaCl/sodium acetate, NaCl/mannitol, NaCl/6% Dextran 70, and glucose. Cardiovascular function, as determined by cardiac output and mean arterial pressure, was restored best with NaCl, NaCl/NaAc, and NaCl/Dex. These three solutions were then evaluated using 18 sheep in 36 experiments. Following a 1-hr baseline period, the sheep were bled to a mean arterial pressure of 50 mm Hg for 2 hr. One of the solutions was then given in a volume of 4 ml/kg over 2 min and the sheep were monitored for 3 hr. Within 3 min of the infusion, cardiac output increased to greater than 100% of baseline for all three solutions. The NaCl-Dex solution sustained a significantly higher cardiac output over the 3-hr observation period than the other solutions. Plasma volume increased for all solutions following infusion. NaCl-Dex maintained plasma volume significantly better than the other solutions. As a further control, an isotonic solution of 6% Dextran 70 in normal saline was studied. It was not as effective as the hypertonic NaCl-Dex in maintaining cardiac output, mean arterial pressure, or plasma volume. Osmolality increased 10% (309 to 326 mOsm/kg H2O), plasma [NA] increased 7% (151 to 161 meq/liter), and plasma [K] decreased from 3.9 to 2.6 meq/liter following the hypertonic infusions. The sheep appeared to tolerate these electrolyte changes well. We conclude that a single bolus infusion of 2400 mOsm NaCl with 6% Dextran 70 best resuscitates sheep that have been subjected to a moderate degree of hemorrhagic shock compared to several other solutions. Its beneficial effects are caused in part by a sustained reestablishment of plasma volume. More studies are needed to document the safety of dextran in the clinical setting of hemorrhagic shock. Small volumes of hypertonic solutions may be valuable in the initial fluid resuscitation of patients in hemorrhagic shock.

Animals↗

PubMed1984

Protein concentration of lymph and interstitial fluid in the rat tail.

Lymph was collected from tail lymphatics of anesthetized rats, subcutaneous interstitial fluid was obtained by implanting nylon wicks, and tendon interstitial fluid was obtained by centrifugation of pieces of tendon. Spontaneous lymph flow rates averaged 70 nl X min-1 X g skin-1. Protein concentrations and colloid osmotic pressures of sampled fluids differed significantly. Tail lymph had the highest protein concentration relative to plasma [lymph-to-plasma ratio 0.71 +/- 0.03 (SE) n = 10], followed by wick fluid (0.62 +/- 0.02, n = 9), with tendon fluid lowest (0.50 +/- 0.03, n = 10). Albumin and immunoglobulin G (IgG) concentrations in samples of tail skin and tendon were assayed by rocket immunoelectrophoresis. Comparison of their distribution volumes at lymph or tendon fluid concentrations, respectively, with interstitial fluid volumes measured as 2-h 51Cr-ethylenediaminetetraacetic acid space minus 5-min 125I-albumin space indicated that 50-60% of the interstitial volume in these tissues is not available for distribution of albumin or IgG. Low lymph flow and high interstitial protein content of rat tail indicate a slow turnover of interstitial protein. This suggests that interstitial washout of protein plays a role in limiting edema only after a sustained or chronic increase in fluid filtration.

Albumins↗

PubMed1984

Effect of nonprotein colloid on postburn edema formation in soft tissues and lung.

