Download on Pulmonary Artery Pressure and

Acute Effects of Intravenous Cocaine
on Pulmonary Artery Pressure and
Cardiac Index in Habitual Crack
Smokers*
Eric C. Kleerup, MD, FCCP; Maylene Wong, MD;
Jose A. Marques-Magallanes, MD; Michael D. Goldman, MD; and
Donald P. Tashkin, MD, FCCP
Background: Some habitual crack cocaine smokers who deny IV drug abuse show decreased
pulmonary transfer of carbon monoxide (Deo). We speculated that repeated elevations in
pulmonary artery pressure (PAP) might cause pulmonary capillary damage and result in a
lowered Deo, or that the reduction could be due to anoxic lung injury secondary to repeated
episodes of cocaine-induced pulmonary vascular constriction.
Study Objective: Compare the acute effects of IV cocaine HCl and placebo on PAP, cardiac stroke
volume, and cardiac output estimated indirectly by continuous Doppler echocardiography.
Design: A single-blind crossover study in which placebo always preceded the active drug.
Subjects: Ten current crack-smoking subjects, 32 to 47 years of age, with a history of limited
previous IV cocaine use.
Methods: PAP, cardiac stroke volume, heart rate, and BP were measured continuously after
injection of placebo followed by cocaine HCl (0.5 mg/kg).
Results: IV cocaine resulted in no significant change in PAP (.0.14±3.3[SD] mm Hg, 95%
confidence interval [CI] for difference .2.48, +2.21). Stroke volume index showed no significant
change after cocaine (.0.1 ±2.0 mL; 95% CI, .1.5, +1.3). Heart rate showed a significant
increase (10.0±7.2 min-1; p=0.0017, 95% CI, +4.9, +15.1). Cardiac index showed a significant
increase (0.48±0.32 L/min; p=0.0012, 95% CI, +0.25, +0.71). Pulmonary vascular resistance
showed no significant change (.44±101 dyne s cm~5/m2, 95% CI, .116, +29).
Conclusions: IV cocaine HCl does not cause short-term increases in PAP or stroke volume index,
but causes an increase in cardiac index due to its chronotropic effect.
.
.
(CHEST 1997; 111:30-35)
Key words: cardiac output; cocaine HCl; pulmonary artery pressure
Abbreviations: AT/ET=acceleration time/ejection time; Ci=cardiac index; CI=confidence interval; Dco=diffusing
of the lung for carbon monoxide; HR=heart rate; mPAP=mean pulmonary artery pressure; NIDA= National
capacity
Institute on Drug Abuse; PAP=pulmonary artery pressure; PVR=pulmonary vascular resistance; SVi=stroke volume
VTI=
time
index;
velocity
integral
have previously shown that heavy, habitual
\^[7e
* cocaine
is associated with a
*
smoking
significant
abnormality in gas transfer (diffusion) in the lung,1
consistent with findings of other investigators.2'3 The
presence of an abnormality in diffusing capacity
suggests structural lung damage. Clinical reports of
*From the Divisions of Pulmonary and Critical Care Medicine,
UCLA School of Medicine, Los Angeles (Drs. Kleerup,
and Tashkin) and VAMC West Los Ange¬
Marques-Magallanes,
les (Drs. Wong and Goldman).
DA08254.
Supported by NIH/NIDA grant ROlrevision
14, 1996;
Manuscript received
June
accepted July 11.
Reprint
requests: Dr. Kleerup, Div of Pulmonary and Critical
Care Medicine, UCLA School of Medicine CHS 37-131, Box
951690, Los Angeles, CA 90095-1690
acute
noncardiogenic ("increased permeability") pul¬
monary edema4 and diffuse alveolar hemorrhage in
temporal association with cocaine use,56 as well as
autopsy evidence of frequent, clinically occult pul¬
monary hemorrhage68 and interstitial pneumonitis
and/or fibrosis7 in lung specimens from cocaine users
who die suddenly, provide support for the concept of
cocaine-induced damage to the alveolar-capillary
membrane. It has been suggested9 that this damage
could result from either (1) a direct toxic effect of the
inhaled cocaine on the alveolar epithelium and/or
endothelium and/or (2) an intense vasocon¬
capillary
strictor effect of cocaine on the pulmonary circula¬
tion, causing a marked reduction in pulmonary cap-
30
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Clinical
Investigations
that leads to anoxic cellular damage.
