Circulation, Vol 89, 2616-2625, Copyright © 1994 by American Heart Association
HL Haber, ER Powers, LW Gimple, CC Wu, K Subbiah, WH Johnson and MD Feldman
BACKGROUND: There is increasing recognition of myocardial angiotensin-
converting enzyme, which is induced with the development of left
ventricular hypertrophy (LVH). The potential physiological significance of
subsequent increased angiotensin I to II conversion in the presence of LVH
is unclear but has been postulated to cause abnormal Ca2+ handling and
secondary diastolic dysfunction. Accordingly, we hypothesized that acute
angiotensin-converting enzyme inhibition would result in decreased
production of angiotensin II and improved active (Ca(2+)-dependent)
relaxation in patients with hypertensive LVH. METHODS AND RESULTS:
Intracoronary (IC) enalaprilat was administered to 25 patients with and
without LVH secondary to essential hypertension. Indexes of diastolic and
systolic LV function were determined from pressure (micromanometer)-volume
(conductance) analysis at steady state and with occlusion of the inferior
vena cava. Patients were divided into those receiving high- (5.0 mg, n =
15) and low-dose (1.5 mg, n = 10) IC enalaprilat during a 30-minute
infusion at 1 mL/min. The high- dose patients were further divided along
the median normalized LV wall thickness of 0.671 cm/m2. The time constant
of isovolumic relaxation (TauL) was prolonged at baseline in patients
receiving high-dose enalaprilat with wall thickness > 0.671 cm/m2 (TauL,
56 +/- 2 versus 44 +/- 2 and 45 +/- 2 milliseconds, respectively, P <
.01 by ANOVA) and shortened only in this patient group (TauL, 49 +/- 3
versus 46 +/- 2 and 43 +/- 2 milliseconds, respectively, P < .01 versus
baseline and other groups by ANOVA). The improvement in TauL was directly
proportional to the degree of LVH (r = .92, P < .001). Although there
was a decrease in LV end-diastolic pressure (23 +/- 2 to 15 +/- 1 mm Hg, P
< .01) and volume (86 +/- 8 to 67 +/- 9 mL/m2, P < .05) in those
patients with a reduction in TauL, this is due to movement down a similar
diastolic pressure-volume relation with no change in chamber elastic
stiffness (0.023 +/- 0.002 to 0.025 +/- 0.004 mL-1, P = NS). CONCLUSIONS:
Intracoronary enalaprilat resulted in an improvement in active
(Ca(2+)-dependent) relaxation in those patients with more severe
hypertensive LVH. The improvement in active relaxation was directly
proportional to the severity of LVH. These results support the hypothesis
that the cardiac renin-angiotensin system is an important determinant of
active diastolic function in hypertensive LVH.
ARTICLES
Intracoronary angiotensin-converting enzyme inhibition improves diastolic function in patients with hypertensive left ventricular hypertrophy
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville.
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