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Myocardial β-Adrenergic Receptor Function and High-Energy Phosphates in Brain Death– Related Cardiac Dysfunction
Circulation
Volume 92, Issue 9, 1 November 1995; Pages 472-478
https://doi.org/10.1161/01.CIR.92.9.472
ARTICLE
Myocardial β-Adrenergic Receptor Function and High-Energy
Phosphates in Brain Death– Related Cardiac Dysfunction
Hartmuth B. Bittner, Edward P. Chen, Carmelo A. Milano, Simon W.H. Kendall, Robert B.
Jennings, David C. Sabiston, Jr, and Peter Van Trigt
ABSTRACT: Background Cardiac failure remains an important problem after heart transplantation
and may be associated with events that occur during brain death (BD) before transplantation. In this
study, cardiac function is studied after BD, and biochemical evaluation of myocardial high-energy
phosphates and the β-adrenergic receptor system is presented. Methods and Results The hearts of
17 mongrel dogs (23 to 31 kg) were instrumented with flow probes, micromanometers, and
ultrasonic dimension transducers to measure ventricular pressure and volume relationships. In a
validated canine BD model, systolic right and left ventricular (RV/LV) function was analyzed by loadinsensitive measurements during caval occlusion (preload-recruitable stroke work, PRSW). The βadrenergic receptor (BAR) density, adenylate cyclase (AC) activity, and myocardial ATP and
creatine phosphate (CP) were measured before and 6 to 7 hours after BD. Results are expressed
as mean±SEM (*P<.05 versus baseline, paired two-tailed Student’s t test). Myocardial function
deteriorated significantly from baseline PRSW (RV, 22±1 erg×103; LV, 75±4 erg×103) by 37±10% for
the RV (P<.001) and 22±7% for the LV (P<.001). BAR density increased from 282±42 to 568±173
fmol/mg for the RV and from 291±64 to 353±56 fmol/mg for the LV. Isoproterenol-stimulated AC
activity was also significantly enhanced after BD. ATP and CP, however, remained unchanged after
BD compared with baseline values before BD. Conclusions BD causes significant systolic
biventricular dysfunction. The loss of ventricular function after BD was more prominent in the right
ventricle and may contribute to early postoperative RV failure in the recipient. These injuries
occurred despite BAR system upregulation after BD. Global myocardial ischemia is unlikely, since
ATP and CP remained normal before and after BD.
Key Words: brain death ◼ receptors, adrenergic, beta ◼ high-energy phosphates
Copyright © 1995 by American Heart Association
A
n important problem associated with cardiac transplantation, unrelated to rejection or
infection, is acute cardiac failure after transplantation. In fact, the early mortality rate after
transplantation has remained unchanged at 10% over the past 5 years.1 This cardiac failure
may be related to myocardial changes occurring after brain death in the organ donor. The “brainhttps://www.ahajournals.org/doi/epub/10.1161/01.CIR.92.9.472
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dead heart-beating cadaver” is known to be associated with donor organ dysfunction, hemodynamic
deterioration, and metabolic and hormonal changes, all of which may contribute to early
posttransplant organ failure, morbidity, and mortality in organ recipients.2 3 Previous studies both in
potential clinical donors and in experimental brain-dead animals have shown brain death to have
major histopathological and functional effects on the myocardium.4 5 6 Furthermore, in the clinical
setting, gradual increases in the amount of inotropic support required to stabilize hemodynamics in
the brain-dead heart-beating donor are frequently observed and may be related to changes in the
myocardial adrenergic system. At the molecular level, β-adrenergic mechanisms play an important
role in supporting contractile function in injured myocardium before the development of overt cardiac
failure7 ; however, little is known about the changes in β-adrenergic receptor density and function
after brain death or the compensatory role of β-adrenergic mechanisms after loss of contractile
performance occurring in association with brain death. In addition, ischemia with depletion of
myocardial high-energy phosphates may also occur after brain death and ultimately affect early
graft function. This study was designed to investigate cardiac dysfunction after brain death in a
validated canine model using functional analysis and load-independent measurements and to
biochemically evaluate myocardial β-adrenergic receptor function and high-energy phosphates.
