Dapsone-associated Heinz body hemolytic anemia in a Cambodian woman with hemoglobin E trait

A Cambodian woman with hemoglobin E trait (AE) and leprosy developed a Heinz body hemolytic anemia while taking a dose of dapsone (50 mg/day) not usually associated with clinical hemolysis. Her red blood cells (RBCs) had increased incubated Heinz body formation, decreased reduced glutathione (GSH), and decreased GSH stability. The pentose phosphate shunt activity of the dapsone-exposed AE RBCs was increased compared to normal RBCs. Although the AE RBCs from an individual not taking dapsone had increased incubated Heinz body formation, the GSH content and GSH stability were normal. The pentose phosphate shunt activity of the non-dapsone-exposed AE RBCs was decreased compared to normal RBCs. Thus, AE RBCs appear to have an increased sensitivity to oxidant stress both in vitro and in vivo, since dapsone does not cause hemolytic anemia at this dose in hematologically normal individuals. Given the influx of Southeast Asians into the United States, oxidant medications should be used with caution, especially if an infection is present, in individuals of ethnic backgrounds that have an increased prevalence of hemoglobin E.     

Increased Heinz body formation and impaired erythrocyte pentose phosphate shunt function during pregnancy

The erythrocytes of 90 pregnant women were evaluated for the presence of in vivo or in vitro oxidant damage. The reduced glutathione (P less than 0.005) and the membrane reduced sulfhydryl (P less than 0.001) concentrations were decreased in fresh erythrocytes. Following incubation with acetylphenylhydrazine, Heinz body formation was significantly increased (P less than 0.001). Both the increase in Heinz body formation and the reduction in membrane reduced sulfhydryl content correlated strongly with duration of pregnancy. Glucose consumption was significantly decreased before, but not after, new methylene blue stimulation. Pentose phosphate shunt activity was impaired both before (P less than 0.05) and after (P less than 0.001) stimulation. No changes were observed in pentose phosphate recycling. The only alteration observed in the activity of the enzymes of the pentose shunt was an elevation of 6-phosphogluconate dehydrogenase activity. Although the clinical significance of these findings remains to be determined, medications with an oxidant potential should be used judiciously during gestation.     

Inhibition of the pentose phosphate shunt by lead: a potential mechanism for hemolysis in lead poisoning

Recent investigations have disclosed a decrease in pentose phosphate shunt activity in hereditary pyrimidine 5'-nucleotidase deficiency. Clinical lead poisoning is associated with an acquired decrease in pyrimidine 5'-nucleotidase activity. The current investigations were undertaken (1) to determine if pentose shunt activity was decreased in erythrocytes exposed to lead, and (2) to compare the mechanism of inhibition to that seen in hereditary pyrimidine 5'-nucleotidase deficiency. Normal erythrocytes incubated with lead acetate in vitro demonstrated increased Heinz body formation, decreased reduced glutathione, a positive ascorbate cyanide test, and a reversible suppression of pentose shunt activity in the intact erythrocyte. Lead acetate added to normal red cell hemolysates markedly inhibited the activities of glucose-6-phosphate dehydrogenase (G6PD) and phosphofructokinase. The mean Kis of lead for glucose-6-phosphate and nicotinamide adenine dinucleotide phosphate (NADP) for G6PD were 1.5 microM and 2.1 microM, respectively, which is within the range of intraerythrocytic lead concentrations found in clinical lead poisoning. Magnesium enhanced the ability of lead to inhibit G6PD. Thus, the shortened erythrocyte survival in lead poisoning appears to be due, in part, to increased oxidant sensitivity secondary to inhibition of G6PD and the pentose shunt. The mechanism of shunt inhibition is, in part, similar to that seen in hereditary pyrimidine 5'-nucleotidase deficiency.     

Impaired antioxidant defense in hemoglobin E-containing erythrocytes: A mechanism protective against malaria?

