Dharam S. Dhindsa

Decreased Affinity of Blood for Oxygen in Patients with Low-Output Heart Failure

Oxygen affinity of blood was measured in 16 patients (nonsmokers) without anemia and with clinical evidence of low cardiac output. Of these patients, 12 were catheterized and showed an arteriovenous oxygen concentration difference across the lungs greater than 5 ml/100 ml. The partial pressure of oxygen required to half-saturate their blood with oxygen (P50) averaged 29.4 mm Hg (SD ± 1.9). Blood from normal subjects (nonsmokers) had an average P50 of 27.3 mm Hg (SD ± 0.9). The decreased oxygen affinity found in blood of patients with low levels of cardiac output is considered as a compensatory adjustment to poor tissue blood flow, promoting the diffusion of oxygen from blood in tissue capillaries to intracellular sites of utilizaton.

Clinically suspect ischemic heart disease not corroborated by demonstrable coronary artery disease. Physiologic investigations and clinical course.

Abstract In 11 patients with angina pectoris and abnormal stress electrocardiograms, no narrowing or obstruction of coronary vessels was visible by selective cut film and coronary cinearteriography. One patient showed chemical evidence of myocardial hypoxia despite normal arteriograms. Similar evidence of impaired myocardial oxygen supply was absent in the remaining 10 patients. We found no abnormality in hemoglobin O 2 affinity which might jeopardize myocardial O 2 supply. The clinical course of these patients, including that during a 1 to 2 year followup period, has not been complicated by myocardial infarction or cardiac failure. In 5 symptoms have decreased.

Comparative studies of the respiratory functions of mammalian blood. VII. Armadillo (Dasypus novemcinctus).

The respiratory characteristics of blood from 4 nine-banded armadillos (Dasypus novemcinctus) were studied. One animal was anemic when studied initially (blood oxygen capacity 9.5 vol %); with treatment its blood oxygen capacity rose and the average blood oxygen capacity for all four animals (excluding the observations during anemia) was 14.8 ± 1.6 vol%. Oxygen dissociation curves for whole blood were constructed at 36°C and were corrected to a plasma pH of 7.40. The mean blood P50 for the animals without anemia was 23.3 ± 1.1 mm Hg. The blood P50 of the anemic armadillo (26.5 ± 0.9 mm Hg) was significantly higher (P < 0.01). The concentration of 2,3-diphosphoglycerate was higher in the blood of the anemic animal (4.33 μM/ml red cells) than in the others (2.83 μM/ml red cells). The Bohr factor (Δlog PO2/ΔpH) was −0.55 ± 0.06. In animals without anemia the red cell count averaged 5.26 million/mm3 and the hematocrit averaged 31%. Armadillo hemoglobin migrates as two bands. The major component migrates at the same rate as human A hemoglobin on starch gel electrophoresis at pH 8.6. Like other burrowing animals, the armadillo has blood with a higher affinity for oxygen than would be predicted for its size. This, and its low rate of oxygen consumption per kilogram, may be considered as adaptations to environmental hypoxia.

Changes in blood oxygen affinity and hemodynamics in anemic dogs

Abstract The effects of anemia on blood oxygen transport were studied using twelve adult male dogs (25–30 kg). Blood was sampled through indwelling catheters. Blood oxygen dissociation curves were constructed at 38 °C and corrected to pH 7.40. Measurements of cardiac output at rest and without anesthesia were made in eight of the dogs. Studies were conducted prior to anemia, during anemia and after recovery. The blood oxygen capacity was lowered from 16.9 ± 2.0 to 6.3 ± 2.3 vol % by bleeding and replacement of the removed plasma. The oxygen partial pressure required to saturate 50 % of the bloods hemoglobin (P 50 ) changed from a mean of 30.9 ± 0.9 mm Hg to a mean of 32.3 ± 1.4 mm Hg during anemia. The dogs were separated into two groups depending upon whether the blood P 50 increased. Six dogs (Group 1) increased their blood P 50 values more than one S.D. above their control values; the other six dogs (Group 2) had blood with average P 50 values during anemia within one S.D. of their mean values during the control period. The degree of anemia was the same in both groups; so was the increase (69%) in cardiac output during anemia. The P O 2 of mixed venous blood dropped during anemia from 41 to 32 mm Hg in Group 1 and from 46 to 27 mm Hg in Group 2. There was no significant difference in oxygen consumption between the control and the anemic studies in either group; the dogs which did not lower their blood oxygen affinities maintained the oxygen delivery to their tissues despite a lower mean capillary oxygen tension.

