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Biomedical subjects

R C Dennis

Publications and source records attributed to R C Dennis.

At least 37 records · Page 2Linked to original sources

Influence of polycythemia on blood volume and thermoregulation during exercise-heat stress.

We studied the effects of autologous erythrocyte infusion on blood volume and thermoregulation during exercise in the heat. By use of a double-blind design, nine unacclimated male subjects were infused with either 600 ml of a NaCl-glucose-phosphate solution containing a approximately 50% hematocrit (n = 6, reinfusion) or 600 ml of this solution only (n = 3, saline). A heat stress test (HST) was attempted approximately 2-wk pre- and 48-h postinfusion during the late spring months. After 30 min of rest in a 20 degrees C antechamber, the HST consisted of a 120-min exposure (2 repeats of 15 min rest and 45 min treadmill walking) in a hot (35 degrees C, 45% rh) environment while euhydrated. Erythrocyte volume (RCV, 51Cr) and plasma volume (PV, 125I) were measured 24 h before each HST, and maximal O2 uptake (VO2max) was measured 24 h after each HST. Generally, no significant effects were found for the saline group. For the reinfusion group, RCV (11%, P less than 0.01) and VO2max (11%, P less than 0.05) increased after infusion, and the following observations were made: 1) the increased RCV was associated with a reduction in PV to maintain the same blood volume as during the preinfusion measurements; 2) polycythemia reduced total circulating protein but did not alter F-cell ratio, plasma osmolality, plasma protein content, or plasma lactate at rest or during exercise-heat stress; 3) polycythemia did not change the volume of fluid entering the intravascular space from rest to exercise-heat stress; and 4) polycythemia tended to reduce the rate of heat storage during exercise-heat stress.

Blood Proteins↗

Effects of granulocytopenia on the hemodynamic responses of dogs during E. coli bacteremia.

In both neutropenic and normal dogs a significant and sustained fall in mean arterial pressure (MAP) occurred within 2 h (P less than .01) of the onset of E. coli bacteremia. The MAP remained depressed (P less than .001) in the neutropenic dogs while it increased to normal by 4 h in the control dogs. The fall in MAP was primarily related to a fall in total peripheral resistance (TPR). Although myocardial performance curves declined in both groups over the 4-h period, cardiac index (CI) and left ventricular stroke work index (LVSWI) were not significantly different from baseline in either group; nor was LV filling as assessed by the pulmonary artery wedge pressure (PAWP). No significant differences between groups were demonstrated between the mean pulmonary vascular resistance (PVR), dead space, shunt, or oncotic pressure for either group. A significant (P less than .01) percent reduction of arterial PO2 (PaO2) occurred in the neutropenic dogs. The pH of both groups fell during the course of the experiment and was significantly lower (P less than .02) in the neutropenic dogs at the termination of the study. A similar percent fall in platelet count, factor VIII, and fibrinogen levels was observed in both groups. Circulating endotoxin levels were paradoxically higher in normal animals and did not correlate with any hemodynamic alteration in either group--except that the earlier, higher endotoxin levels in the normal animals were associated with a more rapid decline in myocardial performance. However, the vasodilation of the neutropenic group was clearly related to the higher level of E. coli circulating since the concentration of E. coli in both groups at 4 h was significantly inversely correlated with the MAP (P less than .001).

Agranulocytosis↗

Elite special forces: physiological description and ergogenic influence of blood reinfusion.

We measured the physical exercise capabilities of U.S. Army Special Forces soldiers (male) and determined the subsequent ergogenic influence of autologous blood reinfusion. Twelve subjects (Ss) completed maximal exercise treadmill testing in a comfortable (Ta = 20 degrees C, Tdp = 9 degrees C) environment. Six Ss were later transfused with a 600 ml autologous red blood cell (50% Hct) NaCl glucose-phosphate solution and completed identical maximal exercise tests 3 and 10 d posttransfusion. Pretransfusion, the 12 Ss had a maximal oxygen uptake (VO2max) of 4.36 +/- 0.56 L . min-1 and 55 +/- 4 ml . kg-1 . min-1 with a heart rate of 188 +/- 10 b . min-1 and ventilatory equivalent for oxygen of 37 +/- 3. For the 6 reinfused Ss, hemoglobin and red cell volume (RCV) increased by 10% (p less than 0.05) and 11% (p less than 0.05), respectively, posttransfusion. Reinfusion increased (p less than 0.05) VO2max from 4.28 +/- 0.22 L . min-1 (54 +/- 5 ml . kg-1 . min-1) to 4.75 +/- 0.42 L . min-1 (60 +/- 6 ml . kg-1 . min-1) and 4.63 +/- 0.21 L . min-1 (59 +/- 6 ml . kg-1 . min-1) at 3 and 10 d posttransfusion, respectively. No significant relationship was found between the individual change in RCV and VO2max values pre- to posttransfusion. We conclude that Special Forces soldiers have high levels of aerobic fitness that can be further increased by blood reinfusion for at least 10 d.

