Diastolic Function
Definitions of heart failure based solely on contractile dysfunction
have been rendered inadequate by the recognition that LV function during diastole
significantly influences overall cardiac performance. The heart serves dual roles,
propelling blood into the high-pressure arterial vasculature during systole and collecting
blood from the low-pressure venous circulation during diastole. Heart failure may
occur from impaired contractility or from altered LV diastolic function. The timing,
rate, and extent of LV filling are determined by several major factors, including
the rate and degree of myocardial relaxation, the intrinsic mechanical properties
of the left ventricle itself and those imposed by external constraints, and the structure
and function of the left atrium, the pulmonary venous circulation, and the mitral
valve.[110]
Although abnormalities in LV diastolic
function may be linked to decreases in myocardial contractility, heart failure may
result from primary diastolic dysfunction in the absence of or before the appearance
of alterations in LV systolic function[111]
[112]
[113]
in a variety of pathologic conditions, including
ischemic heart disease, pressure- or volume-overload hypertrophy, hypertrophic obstructive
cardiomyopathy, and restrictive disease processes.[114]
[115]
The effects of volatile anesthetics on diastolic function in the
normal and diseased heart have been incompletely studied. Volatile agents produce
dose-related prolongation of isovolumic relaxation in vivo ( Fig.
7-5
).[47]
[116]
[117]
[118]
This
delay of isovolumic relaxation may be associated with declines in early LV filling
[27]
[30]
[32]
[47]
but probably is not of sufficient magnitude
to affect LV chamber stiffness. The
Figure 7-5
Effects of desflurane, isoflurane, and halothane on the
time constant of isovolumic relaxation (T0
). *, Significantly (P
< .05) different from control; †, significantly (P
< .05) different from 1.0 minimum alveolar concentration (MAC). (Adapted
from Pagel PS, Grossman W, Haering JM, Warltier DC: Left ventricular diastolic function
in the normal and diseased heart: Perspectives for the anesthesiologist. Anesthesiology
79[Pt 1]:836–854, 1993.)
significance of anesthetic-induced delays in isovolumic relaxation to early coronary
blood flow has not been thoroughly investigated, but coronary blood flow is highest
during this phase of diastole, and delays in relaxation lead to impairment of flow
during halothane anesthesia.[116]
Prolongation
of LV relaxation probably occurs as a result of simultaneous depression of myocardial
contractility and not because of a direct negative lusitropic effect.[119]
Isoflurane, enflurane, and halothane modestly enhance isotonic relaxation of isolated
ferret myocardium in vitro.[120]
Volatile anesthetics cause concentration-related decreases in
the rate and extent of early LV filling concomitant with negative inotropic effects.
Isoflurane and halothane also reduce LV filling associated with atrial systole.
[30]
Isoflurane, desflurane, and sevoflurane do
not alter invasively derived indices of regional myocardial or chamber stiffness,
indicating that LV distensibility is unaffected by these volatile agents ( Fig.
7-6
).[47]
[118]
Although some indirect evidence suggests that halothane affects LV compliance,[121]
[122]
[123]
later
studies[17]
[118]
[124]
using invasively derived measures of LV passive
elasticity and myocardial stiffness indicate that this is not the case. Halothane
increases LV end-diastolic pressure, indicating that the left ventricle operates
on a steeper, less compliant region of the LV end-diastolic pressure-volume relationship;
however, this volatile agent does not directly alter the intrinsic viscoelastic properties
of the myocardium.[1]
The effects of isoflurane and halothane on LV diastolic function
in a canine model of dilated cardiomyopathy have been described.[65]
In contrast to the findings in dogs with normal LV function, isoflurane improved
several indices of LV relaxation and filling in cardiomyopathic dogs despite producing
simultaneous negative inotropic effects. Halothane did not exacerbate preexisting
diastolic dysfunction inherent to this experimental model.
Figure 7-6
Left ventricular (LV) diastolic transmural pressure versus
Lagrangian strain relationships in conscious (squares)
and halothane-anesthetized (triangles) dogs. The
pressure-strain relationship was not altered by halothane anesthesia, indicating
that this volatile anesthetic does not affect intrinsic myocardial stiffness. α,
Gain; β, modulus of myocardial stiffness. (Adapted from Van Trigt P,
Christian CC, Fagraeus L, et al: The mechanism of halothane-induced myocardial depression:
Altered diastolic mechanics versus impaired contractility. J Thorac Cardiovasc
Surg 85:832–838, 1983.)
The findings with isoflurane and halothane were most likely related to favorable
reductions in LV preload produced by these volatile agents and not caused by direct
positive lusitropic effects.[65]
These data further
suggest that isoflurane-induced improvements of LV isovolumic relaxation and filling
dynamics may contribute to relative maintenance of cardiac output in the presence
of LV dysfunction despite simultaneous reductions in contractility.[65]
The findings in cardiomyopathic dogs supported earlier clinical observations[62]
[64]
reporting that patients with severe ischemic
heart disease or congestive heart failure tolerated isoflurane or halothane anesthesia
without acute hemodynamic decompensation.
Some investigations have demonstrated that the afterload dependence
of LV relaxation is markedly enhanced in failing myocardium.[125]
[126]
This observation has important clinical consequences
because afterload reduction may increase LV systolic performance by decreasing impedance
to LV ejection and may increase the rate of LV relaxation and therefore contribute
to improvements in LV diastolic filling and compliance.[127]
The effects of isoflurane and halothane on the afterload dependence of LV relaxation
have been explored in dogs before and after the development of rapid LV pacing-induced
cardiomyopathy.[66]
The afterload dependence of
LV relaxation was unaffected by isoflurane and halothane anesthesia in dogs with
dilated cardiomyopathy ( Fig. 7-7
),
further indicating that these
Figure 7-7
Linear relationship between the time constant of isovolumic
relaxation (τ) and left ventricular end-systolic pressure (Pes
) during
inferior vena caval occlusion (left panels) in a
typical dog before (red squares) and after (black
squares) the development of pacing-induced cardiomyopathy in the conscious
state and during isoflurane and halothane anesthesia. The histograms illustrate
the slope (R) of the τ versus Pes
relationship in the conscious state
(top right panel) and during isoflurane (middle
right panel) and halothane (bottom right panel)
anesthesia before (red bars) and after (black
bars) pacing. a, Significantly (P <
.05) different from normal myocardium. (Adapted from Pagel PS, Hettrick
DA, Kersten JR, et al: Isoflurane and halothane do not alter the enhanced afterload
sensitivity of left ventricular relaxation in dogs with pacing-induced cardiomyopathy.
Anesthesiology 87:952–962, 1997.)
volatile agents do not exert direct actions on LV isovolumic relaxation in failing
myocardium.
