The Effects of Intravenous Nitroglycerin and Isosorbide Dinitrate
on Hemodynamics and Myocardial Metabolism
M.E. Davis, MB, BS, FFARCS, C.J.H. Jones, MB, BS, MRCP, R.O. Feneck, MB, BS, FFARCS,
and R.K. Walesby, MSc, MB, BS, FRCS
Myocardial ischemia before and during coronary
a r t e r y surgery is significant, because patients w h o
develop perioperative myocardial ischemia have an
increased incidence of postoperative myocardial in-
farctions. Thus, the prevention of ischemic episodes
is of great importance. This study was undertaken to
(1) compare the effects of intravenous nitroglycerin
(NTG) w i t h isosorbide dinitrate (ISDN); (2) investi-
gate if the continuous infusion of nitrates had benefi-
cial effects on cardiac performance and metabolism;
and (3) compare the control of blood pressure w i t h
the nitrates versus halothane during a standardized
anesthetic. T w e n t y - o n e patients participated in t h e
study, and all had the following: a radial arterial
catheter, peripheral venous catheter, 7F pulmonary
a r t e r y catheter, and Baim coronary sinus f l o w cathe-
ter. The study was carried out in t h e prebypass
period beginning w i t h a w a k e measurements of base-
line parameters, and ending after median sternot-
omy. The patients w e r e divided into t h r e e groups:
group 1 received an infusion of NTG; group 2 re-
ceived an infusion of ISDN; and group 3, the control,
received neither nitrate, but helothane was added to
control hemodynamics. Measurements w e r e made
at the following t i m e intervals: (1) baseline; (2) after
p OSTOPERATIVE myocardial infarction ac-
counts for up to 40% of deaths following
coronary artery bypass graft (CABG) surgery. 1'2
In 1985, Slogoff and Keats3 reported that epi-
sodes of perioperative myocardial ischemia, de-
fined as ST segment depression greater than or
equal to 0.1 mV, occurred in 36.9% of patients
undergoing CABG surgery, with nearly half the
episodes occurring in the awake patient before
induction of anesthesia. They showed that pa-
tients who had episodes of perioperative myocar-
dial ischemia had an almost threefold increase
(6.9% v 2.5%) in myocardial infarction after
From the Departments of Anaesthesia, Cardiology,
and Cardiothoracic Surgery, The London Chest Hospital
United Kingdom.
Supported by a grant from Schwartz Pharmaceuti-
cals Limited, East Street, Chesham, Buckinghamshire, En-
gland.
Address reprint requests to Dr R.O. Feneck, Consul-
tant Anaesthetist, The Department of Anaesthetics, The
London Chest Hospital, Bonner Road, London E2 9JY, UK.
© 1989 by W.B. Saunders Company.
0888-6296/89/0306-0006
712 Journal of Cardiothoracic Anesthesia, Vol 3, No 6 (December), 1989: pp 712-719
5 minutes of t h e nitrate infusions w h i l e a w a k e
(groups 1 and 2); (3) after induction of anesthesia,
laryngoscopy, and intubation; and (4) after median
sternotomy. In groups 1 and 2, t h e nitrates w e r e
infused at 0.1 m g / k g / h for 5 minutes. Thereafter,
blood pressure control and t r e a t m e n t of episodic
hypertension w e r e achieved by alteration of the rate
of nitrate infusions, or, in group 3, by 0.5% t o 2% of
inspired halothane. Following induction of anesthe-
sia, t h e r e was a reduction of arterial blood pressure,
and during the remainder of the study the systolic
arterial pressure was maintained b e t w e e n 80% and
100% of baseline values. The infusion of the nitrates
in the prebypass period for control of the hyperten-
sive responses to the stimulation of surgery was
associated w i t h significant decreases in right ventric-
ular s t r o k e w o r k index, pulmonary a r t e r y pressure,
pulmonary capillary w e d g e pressure, and pulmonary
vascular resistance. No other significant differences
in either hemodynamic or metabolic parameters
w e r e found b e t w e e n the nitrate and halothane
groups. All t h r e e drugs controlled blood pressure
and avoided ischemic episodes.
© 1989 by W.B. Saunders Company.
CABG surgery, and the incidence of postopera-
tive myocardial infarction (PMI) was indepen-
dent of the time of the ischemia.
Factors that tend to decrease myocardial
oxygen supply or increase demand may be ex-
pected to have a detrimental effect on cardiac
function. In particular, patients undergoing anes-
thesia and surgery may be at special risk because
the effects of anesthetic drugs may cause a
reduction in myocardial oxygen supply, and the
sympathetic response to laryngoscopy, intuba-
tion, and surgery may cause substantial increases
in oxygen demand which may not be met in
patients with multiple coronary artery stenoses.
The use of nitrates for the treatment of
myocardial ischemia in patients with coronary
artery disease (CAD) is well established. How-
ever, the prevention of ischemic episodes via
prophylactic administration of nitrates in the