METHODS
Anesthesia and Monitoring
Seventeen fasted adult male mongrel dogs weighing 23 to 31 kg were anesthetized with 5 mg/kg IV
thiopental sodium (Gensia Laboratories) and 20 mg/kg IM ketamine sodium (Fort Dodge
Laboratories), supplemented as needed until brain death was induced. Each animal received 1.5
mg/kg IV gentamicin sulfate (Elkins-Sinn Inc) and 900 000 U penicillin G benzathine and penicillin G
procaine (Fort Dodge Laboratories). The animals were intubated with a 9F endotracheal tube and
mechanically ventilated with a Bear 1 ventilator (Inter Med, Bear Medical Systems, Inc). The tidal
volume was set at 15 mL/kg, the fraction of inspired oxygen at 100%, and the positive endexpiratory pressure at 3 cm H2O, while the rate-controlled ventilation mode was adjusted to
maintain an arterial partial CO2 pressure between 30 and 40 mm Hg. The arterial pH, partial O2 and
CO2 pressures, O2 saturation, hematocrit, and potassium levels were measured (Gem-Stat,
Mallinckrodt Sensor Systems) at hourly intervals as well as 15 minutes after any ventilator setting
changes were made or medications administered. Blood samples were drawn from a right external
iliac artery catheter, which also was used to record blood pressure (Gould Inc, Cardiovascular
Products Division). Metabolic acidosis was normalized with intravenous sodium bicarbonate 8.4%
(Abbott Laboratories), while the potassium level was maintained between 4.0 and 5.0 mmol/L with
intravenous potassium chloride (Lyphomed Inc) given through an 18-gauge peripheral catheter
introduced into a vein. An esophageal temperature probe was placed, and body temperature was
maintained between 36°C and 37°C throughout the experiments by application of heating pads,
blankets, and heated humidified inspiration gas. The urinary bladder was catheterized
transurethrally to record urine output. ECG monitoring was performed from three limb electrodes.
Study Design and Preparation
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A standard median sternotomy and an anterior pericardiotomy were performed to expose the heart.
A transonic flowmeter (T208X, Transonic Systems Inc) was applied around the ascending aorta and
pulmonary trunk to measure left and right ventricular output. Hemispheric ultrasonic dimension
transducers (1.5 mm OD, No 1-1015-5A, Vernitron) were positioned across the base-apex major
axis, the anteroposterior minor axis diameters of the left ventricle, and the septal–free wall minor
axis diameters of both the right and left ventricles to measure left and right ventricular cavitary
volumes. Millar pressure catheters (MPC-500, Millar Instruments Inc) were placed into the right and
left ventricles, left atrium, and pulmonary artery for continuous pressure recording of right and left
ventricular pressure, end-diastolic right and left ventricular pressure, left atrial pressure, and
pulmonary artery pressure. Dynamic right ventricular volume was measured according to the
ellipsoidal shell subtraction method.8 Right and left ventricular end-systolic pressure-volume and
stroke work/end-diastolic volume relations as end-diastolic segment length or chamber volume were
then evaluated. The relationship between stroke work and either end-diastolic segment length or
chamber volume was quantified by the highly linear relationship of slope and x intercept during vena
caval occlusion.9 The slope (preload-recruitable stroke work, or PRSW) and x intercept (volume) of
these linear regressions represent load-independent indexes of right and left ventricular systolic
function and myocardial contractility. Direct measurements of right and left ventricular filling
pressure were taken at the end of diastole after the a wave and are called right and left ventricular
end-diastolic pressure. Systemic and pulmonary vascular resistance was calculated by standard
formulas applying mean pulmonary and aortic pressure, cardiac output, and end-diastolic left and
right ventricular pressures.
