(Circulation. 1998;97:292.)
© 1998 American Heart Association, Inc.
Inhaled NO and Pulmonary Vasodilation
Bernard G. Krohn, MD
Good Samaritan Hospital,
Los Angeles, Calif
To the Editor:
Hare et al1 concluded that inhaled nitric oxide
(NO) caused selective pulmonary vasodilation in patients
receiving left ventricular assist device support and that
this accounted for the increase in mean left atrial pressure, which
they considered a beneficial hemodynamic effect.
The evidence for pulmonary vasodilation was that
pulmonary vascular resistance (PVR) decreased. However,
pulmonary vasodilation (an observable quantity) and decreased
PVR (a calculated quantity) are not synonymous, and either can exist in
the absence of the other: PVR (dynes · s ·
cm-5)=80x(Mean Pulmonary Artery
Pressure-Mean Left Atrial Pressure)/Cardiac
Output.2
In their patients whose mean pulmonary artery pressure (in
mm Hg) and cardiac output (in liters per minute) were fixed, NO
increased left atrial pressure (LAP), decreasing PVR in the above
equation. The authors, previously observing patients without left
ventricular assist devices, reported that NO increased left
atrial pressure and left ventricular filling pressure while
it decreased stroke volume index, a negative inotropic
effect.3 In the present study, the increased
left atrial pressure also resulted from increased left
ventricular filling pressure. The above standard equation
for PVR omits Poiseuille's factor for the radius of the tubes and
calculates decreased PVR independent of the radius of blood
vessels.
In other patients, assisted by left ventricular assist
devices as NO was inhaled, left ventricular assist device
output was increased, thereby increasing the denominator to give a
lower calculated PVR, again without invoking vasodilation.
What prevents NO from dilating pulmonary blood vessels in
patients who have severe heart failure is the high blood concentration
of norepinephrine in this condition.4
Hare previously reported that the rise in left atrial pressure
resulting from NO was greatest in the patients who had the worst left
ventricular failure.3 These were also
the patients who had the highest blood levels of
norepinephrine4 and were most
susceptible to further ventricular impairment.
The observations in this article are valuable. However, instead of
showing that inhaled NO dilated pulmonary blood vessels and
thereby gave beneficial hemodynamic effects, this study
showed that NO impaired the ventricular contractions in
these patients. The authors had it right the first
time.3
References
1.
Hare JM, Shernan SK, Body SC, Graydon
E, Colucci WS, Couper GS. Influence of inhaled nitric oxide on systemic
flow and ventricular filling pressure in patients receiving
mechanical circulatory assistance. Circulation. 1997;95:2250–2253.[Abstract/Free Full Text]
2.
Grossman W. In: Braunwald E, ed. Heart
Disease. Philadelphia, Pa: WB Saunders; 1992:194.
3.
Hare JM, Loh E, Craeger MA, Colucci WS. Nitric oxide
inhibits the contractile response to ß-adrenergic stimulation in
humans with left ventricular dysfunction.
Circulation. 1995;92:2198–2203.[Abstract/Free Full Text]
4.
Cohn JN, Levine B, Olivari MT, Cohn JN, Levine TB,
Olivari MT, Garber V, Lura D, Francis GS, Simon AB, Rector T. Plasma
norepinephrine as a guide to prognosis in patients with
chronic congestive heart failure. N Engl J Med. 1984;311:819–823.[Abstract]
Response
Joshua M. Hare, MD
Division of Cardiology,
Johns Hopkins University,
Baltimore, Md
Flow, therefore, is proportional to radius to the fourth power
given fixed tube length and fluid viscosity, and in the absence of
"vasodilation" or decreased vascular tone, flow increases must be
compensated for by an increased pressure gradient. In the intact
vasculature, increases in flow reflect, to a large extent, dilatation
of distal arterioles, also termed resistance
vessels.1 2 In some circuits, notably the
pulmonary, recruitment of collapsed arterioles may also
contribute to increases in flow in the proximal conduit
vessels.3 This mechanism, in the absence of an
increase in pressure gradient, would also be considered vasodilation
because effective radius has increased.
In our study, we measured total flow and the pressure gradient across
the pulmonary circuit. Although we had the unique ability to
control the total blood flow in our patients using the left
ventricular assist device (LVAD), we did not control
pulmonary arterial or left atrial pressures. Total
blood flow was maintained constant (fixed LVAD mode) or allowed to
respond to changes in vascular distribution (automatic LVAD mode). The
comparison in our study was between the same patients with either fixed
or variable blood flow. Variables such as circulating
catecholamines were controlled for in the study design
because the same patients were studied consecutively.
In our study, mean pulmonary arterial pressures did
not increase with either fixed or variable flow.
Transpulmonary gradient narrowed only in patients with fixed
flow and was due to a rising left atrial pressure. The best explanation
for an increase in blood flow that is not associated with an increase
in transpulmonary gradient or pulmonary
arterial pressure is vasodilation (as observed in the
automatic-mode group). Similarly, transpulmonary gradient
lowering with fixed pulmonary arterial pressure and
blood flow also reflects vasodilation (as observed in the fixed-mode
group). If ventricular impairment were the explanation for
the rising left atrial pressure in patients in the fixed mode, this
would have been associated with a concomitant rise in pulmonary
arterial pressure and a fixed transpulmonary
gradient.
Thus, we concluded, as we did in our previous
study,4 that NO is a pulmonary
vasodilator in patients with severe heart failure. Although selective
pulmonary vasodilation is beneficial in LVAD patients who can
respond with increased systemic flow, it may not be beneficial in heart
failure because of the increased left atrial pressure.
References
1.
Cooper, CJ, Landzberg, MJ, Anderson TJ,
Charbonneau F, Creager MA, Ganz P, Selwyn AP. Role of nitric oxide in
the local regulation of pulmonary vascular resistance in
humans. Circulation. 1996;93:266–271.[Abstract/Free Full Text]
2.
Grossman W. Clinical measurement of vascular
resistance and assessment of vasodilator drugs. In: Grossman W, Baim
DS, eds. Cardiac Catheterization, Angiography and
Intervention. 4th ed. Philadelphia, Pa: Lea & Febiger;
1991:143–151.
3.
Hakim TS, Michel RP, Chang HK. Partitioning of
pulmonary vascular resistance in dogs by arterial
and venous occlusion. Am J Physiol. 1982;52:710–715.
4.
Loh EH, Stamler JS, Hare JM, Loscalzo J, Colucci WS.
Cardiovascular effects of inhaled nitric oxide in
patients with left ventricular dysfunction.
Circulation. 1994;90:2780–2785.[Abstract/Free Full Text]
