(Circulation. 1995;91:2043-2048.)
© 1995 American Heart Association, Inc.
Articles |
Bradykinin Antagonism Inhibits the Antigrowth Effect of Converting Enzyme Inhibition in the Dog Myocardium After Discrete Transmural Myocardial Necrosis
From the Cardiovascular Division, Department of Medicine and Department of Radiology, University of Minnesota, Minneapolis.
Correspondence to Kenneth M. McDonald, MD, Assistant Professor of Medicine, Cardiovascular Division, University of Minnesota Medical School, Box 508 UMHC, 420 Delaware St SE, Minneapolis, MN 55455.
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Abstract |
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Background Converting enzyme inhibitor (CEI) therapy, but not angiotensin II subtype I receptor blockade, has been shown to attenuate left ventricular remodeling in the dog after transmyocardial direct current (DC) shock. The purpose of this study was to address the importance of preservation of bradykinin to the antiremodeling effect of CEI treatment in this model.
Methods and Results Twenty-four hours after DC shock, adult mongrel dogs were assigned to one of three groups: a control group; a group treated with ramipril 10 mg BID; and a group treated with ramipril 10 mg BID along with a continuous subcutaneous infusion of HOE 140, a bradykinin antagonist. To assess change in left and right ventricular structure, a magnetic resonance imaging (MRI) study was performed 4 weeks after DC shock and compared with a baseline MRI study performed before DC shock. The increase in left ventricular mass (mean±SEM) in the control group was similar to that observed in the CEI–HOE 140 group (+0.73±0.19 versus +0.75±0.18 g/kg, P=NS), but both were greater than the change in mass in the ramipril group (-0.48±0.13 g/kg, P=.004 and P=.0005, respectively). No significant change occurred in left ventricular volume or right ventricular structure in any group. Mean arterial pressure was reduced by ramipril compared with the control group (-8±2 versus +7±2 mm Hg, P=.03), and this effect was not blunted by the addition of HOE 140 (-7±3 mm Hg).
Conclusions Prevention by ramipril of the early increase in left ventricular mass in the DC shock model appears to be related to the preservation of bradykinin.
Key Words: bradykinin • ventricles • angiotensin • enzymes • myocardium
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Transmyocardial direct current (DC) shock in the dog produces moderate-size transmural necrosis of the anteroapical wall of the left ventricle.1 Ventricular remodeling develops as a result of this damage and is characterized by an early increase in left ventricular mass and subsequent chamber dilation.2 These structural changes are associated with a reduction in resting left ventricular ejection fraction, elevated plasma norepinephrine levels, and abnormalities in myocardial metabolism.2 3
Both sulfhydryl-group–containing and carboxyhydryl-type converting enzyme inhibitor (CEI) agents have been successful in attenuating remodeling in this model.4 5 The mechanism explaining the antiremodeling actions of CEI agents in this model remains unknown. A nonspecific reduction in myocardial workload, reduced formation of angiotensin II, or preservation of bradykinin could all play a role. We recently demonstrated that blockade of the angiotensin II subtype I (AT1) receptor was ineffective in attenuating remodeling, arguing against a significant role for angiotensin II and suggesting a possible role for bradykinin in the antiremodeling effect of CEI therapy in this model.5 Supporting this hypothesis are data indicating that the addition of a bradykinin antagonist to CEI therapy negates the antiproliferative effect of these agents in models of vascular wall injury and left ventricular overload.6 7 Therefore, the aim of this study was to investigate the importance of bradykinin to the antiremodeling effect of CEI therapy in the canine model of DC shock.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Study Protocol
Twenty-two adult mongrel dogs were studied. Magnetic resonance imaging (MRI) was performed in all dogs approximately 1 week before the production of myocardial damage by DC shock. Hemodynamic variables were measured under light sedation on the morning of DC shock. After DC shock, dogs were randomized to one of three groups: a control group given no therapy; a group assigned to the CEI, ramipril, at an oral dose of 10 mg BID; and a group given ramipril 10 mg BID along with a continuous subcutaneous infusion of HOE 140 for a period of 4 weeks. This bradykinin antagonist was administered at a dose of 240 µg · kg-1 · d-1 via an Alzet pump (Alza Corp) placed subcutaneously in the high posterior thoracic area. The dose of HOE 140 was based on experience with similar experiments from other laboratories.6 7 A bradykinin challenge was performed at baseline and repeated at the 4-week time point to assess the extent of bradykinin receptor blockade. Dogs were followed for a 4-week period, after which repeat hemodynamic and MRI studies were performed. During the 4-week study period, all dogs were treated in the same manner with respect to diet and physical activity. All aspects of this protocol were carried out in accordance with the guidelines outlined by the American Heart Association and were approved by the University of Minnesota Animal Care Committee.