Induction, Diagnosis, and Validation of Brain Death
Brain death was induced by intracranial pressure rise through inflation of a subdurally placed
balloon with 17.8±0.5 mL of isotonic saline. Brain death was determined to occur when cornea and
pupillary reflexes became absent. After brain death, no inotropic, chronotropic, vasoactive,
analgesic, or anesthetic agents were administered. Electroencephalographic changes were
recorded, and the cessation of neuronal-electrical brain activity by electroencephalogram monitoring
was defined as a recorded unchanged oscillating noisy-spiked curve without high-amplitude waves
or spikes. Brain death was confirmed neuropathologically at the end of the experiments as
described elsewhere.10
Data Acquisition and Analysis
Baseline hemodynamic and functional data and blood samples were collected before and 15, 45,
90, 120, 240, 360, and 420 minutes after brain death was induced. Functional and hemodynamic
data were digitized on-line, collected, and stored on a microprocessor (PDP 11/23; Digital
Equipment Corp). Pressure data and cardiac output were analyzed with software developed in our
laboratory as described elsewhere.9 Briefly, all data were digitized at 500 Hz and filtered by a 50-Hz
low-pass filter, stored on magnetic media, and analyzed on a Zenith Z-386/20 (Zenith Data Systems
Corp).
Myocardial Biopsies
Two left ventricular apical transmural myocardial drill suction biopsies and two right ventricular
transmural excisional biopsies from anatomically identical areas at the right ventricular free wall,
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each weighing between 100 and 120 mg, were taken before (after surgical instrumentation of the
heart and before the acquisition of baseline data) and 6 to 7 hours after the induction of brain death.
The biopsies were instantaneously frozen in liquid chlorodifluoromethane (Laroche Chemicals Inc)
and stored in liquid nitrogen for analysis of the adrenergic receptors and high-energy phosphates.
Four mongrel dogs (23 to 25 kg) were instrumented like the experimental animals and served as
controls. Biopsies were taken from control animals in an identical manner.
Adrenergic Receptor System
Crude myocardial membranes were prepared in the following manner: whole myocardial tissue
samples were homogenized in 5 mL of ice-cold lysis buffer (5 mmol/L Tris-HCl, pH 7.4, 5 mmol/L
EDTA, leupeptin 10 μg/mL, and aprotinine 20 μg/mL). Nuclei and cellular debris were sedimented at
500g for 15 minutes, the supernatant was then passed through a double layer of cheesecloth, and
membranes were then pelleted by centrifugation at 40 000g for 15 minutes. Membranes were
washed with 5 mL of binding buffer (75 mmol/L Tris-HCl, pH 7.4, 12.5 mmol/L MgCl2, and 2 mmol/L
EDTA) and then resuspended in fresh binding buffer. Ligand binding assays were done in duplicate
on membranes in 500 μL of binding buffer with saturating concentrations of the β-adrenergic
receptor radioligand [125I]cyanopindolol as described previously.11
Adenylate cyclase activity was determined under basal conditions, in the presence of
progressively higher concentrations of isoproterenol (1×10−9 to 1×10−4 mol/L) or in the presence of
10 mmol/L sodium fluoride. Incubation was for 10 minutes at 37°C, reactions were terminated by
the addition of 1 mL of ice-cold 0.4 mmol/L ATP, 0.3 mmol/L cAMP, and [H3]cAMP (50 000 cpm/mL).
α-[32P]ATP was isolated and quantified as previously described.12 Basal and isoproterenolstimulated cyclase activities for each membrane preparation were normalized as a percent of the
activity achieved with 10 mmol/L sodium fluoride (which maximally activates stimulatory G protein
directly).