Responses to exercise in the pregnant pygmy goat

Pregnant Pygmy goats were trained to walk on a treadmill up a 10 degree grade at a rate of 1.5 mile/hr for 10 min. Hemodynamic measurements were made in duplicate during late pregnancy and postpartum, at rest and after 3 min of exercise. All kids were weighed within 12 hr of delivery to assess the effect of exercise on fetal growth. Pulse rate, cardiac output and oxygen consumption were higher during pregnancy than postpartum, at rest and also during exercise. Stroke volume increased significantly with exercise. Peripheral vascular resistance (pvr) at rest was lower during pregnancy than postpartum, and decreased significantly during exercise, especially in pregnancy. Exercise was associated with a fall in arterial P(CO2) during pregnancy and postpartum. In goats, as in humans, the increased oxygen demands of pregnancy, during exercise and at rest, are met by an increased cardiac output rather than by increased peripheral oxygen extraction. The individual birth weights of twins, triplets and quadruplets from Pygmy goats who were exercised during late pregnancy were smaller than birth weights of matched newborns from control animals.

Comparative studies of the respiratory functions of mammalian blood X. Killer whale (Orcinus orca linnaeus) and beluga whale (Delphinapterus leucas)

Abstract Respiratory characteristics of blood from two adult killer and two adult beluga whales were studied. Both of these are dolphins; killer whales attain weights up to 7000 kg and belugas up to 700 kg. Oxygen dissociation curves of the blood were constructed at 37 °C and corrected to a plasma pH of 7.40. Beluga whale blood had a significantly higher (P O .01) oxygen capacity than killer whale blood (25.8 ± O .6 vs 21.8 ± O .5 vol%). The mean P 50 values were 25.2 ± O .5 and 24.4 ± O .1 mm Hg, respectively, for killer and beluga whale blood and these are significantly different (P O .05). The Bohr factor for killer whale blood (− O .602 ± O .148 Δ log P O 2 / Δ pH) was not significantly different than that for beluga whale blood (− O .782 ± O .073), but the Haldane effect for killer whale blood (7.0 vol%) was smaller than for beluga whale blood (9.4 vol%). The concentration of 2,3-diphosphoglycerate in killer whale blood was significantly higher (P O .01) than in beluga whale blood(15.12 μ mol/g Hb vs 11.49 ± O .63 μ mol/g Hb). Starch gel electrophoresis showed that killer whale hemoglibin has two major components and beluga whale hemoglobin has only one major component. The fast-moving component of killer whale hemoglobin and the single major component of beluga whale hemoglobin migrate at the same rate as human A hemoglobin. A relationship between body weight and blood oxygen affinity, which is seen in land mammals, is not apparent in the published data for aquatic mammals.

Comparative studies of the respiratory functions of mammalian blood. VIII. Asian elephant (Elephas maximus) and African elephant (Loxodonta africana africana)

Respiratory characteristics of blood from four Asian and three African elephants were studied. Oxygen dissociation curves of whole blood were constructed at 37 °C and corrected to a plasma pH of 7.40. The mean blood P50 values were 25.2 ± 0.5 and 23.2 ± 1.3 mm Hg for Asian and African elephants, respectively, and these values are significantly different (p<0.01). The Bohr factors for both species were similar and averaged -0.351 ± 0.029 Δ log PO2/ΔpH. The Haldane effect was similar in both species (5.5 vol% ΔCCO2 at PCO2 = 40 mm Hg). The concentration of 2,3-diphosphoglycerate in elephant blood is similar to that found in normal human blood. The blood morphology of both species was similar except that the leukocyte count was significantly higher in Asian elephants. Starch gel electrophoresis showed that hemoglobin of Asian elephants travels at a slower rate than hemoglobin of African elephants, but both migrate faster than human A hemoglobin. African elephant (Loxodontu africuna africana) Asian elephant (Elephas maximus) Blood oxygen capacity Bohr effect Haldane effect Hemoglobin electrophoresis Oxygen dissociation curve 2,3-Diphosphoglycerate (2,3-DPG)

Blood oxygen affinity and hemoglobin type in adult, newborn, and fetal pigs.