Red blood cell (RBC) antioxidant defense was investigated in eight individuals with hemoglobin E (Six EE and two E-B⁺ thalassemia) and compared to that in six individuals with thalassemia and ten normal subjects. Individuals with hemoglobin E had increased incubated Heinz body formation (68% ± 18%; p < 0.001) compared to normal and thalassemic RBC (10% ± 2% and 11% ± 5%, respectively). Stimulated pentose phosphate shunt activity was increased in the thalassemic and decreased in the hemoglobin E RBC as compared to normal. The 2,3-diphosphoglycerate (DPG) content of the EE RBC was increased to 5.59 ± 0.69 μmol/ml RBC as compared to normal (4.51 ± 0.77; p < 0.001). In the EE RBC, there was a direct correlation between Heinz body formation and DPG content (r = 0.73). Ascorbic and dehydroascorbic acid (0.1 and 1.0 mM) were able to decrease the degree of Heinz body formation in the hemoglobin E RBC. Ascorbic acid (0.1 mM) prolonged the response of the pentose shunt. Thus impaired antioxidant defense may account for the persistence of the hemoglobin E gene in areas where malaria is endemic. Oxidant medications should be used with caution in individuals of Southeast Asian origin.     

Hemolytic anemia in hereditary pyrimidine 5'-nucleotidase deficiency: nucleotide inhibition of G6PD and the pentose phosphate shunt

We evaluated the erythrocytes of two patients with hereditary pyrimidine 5'-nucleotidase deficiency. Significant findings included an increased reduced glutathione content, increased incubated Heinz body formation, a positive ascorbate cyanide test, and decreased intraerythrocytic pH. The pentose phosphate shunt activity of the patients' red cells as measured by the release of 14CO2 from 14C-1- glucose was decreased compared to high reticulocyte controls. Glucose-6- phosphate dehydrogenase (G6PD) activity in hemolysates from control erythrocytes was inhibited 43% by 5.5 mM cytidine 5'-triphosphate (CTP) and 50% by 5.5 mM in uridine 5'-triphosphate (UTP) at pH 7.1. CTP was a competitive inhibitor for G6P (Ki = 1.7 mM) and a noncompetitive inhibitor for NADP+ (Ki = 7.8 mM). Glutathione peroxidase, glutathione reductase, and 6-phosphogluconate dehydrogenase were not affected by these compounds. Pentose phosphate shunt activity in control red cell hemolysate at pH 7.1 was inhibited to a similar degree by 5.5 mM CTP or UTP. Since the intracellular concentrations of G6P and NADP+ are below their KmS for G6PD, these data suggest that high concentrations of pyrimidine 5'-nucleotides depress pentose phosphate shunt activity in pyrimidin 5'-nucleotidase deficiency. Thus, this impairment of the pentose phosphate pathway appears to contribute to the pathogenesis of hemolysis in pyrimidine 5'-nucleotidase deficiency hemolytic anemia.     

Metabolic effects of antisickling amounts of nitrogen and nor-nitrogen mustard on rabbit and human erythrocytes

Nitrogen mustard (NH2) and Nor-nitrogen mustard (Nor-HN2) both inhibit the polymerization of deoxyhemoglobin S in solution and in intact erythrocytes. Metabolic studies were undertaken to determine the feasability of an extracorporeal treatment with these or related agents. Glucose utilization, hexose monophosphate shunt activity, methemoglobin reduction, and incubation with acetylphenylhydrazine for Heinz body formation were performed, as well as specific assays for hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase, glutathione reductase, ATP, reduced glutathione (GSH), and survival of autologous mustard-treated cells in rabbits. HN2 was found to enter red cells rapidly and bind to intracellular contents. Metabolic studies revealed no significant inhibition or alteration of function by Nor-HN2 at 10 mg/ml of whole blood. Rabbit red cell survival was also normal. HN2, however, inhibited glutathione reductase and blocked the free sulfhydryl group of GSH by forming serveral addition products of alkylated GSH. Heinz body test with acetylphenylhydrazine became positive in HN2-treated cells, and rabbit red cell survival was shortened considerably in the concentration range used to inhibit sickling. Ascorbic acid stimulation of the hexose shunt pathway was inhibited by HN2, but methylene blue stimulation remained unaffected. 14-C-HN2 remains bound to red cells in vivo, and the disappearance of radioactivity is similar to that found with 14-C-DFP (disopropylfluorophosphate). Oxygen affinity of both HN2 and Nor-HN2 treated human red cells remains virtually the same as that found in control samples. It is concluded that Nor-HN2 may be a suitable agent for an extracorporeal therapy, and that each mustard needs to be evaluated individually for its antisickling effects and its suitability for extracorporeal use.     

