NITROUS OXIDE AND CARDIOVASCULAR FUNCTION
Myocardial Contractility and Left Ventricular Diastolic
Function
Experiments in papillary muscle[453]
[454]
[455]
and
isolated
heart preparations[240]
have consistently demonstrated
that nitrous oxide produces a direct negative inotropic effect. Conflicting results
about the influence of nitrous oxide on contractility have been observed in experimental
animals and healthy volunteers. Several problems have contributed to apparently
contradictory results in vivo. Observed changes in contractile function may be influenced
by the actions of nitrous oxide on the systemic circulation or by autonomic nervous
system reflex effects[456]
[457]
because nitrous oxide may increase sympathetic nervous system tone.[458]
[459]
[460]
Studies
using nitrous oxide alone are difficult to perform and interpret because this gas
does not produce total anesthesia at partial pressures less than 1 atmosphere.[461]
[462]
[463]
[464]
[465]
[466]
The
effects of nitrous oxide on contractile function may be influenced by different baseline
anesthetics.[467]
[468]
[469]
[470]
[471]
[472]
[473]
Lack
of use of load-insensitive measures of myocardial contractility has allowed only
qualitative assessment of the effects of nitrous oxide on intrinsic inotropic state
in the intact heart.
Figure 7-23
Effects of desflurane (red squares)
and isoflurane (black squares) on sympathetic nerve
activity (top), heart rate (middle),
and mean arterial pressure (bottom) in healthy volunteers.
Desflurane or isoflurane administration began 2 minutes after anesthetic induction
with sodium thiopental (STP). Sympathetic nerve excitation, tachycardia, and hypertension
were observed in subjects receiving desflurane. *, Different (P
< .05) group response; †, desflurane response different (P
< .05) from STP value; ¥, isoflurane response different (P
< .05) from STP value. (Adapted from Ebert TJ, Muzi M: Sympathetic hyperactivity
during desflurane anesthesia in healthy volunteers: A comparison with isoflurane.
Anesthesiology 79:444–453, 1993.)
The regional PRSW relationship demonstrated that nitrous oxide
depresses myocardial contractility in dogs anesthetized with isoflurane or sufentanil
in the absence of autonomic nervous system activity ( Fig.
7-24
).[474]
Seventy percent nitrous oxide
decreased the PRSW slope (Mw
) by 28% and 41% during sufentanil and isoflurane
anesthesia, respectively. These results indicate that 70% nitrous oxide decreased
contractility to approximately the same extent as 1 MAC of isoflurane. Similar findings
have been reported using LV end-systolic pressure-dimension relationships in acutely
instrumented dogs.[473]
These nitrous oxide-induced
myocardial depressant effects may be offset by concomitant increases in sympathetic
nervous system tone.[459]
The negative inotropic
actions of
Figure 7-24
Effects of nitrous oxide (N2
O) on the preload
recruitable stroke work (PRSW) slope in the presence of isoflurane (I, top
panel) and sufentanil (S, bottom panel)
are shown as a percentage of the control (I or S only, respectively). *, Significantly
(P < .05) different from I or S only; †,
significantly (P < .05) different from I or S
plus 30% nitrous oxide. (Adapted from Pagel PS, Kampine JP, Schmeling WT,
Warltier DC: Effects of nitrous oxide on myocardial contractility as evaluated by
the preload recruitable stroke work relationship in chronically instrumented dogs.
Anesthesiology 73:1148–1157, 1990.)
nitrous oxide may be more pronounced in the presence of preexisting LV dysfunction.
[475]
Nitrous oxide-induced depression of contractile
function appears to overcome the mild sympathomimetic effect of this anesthetic gas
in patients with coronary artery[465]
[470]
[471]
[476]
[477]
[478]
or valvular heart[465]
[479]
disease because increases in baseline sympathetic
nervous system activity cannot be further augmented by nitrous oxide in these clinical
conditions.
The actions of nitrous oxide on LV diastolic function have been
incompletely studied. Modest increases in maximal lengthening velocity and maximal
rate of decline of force have been observed in ferret papillary muscle concomitant
with decreases in contractile state.[455]
No changes
in the rate of isometric or isotonic relaxation were observed,
indicating that nitrous oxide does not substantially modify myocardial relaxation.
[455]
Nitrous oxide can modestly increase segmental
indices of LV chamber compliance and reduce early LV filling in acutely instrumented
dogs.[480]
These findings are supported by evidence
indicating that nitrous oxide may produce LV diastolic dysfunction after cardiopulmonary
bypass in patients undergoing CABG surgery.[478]
Nitrous oxide causes dose-related reductions in the intracellular
Ca2+
transient in vitro.[455]
[481]
This finding indicates that nitrous oxide-induced depression of myocardial contractility
is related to decreases in Ca2s+
availability for contractile activation.
Nitrous oxide does not affect myofibrillar sensitivity to Ca2+
[455]
[482]
or Ca2+
uptake and release from
the SR.[482]
The diastolic Ca2+
transient
is unaffected by nitrous oxide, suggesting that this anesthetic gas does not alter
myocardial relaxation kinetics.[481]