High-Energy Phosphates
Slices for metabolite assays were trimmed free of endocardium, weighed quickly on a Cahn model
DTL microbalance, and placed in 3.6% perchloric acid at 0.5°C. Weighing and transfer to perchloric
acid required 10 to 15 seconds. After 15 to 60 minutes, the tissue slices were homogenized with a
Tri-R homogenizer, allowed to extract for an additional 10 or more minutes, and brought to pH 5.0
with K2CO3 and KOH. The extracts were centrifuged to remove KClO4, and the supernatant was
frozen at −70°C. Samples were assayed by enzymatic techniques for ATP and creatine phosphate
as described previously.13
Experimental Approval and Animal Rights
The experimental setup and procedures conformed to the guidelines established by the American
Physiological Society and the National Institutes of Health (“Guide for the Care and Use of
Laboratory Animals,” National Institutes of Health publication 86-23, revised 1985). The experiments
were approved by the Duke University Institutional Animal Care and Use Committee (DUIACUC
Assigned Registry A477-93-10R3).
Statistical Analysis
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Statistical analysis of data taken before and after brain death was performed with a standard twotailed paired Student’s t test. Baseline values and follow-up data were compared on an IBM
personal computer using statview ii (Abacus Concepts, Inc). The results are expressed as
mean±SEM. A difference was considered statistically significant at P<.05.
RESULTS
Hemodynamic Changes
Inflation of the subdurally placed balloon produced an intracranial pressure increase, global brain
and brain stem ischemia, brain herniation, and compression of the midbrain and medulla oblongata,
which interrupted neurological pathways and intracranial blood supply.14 The Cushing reflex,
characterized by a rise in systolic and diastolic blood pressures as well as bradycardia,15 was
triggered in all 17 animals. In addition to bradycardia, other initial ECG changes seen included
junctional escape beats and complete atrioventricular dissociation. This phenomenon was brief and,
within 30 to 90 seconds of balloon inflation, was followed by a progressive tachycardia in
combination with continued hypertension. Furthermore, cardiac output was also increased during
this period. At the peak of this phenomenon, systolic blood pressure rose from a baseline value of
129±4.6 to 402±15.5 mm Hg, while diastolic blood pressure rose from 87±4.0 to 246±12.3 mm Hg.
In 12 of the animals, systolic blood pressure increased to >500 mm Hg, which was actually beyond
the range of the recording device, while diastolic blood pressure ranged from 300 to 360 mm Hg.
Furthermore, cardiac output rose to values of >10 L/min. The dominant arrhythmias during this peak
period were supraventricular tachycardia and third-degree atrioventricular block. Furthermore, 50%
of the animals developed acute severe ST-segment depression, all of which resolved
spontaneously. The entire hyperdynamic response lasted anywhere from 8 to 20 minutes (mean,
12.8±1.2 minutes) before heart rate and blood pressure declined to or below baseline values.
Cardiac output remained elevated. The cardiovascular and hemodynamic changes occurring after
brain death are summarized in the Table. Diabetes insipidus occurred in all but one animal, with the
urine output after brain death averaging 12.2±0.8 mL · kg−1 · h−1.
Right and Left Ventricular Function After Brain Death
Very high linear relations (r>.95) were obtained between calculated right and left ventricular volume
and pressure-volume loops during transient vena caval occlusion before and after brain death.
Baseline right ventricular PRSW ranged from 11 to 34 erg×103 (mean, 22±1.3 erg×103), while
baseline left ventricular PRSW ranged from 48 to 107 erg×103 (mean, 75±3.9 erg×103). There was
a significant decrease in biventricular PRSW values after brain death (n=17, P<.001). The changes
from baseline biventricular stroke work are demonstrated in Fig 1, while the changes in indexes of
biventricular function, slope (PRSW), and x intercept (volume) occurring after brain death are
displayed in Figs 2 and 3. The average decrease in right ventricular PRSW was 37±10.4% and in
left ventricular PRSW, 22±7.3%.