Pyrimidine 5'-nucleotidase and oxidative damage in red blood cells transfused to beta-thalassemic children

Pyrimidine 5' nucleotidase (P5'N) acquired deficiency has been found in several hematologic disorders including beta-thalassemia. Our previous studies suggested that the aldehydes produced during membrane lipid peroxidation could play a role in P5'N inactivation in thalassemia. To evaluate the effects of the thalassemic "environment" on transfused red blood cells, we tested P5'N, pyruvate kinase (PK), glucose 6-phosphate dehydrogenase (G-6PD) activity, creatine content, reduced glutathione (GSH) levels and the hexose monophosphate shunt (HMS) in the red cells of homozygous transfusion-dependent thalassemic children, immediately following and again one month after transfusion. In red cells aged in thalassemic plasma, P5'N activity, creatine level, GSH stability and stimulated HMS flux were significantly decreased. These results fit in with the presence in thalassemic plasma of molecules interfering with antioxidant red cell defenses. Normal red cells incubated in thalassemic plasma display a significant stimulation of the basal HMS (p less than 0.01). Transfused red cell metabolic alterations could be explained by the plasma pro-oxidant activity and may contribute to reducing red cell survival in the host plasma.     

Antioxidants in sickle cell disease: the in vitro effects of ascorbic acid

The authors examined the ability of antioxidants to prevent in vitro oxidant damage to the sickle red blood cell (RBC). One millimolar ascorbic acid and alpha-mercaptopropionylglycine significantly (p less than 0.005) protected against RBC Heinz body formation during incubation with acetylphenylhydrazine, while cysteine, cysteamine, and methionine did not. The effect of ascorbic acid was concentration dependent with concentrations as low as 0.1 mM having significant antioxidant effects. Ascorbic acid protected the RBC against hydrogen peroxide induced hemolysis as well (p less than 0.05). Ascorbic acid had a significant stimulatory effect on the rate of glucose oxidation by the pentose phosphate shunt (PPS), especially in the sickle RBC. Ascorbic acid did not protect the RBC from a patient with chronic hemolytic anemia due to G6PDTorrance from Heinz body formation, suggesting that an intact PPS is necessary for ascorbic acid to express its antioxidant properties. These data suggest that clinical trials should be undertaken to examine the efficacy of ascorbic acid in the treatment of SCD.     

Abnormal erythrocyte metabolism in hepatic disease.

Erythrocyte (RBC) metabolic studies were done on 114 patients with severe hepatic disease. Heinz body formation after incubation of RBCs with acetyl phenylhydrazine was found to be significantly higher in patients than in controls. RBC-reduced glutathione levels were lower than those of controls both before and after incubation with acetyl phenylhydrazine, and patients with the highest Heinz body counts had the lowest reduced glutathione levels. RBC methylene blue-stimulated hexose monophosphate (HMP) shunt metabolism and glucose recycling through the shunt were significantly lower in patients with active hepatic disease than in controls. There was no difference in resting HMP shunt activity or in resting recycling of glucose. Despite impairment of shunt metabolism, total glucose consumption was greater in patients than in controls. The patients with the lowest stimulated HMP shunt metabolism and glucose recycling had the highest Heinz body counts, lowest reduced glutathione, and highest total glucose consumption. A continuum of abnormal shunt metabolism was seen, from a mild reduction of stimulated HMP shunt activity to a severe combined decrease in both the HMP shunt and glucose recycling. When measured, glutathione reductase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, and transketolase were normal or increased. Sequential studies were done on 11 patients who had abnormal metabolic studies. Coincident with improvement of HMP shunt metabolism, the Heinz body counts became lower, reduced glutathione higher, hematocrit higher, and liver function improved. Impaired HMP shunt metabolism appears to be a common, acquired RBC abnormality in patients with severe, active liver disease.     

Effects of Oxygen on Red Cells during Liquid Storage at +4°C

Red cells collected in CPD and suspended in SAGM medium were stored in plastic (PVC) containers for 42 days at +4 degrees C. Comparison was made between aerobic storage (normal air exposure) and anaerobic storage (exposure to nitrogen gas). The air-exposed units showed a strong increase in pO2 and oxygen saturation as a result of oxygen penetration into the bags from outside. This resulted in a decrease in ATP and adenylate energy charge, a slower metabolization of adenine and hypoxanthine to AMP and IMP, respectively, and a faster decrease in red cell fluidity. To explain the findings it is concluded that aerobic storage causes an increased need of high-energy phosphate groups, possibly used for replacement of the phospholipid membrane bilayer or in repair of phosphate bonds in the cytoskeleton. It is further proposed that a slight formation of hydrogen peroxide from free oxygen radicals moderately increases the oxidation of reduced (GSH) to oxidized (GSSG) glutathione and slightly enhances the need for reduced nicotinamide-adenine dinucleotides mainly provided by increased flux through the pentose phosphate shunt.     