perioperative period is not as widely practiced.
Nitroglycerin (NTG) and isosorbide dinitrate
(ISDN) are widely used nitrates. This study was
designed to compare the hemodynamic and myo-
INTRAVENOUS NITRATES BEFORE AND DURING SURGERY
cardial metabolic effects of these two compounds
when used by continuous infusion to control
blood pressure in the prebypass period. Further-
more, the study assessed whether or not, in the
presence of significant CAD, the administration
of nitrates could be shown to have any beneficial
effect over the control of blood pressure using
halothane.
MATERIALS AND METHODS
Twenty-one patients, all male, scheduled for elective
CABG, gave their informed consent to participation in this
study, which had the approval of the local ethical committee.
All patients had good left ventricular function, as assessed by
left ventricular cineangiography, and left ventricular end-
diastolic pressures of less than 15 mm Hg. All had angiograph-
ically proven multiple coronary artery stenoses. Patients were
excluded from the study if they had known intolerance to
nitrates.
Full antianginal medication (fl-blockers, nitrates, and
calcium antagonists) was continued up to and including the
morning of surgery. Premedication consisted of diazepam, 15
to 20 mg, orally, 2 hours preoperatively, and papaveratum, 15
to 20 mg, and scopolamine, 0.3 to 0.4 mg, intramuscularly, 1
hour later. In all patients, the following catheters were placed
under local anesthesia: a radial arterial catheter, peripheral
venous catheter, 7F thermodilution pulmonary artery cathe-
ter, and an Elecath Bairn coronary sinus flow catheter. The
latter two catheters were inserted via introducers in the right
internal jugular vein, and were guided into position under
x-ray control.
The anesthetic technique was a benzodiazepine, nar-
cotic, relaxant sequence. Fentanyl, 30/~g/kg, was given on
induction with up to 5 mg of midazolam. Pancuronium was
used to achieve neuromuscular relaxation, and the patients'
lungs were ventilated with 100% oxygen. The study was
undertaken in the prebypass period and began with measure-
ment of the baseline parameters in the awake patient. The
final set of readings was taken just after median sternotomy.
The patients were divided into three groups in a
randomized manner. Group 1 received a continuous intrave-
nous infusion of NTG; group 2 received a continuous intrave-
nous infusion of ISDN; and group 3 received no nitrate. In
groups 1 and 2, blood pressure control was achieved by
alteration of the rate of the nitrate infusions. In group 3, the
control group, blood pressure control was achieved with
halothane. Measurements were made at the following four
times during the study: (1) baseline; (2) after 5 minutes of
nitrate infusions; (3) after induction of anesthesia, laryngos-
copy, and intubation; and (4) immediately after median
sternotomy. At each time, hemodynamic and metabolic
parameters were recorded. (Tables 1 and 2). The coronary
vascular resistance (CVR) and the myocardial metabolic
indices were calculated using the formulae shown in the
Appendix.
In group 1, NTG, 1 mg/mL, was infused initially at a
rate of 0.1 m g / k g / h (approximately 1.5 gg/kg/min) for 5
minutes. Similarly, in group 2, ISDN, 1 m g / m L , was infused
at a rate of 0.1 m g / k g / h for 5 minutes. In both of these
713
Table 1. Measured Parameters
Hemodynamic
Heart rate
Arterial blood pressure (systolic, diastolic, and mean)
Right atrial pressure
Pulmonary artery pressure
Pulmonary capillary wedge pressure
Cardiac output
Coronary sinus blood flow
Great cardiac vein blood flow
Metabolic
Oxygen content (arterial)
Oxygen content (coronary sinus)
Oxygen content (great cardiac vein)
Lactate concentration (arterial)
Lactate concentration (coronary sinus)
Lactate concentration (great cardiac vein)
groups, episodic hypertension was treated by increasing the
rate of nitrate infusion.
The electrocardiogram was monitored using a modi-
fied V 5 lead with an Oxford cassette recorder for analysis of
ST segment changes. The protocol stated that any ischemic
changes had to be treated with a nitrate in the appropriate
manner. The cardiac output (CO) was measured using the
thermodilution technique (Gould Hemodynamic Profile Com-
puter Model SP1445). Multiple thermodilution injections
were carried out, and the means were calculated. The
injection times were timed to coincide with the end of
expiration. The Elecath Baim Catheter (Electro-Catheter
Corporation, N J) enabled coronary sinus blood flow (CSBF)
and great cardiac vein blood flow (GCVBF) to be determined
using a continuous thermodilution technique. 4.5 Samples of
blood were taken simultaneously from the great cardiac vein,
the coronary sinus, and the radial artery. Hemoglobin concen-