Adult↗

Coronary constrictor effect of stroma-free hemoglobin solutions.

A coronary vasoconstrictor effect of human stroma-free hemoglobin (SFH) was identified in isolated rabbit hearts perfused with Krebs-Henseleit buffer or whole rabbit blood at a constant coronary flow rate. In buffer-perfused hearts, SFH in concentrations of 5 to 200 mg/dl produced dose-related increases of coronary perfusion pressure. At a concentration of 150 mg/dl, SFH, equilibrated with CO to form carboxyhemoglobin, caused an increase in perfusion pressure (55 +/- 7 mmHg), similar to that observed with oxyhemoglobin (57 +/- 6 mmHg); addition of potassium ferricyanide to form methemoglobin reduced the increase of perfusion pressure to 34 +/- 5 mmHg (P less than 0.05). The vasoconstrictor activity could not be eliminated by dialyzing against the perfusion buffer. Human SFH prepared by different methods had similar vasoconstrictor activity. Rabbit SFH and human SFH were equi-effective in the rabbit heart. Less constrictor activity of SFH was evident in rat and guinea pig heart. Polymerized, pyridoxalated SFH had greatly reduced constrictor effect compared with unmodified or pyridoxalated tetramer SFH. In blood-perfused hearts, increasing plasma hemoglobin to 1.6 +/- 0.1 g/dl, without changing total hemoglobin or arterial O2 content, increased coronary perfusion pressure by 36 +/- 13 mmHg (P less than 0.05). We conclude that stroma-free hemoglobin solutions exert a coronary vasoconstrictor effect that is unrelated to O2 delivery.

Animals↗

Effect of sample dilutions on arterial blood gas determinations.

A study was undertaken to determine the blood gas effects of incompletely purging heparinized saline flush solution from an indwelling arterial catheter and pressure tubing. Hematocrit and blood gases were measured after withdrawing 0, 2, 4, 6, 8, and 10 ml of flush-blood solutions before sampling from a 20-ga radial artery catheter and 7-ft pressure tubing and stopcock. The pH and hematocrit were nearly unchanged between purging volumes of 8 and 10 ml. The PaO2 had a 2.4% error, while the PaCO2 had a 4.4% error. Because there is no standard arterial line setup, it is recommended that each ICU undertake a similar study to determine the optimal volume of aspirated flush-blood solution before blood gas sampling, in order to achieve accurate blood gas results and minimize blood waste.

Blood Gas Analysis↗

Effect of erythrocyte storage and oxyhemoglobin affinity changes on cardiac function.

Storage of blood can depress erythrocyte 2,3-diphosphoglycerate (DPG) levels and thereby increase oxyhemoglobin affinity and potentially decrease capillary-to-tissue oxygen transport. We measured myocardial function and metabolism in isolated rabbit hearts with fixed coronary flow under basal conditions and during isoproterenol stress at 37 and 30 degrees C, comparing high and low oxyhemoglobin affinity (OHA) erythrocytes. The high OHA state resulted from standard storage conditions, which caused depressed values of DPG and P50 (the oxygen tension at which hemoglobin is 50% saturated). The low OHA erythrocytes were initially stored and then underwent biochemical treatment to restore the DPG and P50 values to normal. The low OHA cells released more oxygen, and myocardial oxygen consumption and contractile function were increased relative to the high OHA cells during both the basal and stress states at both 37 and 30 degrees C. These observations may be relevant for patients with limited coronary flow when such patients receive large transfusions of stored blood.

Animals↗

Cardiopulmonary function following transfusion of three red blood cell products in elective abdominal aortic aneurysmectomy.

