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G S Moss

Publications and source records attributed to G S Moss.

At least 55 records · Page 3Linked to original sources

Hemoglobin solution--from tetramer to polymer.

Efforts to produce a clinically acceptable hemoglobin solution which could function as a temporary oxygen carrier have evolved through several stages. Beginning with the simple tetramer, we have lowered the affinity state by pyridoxylation and then polymerized the modified tetramer. This new substance, polyhemoglobin, has a normal oxygen capacity and a half-life of 38 hours. Issues of nephrotoxicity and immunocompetence after infusion remain to be defined.

Animals↗

Hemoglobin solution--from tetramer to polymer.

Efforts to produce a clinically acceptable hemoglobin solution that could function as a temporary oxygen carrier have evolved through several stages. Beginning with the simple tetramer, we have lowered the affinity state by pyridoxylation and then polymerized the modified tetramer. This new substance, polyhemoglobin, has a normal oxygen capacity and a half-life of 38 hours. Issues of nephrotoxicity and immunocompetence after infusion remain to be defined.

Animals↗

Polymerized pyridoxylated hemoglobin: a red cell substitute with normal oxygen capacity.

Polymerization of pyridoxylated stroma free hemoglobin (poly SFH-P) yields a solution with a normal hemoglobin concentration, normal colloid osmotic pressure (COP), and a suitable P50. In the present study we compared its in vivo O2-carrying capacity and intravascular persistence with those of pyridoxylated hemoglobin (SFH-P), following a partial exchange transfusion (900 ml) in adult baboons (n = 4 in each group). Poly SFH-P in plasma had an O2-carrying capacity that was 77% greater than that achieved with SFH-P (8.0 versus 4.5 vol%). Furthermore, poly SFH-P provided 5.0 vol% at the end of 24 hours and 2.5 vol% at the end of 48 hours; in contrast SFH-P provided only 2.2 vol% at the end of 6 hours and none within 24 hours. A normal COP was maintained throughout the postexchange period with poly SFH-P despite a 68% increase in plasma protein concentration (from 7.1 to 11.9 gm/dl). The plasma P50 of poly SFH-P decreased from 16 torr immediately after exchange to 12 torr at the end of 48 hours. The in vivo rate of conversion to methemoglobin was similar with both solutions. Polymerized pyridoxylated hemoglobin is currently the only modification of hemoglobin solution that approximates the O2-carrying capacity of whole blood and can be infused without altering the plasma COP.

Animals↗

Assessment of a 35% fluorocarbon emulsion.

We have previously reported on the efficacy of a 20% fluorocarbon emulsion (Fluosol-DA, 20%) as an acellular O2 carrier at an FIO2 = 1.0. We are concerned, however, about the potential O2 toxicity that may result from extended exposure to FIO2 = 1.0. The O2 content of the fluorocarbon phase is linearly related to both the FIO2 and the fluorocarbon concentration (Fct). It should therefore be possible to maintain the same O2 content by raising the Fct using a higher fluorocarbon concentration and lowering the FIO2. The purpose of this report is to assess the ability of a 35% fluorocarbon emulsion (Fluosol-DA, 35%) at an FIO2 = 0.6 to support hemodynamics and O2 transport. Five adult baboons were paralyzed, anesthetized, intubated, and mechanically ventilated at FIO2 = 0.6. An isovolemic total exchange transfusion (E.T.) with Fluosol-DA, 35% was performed. Measurements were made at Hct's of 20, 10, 5, and less than 2%. All animals survived the exchange. Total arterial O2 content fell from 17.4 +/- 0.7 to 3.3 +/- 0.2 vol% (p less than 0.01), and O2 delivery decreased from 21.8 +/- 2.2 to 5.1 +/- 0.7 cc/min-kg (p less than 0.01) during the exchange. There was no significant change in MAP, H.R., C.O., or VO2 during the exchange transfusion. Fluosol-DA, 35% maintains normal hemodynamics and O2 transport despite a marked fall in arterial O2 content and total O2 delivery. Fluosol-DA, 35% is thus an effective O2 carrier at the safe FIO2 of 0.6.

Animals↗

Errors in calculating cardiac output due to administration of perfluorochemicals.

Intravenous administration of perfluorochemicals (PFC) will alter the density (rho)B, the gravimetric specific heat (c)B, and the volumetric specific heat (rho c)B of blood. Changes in hematocrit also influence (rho c)B. The calibration constant employed in the determination of cardiac output (CO) by thermal dilution depends inversely on (rho c)B. We estimate the effect of addition of PFC and changes in hematocrit on (rho c)B. Consider blood to be a mixture of red cells, emulsified PFC particles, and plasma. This leads to the equation: (rho c)cB = 0.96 - 0.11Hct - 0.48Fct. Here Hct and Fct are the fractional volume concentrations of red blood cells and PFC, and (rho c)cB is the calculated specific heat based on the actual composition of blood. CO can be corrected for changes in (rho c)B by the equation: (CO)c = [(rho c)sB/(rho c)cB](CO)o. Here (CO)o is the observed cardiac output, (rho c)sB is the standard specific heat of blood used in the calculation of (CO)o, and (CO)c is the corrected cardiac output. We have observed laboratory situations where the correction factors have been as high as 10%.