trations and oxygen saturations were measured with an
oximeter (Radiometer OSM 2 Hemoximeter). PaO 2 was
measured with an ABL3 Blood Gas Analyzer (Radiometer,
Copenhagen, Denmark). Lactate concentrations were mea-
sured using a commercially available enzymatic UV system
Table 2. Derived Parameters
Hemodynamic
Cardiac index
Stroke volume and stroke index
Left ventricular stroke work
Right ventricular stroke work
Pulmonary vascular resistance
Systemic vascular resistance
Coronary vascular resistance
Metabolic
Lactate extraction (coronary sinus)
Lactate extraction (great cardiac vein)
Oxygen consumption (coronary sinus)
Oxygen consumption (great cardiac vein)
Oxygen extraction (coronary sinus)
Oxygen extraction (great cardiac vein)
714
(Boehringer M a n n h e i m G m b H , Federal Republic of Ger-
many).
Student's t test was used to identify significant differ-
ences between the mean values at each time interval. In
addition, mean values at baseline were compared with the
mean values at the other three sequential time intervals. The
results are plotted graphically as means _+ SEM, with levels
of significance indicated.
RESULTS
Table 3 shows the demographic data. Both
N T G and ISDN were infused initially in the
awake patient at the rate of 0.1 m g / k g / h for the
first 5 minutes of the study. In group 1, this
meant a mean infusion rate of N T G of 129.7
ug/min, and for ISDN, a mean infusion rate of
139.2 #g/min.
Following induction of anesthesia there
were decreases in systolic and diastolic arterial
blood pressures (Fig 1). In all three groups, a
20% reduction in systolic arterial blood pressure
was aimed for in order to produce a comparable
hemodynamic situation. In group 1, a total of 9
mg of N T G was required to achieve this reduc-
tion in blood pressure, while in group 2, a total of
9 mg of ISDN was used. In group 3, the control
group, up to 2% inspired halothane was used to
control the arterial blood pressure.
During the remainder of the study, the
systolic arterial blood pressure was maintained
between 80% and 100% of baseline values. In
group 1, the mean infusion rate of N T G was
202.0/tg/min; in group 2, the mean infusion rate
of ISDN was 260.6 t~g/min; in group 3, blood
pressure control was achieved with between 0.5%
and 2.0% of inspired halothane. Blood pressure
control was effective in all groups (Fig 1). Aver-
age diastolic arterial blood pressures were 72.2
mm Hg at baseline, 62.7 mm Hg after induction
of anesthesia, and 66.9 mm Hg after sternotomy.
Heart rate (HR) remained within accept-
able limits throughout the study. However, the
heart rates recorded at time 4 were higher in both
nitrate groups than in the halothane group, the
difference between ISDN and halothane being
Table 3. Demographic Data
No. in study 21 (21 male, 0 female)
44-70 (mean 56.95)
Age (yr)
Weight (kg) 60-101 (mean 81.04)
Height (cm) 160-188 (mean 174.59)
Body surface area (m 2) 1.64-2.23 (mean 1.96)
CAD Duration (yr) 0.08-14.0 (mean 5.22)
Vessel disease 2v (4), 3v (15), 4v (2)
DAVIS ET AL
BLOOD PRESSURE
SYSTOLIC / DIASTOLIC
rmmH~
150
140
T \
130
120
ii0 "<-- \ ,// /"
i00
90
80
70
60
50
40
1 2 3 4
Fig 1. Control of systolic and diastolic arterial
blood pressures by continuous intravenous infusion of NTG
and ISDN using inspired halothane as control. Plots are
means _+ SEM (1) Baseline, (2) after 5 minutes of nitrate
infusion, (3) after induction of anesthesia, and (4) after
sternotomy. (. . . . . ), NTG; ( - - -), ISDN; ( - - ) , control.
significant (P < 0.05). Between times 1 and 4,
the percentage increases in heart rate were:
group 1, 32%; group 2, 36%; and group 3, 14%
(Fig 2).
Right atrial pressure (RAP) differences
among the three groups were not significant
except at time 4, when the RAP in the nitrate
groups was decreased. This decrease was signifi-
cant for ISDN (P < 0.05) (Fig 2). Cardiac index
was maintained throughout the study, and there
were no significant differences in cardiac index
among the three groups (Fig 2).
The systemic vascular resistance (SVR)
was decreased by both nitrates during the 5-
minute awake infusion, recorded at time 2. At
the same infusion rate, ISDN had a greater
effect, producing a 9.8% reduction compared
with a 3.0% reduction by N T G (Table 4). The
CVR showed no significant differences among
the three groups throughout the study. Between
times 1 and 4, the changes in CVR were: group 1,
+1.1%, group 2, +17%, and group 3, - 3 . 5 %
(Table 5). The changes in left ventricular stroke
work index (LVSWI) for all groups are shown in
Table 6.
Pulmonary artery pressures (PAP) were
not significantly changed by the nitrate infusions
in the first 5 minutes of the study; they were
decreased following induction of anesthesia in all
three groups. Group 1 showed significant de-
INTRAVENOUS NITRATES BEFORE AND DURING SURGERY 715