illary perfusion
However, a vasoconstrictor effect of cocaine on the
intact pulmonary circulation has not yet been dem¬
onstrated experimentally in man. The possibility of
cocaine-induced pulmonary vasoconstriction is sug¬
by the following: (1)andan autopsy report reveal¬
gestedmedial
hypertrophy hyperplasia involving
ing
small or medium-sized pulmonary arteries in 20% of
young cocaine users (without evidence of foreignbody microembolization) who died
suddenly from
acute cocaine intoxication;10 (2) a report of biopsy
specimen-proved symptomatic pulmonary vascular
disease (intimal and medial hypertrophy of muscular
arteries) in a small group of crack-smok¬
pulmonary
with borderline to severe pulmonary
women
ing
vitro studies of rabbit pulmo¬
hypertension;11 (3) in with
either intact or denuded
nary artery segments
endothelium;12 (4) studies in animal models in which
cocaine has been reported to accentuate pulmonary
arterial pressor responses;13 and (5) a recent clinical
report of pulmonary arterial hypertension in asymp¬
tomatic IV cocaine users.14 This latter finding, how¬
ever, could be secondary to microembolization of
particulate material injected IV, rather than to a toxic
effect of cocaine itself on the pulmonary circulation.
In the absence of any reports of direct evidence of
cocaine effects on pulmonary hemodynamics in man,
we estimated pulmonary vascular pressures and re¬
by Doppler echocardiography
noninvasivelyusers
and examined the shortterm effect of experimental administration of co¬
caine in the same subjects. We hypothesized that IV
cocaine HCl would acutely produce pulmonary arterial/arteriolar vasoconstriction, as manifested by an
increase in pulmonary artery pressure (PAP) out of
proportion to the increase in cardiac output esti¬
mated by Doppler echocardiography.
sistance
in ten habitual crack
Materials
and
Methods
Subjects
Ten healthy current crack-smoking subjects, nine men and one
woman, were recruited for experimental cocaine administration
studies from chemical dependency treatment programs in the
local community (after relapse) and from a cohort of crack
smokers participating in ongoing studies of the pulmonary effects
of habitual use of cocaine. Inclusionary criteria included age 25
to 50 years, current smoking of alkaloidal (crack) cocaine on a
regular basis, and previous occasional use of IV cocaine (from 1
to 12 times per lifetime). Exclusionary criteria included the
following: IV drug abuse more than 12 times per lifetime or
within the previous year; history of smoking (>20 times/lifetime)
other illicit substances (eg, phencyclidine, heroin, opium, methamphetamine) except for cannabis; a history of chronic lung
disease (eg, asthma, interstitial lung disease); history or clinical
evidence of systemic or pulmonary hypertension; history of
coronary artery disease, angina, arrhythmia, or congenital heart
disease; abnormal 12-lead ECG; history or clinical evidence of
hyperthyroidism or peripheral vascular disease; history of stroke,of
seizure disorder, or other neurologic abnormality; history
significant psychiatric disorder; or pseudocholinesterase defi¬
ciency. Women of child-bearing potential were not studied if they
were pregnant, lactating, or not using a medically acceptable
method of contraception. A urine pregnancy test was performed
all female subjects at the beginning of each study day to detect
unsuspected pregnancy. Subjects without measurable tricuspid
on
regurgitation by Doppler echocardiography (see below)
were
excluded from analysis. Eligible volunteers were studied after
signing informed consent forms approved by the UCLA School of
Medicine Human Subject Protection Committee and the West
Los Angeles VA Medical Center Human Studies Committee.