Red cell metabolism in hereditary pyrimidine 5''-nucleotidase deficiency: effect of magnesium

Since pyrimidine nucleotides avidly bind magnesium, we tested the hypothesis that the haemolytic anaemia in hereditary pyrimidine 5'-nucleotidase (P5N) deficiency is due to a state of functional magnesium depletion in the red cell (RBC). In haemolysates from normal subjects, cytidine triphosphate (CTP) inhibited the activity of pyruvate kinase in a competitive manner for magnesium. The CTP Ki was 0.4 mmol/l. CTP inhibited the activity of hexokinase in a competitive manner for ATP (Mg-ATP2-) with a Ki of 4 mmol/l. The inhibitory effect of CTP on both enzymes was overcome by increasing the magnesium content of the test system. Since CTP appeared to inhibit enzymes which required magnesium as a cofactor or Mg-ATP2- as a substrate, we tested the effect of exogenous magnesium on the metabolism of P5N deficient RBC. The autohaemolysis test, the incubated Heinz body assay and the rate of glucose oxidation by the pentose phosphate shunt were abnormal in the intact RBC from a patient with hereditary P5N deficiency. The addition of MgCl2 (6-10 mmol/l) did not improve these abnormal in vitro measures of metabolism in the P5N deficient RBC. This lack of effect of exogenous magnesium may be due to the slow uptake of magnesium by the human RBC.     

Progressive dysfunction of monocytes associated with iron overload and age in patients with thalassemia major

We evaluated phagocytic and lytic activities of peripheral blood monocytes (PBMo) from patients with thalassemia major (ThP) using C pseudotropicalis as the target. PBMo from ThP showed decreased lytic activity (P less than .001), whereas the phagocytic activity did not differ from that of the controls. Significant inverse correlations were found between lytic activity of PBMo and age of patients (r2 = .47; P less than .01) and also between lytic activity and serum ferritin levels (r2 = .65; P less than .001). No association was found between lytic activity and other variables (blood transfusion regimens, therapy with desferrioxamine, liver damage, and the presence of sHBAg). Splenectomy showed no positive effect on PBMo functions from ThP. Our results suggest that PBMo from ThP have an intracellular defect in their microbicidal mechanisms associated with iron overload. This cell dysfunction could be responsible, at least in part, for the increased susceptibility to infections reported in ThP.     

The Effect of the Nitrite Ion on Intact Human Erythrocytes

The mode of action of the nitrite ion on intact human erythrocytes has beeninvestigated under varying experimental conditions. Nitrite appeared to actdirectly to cause methemoglobin formation and GSH depletion. Evidencewas presented to show that such depletion does not occur in the presence ofa normal and active pentose phosphate pathway, and to suggest that methemoglobin formation buffers the erythrocyte against nitrite-induced oxidationof GSH.

Both in the presence and absence of glucose, nitrite in high concentrationwas found to cause increased rates of oxidative destruction of hemoglobinwith Heinz body formation, and of loss of osmotic integrity. It was suggestedthat nitrite acts by "simple" oxidation of the -SH groups of globin and othererythrocytic components, and possibly by causing deamination of cellularproteins.

The results were discussed, with reference to the significance of cellularprotective mechanisms under evolutionary or environmental conditions whichinvolve intermittent exposure to high concentrations of the nitrite ion.