HEART RATE Table 5. Percent Change in Coronary Vascular Resistance

Beat / mln
(ram H g / m L / m i n ) for Each S t u d y / T i m e Period
1O0
90 Group 1 Group 2 Group 3
80 L-
____J Time (NTG) (ISDN) (Halothane)
70
5O ____ _z~ Mean baseline
50
CVR 1 0.90 0.94 0.84
Poatinfusion
MEAN BLOOD PRESSURE
mmH~ (awake) 2 0.90 0.78
(no change) (-- 17.0%)
120
Ii0 Postanesthesia 3 0.82 0.87 0.70
I00 (--8.8%) (+11.5%) (--16.6%)
90
80 Poststernotomy 4 0.91 1.10 0.81
70
50
(+10.9%) (+26.4%) (+15.7%)
50 Total change (%) +1,1% +17.0% --3.5%

RIGHT ATRIAL PRESSURE

m~H 5
4
than anesthesia alone. At time 4, the PCWP for
lO [ I T ISDN was significantly lower than for halothane
5 F- ......... -£-- . . . . . . . . . . i- ~ ~ -'--'~ (P < 0.01) (Fig 3). Pulmonary vascular resis-
0 tance (PVR) was significantly lower for NTG
than for halothane at time 4 (P < 0.01). Also at
CARDIAC INDEX
time 4, a significant difference between the two
K

nitrate groups had developed, PVR for NTG was

3 I
2
T r
~.~" ~ . ~ ~ - - I - - ~ ~ .
l ~
1 2
Fig 2. Effect of continuous intravenous infusion of
NTG and ISDN on heart rate, mean blood pressure, right
atrial pressure, and cardiac index. Means _+ SEM. Signifi-
cant difference from control, (*) ( P < 0 . 0 5 ) . (. . . . . ),
NTG; (- - -), ISDN; ( - - ) , control.
creases in mean PAP compared with group 3 at
times 3 (P < 0.05) and 4 (P < 0.01). Group 2
showed a significant decrease compared with
group 3 at time 4 (P < 0.01) (Fig 3). The
pulmonary capillary wedge pressures (PCWP)
remained unchanged during the 5-minute awake
infusion. The induction of anesthesia in patients
receiving the nitrates produced a greater decline
in pulmonary capillary wedge pressure at time 3
lower than with ISDN (P < 0.05) (Fig 3). Right
_~ ~_
_.~z-. - - . -. . . . J
---J" ventricular stroke work index (RVSWI) showed
3 4
no significant differences among the groups at
time 2. Both nitrate groups, when compared with
the halothane group, showed significant de-
creases in RVSWI at time 3 (P < 0.05). Simi-
larly, at time 4, the decrease in RVSWI for
each of the nitrates compared with halothane
was significant, NTG (P < 0.05) and ISDN
(P < 0.01) (Fig 3).
The lactate extractions, both globally and
regionally, showed no significant differences be-
tween the two nitrate groups and the halothane
group. However, at time 2, the coronary sinus
lactate extraction for ISDN was significantly
greater than for NTG (P < 0.05) (Fig 4). The
myocardial oxygen consumption (M'VO2), glob-
ally and regionally, showed no significant differ-