β-Adrenergic Receptors
After brain death, β-adrenergic receptor density increased insignificantly, from 282±42 to 568±173
fmol/mg, in the right ventricle (n=10, P=.08) and significantly, from 291±64 to 353±56 fmol/mg, in the
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left ventricle (n=15, P<.05). No significant change in the left ventricular β-adrenergic receptor
density was observed in the control group (Fig 4). There was an insignificant (P=.1) increase in
unstimulated biventricular adenylate cyclase activity for the right ventricle (n=10, P=.2) and for the
left ventricle (n=13, P<.05) (Fig 5). However, isoproterenol-stimulated adenylate cyclase activity
increased significantly, from 31.4±2.0% to 34.1±1.7%, in the right ventricle (n=13, P<.05) and from
31.8±1.4% to 40.8±1.3% in the left ventricle (n=13, P<.05). No significant change was observed in
control animals (Fig 6). Fig 7 displays the increased adenylate cyclase activity evaluated for all the
prepared right and left ventricular biopsy membranes collectively. EC50 (the concentration of
isoproterenol required to achieve a 50% adenylate cyclase response) was reduced after brain death
from 295 to 194 nmol/L for the right ventricle and from 278 to 185 nmol/L for the left ventricle.
ATP and Creatine Phosphate
Right ventricular myocardial ATP content decreased insignificantly (n=10, P=.5), from 19.6±0.8
μmol/g at baseline to 18.0±1.2 μmol/g at 6 to 7 hours after brain death. Creatine phosphate in the
right ventricle decreased insignificantly (n=15, P=.3), from 25.7±5.1 μmol/g at baseline to 19.2±4.4
μmol/g at 6 to 7 hours after brain death. Furthermore, left ventricular ATP decreased insignificantly,
from 23.2±1.5 to 21.6±3.1 μmol/g, and creatine phosphate increased insignificantly (n=15, P=.2),
from 18.3±5.4 to 23.9±5.3 μmol/g. These changes are summarized in Fig 8.
DISCUSSION
Cardiac function and metabolism after brain death has been under intense investigation for more
than 10 years. In 1984, Novitzky et al16 introduced an experimental baboon brain death model and
noted that left ventricular contractility changes, conversion from aerobic to anaerobic metabolism,
myocardial depletion of high-energy phosphates, and hormonal alterations occurred in association
with brain death. Other experimental brain-death models were subsequently established, and the
effects of brain death on cardiopulmonary function, hemodynamics, and metabolism as well as
changes in endocrine function were described.17 18 19 20 In a clinical study of 172 donor hearts,
Darracott-Cancovic et al3 investigated the association of myocardial damage in the donor with
recipient survival after cardiac transplantation. The mortality rate of patients receiving hearts with
impaired myocardial function before transplantation was 44%, compared with 6% for recipients of
undamaged hearts.
Later, the first attempts to investigate the effects of brain death on myocardial function with
objective analysis using load-insensitive measurements (PRSW) used experimental brain death
models in various species.21 22 These studies showed significant early myocardial dysfunction after
brain death.
Bittner et al10 subsequently introduced a neuropathologically validated canine brain-death model
by which to study donor organ function as well as organ preservation modalities and documented
deleterious effects of brain death on cardiopulmonary hemodynamics and function.
The present study used load-insensitive measurements to objectively analyze myocardial
performance in this validated canine brain-death model and demonstrated that brain death has a
significant impact on cardiac function in the organ donor. After 6 hours of brain death, biventricular
systolic function and contractility, expressed by the linear relationship and regression of loadhttps://www.ahajournals.org/doi/epub/10.1161/01.CIR.92.9.472
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independent recruitable stroke work (PRSW) and cavity volume, were significantly decreased, more
prominently in the right than in the left ventricle. This decrease in PRSW represents an objective
loss of myocardial function for the left as well as the right ventricle and was 22% and 37%,
respectively. Furthermore, no inotropic support was given, and in this setting, any potential for
recovery of biventricular function to baseline values was not observed over the course of 6 to 7
hours after brain death.
Myocardial ischemic injury leading to cardiac dysfunction in the organ donor as a potential result
of brain death has also been addressed by various investigators who performed histopathological
examinations of myocardial tissue in experimental brain-dead animal models.6 23 24 Furthermore,
Meyers et al22 did not show any differences in the coronary blood flow after brain death in an
experimental brain-death model using the microsphere technique. In this investigation, global
myocardial ischemia after brain death is unlikely, since myocardial ATP and creatine phosphate
content remained unchanged before and after brain death. Together, these two studies suggest that
significant myocardial ischemia is not present after brain death and does not contribute to post–
brain death cardiac dysfunction.
