Download The Control of Oxygen Affinity of Red Cells with Hb

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constant. In haemolysis the degree of anaemia seen
in the steady state is also controlled by the same
mechanism, the rate of red cell destruction only
playing a minor role. These findings are of some
importance in the logical management of these and
other patients with haemolysis.
F. IMMUNE RESPONSES TO THE Rh ANTIGEN
P. L. MOLLISON
MRC Experimental Haematology Unit, St Mary’s
Hospital Medical School, London, W.2
If a single injection of Rh-positive red cells is given
to Rh-negative subjects, primary immunization is
induced in a large proportion, provided the dose
of red cells exceeds about 0.02 ml. After a relatively
large dose (200 ml) anti-Rh can be detected serologically in all immunized subjects but after a small
dose (1 ml) the only evidence of primary immunization
may be the rapid clearance of antigen.
Even when repeated injections of adequate amounts
of Rh-positive red cells are given to a series of Rhnegative subjects, about 30% produce no trace of
anti-Rh and may be described as non-responders.
Such subjects have their counterparts in mice, in
whom it has been shown that failure of response to
a particular antigen may be due to lack of the
appropriate ‘specific immune response’ gene.
Primary immunization can be suppressed by giving
approximately 25 pg IgG anti-Rh with each ml of Rhpositive red cells and this ratio seems to be effective
even when 200 ml red cells are injected. Although
it has been suggested that very small amounts of
IgG anti-Rh, or moderate amounts of IgM anti-Rh,
may augment Rh immunization, evidence that they
do so is not strong.
COMMUNICATIONS
1. THE CONTROL O F OXYGEN AFFINITY O F
RED CELLS WITH Hb-SHEPHERDS BUSH
A. MAYand E. R. HUEHNS
Department of Clinical Haematology, University
College Hospital Medical School, London WC1E 6 H X
A change in the oxygen affinity of haemoglobin is
caused by an alteration in the equilibrium between
the high and low affinity forms of haemoglobin,
and the structure of abnormal haemoglobins can affect
this equilibrium either by directly increasing the
stability of one form in relation to the other or by
altering the interaction of haemoglobin with environmental factors such as pH or 2,3-DPG.
The abnormal oxygen affinity Seen in the red cells
in sickle cell disease is a good example of a reduced
oxygen affinity caused by increased stability of the
deoxy form of haemoglobin. In Hb-Hiroshima
(B146 His-tAsp) the effect of pH (Bohr effect) on
the oxygen affinity is grossly reduced. No abnormal
haemoglobin with a reduced interaction with 2,3diphosphoglycerate (2,3-DPG) has to our knowledge
been described. Haemoglobin Shepherds Bush has
the substitution 874 (El8 Gly-tAsp) and the
introduction of the polar side chain into the haem
pocket causes the instability and haemolytic anaemia
already described (White, Brain, Lorkin, Lehmann
& Smith, 1970, Nature, 225, 941). The red cells
containing 25% of this abnormal haemoglobin
have a significantly raised oxygen affinity with a normal 2,3-DPG concentration. Studies of the purified
haemoglobin without 2,3-DPG show only a small
difference in oxygen afIinity between Hb-A and HbShepherds Bush: p50 Hb-A = 5.5 mmHg, Hb-ShB =
4.2 mmHg (0.05 M Bis Tris buffer, pH 7.09, 37”),
A log p50 = 0.12. After addition of 2,3-DPG (2 moles
2,3-DPG per mole Hb) the oxygen affinities of both
Hb-A and Hb-ShB were reduced: p50 Hb-A = 20
mmHg, Hb-ShB = 9 mmHg, A log p50 = 0.35.
Further experiments showed that in mixtures of
Hb-A and Hb-ShB no interaction between haemoglobin was detected. These results adequately explain
the raised oxygen affinity found in red cells and it is
suggested that this is mainly due to decreased interaction of Hb-ShB with 2,3-DPG.
2. BAROREFLEX SENSITIVITY I N PATIENTS
ON LONG-TERM HAEMODIALYSIS
T. G. PICKERING,
B. GRUIBINand D. 0. OLIVER
Radcliffe Infirmary and Churchill Hospital, Oxford
(Introduced by P. SLEIGHT)
Baroreflex sensitivity was measured in thirty-two
patients on long-term haemodialysis by relating the
reflex bradycardia that follows a standard rise of
arterial pressure induced by an intravenous injection
of phenylephrine to the height of the pressure rise.
Baroreflex sensitivity was less in the older patients and
in those with higher pressures. When compared
with a control group of subjects not on dialysis
reflex sensitivity was about half the expected value.
Haemodialysis improved reflex sensitivity over the
long term but did not have any consistent immediate
effect. Reflex sensitivity changed very little in any
one subject on repeated testing at different arterial
pressures, indicating resetting of the reflex. Thus in
contrast with the inverse relation between arterial
pressure and reflex sensitivity found earlier for
patients with untreated hypertension (Gribbin,
Pickering, Sleight & Peto, 1971, Circularion Research,
in press), acute changes are not necessarily associated
with any change of reflex sensitivity. Patients who
had had malignant hypertension in the past tended
to have lower reflex sensitivities than others whose
pressure had never been raised.