Procedures
Preliminary examination procedures included the following: a
detailed respiratory and drug use questionnaire modified from
the American Thoracic Society/National Heart, Lung and Blood
Institute respiratory questionnaire15 and National Institute on
Drug Abuse (NIDA) National Survey on Drug Abuse16; medical
history and physical examination; serum pseudocholinesterase
determination; urine drug screen; 12-lead ECG; spirometry and
single-breath diffusing capacity for carbon monoxide (Deo)
measurement (adjusted for hemoglobin17 and carboxyhemoglobin18); and a urine pregnancy test in female subjects. Eligible
volunteers were advised to refrain from smoking cocaine or
marijuana, taking any prescription or over-the-counter medica¬
tion, or consuming any caffeine-containing beverage for at least
8 h prior to visiting the laboratory. They were also admonished
not to smoke tobacco for at least 2 h before testing or to use any
antihistamine preparation for at least 48 h. Studies were per¬
formed with a physician in attendance and emergency resuscita¬
equipment nearby.
beginning of each study, the amount of daily drug use
(crack cocaine, marijuana, tobacco, and other drugs) during the
tion
At the
preceding week and the time of last use were ascertained by
questionnaire (self-report), and a urine sample was obtained for
determination of cocaine metabolite (benzoylecgonine). A 12lead ECG was performed. A catheter was inserted in an arm vein
for injection of saline solution or cocaine HCl. A standard
two-dimensional echocardiogram (Acuson 128XP; Mountain
View, Calif) was performed to rule out structural malformations
and to assess right ventricular outflow diameter. Finger arterial
blood pressure was monitored continuously and noninvasively on
the second or third finger of the left hand (Finapres 2300E;
Ohmeda; Boulder, Colo). The sum of chest and abdominal wall
excursions (proportional to tidal volume) measured by inductive
plethysmography (Respitrace Plus; Non-Invasive Monitoring Sys¬
tems; Miami Beach, Fla) was recorded directly on the echocar¬
diographic recording tape. Doppler echocardiographic assess¬
ment of the right ventricular outflow tract was performed
continuously from before administration of placebo until after
return to baseline following cocaine administration.
The cocaine HCl was obtained from the NIDA in crystalline
form. The dose of IV cocaine HCl (0.35 to 0.5 mg/kg) used was
selected since it has been shown to yield euphoric effects
comparable to those achieved during recreational use of co¬
caine19 and to be below the dose levels associated with significant
cocaine toxicity, according to unpublished NIDA guidelines for
experimental cocaine administration. The subject was blinded to
the administration of drug vs placebo. For each subject, the first
injection consisted of a volume of 0.9% NaCl identical to that of
the cocaine administered later, injected over 30 s, and followed
by 6 mL 0.9% NaCl flush over 60 s. The second injection
consisted of (1) cocaine HCl (7.67
mg/mL in 0.9% NaCl)
CHEST / 111 / 1 / JANUARY, 1997
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at
a
31
Table 1.Demographic, Smoking, and Physiologic
Characteristics (n=10; 9 Men, 1 Woman)
Age, yr
Cocaine,
g/wk
Tobacco, cigarettes per day (n 7*)
Marijuana, joints per week (n=6*)
=
Deo, % predicted
DcoA7Af, % predicted
*
Current smokers of tobacco and/or
f Dco/Va=ratio
Mean±SD
Range
38.7±4.9
0.93±0.58
13.6+12.9
7.8±9.9
75.1±4.9
85.4±9.1
32-47
0.25-2.2
3-40
0.2-21
67-80
66-100
marijuana.
of diffusing capacity to alveolar volume.
dose of 23 mg (2
subjects, average dose 0.35 mg/kg lean body
weight [body mass index of 22.0]) or (2) cocaine HCl (5 mg/mL
in 0.9% NaCl) at a dose of 0.5 mg/kg lean body weight (8
subjects, average dose 36.5±4.6 [SD] mg). This also was injected
over 30 s and followed by a 6-mL flush of 0.9% NaCl over 60 s.
The change in dose from 0.35 to 0.5 mg/kg was made after the
first 2 subjects had been studied to assure a consistent chrono¬
tropic response based on the results of concurrent studies.