Cardiac Output↗

Alveolar pressure in fluid-filled occluded lung segments during permeability edema.

In a model of increased hydrostatic pressure pulmonary edema Parker et al. (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 267-276, 1978) demonstrated that alveolar pressure in occluded fluid-filled lung segments was determined primarily by interstitial fluid pressure. Alveolar pressure was subatmospheric at base line and rose with time as hydrostatic pressure was increased and pulmonary edema developed. To further test the hypothesis that fluid-filled alveolar pressure is determined by interstitial pressure we produced permeability pulmonary edema-constant hydrostatic pressure. After intravenous injection of oleic acid in dogs (0.01 mg/kg) the alveolar pressure rose from -6.85 +/- 0.8 to +4.60 +/- 2.28 Torr (P less than 0.001) after 1 h and +6.68 +/- 2.67 Torr (P less than 0.01) after 3 h. This rise in alveolar fluid pressure coincided with the onset of pulmonary edema. Our experiments demonstrate that during permeability pulmonary edema with constant capillary hydrostatic pressures, as with hemodynamic edema, alveolar pressure of fluid-filled segments seems to be determined by interstitial pressures.

Animals↗

Angiotensin-converting enzyme (ACE) in sepsis.

Angiotensin-converting enzyme (ACE) is localized to the luminal surface of pulmonary endothelial cells, where it converts angiotensin I and activates bradykinin. Sepsis may result in endothelial cell dysfunction. We have previously reported that the marked decrease in serum ACE in patients with the Adult Respiratory Distress Syndrome (ARDS) is present only in septic patients. Serum was evaluated in seven baboons made septic by the infusion of live E coli. There was a significant decline in serum ACE from a control value of 41.5 +/- 4.2 to 25.8 +/- 2.2 at 8 h (P less than 0.05), which correlated with the 65 +/- 11 torr decline in mean arterial pressure. There was no change in PaO2. We conclude that sepsis results in marked depletion of serum ACE activity, which corresponds to the decrease in mean arterial pressure, and may reflect reduced bradykinin inactivation.

Animals↗

An appraisal of polymerized pyridoxylated hemoglobin as an acellular oxygen carrier.

Polymerized pyridoxylated hemoglobin provides a means of obtaining an acellular oxygen carrier that can be infused at a normal hemoglobin concentration, with a normal COP and is stable in vivo. We have also shown that rats can survive a total exchange transfusion with poly SFH-P (Sehgal et al, 1980). It thus become a prime candidate for further in vivo assessment of its oxygen transport characteristics.

Blood Substitutes↗

Clinical experience with Fluosol-DA.

In summary, we remain optimistic about the potential value of perfluorochemicals as acellular oxygen carriers. The results of our first patient show that at an FiO2 of 1.0, Fluosol-DA was not necessary. The oxygen content of the plasma alone was adequate, although the FiO2 was at an unsafe level. At the safe FiO2 of 0.6, however, the Fluosol-DA was needed, since the oxygen content of the plasma was inadequate. Fluosol-DA was thus necessary and effective. At an FiO2 = 0.6, the total of the oxygen content of plasma and the oxygen content of Fluosol-DA was adequate. Although these results are encouraging, the temporary nature of this benefit is an important limitation. We hope that the additional data from both our clinical study and the multicenter study will help resolve some of these questions in the future.

Adult↗

Fluorocarbon emulsions: methodology to assess efficacy.

The fluorocarbon emulsion Fluosol-DA (20%) is an acellular O2 carrier that has potential as a red cell substitute. Clinical evaluation of efficacy requires knowledge of the ability of the perfluorochemical (pfc) phase to both load and unload O2. A method is described to measure the oxygen dissolved in the pfc and aqueous phases, and the oxygen chemically bound to hemoglobin, during use of this drug. These O2 contents are used to calculate the contribution of the pfc phase to total O2 delivery and O2 consumption (VO2) and the fractional extraction of O2 in the pfc phase. The technique requires a blood gas analyzer, a microhematocrit centrifuge, and a standard co-oximeter found in many blood gas laboratories. This technique appears to be simple and reliable, and should facilitate the evaluation of efficacy of fluorocarbon emulsions.

Animals↗

Hemoglobin solutions as red cell substitutes.

Hemoglobin solutions have potential as temporary red cell substitutes. Their efficacy has been demonstrated by their ability to maintain life-supporting levels of O2 consumption and CO2 production in animals virtually free of red cells. They do not exhibit major toxic effects, but transient alterations in renal function remain a concern. Cardiac output does not increase in the face of acute anemia associated with isovolemic exchange transfusion with hemoglobin solution. However, cardiac reserve does not diminish significantly after infusion of hemoglobin solution. Alterations in production techniques may lead to a polymerized hemoglobin solution that has a hemoglobin concentration and P50 close to fresh whole blood. Though this development is encouraging, it is clear that no perfect red cell substitute currently is available.

Animals↗