Table 4. Percent Change in Systemic Vascular Resistance Table 6. Percent Change in Left Ventricular Stroke W o r k
(dyne • s • cm -5) for Each S t u d y / T i m e Period Index (g • m / b e a t / m 2) for Each S t u d y / T i m e Period
Group 1 Group 2 Group 3 Group 1 Group 2 Group 3
Time (NTG) (ISDN) (Halothane) Time (NTG) (ISDN) (Halothane)
Mean baseline Mean baseline
SVR 1 1703 2023 1654 LVSWI 1 37.9 39.1 46.6
Postinfusion Postinfusion
(awake) 2 1651 1823 (awake) 2 40.1 39.0
(--3.0%) (--9.8%) (+5.8%) (no change)
Postanesthesia 3 1650 1576 1419 Postanesthesia 3 24.4 22.1 27.3
(nochange) (--13.5%) (--14.2%) (--39.1%) (--43.3%) (--41.6%)
Poststernotomy 4 1806 2010 1909 Poststernotomy 4 26.1 22,3 26.3
(+9.4%) (+27.5%) (+34.5%) (+6.9%) (no change) (--3.6%)
Total change (%) +6.0% --0.6% +15.4% Total change (%) --31.1% --42.9% --43.5%
716 D A V I S ET A L

PULMONARY ARTERY PRESSURE LACTATE EXTRACTION

~ g per cent

20 T 4O

30
i
15
i "~--- ~. ~ " i ~ ~ __.__T
lO "'-r--. . . . . . . -I
2O
r- . . . . . . . . . T . . . . . . . . I ---].
i0

PULMONARY CAPILLARY ~FHDGE P R E S S U R E

m=Hg MYOCARDIAL OXYGEN CONSUMPTION (MVO=)
ml O m / m i n

k5
L --~ 14
i0 T T
13
12
ii
I0
9
PULMONARY VASCULAR RESISTANCE 8
dyne-see-ore -s 7

200

180
l?O
1_ . . . . .
_L per cent
OXYGEN EXTRACTION

i00 ++
65
i40 "~-~. ~.
130 55 L ~

LI0
100 ..o T ........... T ........... -]
90

CORONARY SINUS BLOOD FLOW

RIGHT VENTRICULAR STROKE ~ORK INDEX ml/min
~m-mlbeaz/m ~
150
7 140
130
!20
llO
3 ~ _.~ L00
9O
8O

I 2 3 4
'1
1 2 3 4

Fig 3. Effect of continuous intravenous infusion of

NTG and ISDN on mean pulmonary artery pressure, pulmo-
nary capillary wedge pressure, pulmonary vascular resis-
tance, and right ventricular stroke w o r k index. Means -+
SEM. Significant difference from control, (*) ( P < 0.05);
(**) (P<0.01), and between nitrates, ( + ) ( P < O . 0 5 ) .
(. . . . . ), NTG; (- - - ) , ISDN; ( - - ) , control.
Fig 4. Effect of continuous intravenous infusion of
NTG and ISDN on coronary sinus (global) lactate extraction,
global myocardial oxygen consumption (M~O2), global oxy-
gen extraction, and coronary sinus blood flow. Means _+
SEM. Significant difference from control, (*) (P < 0.05), and
b e t w e e n nitrates, ( + ) ( P < 0 . 0 5 ) ; (++) (P<0.01).
(. . . . . ), NTG; ( - - - ) , ISDN; ( - - ) , control.

ences between the nitrates and halothane. At
time 2, the global M'~O 2 for I S D N was signifi-
cantly greater than for N T G (P < 0.05) (Fig 4).
Global oxygen extraction for N T G decreased
significantly at time 2 (P < 0.05). Comparison
between nitrates at time 2 showed global oxygen
extraction for I S D N to be significantly higher
than for N T G (P < 0.01) (Fig 4). There was no
significant change in coronary sinus blood flow
(CSBF) throughout the study; neither were there
any significant differences among the three groups
at any of the time intervals (Fig 4).
Table 7 shows mean CSBF and mean
G C V B F for each group at each time interval as
measured in this study. The mean baseline CSBF
was 114.2 m L / m i n , and the mean baseline
G C V B F was 56.8 m L / m i n , or 49.7% of the
coronary sinus blood flow. There was no ST seg-
ment depression greater than or equal to 0.1 mV
on the electrocardiogram (ECG).
DISCUSSION
This study was carried out in the prebypass
period of CABG surgery and was designed to
compare an infusion of N T G and I S D N . They
were compared initially at a fixed rate in the
awake patient, and subsequently at rates that
were sufficient to control the hypertensive re-
sponse to stimulation during anesthesia and sur-
gery.
INTRAVENOUS NITRATES BEFORE AND DURING SURGERY 717