Submitted on February 6, 1962 Accepted on July 3, 1962     

Elevated glutathione accelerates oxidative damage to erythrocytes produced by aromatic disulfide

It has been shown that certain dogs have erythrocytes characterized by an inherited high concentration of reduced glutathione (GSH), five to seven times the normal level (high-GSH RBCs). We examined whether increased GSH in dog erythrocytes leads to increased protection against oxidative damage induced by acetylphenylhydrazine (APH) and/or 4-aminophenyl disulfide (4-AD). When erythrocytes were incubated with 30 mmol/L APH, the Heinz body count was appreciably higher in normal RBCs than in high-GSH RBCs, while there was no difference in the increase of the methemoglobin (metHb) concentration in both RBCs. In contrast, both the Heinz body count and metHb production were much higher in high-GSH RBCs than in normal RBCs when erythrocytes were incubated with 4-AD. Furthermore, the generation of the superoxide in erythrocytes treated with 4-AD, which was measured by spin trapping combined with electron spin resonance (ESR), was obviously higher in high-GSH RBCs than in normal RBCs. These results clearly indicate that erythrocyte GSH is an important defense against oxidative damage induced by certain compounds such as APH, but that, in contrast, elevated GSH appears to accelerate oxidative damage to erythrocytes produced by aromatic disulfides, such as 4-AD, which generated a superoxide in erythrocytes via its redox reaction with GSH.     

Blood pressure and erythrocyte Na+ transport systems in a French urban male population

This paper reports an investigation of blood pressure (taken as a continuous variable) as a function of: erythrocyte Na+ content; Na+,K+ pump; Na+,K+ cotransport and Na+,Li+ countertransport fluxes, and passive cation permeabilities in fresh erythrocytes from 129 French males who were living in an urban area and were not under treatment for any medical condition (after allowing for the effects of age, body mass index, alcohol and tobacco consumption). In contrast with previous findings in a North American population, we were unable to confirm that blood pressure was correlated with erythrocyte Na+ content and Na+,K+-AT-Pase activity. Conversely, the only transport parameter correlated (negatively) with blood pressure was outward Na+,K+ cotransport [r = -0.20, P less than 0.05 and r = -0.19, P less than 0.05, for systolic (SAP) and diastolic arterial pressure (DAP), respectively; n = 114]. When allowing for age, body mass index and alcohol consumption, the correlation coefficient between the Na+,K+ cotransport system and blood pressure increased from -0.20 to -0.28 (P less than 0.01) for SAP and from -0.19 to -0.28 (P less than 0.01) for DAP (n = 105). We conclude that the correlations between blood pressure and erythrocyte Na+ transport function could differ between North American and French (or Mediterranean) populations. In any case, a decreased pump or outward Na+,K+ cotransport activity may lead hypertensive subjects to a similar increase in cell Na+ (and Ca2+) content in the vascular wall.     

Effects of high fat-feeding to rats on the interrelationship of body weight, plasma insulin, and fatty acyl-coenzyme A esters in liver and skeletal muscle.

Rats fed a high-saturated fat diet consumed more energy, gained more weight, and displayed hyperinsulinemia (P less than .05) without an elevation in the fasting plasma glucose level, compared with animals on two different high-carbohydrate diets. The total fatty acyl-coenzyme A (CoA) concentration was 18% (P less than .0001) and 46% (P less than .0001) higher in liver and skeletal muscle, respectively, from rats fed the high-fat diet compared with each of the other diet groups. Major long-chain fatty acyl-CoA molecular species of both tissues in high fat-fed rats reflected the fatty acid profile of the diet. Approximately 29%, 21%, and 16% of total liver and skeletal muscle fatty acyl-CoAs were comprised of oleoyl-CoA, palmitoyl-CoA, and stearoyl-CoA, respectively. The amounts of these three fatty acyl-CoA esters were significantly higher in liver and skeletal muscle after high-fat feeding than with the other diet treatments (P less than .0001). In contrast, the concentration of linoleoyl-CoA was lower in both tissues after high-fat feeding (P less than .0001). In rats fed the high-fat diet, plasma insulin levels were significantly correlated with gain in body weight or body weight (r = .80, P less than .001 for insulin and gain in body weight; r = .73, P less than .001 for insulin and body weight). Total fatty acyl-CoA ester content in liver and skeletal muscle was also strongly correlated with the plasma insulin concentration in high fat-fed rats (r = .80, P less than .001 for liver; r = .78, P less than .001 for skeletal muscle).(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxidative process in erythrocytes of individuals with hemoglobin S