MRI Studies
MRI was used to assess global and regional
structural changes at
baseline and 4 weeks after DC shock. The MRI studies were performed on
a Siemens Medical Systems 1.5-T superconducting MRI system equipped
with standard hardware. To increase the signal-to-noise ratio, an 18-cm
Helmholtz coil was used. All of the imaging sequences were synchronized
to the ECG R wave obtained from leads placed on the shaved skin surface
of the dog.
Scout images were taken in the axial plane with an ultrafast gradient-echo sequence (TurboFlash). The parameters for this sequence were TR/TE/flip angle, 6 ms/3 ms/8°, respectively, and a matrix of 128x256 within a field of view of 250 mm. The delay after the inversion pulse was kept to a minimum, 15 ms, resulting in a bright blood signal and a hypointense myocardium. From axial scout images, a long-axis view of the left ventricle was obtained. Aside from providing assistance in defining the short-axis plane, the TurboFlash sequence also provided information on how many short-axis cine sequences (described below) were needed to image the myocardium from apex to base. The short-axis TurboFlash images covered the heart from apex to base with a slice thickness of 10 mm with no interslice gap. Slices were acquired individually and took approximately 800 ms.
From the long-axis scout image, short-axis segmented cine TurboFlash slices were performed to cover the heart apex to base with a slice thickness of 10 mm. The parameters of the segmented sequence were TR/TE/flip angle, 6.5 ms/3 ms/20°, with a matrix of 156x256 and a field of view of 30 cm. The sequence was implemented with three phase-encode lines per cardiac phase, requiring 52 heartbeats per acquisition. The temporal resolution of this sequence was 19.5 ms per cardiac phase. Each myocardial level took <2 minutes to acquire, since two acquisitions were used and the average heart rate of the dog was 120 beats per minute. The average number of short-axis slices needed to image the entire heart apex to base was six or seven. This protocol provided high signal-to-noise ratio, movielike images of the entire heart in <15 minutes.
Endocardial and epicardial volumes of each end-diastolic short-axis slice were calculated by computer-assisted planimetry. The total endocardial volume (obtained by summing values from all short-axis slices) was subtracted from the total epicardial volume and multiplied by 1.05 g/cm3 (specific gravity of myocardium) to give the total mass of the left ventricle.
Regional estimates of left ventricular mass and volume were also calculated. Damage produced by DC shock is consistently in the anteroapical region.1 Therefore, the short-axis cuts of the left ventricle were divided into the two most apical slices (damaged zone), the middle two slices (peri–damaged zone), and the two or three slices at the base of the heart (remote zone). The remote zone contained two or three slices, depending on whether six or seven short-axis slices were required to encompass the heart. This number was consistent within animals between the baseline and final studies at 4 weeks.
Right ventricular mass and end-diastolic volume were also calculated from the short-axis views. Epicardial and endocardial volumes of each short-axis slice were outlined. The septal border of the right ventricle was common to both tracings. The mass and volume of the right ventricle was obtained by the same method as used for calculation in the left ventricle. The right ventricle was not examined on a regional basis.
Hemodynamic Studies
Hemodynamic studies were carried out in
awake, lightly sedated
dogs (Innovar 2 mL, consisting of fentanyl 0.8 mg and droperidol 80
mg). Percutaneous catheterization was performed after local lidocaine
anesthesia. A balloon flotation catheter was positioned in the
pulmonary artery from the external jugular vein, and an aortic catheter
was advanced into the root of the aorta from the femoral artery. Mean
aortic pressure, pulmonary capillary wedge pressure, pulmonary arterial
pressure, and right atrial pressure were monitored with Statham P23dB
transducers and a Hewlett Packard 77588 eight-channel physiological
recorder. Cardiac output was determined by thermodilution from the
pulmonary artery with a Lexington cardiac output computer and 5 mL of
iced saline injected into the right atrium.
Hemodynamic studies were performed at baseline and at 4 weeks after DC shock. Studies performed in dogs treated with ramipril were carried out 16 hours after the last dose of drug. The hemodynamic studies were separated from the MRI studies by at least 24 hours.
Transmyocardial DC Shock
Discrete left ventricular necrosis
was produced under general
anesthesia (sodium pentobarbital) by repeated transmyocardial DC shock.
