scholarly journals BLOOD PLASMA PROTEIN PRODUCTION AS INFLUENCED BY VARIOUS DEGREES OF HYPOPROTEINEMIA AND BY AMINO ACIDS

1941 ◽  
Vol 73 (5) ◽  
pp. 571-580 ◽  
Author(s):  
S. C. Madden ◽  
A. P. Turner ◽  
A. P. Rowe ◽  
G. H. Whipple

When blood plasma proteins are depleted by bleeding with return of the washed red blood cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a uniform plasma protein production on a basal low protein diet. These dogs are clinically normal but their resistance to infection is distinctly below normal. Introduction of variables into this standardized existence gives information relative to plasma protein production. Plasma protein production under these conditions with a plasma protein concentration of 3.5 to 4.2 gm. per cent is relatively constant. As the plasma protein concentration rises the plasma protein removed falls rapidly (Table 1). At 4.6 gm. per cent the protein removed is less than 50 per cent of the amount removed at a plasma protein level of 4.0 gm. per cent. Cystine appears to be an important amino acid for plasma protein formation. This shows in Table 2 and is supported by data coming from published experiments. These experiments related to the factors which control plasma protein production bear on the problems of shock, hemorrhage, and protein wastage and their treatment by plasma injections which hold the attention of surgeons and physiologists at the moment. Again we would emphasize the fluidity of body protein including plasma protein—an ebb and flow between protein depots and plasma protein—a "dynamic equilibrium" of body protein. A discussion of the passage of large protein molecules through cell borders is submitted.

1934 ◽  
Vol 59 (3) ◽  
pp. 269-282 ◽  
Author(s):  
Russell L. Holman ◽  
Earle B. Mahoney ◽  
George H. Whipple

Large amounts of normal blood plasma can be given intravenously to normal dogs over several weeks without causing any significant escape by way of the urine. There appears to be no renal threshold for plasma protein even with high plasma protein concentration (9.7 per cent). Dogs receiving sugar by mouth and plasma by vein can be kept practically in nitrogen equilibrium and it would seem that the injected protein must be utilized by the body. If this can happen in this emergency we may suspect that normally there is a certain amount of "give and take" between body protein and plasma protein. Plasma protein fed by mouth under identical conditions shows the same general reaction as noted with plasma by vein but the urinary nitrogen is a little higher and suggests that the injected protein is utilized a little more completely to form new protein. The difference may be explained as due to deaminization in the case of protein by mouth. During fasting periods the blood plasma proteins are used up and the total circulating protein may even decrease to one-half the normal level. The plasma protein concentration changes but little and the significant change is a shrinkage of plasma volume. All these facts point to a dynamic equilibrium between tissue protein and plasma protein depending upon the physiological needs of the moment. In the absence of food protein the body can use material coming from one body protein to fabricate badly needed protein material of different character.


1940 ◽  
Vol 71 (3) ◽  
pp. 283-297 ◽  
Author(s):  
S. C. Madden ◽  
C. A. Finch ◽  
W. G. Swalbach ◽  
G. H. Whipple

When blood plasma proteins are depleted by bleeding with return of the washed red blood cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a uniform plasma protein production on a basal low protein diet. These dogs are clinically normal. Introduction of variables into their standardized life gives insight into the production of plasma protein. Casein retested as the basal protein in the ration may show high yield of plasma protein, equal to 33 per cent of the protein fed. This equals the potency of liver protein (17 to 33 per cent) and approaches the utilization of plasma protein by mouth (40 per cent). Zein has no effect upon plasma protein regeneration but when it is supplemented with cystine, tryptophane, lysine, and glycine, there is a doubling of the liver basal plasma protein production and a retention of the fed protein nitrogen. Threonine does not modify the above reaction. Liver protein supplemented with cystine, leucine, glutamic acid, and glycine in the basal diet yields double the amount of new formed plasma protein compared with liver alone. This combination is then as potent as plasma protein itself when given by mouth—40 per cent utilization. Tyrosine or lysine, arginine, and isoleucine do not modify the above responses. Methionine is not as effective as cystine in supplementing gelatin and tyrosine to produce plasma protein. Cystine, leucine, and glutamic acid appear to be of primary importance in the building of new plasma protein in these experiments. Plasma protein formation is dependent upon materials coming from the body reserve and from the diet. Given an exhaustion of the reserve store there is very little plasma protein produced during a protein fast (3 to 6 gm. per week). A turpentine abscess does not modify this fasting plasma protein reaction. Homologous plasma given by vein will promptly correct experimental hypoproteinemia due to bleeding. It will maintain nitrogen equilibrium and replenish protein stores. Even during hypoproteinemia plasma protein may promptly pass out of the circulation to supply body needs for protein. Perhaps the most significant concept which derives from all these experiments is the fluidity of the body protein (including plasma protein)—a ready give and take between the protein depots—a "dynamic equilibrium" of body protein.