Table 7. Coronary Sinus and Great Cardiac Vein Blood pressure, pulmonary vascular resistance (PVR),
Flows (mL/min) RVSWI, and LVSWI are all theoretically bene-
Group 1 Group2 Group3 ficial in reducing myocardial oxygen demand. 13
Time (NTG) (ISDN) (Halothane)
Thus, from the present data it would seem that
Coronary sinus
those factors affecting oxygen supply and de-
Mean baseline flow 1 116.8 112.0 113.8
Postinfusion (awake) 2 112.0 132.0
mand were appropriately controlled and oxygen
Postanesthesia 3 124.2 102.7 103.4 balance was well maintained. Indeed, preserva-
Poststernotomy 4 110.7 79,8 100.2 tion of aerobic metabolism in both groups was
indicated by the lactate-extraction measure-
ments.
Great cardiac vein
Mean baseline flow 1 56.7 56.4 57.3
The mechanism whereby nitrates exert their
Postinfusion (awake) 2 50.4 57.4 antianginal effects is multifactorial. The effects
Postanesthesia 3 48.3 48.6 56.1 can be classified as either direct myocardial
Poststernotomy 4 48.9 45.8 43.5 effects or peripheral vascular effects.
Nitroglycerin causes dilation of large coro-
The best accepted indicator of myocardial nary arteries; it dilates stenosed arteries as well
ischemia, electrocardiographic ST segment as normal arteries. Nitrates redistribute blood
change, is known to occur late, with metabolic flow along collateral channels and from epicar-
changes and mechanical dysfunction preceding dium to endocardium. ~4"16 By reducing left
ECG changes. With impending ischemic change, ventricular end-diastolic pressure, nitrates in-
there is a shift from aerobic to anaerobic metabo- crease the transmyocardial perfusion pressure
lism, evidence of dysfunction such as regional and promote subendocardial coronary blood flow.
wall motion abnormality, and finally ECG The effects of nitrates on decreasing oxygen
changes. 6 These alterations may occur in small demand are probably more important than in
areas of the myocardium and may only be increasing oxygen supply. ]7,18
detectable if methods are available for analyzing The major peripheral effect of N T G is to
regional performance or regional metabolism. dilate venous capacitance vessels, 19reducing ven-
Echocardiography, 7 radionuclear imaging, 8 and tricular volume, which reduces the wall tension
conventional ventriculography 9 all have a place required to produce a given pressure, hence
in detection of wall motion abnormalities, but the reducing the ventricular oxygen requirements.
latter two techniques may be difficult to accom- To a lesser extent, nitrates cause peripheral
plish in a surgical setting. arteriolar vasodilation which reduces afterload
The preservation of the myocardial oxygen and contributes to the decrease in oxygen require-
balance relies on controlling the factors that ments. 20
determine myocardial oxygen supply and de- There is evidence that N T G and ISDN
mand.l° Patients receiving N T G or ISDN showed have different effects on some hemodynamic
a tendency to tachycardia, which theoretically indices, N T G mainly affecting the systemic
could reduce diastolic coronary filling time and venous capacitance vessels and PVR, and ISDN
hence blood flow. 11 However, both groups had mainly influencing the SVR and the pulmonary
small reductions in P C W P which, if reflected in vascular resistance. 21 These findings are not uni-
LVEDP, would be expected to result in improved versal and Luther et al did not find any differ-
perfusion to the subendocardial areas. Diastolic ences in the hemodynamic effects of intravenous
blood pressure was well maintained in both ISDN and NTG. 22 A recent study compared the
nitrate groups, favoring preservation of coronary use of ISDN with N T G for the control of
perfusion pressure, which is usually defined as perioperative hypertension, z3 Both nitrates were
aortic diastolic blood pressure minus left ventric- effective in controlling increased systolic blood
ular end-diastolic pressure. ~2 Neither CSBF, pressure, the effective dose of ISDN being 6.5
GCVBF, nor CVR measurements showed any ~zg/kg/min compared with a dose of 3.8 # g / k g /
significant differences between the N T G and rain for NTG.
ISDN groups. In the present study, the effects of the
The reductions in PAP, systemic arterial infusion of nitrates on hemodynamic and meta-
718 DAVIS ET AL