The understanding of the oxidative stress mechanisms helps to explain many of the processes of cellular lesion and death, especially those related to the hemolytic diseases. Sickle cell anemia, thalassemias and G6-PD deficiency are among the more frequent genetic anomalies accompanied by oxidative stress. In the sickle cells, one of the factors that predisposes to the hemolytic process is the oxidative degradation of the hemoglobin S due to its deoxigenation leading to hemichrome formation and precipitation as Heinz bodies. The oxidative stress contributes to the sickle process and shortening of the erythrocyte survival. Here we analyzed the oxidative process in erythrocytes of patients with two different genotypes for HbS (AS and SS). Units of blood from donors of the Center of Hematology and Hemotherapy of Paraná (HEMEPAR), from normal individuals (AA) and from heterozygote individuals (AS), and venous blood collected from patients with sickle cell anemia (SS) were analyzed. In order to evaluate the protective action of the vitamins C and E in oxidative stress, erythrocytes were treated with antioxidant substances, vitamin C and vitamin E, and then treated with the oxidant tert-butilhydroperoxide (TBHP). The oxidative action induced by TBHP was observed in erythrocytes AA相似文献   

The Haemolytic Action of Dapsone: The Effect on Red-Cell Glycolysis

Some aspects of red-cell metabolism were studied in blood samples taken from patients on long-term dapsone therapy. Glucose consumption by the Enibden-Meyerhof pathway (EMP) was not abnormal and adenosine-triphosphate (ATP) levels lay within the normal range and were well maintained during incubation. Hexose monophosphate pathway (HMP) activity was increased above that which would be expected from the age of the red-cell population. Red-cell reduced glutathione (GSH) levels tended to be lower than normal, proportional to the dose of dapsone and GSH levels were unstable on incubation. Red-cell fractionation studies showed that the older cell fraction had lower GSH levels and more Heinz bodies but proportionally greater HMP activity than the younger cell fraction. It is suggested that the low GSH levels are probably due to the binding of GSH to sulphydryl groups in haemoglobin and possibly the red-cell membrane. The increased HMP activity in the older cells may, in part, be a compensatory mechanism.     

Abnormal erythrocyte metabolism in hepatic disease: effect of NADP repletion.

Erythrocytes from ten patients with severe liver disease displayed low methylene blue-stimulated hexose monophosphate (HMP) shunt activity and glucose recycling despite elevated total glucose consumption when compared to controls. Heinz body formation was increased and reduced glutathione concentration significantly decreased. After hemolysis, no differences in methylene-blue estimulated HMP shunt activity or glucose recycling could be demonstrated between patients and controls. The addition of 2- and 4-mM NADP to the hemolysates produced significantly greater HMP shunt activity and glucose recycling in the patients' hemolysates. The addition of NADPH to the incubation mixture produced no significant stimulation of either HMP shunt activity or glucose recycling, unless methylene blue was also added. Omission of NAD or phosphate from the incubation mixture produced no change in shunt metabolism. The absence of supplemental ATP resulted in extremely low shunt metabolism and refractoriness to NADP stimulation in both patients and controls. In the absence of additional magnesium, a reduction of shunt metabolism was noted. These data suggest that the defect in stimulated shunt metabolism in the intact erythrocytes of patients with hepatic disease does not result from an absolute enzyme deficiency, but rather from an unavailability of NADP or other cofactor.     

Diameters of the orifices of the aorta and pulmonary trunk in normal children--an angiocardiographic study

The diameters of the orifices of the pulmonary trunk and aorta were measured from cineangiocardiographic films in 35 children (mean age 7 years and 6 months, mean height 124.3 cm) without heart disease. Measurements were obtained in the lateral projection in early systole. Calipers and a micrometer were used and the values were expressed to the nearest 0.5 mm. The measured size of the intracardiac catheter was used for calibration. The mean ratio of the squared diameters of the orifices was 1.22:1 (SD 0.17). The diameter of the orifice of the pulmonary trunk/100 cm of body height (14.0 +/- 2.0 mm) was greater than that of the aortic (12.7 +/- 2.0 mm) (P less than 0.01). Significant linear correlation was found between the diameter of the orifice of the pulmonary trunk and body height (r = 0.71, P less than 0.001), weight (r = 0.67, P less than 0.001), and surface area (r = 0.70, P less than 0.001). Similar correlations were found for measurements of the aortic orifice and body height (r = 0.70, P less than 0.001), weight (r = 0.71, P less than 0.001), and surface area (r = 0.71, P less than 0.001), and between the diameters of the two orifices themselves (r = 0.91, P less than 0.001). Body weight is more affected than body height in various types of congenital heart disease. The relationship of the sizes of the orifices of the pulmonary trunk and aorta to body height may therefore be more applicable than their relation to body weight and surface area.