1941 ◽  
Vol 73 (6) ◽  
pp. 727-743 ◽  
Author(s):  
S. C. Madden ◽  
L. J. Zeldis ◽  
A. D. Hengerer ◽  
L. L. Miller ◽  
A. P. Rowe ◽  
...  

When blood plasma proteins are depleted by bleeding with return of the washed red cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a uniform plasma protein production on a basal diet limited in protein. Such dogs are clinically normal but have a lowered resistance to infection and certain intoxications. Casein digests given by vein or subcutaneously to such plasma depleted dogs are effective in promoting abundant new plasma protein production. Casein digest L by vein is equivalent to whole liver of like protein equivalence by mouth. The ratio of new plasma protein production to protein intake is 20 to 25 per cent in both instances. Casein digest L by vein gives the same response in plasma protein output as the same digest by mouth. Protein digest X by vein requires addition of tryptophane and cysteine to be effective in plasma protein production. The added cysteine sulfur is more than 95 per cent retained by the dog. The speed of digest injection has no effect on its utilization, within the range tested. Casein digest L given by vein to non-depleted dogs is less well utilized than in dogs depleted of plasma protein.


1935 ◽  
Vol 61 (2) ◽  
pp. 261-282 ◽  
Author(s):  
W. T. Pommerenke ◽  
H. B. Slavin ◽  
D. H. Kariher ◽  
G. H. Whipple

When blood plasma proteins are depleted by bleeding, with return of washed red cells (plasmapheresis) it is possible to bring the dog to a steady state of low plasma protein and uniform plasma protein production on a basal diet. Such dogs are excellent test subjects by which the potency of various diet factors for plasma protein regeneration can be measured. To regenerate plasma proteins in any significant amount the depleted dog requires food protein. Some proteins are very potent for new plasma protein production and others are utilized poorly. Beef serum is very potent and its proteins (2.6 gm.) will produce 1 gm. of new plasma protein in the depleted dog—a potency ratio of 2.6. Kidney protein stands at the bottom of our list and the dog needs 21 gm. of kidney protein to regenerate 1 gm. of plasma protein—a potency ratio of 21.0. Some grain proteins approximate the potency of beef serum and may show potency ratios of 2.7 to 4.6. Some of these grain proteins appear to favor the production of globulin more than albumin in the plasma. Skeletal muscle, gizzard (smooth muscle), lactalbumin and egg white fall into a favorable group with a potency ratio of 5.3 to 6.0. Whole liver, liver fractions, casein, and beef heart are a little less potent and present potency ratios of 6.5 to 8.0. Many of these food substances favor the production of albumin more than globulin. Pancreas and salmon muscle show less favorable potency ratios of 19.0 and 15.0 respectively. Fasting periods indicate that these depleted dogs can produce little if any new plasma protein. Iron feeding in some unexplained manner will influence body metabolism so that an excess of plasma protein will be produced. These observations have a bearing on clinical conditions associated with hypoproteinemia and give suggestions for diet aid or control in some of these abnormal states. The make-up of the diet is obviously of great interest and it is possible that protein combinations may be more potent than a single protein or that food potency ratios may differ in health and disease.


1938 ◽  
Vol 67 (5) ◽  
pp. 675-690 ◽  
Author(s):  
S. C. Madden ◽  
W. E. George ◽  
G. S. Waraich ◽  
H. Whipple

When blood plasma proteins are depleted by bleeding, with return of the washed red cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a uniform plasma protein production on a basal low protein diet. These dogs are clinically normal with normal appetite, no anemia and normal nitrogen metabolism. These dogs become test subjects by which various factors relating to plasma protein production may be tested. The normal dog (10 to 13 kg.) has a substantial reserve store of plasma protein building material (10 to 60+ gm.) which requires 2 to 6 weeks plasmapheresis for its complete removal. After this period the dog will produce uniform amounts of plasma protein each week on a fixed basal diet. Dogs previously depleted by plasmapheresis and then permitted to return to normal during a long rest period of many weeks, may show much higher reserve stores of protein building material in subsequent periods of plasma depletion (see Table 1). Under uniform conditions of low protein diet intake when plasmapheresis is discontinued for 2 weeks the plasma protein building material is stored quantitatively in the body and can subsequently be recovered (Table 4) in the next 2 to 3 weeks of plasmapheresis. Given complete depletion of plasma protein building reserve stores the dog can produce very little (2± gm. per week) plasma protein on a protein-free diet. This may be related to the wear and tear of body protein and conservation of these split products. Abscesses produced in a depleted dog during a fast may cause some excess production of plasma protein which is probably related to products of tissue destruction conserved for protein anabolism. Gelatin alone added to the basal diet causes very little plasma protein production but when supplemented by tryptophane gives a large protein output, while tryptophane alone is inert.