We studied the effect of a nonprotein colloid solution--namely low molecular weight dextran (LMWD)--on edema formation in burned and nonburned soft tissue and lung. Adult sheep with lung and bilateral flank lymph fistulas were given a unilateral 25% to 30% full-thickness burn under ketamine anesthesia and followed for 72 hours. Resuscitation (24-hour period) was performed with lactated Ringer solution (LR) (n = 9) or 10% LMWD in saline (n = 8) to restore baseline vascular pressures and cardiac output. Interstitial edema and microvascular protein permeability were monitored by lymph flow (QL) and lymph to plasma protein ratio, respectively. With LR, QL values in nonburned skin and lung were increased twofold to threefold in the first 24 hours, while with LMWD, values remained at baseline. The nonburn edema with LR was due to the burn-induced hypoproteinemia state. The prevention of this process with LMWD was due to the generation of a twofold to threefold increase in the plasma to interstitial colloid osmotic pressure (COP) gradient. Burn QL was increased fivefold in both groups despite a higher COP gradient with LMWD. Net fluid requirements for the first 24 hours were 75 and 35 ml/kg for animals treated with LR and LMWD, respectively. After cessation of dextran administration in the second 24 hours, the COP gradients for the two groups were equal but QL in nonburned skin and net fluid requirements now increased significantly in the LMWD group. The development of nonburn edema was believed to be due to the persistent hypoproteinemic state. We conclude that edema formation in nonburned tissues, which is due to hypoproteinemia, accounts for a substantial amount of the net fluid requirements after thermal injury. This process can be prevented by infusion of a nonprotein colloid as long as the COP gradient is increased. Edema in burned tissue appears to be unaffected by changes in COP.

Animals↗

PubMed1984

Small-volume resuscitation with hypertonic saline (2,400 mOsm/liter) during hemorrhagic shock.

We compared small-volume resuscitation using either normal saline or hypertonic saline (2400 mOsm/liter) during hemorrhagic hypotension. Six unanesthetized sheep were bled to 50 mm Hg mean arterial pressure and maintained for 2 h. During this shock period cardiac output decreased 40-50% of baseline, while total peripheral resistance increased 20-30%. Then the response to a bolus injection of either hypertonic saline or normal saline, randomly chosen, was studied for an additional 2 h. The volume injected was 145-175 ml, equal to 10% of total shed blood volume. After data collection all shed blood was returned. Several days later, the protocol was repeated on each sheep with the alternate solution. After hypertonic saline the mean arterial pressure increased 48 mm Hg to 83% of control; with normal saline, mean arterial pressure increased 26 mm Hg. Cardiac output recovered to 95% of control immediately after infusion of hypertonic saline, while no significant increase was observed with normal saline. Ten minutes after injection of hypertonic saline, plasma volume increased approximately 360 ml, but with normal saline no increase was observed. We conclude that small-volume injection of hypertonic saline can dramatically improve circulatory function during hemorrhagic shock, as evidenced by expansion of plasma volume, increased cardiac output, and reduced peripheral resistance.

Animals↗

PubMed1983

Effects of hypoproteinemia and increased vascular pressure on lung fluid balance in sheep.

We compared the effects of a sustained decrease in plasma oncotic pressure on lung fluid balance with those of an increase in vascular pressure in six unanesthetized sheep. Initial plasma protein concentration of 58.0 +/- 2.2 (SE) mg/ml was quickly reduced to 34.0 +/- 1.4 mg/ml via plasmapheresis and held at this value for 24 h. Red cells were returned with lactated Ringer solution infused at a rate adjusted to maintain central venous pressure; cardiac output and pulmonary vascular pressures also remained at base line. Steady-state lymph flows increased from a base-line value of 8.8 +/- 3.2 to 20.1 +/- 5.6 ml/h, while the lymph-to-plasma protein concentration ratio ( [L/P] ) decreased from 0.65 +/- 0.03 to 0.44 +/- 0.04. Decreased lymph protein resulted in reestablishment of base-line plasma-to-lymph oncotic gradient. The increased lymph flow was not the result of increased filtration forces, since all vascular pressures and the oncotic gradient were unchanged; nor was it due entirely to increased surface area since [L/P] was decreased. The decrease in plasma oncotic pressure, delta pi P, was twice as effective at increasing lymph flow (1.66 ml X h-1 X mmHg-1, delta pi P) as an equivalent increase in microvascular pressure, delta PC, at normal plasma protein concentration (0.82 ml X h-1 X mmHg-1, delta PC). Elevation of microvascular pressure during hypoproteinemia had a greater effect on lymph flow (1.44 ml X h-1 X mmHg-1, delta PC) than at normal plasma protein concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