Individual beats from the Doppler spectral recordings ob¬
tained at end-expiration at approximately 1-min intervals were
analyzed for acceleration time/ejection time (AT/ET), velocity
time integral (VTI), and instantaneous heart rate (HR). Ectopic
and postectopic beats were excluded from analysis. Mean pul¬
monary arterial pressure (mPAP) was estimated from AT/ET.20
Stroke volume was calculated from the product of right ventric¬
ular outflow tract cross-sectional area and VTI.21 Cardiac output
was calculated as the product of HR and stroke volume. Right
atrial pressure was estimated at 5 mm Hg (no subject had
evidence of jugular venous distention). Pulmonary vascular resis¬
tance was calculated from the Doppler-estimated mPAP divided
by the cardiac index (Ci). Stroke volume, cardiac output, and
pulmonary vascular resistance (PVR) were indexed to body
surface area for intersubject comparisons.
A physician was present at all times during the cocaine infusion
Table
experiments. Following
cocaine administration, subjects were
carefully monitored for evidence of acute cocaine toxicity such as
systemic hypertension, tachycardia, clinically significant arrhyth¬
chest
or headache.
pain,
mia,
Data Analysis
Paired t
tests
were
used
to
compare measurements obtained
following placebo with (1) those obtained in the first 5 min
following cocaine, and (2) all measurements following cocaine
until returned to baseline. A Hotelling T2, a multivariant ana¬
logue of the ^-statistic, was used to assess differences in mPAP,
HR, stroke volume index (SVi), Ci, and PVR index given their
correlation structure.22 A repeated-measures model using the
variance of each subject during the measurement period was
used to derive 95% confidence intervals (CIs) for the difference
between cocaine and placebo values.23
Results
smoking history,areand diffusing
capacity
shown in Table 1.
study
participants
Subjects were young to middle-aged adults who, on
the average, were heavy smokers of cocaine base
(mean of 0.93 g/wk). Most were also current smokers
of tobacco and marijuana. Deo was mildly reduced
(<75% predicted) in 4 of the 10 subjects.
Valid echocardiographic observations at end-expi¬
ration were obtained (mean±SD) 10.0±3.3 times
(range, 5 to 16 times) following placebo infusion,
7.0±3.0 (3 to 10) times in the first 5 min following
cocaine infusion, and 15.8±6.0 (7 to 24) times over
the full observation period of 16.0±6.5 (10.0 to 31.9)
min following cocaine infusion. Mean results are
shown in Table 2
Mean age,
of the
and Figure 1.
2.Hemodynamic Changes Following Cocaine Administration*
Cocaine
First 5 min After Cocaine
Placebo
Mean
mPAP,
mm
Hg
SVi, mL/m2
HR, min-1
18.0±5.7 (10.5, 32.9)
Mean
All Measurements After Cocaine
Change
17.8±6.6 (11.0, 33.0) -0.14±3.3 (-4.7, 6.0)
18.0+5.9 (10.4, 30.4)
index,
dyne
.
s
*
cm~5/m2
(-5.1, 6.2)
p=NS
p=NS
p=NS
44.5±9.0 (30.5, 60.0) 44.4±8.5 (29.9, 56.7)
95% CI -2.5, 2.2
95% CI -2.6, 2.6
-0.1±2.0 (-3.3, 3.1) 46.1±8.5 (34.0, 58.3)
1.6±2.5 (-1.7, 5.2)
62.4±7.9 (47.5, 73.8) 72.4±10.7 (59.1, 92.8)
95% CI -1.5, 1.3
95% CI -0.2, 3.3
10.0±7.2 (0.6, 21.8)
75.4±10.8 (58.0, 91.8) 13.0+7.6 (1.7, 26.9)
2.72±0.57 (1.65, 3.70) 3.20±0.69
(1.96,4.74)
300±177(88, 722)
256±181
(75, 681)
p=0.0004
95% CI 4.8, 15.1
95%
CI 7.6, 18.5
0.48±0.32 (0.11,1.04) 3.45+0.72(2.50,5.17) 0.73±0.39 (0.24, 1.47)
p=0.0012
PVR
0.01±3.6
p=NS
p=0.0017
Ci, L/min/m2
Change
Mean
p=0.0002
95% CI 0.2, 0.7
95%
44± 101 (-154, 144) 232±161 (61, 600)
p-NS
CI 0.5, 1.0
68±132 (-306, 114)
p=NS
95% CI -116, 29
95% CI, -162, 26
*For each subject, a mean of the placebo, first 5 min after cocaine, and all values after cocaine is calculated as well as the change (mean difference
[after cocaine-mean placebo]). The table displays group (10 subjects) values as mean±SD (low, high), p value (repeated measures model), 95%
CI (low, high).