A previous study has shown that this method produces a moderate-sized
area of transmural necrosis on the anteroapical wall of the left
ventricle involving 17±6% of the total left ventricular
myocardium.1 The dogs were intubated and prepared for the
DC shock procedure after the measurement of baseline hemodynamic values
as previously described. A small area of the left side of the chest
over the maximal precordial impulse was shaved. A pigtail catheter was
placed across the aortic valve and then advanced 1 cm to distance it
from the conduction tissue at the base of the heart. A premeasured soft
metallic guide wire was then passed through the catheter, with 5 mm of
wire extending beyond the catheter tip into the left ventricular
cavity. One electrode paddle was placed on the left chest at the point
of maximal cardiac impulse. The second electrode was connected to the
proximal end of the guide wire at its site of entry into the femoral
artery. One shock of 80 J/kg body wt was administered at 20- to
60-second intervals. Heart rhythm was monitored by ECG throughout the
procedure. Rarely, cardioversion (80-J shock) was needed to terminate a
hemodynamically significant run of ventricular tachycardia. In these
instances, this cardioversion was counted as one of the individual
shocks for that dog. Temporary bradyarrhythmias occasionally occurred
after DC shock, but these rarely persisted or required intervention.
Two hours after completion of the DC shock procedure, left ventricular
end-diastolic pressure was measured with a pigtail
catheter. The left ventricular end-diastolic pressure value
was obtained as an index of myocardial damage.1 The guide
wire and pigtail catheter were then removed, and hemostasis was
achieved by pressure at the femoral site. Dogs were then transferred to
a postoperative care area, where they were observed for a period of 24
hours.
Bradykinin Challenge
Bradykinin challenge was administered at
baseline and at 4 weeks
to dogs receiving HOE 140. The challenge at 4 weeks was performed while
the HOE 140 infusion was still in progress. The maximal decrease in
systolic blood pressure was noted after bolus intravenous injections of
bradykinin at strengths of 25, 100, and 200 ng/kg.
Statistics
Comparisons of the changes in left and right
ventricular mass
and volume between the three groups were made by ANOVA. If the pattern
of change within the three groups was different by ANOVA, unpaired
t tests were used to assess intergroup changes. Level of
significance was adjusted for multiple comparisons (P
.016)
by the method of Bonferroni. The same approach was used to analyze
changes in regional left ventricular structure and hemodynamic
parameters. The significance of the change in systolic blood pressure
with bradykinin was assessed by paired t tests. All values
expressed represent mean±SEM.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Twenty-two adult mongrel dogs were studied. One dog did not survive the DC shock procedure. Three animals developed permanent complete heart block either acutely or during the convalescent period after DC shock. Data on the remaining 18 dogs are presented.
After DC shock, dogs were randomly assigned to a control group receiving no therapy (n=6; mean body weight, 20±1 kg), to treatment with ramipril 10 mg BID (n=6; mean body weight, 17±1 kg), and to a group that received ramipril 10 mg BID along with a continuous subcutaneous infusion of HOE 140 (n=6; mean body weight, 21±1 kg). Left ventricular end-diastolic pressure was similar in all groups 2 hours after DC shock (control, 14±1 mm Hg; ramipril, 16±3 mm Hg; ramipril+HOE 140, 15±2 mm Hg).
Structural Changes in the Left and Right Ventricle
Global Structural Changes
There was a significant
difference between groups with respect to
the change in left ventricular mass over the 4-week period
(P=.0002) (Fig 1
). The change in ventricular
mass in the control group was similar to that observed in the CEI–HOE
140 group (+0.73±0.19 versus +0.75±0.18 g/kg), but
both were
significantly different from the change in mass in the ramipril-treated
group (-0.48±0.13 g/kg, P=.004 and
P=.0005,
respectively).
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Left ventricular end-diastolic volume did not demonstrate a significant change from baseline to 4 weeks in any of the groups, going from 58.3±2.6 to 61.4±3.9 mL in the control group, from 60.7±3.9 to 59.9±3.4 mL in the group receiving ramipril and HOE 140, and from 49.4±3.6 to 51.4±3.9 mL in the ramipril-treated group.
Right ventricular mass showed no change over the 4-week observation period, going from 1.75±0.1 to 1.79±0.12 g/kg in the control group, from 1.64±0.08 to 1.59±0.1 g/kg in the group treated with ramipril and HOE 140, and from 1.48±0.07 to 1.5±0.09 g/kg in the group receiving ramipril. Similarly, end-diastolic volume did not change in the right ventricle: 62.0±3.0 to 67.1±7.0 mL in the control group, 62.0±5.0 to 61.2±6.1 mL in the ramipril and HOE 140 group, and 47.8±4.9 to 48.1±3.9 mL in the ramipril group.