In order to evaluate the importance of red cell O(2) affinity of transfused blood on cardiac performance and adverse effects of transfusion on lung function, a prospective double-blind protocol was used in 27 patients undergoing abdominal aortic aneurysmectomy. Three types of blood were administered: packed red cells (PC), washed red cells (WC) and high 2,3 DPG red cells (2,3 DPG). An average of 4.5 units of blood was used per patient. Transfusion of 2,3 DPG blood resulted in maintenance of in vivo P(50) during surgery and an increase to 31.2 torr after operation (p < 0.001). An intraoperative fall in in vivo P(50) to 23.2 +/- 2.0 torr was observed in patients who were transfused with PC (p < 0.001) and to 25.1 +/- 2.6 torr with WC (p < 0.005). A fall in body temperature averaging 2.2 C intraoperatively was noticed in all three groups. After operation, in vitro P(50) decreased in patients transfused with PC (p < 0.005) and WC (p < 0.005) while it remained unchanged in the high 2,3 DPG group. This was consistent with the decrease of red cell 2,3 DPG in the PC (p < 0.001) and WC groups (p < 0.01) and maintenance in the 2,3 DPG group. Left ventricular stroke work and volume loading Starling type myocardial performance curves were similar for the three groups. Microaggregates measured by Coulter counting and screen filtration pressure were the same for all three products in samples drawn on both sides of the 40 microm transfusion filter. There was no relationship of transfusion volumes or type of blood product to changes in lung function (physiologic shunting, dynamic compliance and pulmonary arterial pressure) in the three groups of patients. The false negative, beta, error of missing a true 25% difference was less than 10%. It is concluded that 2,3 DPG enriched red cells improved oxygen availability, but that a 4.5 unit transfusion of any of the three blood products did not influence lung function or myocardial performance following aneurysmectomy.

2,3-Diphosphoglycerate↗

Improved oxygen delivery to the myocardium during hypothermia by perfusion with 2,3 DPG-enriched red blood cells.

The oxygen affinity of red cells increases stepwise with temperature reductions below 37 degrees C. In vitro studies demonstrated that biochemically modified red cells with increased 2,3 diphosphoglycerate (2,3 DPG) (150% and 250% of normal) exhibited significantly less oxygen affinity at 24 degrees C than did unmodified cells. At 15 degrees C, significant attenuation of affinity was observed with 250%, but not 150%, of normal 2,3 DPG cells. Measurements made of isolated fibrillating dog hearts during perfusion at 24 degrees C alternately with unmodified (80% of normal 2,3 DPG) and modified (300% of normal 2,3 DPG) red cells demonstrated significantly greater oxygen consumption, higher coronary sinus partial pressures of oxygen and carbon dioxide, higher in vitro P50 values, and lower arterial and coronary sinus lactate levels during perfusion with modified as compared with unmodified cells. This evidence, indicating improved oxygen delivery to hypothermic dog hearts by red cells with 300% of normal 2,3 DPG activity, suggests that high 2,3 DPG cells might protect myocardial tissue in patients undergoing hypothermic cardiac operation.

Animals↗

Comparative evaluation of new fine-screen filters: effects on blood flow rate and microaggregate removal.

Fine-screen filters were studied in a simulated clinical situation wherein ten units of outdated concentrated erythrocytes were rapidly transfused per filter to determine flow rates and effectivenesses of debris removal. Preliminary studies to evaluate flow rates with outdated whole blood indicated that the Bentley PFF-100, Fenwal 4C9003, and Biotest MF-10 fine-screen filters allowed flow rates sufficient to justify further detailed testing. For comparative purposes, the filter the authors have used clinically, the Pall Ultipor 40-micrometers filter, was studied again. As many as ten units of outdated, concentrated erythrocytes (hematocrits 75--85 per cent) were infused through each of the fine-screen filters at 300 torr pressure. All filters (except one of five Pall filters) accepted all ten units. The Bentley PFF-100 filter allowed the highest flow rates, such that the tenth unit of erythrocytes required 5 +/- 3 min (1 SD) to pass the filter. The Biotest MF-10, Bentley PFF-100 and Fenwal 4C9003 filters retained more debris/g erythrocytes, decreased screen filtration pressure, and eliminated more particulate matter (as determined by Coulter counter testing) than did the Pall Ultipor filter. When three or more units of blood are transfused, any of the four filters tested is cost-effective when compared with the current 170-micrometer standard transfusion filter.

Blood Flow Velocity↗

Measuring percent oxygen saturation of hemoglobin, percent carboxyhemoglobin and methemoglobin, and concentrations of total hemoglobin and oxygen in blood of man, dog, and baboon.