32
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Clinical
Investigations
first 5 min following cocaine administration,
placebo,
and all measurements following cocaine administra¬
tion, respectively. The maximum mean increase was
6.0 mm
and
maximum
32
28
X
E
e
24
«
20
£
16
12
All
5 min
Placebo
post Cocaine
5 min
All
post Cocaine
Figure 1. mPAP and change in mPAP after placebo and cocaine.
A: mean absolute value of mPAP. B: mean change in mPAP after
cocaine.mean after placebo. 5 min postcocaine represents the
first 5 min following cocaine infusion; all postcocaine represents
all data after cocaine infusion. The horizontal lines represent
individual subject data. The dashed line represents the group
mPAP. The vertical gray bars represent the 95% CI for the
difference. The labeled midpoint tick is the mean difference.
Mean PAP following placebo was slightly elevated
(18.0±5.7 mm Hg, mean±SD; 7 of 10 subjects
>16), compared with normal (9 to 16 mm Hg24),
(Fig 1, left). Mean PAP did not change significantly
comparing placebo to either the first 5 min following
cocaine infusion or all measurements obtained fol¬
lowing cocaine infusion (Fig 1, right, and Table 2).
The 95% CI for the difference in mPAP between
and cocaine was .2.5 to +2.2 mm Hg for
placebo
the first 5 min. This was determined from a repeat¬
ed-measures model using the variance of each sub¬
ject during the measurement period. Each point in
Figure 1 represents a mean of between 3 and 24
individual measurements. The 95% CI was derived
from 100, 65, and 158 individual measurements for
1.2
1.0
0.8
u
c
mean decrease was
Hg the
in the first 5 min
for
individual
Hg any
The subject with
administration.
cocaine
following
the highest mPAP during placebo (32.9 mm Hg) did
not respond differently from the others (change in
mPAP, 0.1 mm Hg in the first 5 min).
Mean SVi following placebo (44.5±9.0 mL/m2,
mean±SD) was within the normal range (30 to 65
mL/m2).24 SVi did not change significantly compar¬
ing placebo to the first 5 min following cocaine
-4.7
0.6
0.4
0.2
infusion. The 95% CI for the difference in SVi
between placebo and cocaine was .1.5 to +1.3
mL/m2 for the first 5 min.
Mean HR following placebo (62.4±7.9 min-1,
mean±SD) was within the normal range (60 to 90
min-1),25 although 3 subjects had mild bradycardia.
Mean HR significantly increased (p=0.0017) com¬
paring placebo to the first 5 min following cocaine
infusion (72.4±10.7 min-1, an increase of 10.2±7.0
min-1). The 95% CI for the difference in HR
between placebo and cocaine was +4.8 to +15.1
min-1 for the first 5 min.
With the SVi remaining the same and the HR
increasing, the calculated product, Ci, increased.