Regional Structural Changes
The changes in mass in
the damaged zone, the peri–damaged zone,
and the remote zone in the left ventricle were significantly different
between groups over the 4-week period (P=.02, .05, and .03,
respectively).
The changes in left ventricular mass in all three
regions were similar
between the control group and the group receiving ramipril and HOE 140
(damaged zone, +0.14±0.13 versus +0.33±0.14 g/kg,
P=.3;
peri–damaged zone, +0.25±0.08 versus 0.15±0.41 g/kg,
P=.7; remote zone, +0.43±0.11 versus
0.24±0.12 g/kg,
P=.4) (Fig 2). Comparison between changes in
the control group and ramipril-treated group revealed significant
differences in the peri–damaged zone (+0.25±0.08 versus
-0.22±0.4
g/kg, P=.0006) and the remote zone (0.43±0.11 versus
-0.04±0.22 g/kg, P=.008), with a similar trend in
the
damaged zone (+0.014±0.13 versus -0.24±0.21,
P=.04). The
regional changes in the ramipril group were significantly different
from the ramipril–HOE 140 group in the damaged zone
(P=.001) and the peri–damaged zone
(P=.003),
with a similar trend in the remote zone (P=.02).
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There was no significant difference in changes in regional left ventricular volume measurements between the three groups. In the damaged zone, volume changed from 9.1±0.8 to 9.6±0.9 mL in the control group, from 7.2±0.8 to 9.0±1.6 mL in the ramipril and HOE 140–treated group, and from 9.8±1.7 to 8.1±1.2 mL in the ramipril-treated group. The changes in the peri–damaged zone were as follows: from 18.6±1.1 to 18.0±1.2 mL in the control group, from 18.8±1.7 to 18.3±0.8 mL in the ramipril and HOE 140–treated group, and from 17.5±1.8 to 19.0±1.6 mL in the ramipril-treated group. In the remote zone, volume changed from 30.6±1.6 to 34.0±1.9 mL in the control group, from 24.8±1.9 to 32.5±3.8 mL in the ramipril and HOE 140–treated group, and from 22.0±1.3 to 24.2±2.2 mL in the ramipril-treated group.
Hemodynamics
Mean arterial pressure differed between groups
over the 4-week
study period (P=.02) (Table). The increase in
arterial pressure of 7±2 mm Hg in the control group was significantly
different from the decrease in the group treated with ramipril and HOE
140 (-7±3 mm Hg, P=.015) and displayed a similar
trend
compared with the ramipril-treated group (-8±2 mm Hg,
P=.03). No significant change occurred in the other
hemodynamic parameters (Table).
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Bradykinin Challenge
The vasodepressor response to
incremental bolus injections of
bradykinin was significantly attenuated by HOE 140 (Fig 3). The
reduction in systolic blood pressure at baseline
was greater than at 4 weeks at the 25-ng/kg dose (-5±1 versus
-1±2
mm Hg, P=.06), the 100-ng/kg dose (-17±4 versus
-4±3
mm Hg, P=.02), and the 200-ng/kg dose (-24±4
versus
-7±4 mm Hg, P=.01).
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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Attenuation of ventricular remodeling after myocardial necrosis has become a focus of experimental and clinical research.8 9 10 11 12 13 A consistent feature of recent studies has been that CEIs attenuate the remodeling process.4 5 8 12 13 14 15 A reduction in myocardial workload may contribute to this antiremodeling effect, but other agents that potentially reduce myocardial workload have not been successful in inhibiting remodeling.13 16 Raya and colleagues16 demonstrated that hydralazine was ineffective in attenuating progressive left ventricular enlargement in the rat infarct model. Moreover, in the clinical setting after infarction, preload reduction with furosemide failed to inhibit remodeling.13 Another potential explanation for the antiremodeling action of CEI agents is the blockade of angiotensin II formation. This peptide can stimulate myocyte hypertrophy and growth of the cardiac interstitium.17 18 19 20 In certain experimental settings, AT1 receptor blockade attenuates structural change in the myocardium.21 22 However, in the canine DC shock model, DUP 532, an AT1 receptor blocker, failed to prevent remodeling.5 Therefore, we have turned our attention to the potential role of bradykinin to explain the antiremodeling effect of CEI therapy in this model.23 Indeed, observations from a rat ventricular overload model and a vascular injury model support the hypothesis that preservation of bradykinin may explain the antiremodeling action of CEI agents.6 7
These data provide original observations on the role of bradykinin in the structural response of the left ventricle to discrete myocardial necrosis. In this study, left ventricular mass increased in the control group over the 4-week study period. This structural change was attenuated by ramipril, confirming our previous observations with sulfhydryl-containing and nonsulfhydryl CEI agents.4 5 However, the complete inhibition of this effect of ramipril by HOE 140 supports the hypothesis that the preservation of bradykinin by CEI therapy is the major mechanism by which these agents attenuate myocardial mass increase in this canine model. It should be noted that this model produces modest myocardial damage, equivalent to a small infarction.1 It is possible that mechanisms important to the remodeling process in this model may not be as relevant in models of more extensive myocardial damage.
