The Influence of Injections of Homologous Hemoglobin on the Kidneys of Normal and Dehydrated Animals

Lalich, Joseph J.

doi:10.1084/jem.86.2.153

Cited by 28 publications

(16 citation statements)

References 6 publications

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“…The postmortem findings generally agreed with those previously reported (1). An additional finding of considerable interest was minimal to extensive central necrosis of the liver, observed in 3 of 5 rabbits dying in uremia.…”

Section: Results Of Water Deprivation and Intravenous Injections Of 1supporting

confidence: 90%

“…I t has been reported in a previous paper t h a t hemoglobinuric nephrosis can be consistently produced when rabbits are deprived of water prior to repeated intravenous injections of hemoglobin (1). Since dehydration favors the precipitation of pigment casts in the kidney tubules of rabbits given hemoglobin, studies of fluid changes in which sodium thiocyanate dissolves before and after dehydration seemed desirable.…”

Section: T H E I N F L U E N C E O F a V A I L A B L E F L U I D On Tmentioning

confidence: 99%

“…Studies.--The animals which died were autopsied and studied as previously described (1). The rabbits which survived were subjected to surgical 158 FLUID AND HEMOGLOBIN'URIC NEPHROSIS removal of the left kidney I1 to 16 days after the initial injection of hemoglobin.…”

Section: Gross Observations and Histologicmentioning

confidence: 99%

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The Influence of Available Fluid on the Production of Experimental Hemoglobinuric Nephrosis in Rabbits

Lalich

1948

Journal of Experimental Medicine

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The importance of previous dehydration on the production of hemoglobinuric nephrosis is substantiated. Hemoglobinuric nephrosis regularly occurred in rabbits 3 to 16 days following the injections of hemoglobin. Five of 15 animals died of fatal hemoglobinuric nephrosis; the combined kidney weight in these exceeded the weight of the kidneys of control rabbits and of those which survived. Additional observations, not previously made, are focal necrosis of the liver and pulmonary edema in some of the rabbits which died. A relationship was evident between the quantity of available fluid and the severity of the hemoglobinuric nephrosis which developed after injections of hemoglobin.

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Section: Results Of Water Deprivation and Intravenous Injections Of 1supporting

confidence: 90%

Section: T H E I N F L U E N C E O F a V A I L A B L E F L U I D On Tmentioning

confidence: 99%

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The Influence of Available Fluid on the Production of Experimental Hemoglobinuric Nephrosis in Rabbits

Lalich

1948

Journal of Experimental Medicine

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“…Furthermore, Baek et al showed, that administration of exogenous human haptoglobin prevented renal damage after an exchange transfusion with 28-day-old blood in guinea pigs 19 . Additional studies suggest that cell-free hemoglobin causes significant renal damage when it acts as a secondary injury following an initial event that compromises renal function 28,35,45,46 . In the current study, we combined a murine model of hemorrhagic shock-induced renal damage with a transfusion model of stored blood to mimic the multifactorial genesis of kidney injury occurring in clinical settings.…”

Section: Discussionmentioning

confidence: 99%

Haptoglobin or Hemopexin Therapy Prevents Acute Adverse Effects of Resuscitation After Prolonged Storage of Red Cells

et al. 2016

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Background Extracellular hemoglobin and cell-free heme are toxic breakdown products of hemolyzed erythrocytes. Mammals synthesize the scavenger proteins haptoglobin and hemopexin, which bind extracellular hemoglobin and heme respectively. Transfusion of packed red blood cells (PRBCs) is a life-saving therapy for patients with hemorrhagic shock. Because erythrocytes undergo progressive deleterious morphological and biochemical changes during storage, transfusion of PRBCs that have been stored for prolonged intervals (SRBCs; stored for 35–40 days in humans or 14 days in mice) increases plasma levels of cell-free hemoglobin and heme. Therefore, in patients with hemorrhagic shock, perfusion-sensitive organs such as the kidneys are challenged not only by hypoperfusion, but also by the high concentrations of plasma hemoglobin and heme that are associated with the transfusion of SRBCs. Methods To test whether treatment with exogenous human haptoglobin or hemopexin can ameliorate adverse effects of resuscitation with SRBCs after two hours of hemorrhagic shock, mice receiving SRBCs were given a co-infusion of haptoglobin, hemopexin or albumin. Results Treatment with haptoglobin or hemopexin but not albumin improved the survival rate and attenuated SRBC-induced inflammation. Treatment with haptoglobin retained free hemoglobin in the plasma and prevented SRBC-induced hemoglobinuria and kidney injury. In mice resuscitated with fresh PRBCs, treatment with haptoglobin, hemopexin, or albumin did not cause harmful effects. Conclusions In mice the adverse effects of transfusion with SRBCs after hemorrhagic shock are ameliorated by treatment with either haptoglobin or hemopexin. Haptoglobin infusion prevents kidney injury associated with high plasma hemoglobin concentrations after resuscitation with SRBCs. Treatment with the naturally occurring human plasma proteins haptoglobin or hemopexin may have beneficial effects in conditions of severe hemolysis following prolonged hypotension.

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“…One of these animals had intestinal intussusception, the others presumably died of acidosis and dehydration. Rabbits 13 and 28 were (12,20) in which the rabbits were fed rabbit pellets, a larger number (10 of 18 rabbits) in the present study had unusually low available fluid volumes prior to fasting and dehydration. This condition we attribute to the acidotic influence of the diet.…”

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confidence: 68%

The Role of Aciduria in the Development of Hemoglobinuric Nephrosis in Dehydrated Rabbits

Lalich

Schwartz

1950

Journal of Experimental Medicine

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The effect of acid diets, fasting, and dehydration on the urine pH and the kidneys was determined in 11 control animals. Hyaline casts in the collecting tubules and interstitial medullary edema were observed in the 8 that survived. The test rabbits were subjected to the same treatment as the controls but, in addition, received 1.8 gm./kilo of intravenous homologous hemoglobin. Eleven of 18 animals died of hemoglobinuric nephrosis. The rabbits which died of hemoglobinuric nephrosis exhibited significant alterations in two or more of the following: kidney weight, pigment cast accumulation, and elevations of NPN. The theories which have been advanced to explain the pathogenesis of hemoglobinuric nephrosis are evaluated in the light of the present observations. It is proposed on the basis of them that antecedent tubular damage is of primary importance in the pathogenesis of hemoglobinuric nephrosis.

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The Influence of Injections of Homologous Hemoglobin on the Kidneys of Normal and Dehydrated Animals

Cited by 28 publications

References 6 publications

The Influence of Available Fluid on the Production of Experimental Hemoglobinuric Nephrosis in Rabbits

The Influence of Available Fluid on the Production of Experimental Hemoglobinuric Nephrosis in Rabbits

Haptoglobin or Hemopexin Therapy Prevents Acute Adverse Effects of Resuscitation After Prolonged Storage of Red Cells

The Role of Aciduria in the Development of Hemoglobinuric Nephrosis in Dehydrated Rabbits

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