Mean Ci following placebo (2.72±0.57 L/m2,
mean±SD, 6 of 10 less than 2.8) was slightly below
normal range (2.8 to 4.2 L/m2).24 Mean Ci signifi¬
cantly increased (p=0.0012) comparing placebo to
the first 5 min following cocaine infusion (3.20±0.69
L/m2, an increase of 0.48±0.32 L/m2). The 95% CI
for the difference in Ci between placebo and cocaine
was +0.25 to +0.71 L/m2 for the first 5 min. A
correlation was found between change in
significant
HR and change in Ci (r2=0.91), but not between
in SVi and change in Ci (r2=.0.24) (Fig 2).
change
PVR index was highly variable. Mean PVR index
following placebo infusion (300±177 dyne*s-cm~5/m2,
2 subjects above 430 dyne*s-cm-5/m2, 5 below 250
dyne-s*cm 5/m2) was within the normal range (250 to
430 dyne-s cm-5/m2).24 Mean change in PVR index
(-44±101 dyne-s-cm~5/m2) from placebo to the first 5
min after cocaine administration was also highly vari¬
able and not statistically significant (95% CI .116 to
+29
0.0 f-5
-1-1-1-1_
0
?
O
Change
Change
5
15
10
20
in Heart Rate (min1)
in Stroke Volume (ml)
25
Figure 2. Correlation of Ci with HR and SVi after placebo and
Squares represent change in HR (mean of first 5 min
cocaine.
following
placebo); circles represent
change
represent the mean of ten
The abscissa scale pertains both to HR (min^1) and
subjects.
stroke volume
cocaine minus mean
in SVi. The filled square and circle
(mL).
mm
dyne-s-cm~5/m2).
Systemic BP increased following cocaine adminis¬
tration. Maximal systemic systolic BP increased from
138±19 mm Hg following placebo to 166±22 mm
Hg following cocaine. Maximal systemic diastolic BP
also increased from 77 ±12 mm Hg after placebo to
94±14 mm Hg after cocaine. The median time to
the maximal systemic systolic BP following cocaine
administration was 2.8 min and to maximal diastolic
BP, 2.0 min.
CHEST 7111/1/ JANUARY, 1997
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33
Discussion
reuptake of catecholamines at
nerve
endings, causing a local increase in
adrenergic
and
norepinephrine dopamine levels and sensitization to systemic catecholamines (epinephrine).26'27
As a consequence, cocaine produces systemic vaso¬
constriction that is blocked by a-adrenergic blocking
agents (phentolamine) and potentiated by (3-adrenergic blockade.28-30 In addition to pulmonary toxicity,31'32 cocaine may also have direct toxic effects on
end organs such as the myocardium, independent of
Cocaine blocks the
neurogenic effects.33-35
Dogs receiving a continuous infusion of cocaine at
0.5 mg/kg/min show a decrease in stroke volume and
cardiac output, but no change in mPAP or HR.36 In
rabbit pulmonary artery segments, norepinephrine
contracted the larger intrapulmonary vessels, but this
vasoconstrictor effect was not potentiated by co¬
caine.37 The latter results are contrary to a later
report in abstract form demonstrating cocaineinduced vasoconstriction of rabbit pulmonary artery
segments.12
Previous
reports of echocardiographic
measure¬
asymptomatic IV cocaine users have shown
elevations in estimated PAP (systolic PAP >30 in 8
of 13 subjects).14 The pulmonary hypertension has
ments in
be due to granulomatous
injected insoluble agents (talc,
corn starch, microcrystalline cellulose). However, an
autopsy study demonstrated pulmonary artery me¬
dial hypertrophy in the absence of foreign particle
microembolization in 4 of 20 deaths from cocaine
overdose,10 raising the possibility that repeated epi¬
sodes of cocaine-induced acute pulmonary vasocon¬
been hypothesized
inflammation from
to
produce pulmonary hyper¬
However, acute
administration of intranasal cocaine, 2 mg/kg, results
in an increase in HR and Ci, but no change in mPAP
or SVi assessed at 15, 30, or 45 min by pulmonary
artery catheterization.38
Since cocaine-induced subjective effects and
of short duration, we postulated that
tachycardia inaremPAP
might be transient. Noninvasive
any change
measurement of mPAP using the AT/ET at the right
ventricular outflow tract has a good correspondence
to pressures measured by pulmonary artery cathe¬
terization (r=0.94)39 and also allows almost contin¬
uous measurements that can be gated to end-expi¬
ration. Using a moderate dose of cocaine, this study
shows no change in mPAP compared with placebo.