bolic indices were compared with the effects of a
nonnitrate infusion technique in which halothane
was used for blood pressure control. Halothane
has been used to decrease myocardial ischemia,
and it has been shown to decrease myocardial
infarct size. 24
However, another study showed that an
inspired concentration of halothane well toler-
ated by m y o c a r d i u m supplied by a normal coro-
nary artery commonly produces dysfunction char-
acteristic of myocardial ischemia in an area
supplied by a critically narrowed coronary ar-
tery. 25 The cause of the dysfunction appeared to
be a localized decrease in coronary perfusion,
most probably associated with a pressure gradi-
ent across a constriction in a coronary artery.
Thus, despite normal h e m o d y n a m i c values and a
normal ECG, such an area of m y o c a r d i u m m a y
become compromised during anesthesia, and this
m a y be an important cause of myocardial infarc-
tion.
M a n y reports have suggested that halothane
anesthesia causes a significant dose-dependent
reduction in myocardial performance. 26'27 How-
ever, there is no evidence in h u m a n s that
halothane, in contrast with isoflurane, causes an
adverse redistribution of coronary b l o o d flow
away from ischemic areas, thus producing a
coronary steal phenomenon. 28 In the present
study, fentanyl, 30 ~ g / k g , allowed minimal use
of inspired halothane in the control group. Arte-
rial blood pressure was as well controlled by
halothane as with the nitrates. At the time of
sternotomy, the heart rate remained lower in the
control group. PAP, P C W P , P V R , and R V S W I
were all significantly higher in the control group
than in the nitrate groups at this time. There
were no significant differences in metabolic indi-
ces or coronary sinus blood flow between the
control group and the nitrate groups at the time
o f sternotomy.
In summary, this study has shown that
there are theoretically significant beneficial ef-
fects associated with the infusion of nitrates as
opposed to the nonnitrate technique. These bene-
ficial effects were restricted to h e m o d y n a m i c
parameters. They are theoretical since there
were no demonstrable adverse effects from blood
pressure control with halothane, and no benefi-
cial effects of nitrates were found on myocardial
metabolism when compared with halothane.
Although the hypothesis that all patients at
risk from myocardial ischemia would benefit
from intravenous nitrates prior to and during
surgery remains unproven by the study, the data
show that prophylactic nitrate infusions will
produce some significant and theoretically useful
differences in h e m o d y n a m i c variables.

APPENDIX
The CVR was calculated using the followingformula:
MAP RAP -

CVR -- CSBF mm Hg/mL/min

MAP RAP -

×8× 10 4 dyne • s • cm 5
CSBF
where MAP = mean arterial pressure (ram Hg); RAP = right atrial pressure (mm Hg); and CSBF = coronary sinus blood flow
(mL/rain).
Myocardial metabolic induces were calculated using the followingformulae:
Oxygen content ( C a O 2 ) = (Hb × Sat% x 1.36) + 0.003 × PaO2 (mL/dL)

Myocardial oxygen consumption (global) (MVO2) = (CaO2 - CcsO2) × CS Flow (raL/rain)

Myocardial oxygen consumption (regional) (MVO2)r = (CaO2 - CgcvO2) x GCV Flow (mL/min)

Ca02 - CcsOz
Myocardial oxygen extraction -- Ca02 × 100%

Calaet CVlact
- -

Myocardial lactate extraction = Calaet × 100%

where CaO2 is arterial oxygen content; CcsO2is coronary sinus oxygen content; Calact is arterial lactate concentration; and Cv~actis
venous lactate concentration (either cs or gcv).
INTRAVENOUS NITRATES BEFORE AND DURING SURGERY
ACKNOWLEDGMENT
The authors are indebted to and wish to express their thanks to Dr E. Lockey, MD, BSc, FRCPath, Consultant Chemical
Pathologist at the London Chest Hospital, for measurement of the metabolic indices, and to the surgeons and cardiologists of the
London Chest Hospital for their cooperation.
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