1939 ◽  
Vol 69 (5) ◽  
pp. 721-738 ◽  
Author(s):  
S. C. Madden ◽  
W. A. Noehren ◽  
G. S. Waraich ◽  
G. H. Whipple

When blood plasma proteins are depleted by bleeding with return of the washed red blood cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a uniform plasma protein production on a basal low protein diet. These dogs are clinically normal. By the introduction of variables into their standardized existence insight into the formation of plasma proteins can be obtained. The liver basal diet maintains health in such hypoproteinemic dogs during periods as long as a year. 17 to 27 per cent of its protein content (entirely liver protein) is presumably converted into plasma protein. Gelatin alone added to the liver basal diet causes very little if any extra plasma protein production. The addition to gelatin of cystine, or tyrosine, or tryptophane, or of both tyrosine and tryptophane has little or no effect on its potency for plasma protein production. When gelatin is supplemented by cystine and either tryptophane or tyrosine, 25 to 40 per cent of the protein content of the combination is converted into plasma protein—an efficiency equaling that of any protein hitherto tested. Preliminary experiments indicate that methionine cannot substitute for cystine nor can phenylalanine substitute for tyrosine in the efficient combination of gelatin plus cystine plus tyrosine. Laked red blood cells given by vein afford little or no material for plasma protein formation. When the reserve stores of plasma protein building material are exhausted the dog can form little if any plasma protein during protein-free diet periods.


1998 ◽  
Vol 274 (3) ◽  
pp. H937-H944 ◽  
Author(s):  
M. Miyamoto ◽  
D. E. McClure ◽  
E. R. Schertel ◽  
P. J. Andrews ◽  
G. A. Jones ◽  
...  

In previous studies, we observed left ventricular (LV) systolic and diastolic dysfunction in association with interstitial myocardial edema (IME) induced by either coronary venous hypertension (CVH) or lymphatic obstruction. In the present study, we examined the effects of myocardial edema induced by acute hypoproteinemia (HP) on LV systolic and diastolic function. We also combined the methods of HP and CVH (HP-CVH) to determine their combined effects on LV function and myocardial water content (MWC). We used a cell-saving device to lower plasma protein concentration in HP and HP-CVH groups. CVH was induced by inflating the balloon in the coronary sinus. Six control dogs were treated to sham HP. Conductance and micromanometer catheters were used to assess LV function. Contractility, as measured by preload recruitable stroke work, did not change in control or HP groups but declined significantly (14.5%) in the HP-CVH group. The time constant of isovolumic LV pressure decline (τ) increased significantly from baseline by 3 h in the HP (24.8%) and HP-CVH (27.1%) groups. The end-diastolic pressure-volume relationship (stiffness) also increased significantly from baseline by 3 h in the HP (78.6%) and HP-CVH (42.6%) groups. Total plasma protein concentration decreased from 5.2 ± 0.2 g/dl at baseline to 2.5 ± 0.0 g/dl by 3 h in the HP and HP-CVH groups. MWC of the HP (79.8 ± 0.25%) and HP-CVH groups (79.8 ±0.2%) were significantly greater than that of the control group (77.8 ± 0.3%) but not different from one another. In conclusion, hypoproteinemia-induced myocardial edema was associated with diastolic LV dysfunction but not systolic dysfunction. The edema caused by hypoproteinemia was more than twice that produced by our previous models, yet it was not associated with systolic dysfunction. CVH had a negative inotropic effect and no significant influence on MWC. IME may not have the inverse causal relationship with LV contractility that has been previously postulated but appears to have a direct causal association with diastolic stiffness as has been previously demonstrated.


1981 ◽  
Vol 53 (12) ◽  
pp. 1281-1284 ◽  
Author(s):  
G. TORRI ◽  
L. STELLA ◽  
G. PRADELLA ◽  
E. MAESTRONE ◽  
C. MARTANI

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