Abstract The oxygen-binaing properties of whole blood and hemoglobin solutions from adult, newborn and fetal pigs were studied and related to biochemical characteristics of the hemoglobins and the concentrations of 2,3-diphosphoglycerate (2,3-DPG). The P50 at a plasma pH of 7.40 and 38°C was 32.5 mm Hg for adult pig blood and 22.0 mm Hg for fetal pig blood. The P50 of blood from newborn pigs within 24 hr of birth was 25.0 mm Hg at an intracellular pH of 7.20 and 39.5°C. The red cell 2,3-DPG concentration was twice as high in fresh maternal blood as in blood drawn from the newborn within 24 hr after birth. The P50 of hemoglobin solutions from adult, newborn and fetal pigs was the same after dialysis against phosphate or bicarbonate buffers; dialysates stripped of 2,3-DPG responded identically to the addition of excess amounts of 2,3-DPG. The hemoglobin of the miniature pig in late fetal life is indistinguishable from adult pig hemoglobin on the basis of starch gel electrophoresis, visible and ultraviolet absorption spectra, resistance to alkali denaturation, and the peptide patterns after tryptic hydrolysis. Our evidence suggests that the same hemoglobin is synthesized during late fetal and adult life in the pig and that the higher oxygen affinity of fetal pig blood is maintained by a lower concentration of red cell 2,3-DPG.

Postoperative hemodynamic and electrophysiologic evaluation of the interatrial baffle procedure

Hemodynamic and electrophysiologic studies were performed in 11 children with dextrotransposition of the great arteries an average of 26 months after the interatrial baffle procedure and, in 2 patients, additional closure of a ventricular septal defect. All children are clinically well. Right to left shunts ranging from 28 to 63 percent of systemic blood flow were found at the superior vena caval-baffle junction in four children. The superior vena caval-baffle gradient averaged 7 mm Hg (range 0 to 22). Right ventricular stroke work index averaged 39 g-m/beat per m2 and right ventricular end-diastolic pressure 9 mm Hg. These values were not significantly different from the values for the systemic left ventricle in a comparable group of normal children (average left ventricular stroke work index 45 g-m/beat per m2 and average left ventricular end-diastolic pressure 8 mm Hg). Cardiac index, heart rate and arteriovenous oxygen difference were also normal. No child has complete heart block. His bundle recording demonstrated normal H-V intervals (range 27 to 40 msec); 4 of the 11 had a prolonged A-H interval. Left ventricular systolic pressure was less than 40 mm Hg in all but two children who had significant subpulmonary stenosis. Pulmonary vascular resistance averaged 1.9 units and was decreased in all children. We conclude that up to 37 months postoperatively, despite some residual abnormalities, the clinical and hemodynamic condition of these children is excellent.

Comparative studies of the respiratory functions of mammalian blood IX. ring-tailed lemur (Lemur catta) and black lemur (Lemur macaco)

Respiratory characteristics of blood from 12 ring-tailed and 10 black lemurs were studied. The animals were adults of both sexes. The blood oxygen capacities for ring-tailed and black lemurs were 21.2 ± 1.7 and 21.7 ± 2.2 vol.%, respectively. Oxygen dissociation curves of whole blood were constructed at 38°C and were corrected to a plasma pH of 7.40 by using the Bohr factor determined in this study. The blood of ring-tailed lemurs has a significantly lower (P < 0.01) affinity for oxygen (P50 = 37.0 ± 1.1 mm Hg) than the blood of black lemurs (P50 = 32.9 ± 1.1 mm Hg). Ring-tailed lemur blood has a significantly larger Bohr factor than does black lemur blood. Starch gel electrophoresis showed two major components of hemoglobin from the ring-tailed lemurs and only one major component for black lemur hemoglobin. The Haldane effect was similar for both species. The concentration of 2,3-DPG was significantly lower (P < 0.01) in ring-tailed lemur blood than in black lemur blood (4.45 ± 0.47 vs 5.75 ± 0.58 μmol/g Hb, respectively). There is a trend toward decreasing blood oxygen affinity as one ascends the primate evolutionary scale, which may be secondary to the trend toward a larger adult body weight.