In addition, this report demonstrates that the myocardial β-adrenergic receptor system is
upregulated after brain death. Upregulation consists of increased β-adrenergic receptor density,
increased isoproterenol-stimulated adenylate cyclase activity, and increased sensitivity to
isoproterenol (reduced EC50) and emphasizes that myocardial dysfunction after brain death cannot
be related to dysfunction of the β-adrenergic receptor system.
The mechanisms contributing to β-adrenergic upregulation remain unclear. Ischemia has
previously been shown to increase β-adrenergic receptor density25 26 ; however, the presence of
high-energy phosphates after brain death in this study demonstrates that significant ischemia is not
present. Furthermore, hormonal changes associated with brain death, such as decreased cortisol,27
may contribute to receptor upregulation.28
Finally, changes in the levels of myocardial catecholamines (which were not measured in the
present study) may accompany brain death and lead to β-adrenergic receptor upregulation. In the
validated canine brain-death model, a catecholamine storm, occurring ≈30 to 90 seconds after brain
death and associated with severe tachycardia and hypertension, is well described.10 The braindeath model described in this study may not represent every clinical situation of brain death. There
are other mechanisms of brain death in the organ donor population that do not involve a sudden
increase in intracranial pressure with marked elaboration of endogenous catecholamines. However,
the brain-death model used in this study does replicate the clinical findings of most patients who
suffer brain death from a sudden rise in intracranial pressure due to acute intracranial hemorrhage
or head trauma. Severe head injury is the cause of death in 56% to 77% of actual organ donors.29
The importance of this catecholamine storm lies in its potential to cause cardiopulmonary
damage. Many investigators have associated the catecholamine increases occurring after brain
death with myocardial injuries, ischemic insults, infarctions, and hemodynamic instability and
death.30 31 32 33 34 The molecular basis for catecholamine-mediated cardiotoxicity is unclear at
present, however, and probably complex.35
Presumably, biventricular injury occurred during the hyperdynamic response when systolic blood
pressure increased to more than 500 mm Hg while systemic as well as pulmonary vascular
resistance doubled. This may have resulted in cardiomyocyte injury and subsequent biventricular
distension. Right and left ventricular end-diastolic volumes, as measured by sonomicrometry,
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increased significantly after 6 hours of brain death, suggesting an increase in myocardial fiber
length before contraction. At the cellular level, the sarcomere units were stretched beyond their
normal working range, resulting in the disengagement of actin filaments from the M band and a
reduction in the number of possible cross-bridge interactions. This may account for the altered
Frank-Starling mechanism as reflected by an increase in right and left end-diastolic pressures and
decrease in stroke work. To evaluate further the mechanical aspect of biventricular dysfunction in
the the brain-dead heart-beating organ donor, the viscoelastic properties of right and left ventricular
myocardium and diastolic function require a thorough investigation.
In summary, the present study demonstrates significant biventricular dysfunction after brain
death in a validated canine model, which may be a clinically important cause of acute cardiac failure
after transplantation. The results of this investigation also suggest that neither ischemia nor
downregulation of the β-adrenergic system may account for this decreased cardiac function. Highenergy phosphate levels were maintained, and the β-adrenergic receptor system was actually
upregulated. In fact, myocardial performance after brain death may actually be enhanced by
catecholamines or β-adrenergic agonists. Further studies are necessary to determine the cause of
cardiac dysfunction after brain death in the organ donor.
Figure 1. Graph showing systolic right (RV, ▪) and left ventricular (LV, ♦) myocardial performance measured by
preload-recruitable stroke work (PRSW) before (0) and after induction of brain death in 17 animals. The
increase in ventricular function after induction of brain death may be related to the immediate catecholamine
surge after brain death. Right and left ventricular function decreased significantly, by 37% and 22%, after brain
death. *P<.001.