We used an automated four-wavelength spectrometer to measure the concentration of total hemoglobin, percent oxyhemoglobin, carboxyhemoglobin, and methemoglobin, and concentration of oxygen bound to hemoglobin in the blood of humans, dogs, and baboons under clinical and various experimental conditions. Measurements of total hemoglobin and methemoglobin with this simple method were comparable to those with standard spectrometric procedures. Carboxyhemoglobin measurements were comparable to those made with gas chromatography, and measurements of oxygen content were comparable to those made with the galvanic cell method. The new instrument is as accurate as the comparison methods used to evaluate it in all parameters, is reliable, and measurements take only 63 s per sample. In addition, it requires minimal operator training, infrequent need for calibration, and no sample preparation.

Animals↗

In vitro measurement of P50--the pH correction, and use of frozen red blood cells as controls.

The Unicam Spectrophotometer, the IL 282 CO-Oximeter, and the Hemoscan were used to measure the in vitro P50 using 1, 20--45, and 50% hematocrit values of red blood cells suspended in autologous plasma or phosphate buffered saline at pH of 6.7--7.7. The relation between pH and P50 was a linear correlation for washed red blood cells by all three methods whereas the relation between pH and P50 was a log correlation for red blood cells in plasma. Multiple units of red blood cells with low 2,3 diphosphoglycerate (2,3 DPG) and increased affinity for oxygen, with normal 2,3 DPG and normal affinity for oxygen, and above normal 2,3 DPG and decreased affinity for oxygen, were frozen in 10 ml aliquots with 40% w/v glycerol and maintained at -80 degrees C. One tube of each level of 2.3 DPG was thawed, washed, and suspended in buffer daily to yield P50 values of 17.5 +/- 0.67, 29.7 +/- 0.92, or 41.2 +/- 0.72 torr at pH 7.2 in order to have a control of both instrumentation and personnel.

Diphosphoglyceric Acids↗

Human red blood cells with normal or improved oxygen transport function prepared and frozen in the primary polyvinyl chloride plastic blood collection container.

This is a report a a new system for freezing human red blood cells in the same polyvinyl chloride plastic container in which the blood is collected and separated into components. This polyvinyl chloride plastic collection bag with integrally attached transfer packs for blood collection, component separation, red blood cell biochemical modification, freezing, storage, and post-thaw dilution before washing, represents a major advancement in the freeze-preservation process. The label with the donor's blood type and identification number affixed to the bag at the time of collection remains in place throughout the freezing and thawing process. The transfused red blood cells are of superior quality, and the processing cost is less than with other methods of freeze-preservation. There is a lower risk of contamination with these red blood cells because manipulation of the product is kept at a minimum. "Rejuvenation", a bioengineering process by which outdated red blood cells can be salvaged, can be incorporated into the preservation process using one of the attached transfer packs of the primary collection bag. This process has been introduced as a possible means of alleviating the dramatic blood shortages which occur periodically. Red blood cells may also be "rejuvenated" after storage in the liquid state to increase their 2,3 DPG and ATP levels to 150 to 200% of normal, and these red blood cells with improved oxygen transport function have been administered to anemic patients with and without cardiopulmonary insufficiency, patients undergoing cardiopulmonary bypass and treatment with hypothermia during cardiac surgery, and in instances where nonhemolytic transfusion reactions might be expected.

Adenosine Triphosphate↗

Transfusion of 2,3 DPG-enriched red blood cells to improve cardiac function.

Attempts were made to enhance oxygen availability in patients undergoing coronary artery bypass operations by transfusing red blood cells enriched in 2,3 diphosphoglycerate (2,3 DPG) to 150% of normal. In this study of 22 patients, 11 received red blood cells with high 2,3 DPG levels and 11 received red blood cells with 70% of normal 2,3 DPG levels (control). Immediately following cardiopulmonary bypass the 11 patients who received high 2,3 DPG red blood cells had a P50 value of 31.6 mm Hg; the value in control patients was 28.3 mm Hg (p less than 0.05). Oxygen consumption values were 135 and 106 ml/min/m2, respectively (p less than 0.05). Mixed venous oxygen tensions were similar in the two groups, but the arteriovenous content difference was higher in the high 2,3 DPG group (p less than 0.05). Cardiac indices increased significantly in response to a fluid load in the high 2,3 DPG group compared with controls at comparable filling pressures. We believe the improved myocardial performance in response to a fluid challenge is a result of increased oxygen availability.

Blood Transfusion↗