We also establish a 95% CI for the group mean that
defines the change in mPAP and makes it
narrowlythat
change isin mPAP
significant
unlikely a clinicallyThis
lack of
occurred in this
striction
eventually
tension and medial hypertrophy.
might
group.
change present
in the first 5 min after infusion of cocaine and for all
cocaine.
measurements
It is possible that higher doses of cocaine or a
following
different route of administration might provoke a
or decrease in mPAP. However,
significant increase
make acute untoward side
also
would
doses
higher
in
effects more likely this volunteer subject popula¬
tion. Although it is possible that some subjects are
and some are nonresponders to pulmo¬
responders
effects of cocaine, the outlying sub¬
vasomotor
nary
initial mPAP did not
with
either
high orthelowremainder
jects
of the group
from
respond differently
in our study. In dogs, tachyphylaxis to the hyperten¬
sive and myocardial oxygen consumption effects
occurs at higher doses of cocaine (0.8 mg/kg) admin¬
istered at 1-h intervals, but lower doses result only in
an elevation of the baseline hemodynamic vari¬
ables.40 Although our subjects stated that they had
refrained from smoking cocaine in the 8 h prior to
the study day, it is possible they did not abstain or
that the duration of abstinence was insufficient.
However, we did observe the expected chronotropy
and systemic BP increases after cocaine, so that it is
less likely that our failure to demonstrate acute
vasoconstriction following cocaine was
pulmonary
due to the development of tolerance as a result of
cocaine use.
recent
The marked difference in response to cocaine
between the systemic and pulmonary vasculature
may be due to several factors. First, the greater
compliance of the pulmonary vasculature may pre¬
vent rises in PAP through the recruitment of addi¬
tional, previously collapsed vessels, even though all
the vessels might be constricted secondary to cocaine
administration (excess capacitance). Second, the pul¬
monary vascular system may be unable to respond to
a given constrictor stimulus to the same degree as
the systemic vasculature due to decreased or absent
smooth muscle in the pulmonary arteries and arterioles (decreased responsivity). Finally, the pulmo¬
nary vascular smooth muscle may have a lower
for stimulation by
density of adrenergic receptors
catecholamines causing less constriction in response
to local increases in norepinephrine and dopamine
than in the systemic circulation (decreased sensitiv¬
ity).In
the absence of apparent change in the mPAP
administration of cocaine, it is difficult
during acute microvascular
to postulate
damage due to repeated
vasoconstriction as an explanation for low Deo ob¬
served in some crack cocaine users. Moreover, the
lack of a marked elevation in mPAP either acutely
cocaine administration or
following experimental
cocaine smokers argues
chronically in habitual ofcrack
against redistribution blood flow to upper lung
zones resulting from pulmonary hypertension with
34
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Clinical
Investigations
compensatory recruitment of capillaries from upper
zones as an explanation for pseudonormalizalung
tion of Deo in crack smokers with cocaine-related
lung injury.
ACKNOWLEDGMENTS: The authors thank Ruth Barre,
Enoch Y. Lee, and Becky Lopez for their technical assistance and
James Sayre for his statistical expertise.
References
1 Tashkin DP, Khalsa M-E, Gorelick D, et al. Pulmonary status
of habitual cocaine smokers. Am Rev Respir Dis 1992;
145:92-100
2 Weiss RD, Tilles DS, Goldenheim PD, et al. Decreased
single breath carbon monoxide diffusing capacity in cocaine
freebase smokers. Drug Alcohol Depend 1987; 19:271-76
3 Itkonen J, Schnoll S, Glassroth J. Pulmonary dysfunction in
'freebase' cocaine users. Arch Intern Med 1984; 144:2195-97
4 Cucco RA, Yoo OH, Cregler L, et al. Nonfatal pulmonary
edema after 'freebase' cocaine smoking. Am Rev Respir Dis
1987; 136:179-81
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