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Figure 2. Graph showing right ventricular (RV) x-intercept data of 17 animals representing an increased post–
brain death end-diastolic volume (EDV), which indicates a progressive deterioration of right ventricular function
after brain death (right line) compared with baseline (left line).
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Figure 3. Graph showing left ventricular (LV) x-intercept data of 17 animals representing an increased post–
brain death end-diastolic volume (EDV), which indicates a progressive deterioration of left ventricular function
after brain death (right line) compared with baseline (left line).
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Figure 4. Bar graph showing that β-adrenergic receptor density increased significantly in the left ventricular
(LV) myocardium after 6 to 7 hours of brain death (BD). No significant increase was found for the right ventricle
(RV), although there was a trend toward increased receptor numbers (P<.08). In the control group (CTL), there
was no significant change in β-adrenergic receptor density. Control biopsies were taken from the apex of the
heart.
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Figure 5. Bar graph showing that unstimulated adenylate cyclase activity of the right (RV) and left (LV)
ventricular myocardium was not significantly different 6 to 7 hours after brain death (BD) compared with
baseline values. There was also no significant difference in the control group (CTL). Control biopsies were
taken from the apex of the heart.
Figure 6. Bar graph showing that a significant increase in isoproterenol-stimulated adenylate cyclase activity
was observed for the right (RV) and left (LV) ventricular myocardium after 6 to 7 hours of brain death (BD). The
increase was 10% for the RV and 28% for the LV.
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Figure 7. Bar graph showing that after brain death (BD), the concentration of isoproterenol at which 50%
maximal adenylate cyclase response is achieved (EC50) is markedly reduced for the right (RV) and left (LV)
ventricular myocardium, indicating an increased sensitivity of the β-adrenergic receptor system.
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Figure 8. Bar graphs showing concentrations of the myocardial high-energy phosphates ATP and creatine
phosphate (CP). Global myocardial ischemia is unlikely after brain death (BD), because right (RV) and left (LV)
ventricular myocardial ATP and CP did not change significantly from baseline values before and after 6 to 7
hours of BD.
Table 1. Hemodynamic Changes After Brain Death (Table view)
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Time, min
0
120
240
360
420
HR, bpm
116 (3)
1261 (3)
121 (3)
123 (6)
104 (9)
MBP, mm Hg
101 (4)
753 (5)
623 (5)
473 (6)
313 (9)
CO, mL/min
1451 (87)
1439 (118)
1671 (177)
20491 (234)
20581 (303)
LVEDP, mm Hg
6.3 (0.4)
7.3 (0.7)
9.02 (1.1)
9.43 (0.5)
9.83 (0.3)
RVEDP, mm Hg
1.2 (0.3)
1.4 (0.5)
2.22 (0.6)
3.03 (0.6)
3.73 (0.3)
SVR, dyne · s · cm−5
5752 (384)
46021 (570)
33703 (493)
19343 (321)
11983 (413)
PVR, dyne · s · cm−5
387 (37)
290 (38)
2831 (35)
2871 (29)
2611 (43)
HR indicates heart rate; bpm, beats per minute; MBP, mean arterial blood pressure; CO, cardiac output; LVEDP and RVEDP, left and
right ventricular end-diastolic pressures; and SVR and PVR, systemic and pulmonary vascular resistance before (0) and after brain
death was induced. Values in parentheses are SEM.
1
P<.05,
2
P<.01,
3
P<.001.
ARTICLE INFORMATION
Reprint requests to Hartmuth B. Bittner, MD, PO Box 3333, Duke University Medical Center, Durham, NC 27710.
Presented at the 67th Scientific Sessions of the American Heart Association, Dallas, Tex, November 14-17, 1994.
Affiliations
From the Department of General and Cardiothoracic Surgery and Department of Pathology (R.B.J.), Duke
University Medical Center, Durham, NC.
Acknowledgments
This study was supported in part by grant HL-09315-30 awarded by the National Institutes of Health to Drs
Sabiston and Van Trigt.
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