The mechanism explaining the potential antiremodeling action of bradykinin may relate to increased nitric oxide synthesis or an effect on prostaglandin metabolism. Agents such as bradykinin that increase extracellular cGMP may possess direct antiproliferative activity.23 Future work in this model looking at the effect of nitric oxide synthase inhibition and prostaglandin synthase inhibition on the antiremodeling action of CEI agents will provide further clarification of the mechanism of action of bradykinin in this setting.
The importance of bradykinin levels not augmented by CEI therapy to the remodeling process in this model was not assessed. If nonstimulated bradykinin levels were important to the control of growth after injury in this model, a group receiving HOE 140 alone might have displayed more prominent structural changes than those occurring in the control group. Relatively few data are available on this subject from other experimental models. In the rat carotid injury model, Farhy and colleagues6 demonstrated that HOE 140 on its own did not result in increased growth compared with control injured vessels. While preliminary data from de Blois et al24 suggest that basal bradykinin activity may have an antigrowth effect in the same model, it may be necessary to increase bradykinin levels from subthreshold to biologically active levels to allow for the development of this effect.
The observation from this study that preservation of bradykinin may be the mechanism whereby CEI therapy attenuates the early increase in mass after DC shock may support a unifying hypothesis for the pharmacological prevention of remodeling in this model. A previous experiment from this laboratory demonstrated that nitrates can also prevent remodeling.25 It is possible that increased intracellular cGMP explains the antiproliferative effect of both agents.
Information from other models on the regional response to discrete myocardial damage is limited. Olivetti and colleagues26 suggest that myocyte hypertrophy in the rat is most marked in the peri-infarct zone. However, the regional changes in ventricular mass in this model were similar in the damaged, peri–damaged, and remote zones, indicating that the response to injury was not confined to the myocardium around the anteroapical necrotic zone. The regional changes in the group receiving ramipril and HOE 140 were similar to those in the control group. The reduction in mass in the damaged and peri–damaged zones in the ramipril-treated group probably reflects the effect of therapy as well as the loss of tissue due to necrosis in the damaged zone.
No significant change was observed in left ventricular end-diastolic volume in the control group. Remodeling after DC shock, despite the modest variation in the size of ventricular injury,1 is reproducible and is characterized by an early increase in ventricular mass, with subsequent chamber dilation.2 The timing of the development of chamber dilation is somewhat variable but is almost uniformly present 16 weeks after DC shock.2 4 25 Use of a shorter follow-up period in this study, in part as a result of the practical difficulty in maintaining continuous subcutaneous infusions of HOE 140 over 16 weeks, probably explains the failure to document a significant change in ventricular volume. However, extensive experience with this model indicates that the early increase in ventricular mass is closely associated with later development of chamber dilation.2 3 4 5 25 These data strongly suggest that chamber dilation would have been observed in both the control and ramipril–HOE 140 groups if the follow-up had been extended. Likewise, no significant remodeling had developed in the right ventricle by 4 weeks, indicating that the already reported structural changes in this chamber27 probably reflect a late manifestation of remodeling in the DC shock model.
While the addition of the bradykinin antagonist negated the antigrowth effect of ramipril, the hypotensive effect of the CEI compound was not blunted. These data may indicate that the antiremodeling effect of ramipril is not closely related to the hemodynamic effect of this agent. However, measurement of arterial pressure and pulmonary wedge pressure does not completely describe myocardial workload. In other models, the impact of bradykinin antagonism on the blood pressure–lowering effects of CEI therapy appears to be variable. In a vascular injury model,6 in which there is no increase in cardiac afterload, the blood pressure–lowering effect of CEI therapy appears not to be influenced by bradykinin antagonism. This also appears to be true in settings in which increased afterload is not associated with a stimulated renin-angiotensin system, as is the case with the spontaneously hypertensive rat.28 29 When the renin-angiotensin system is stimulated,30 31 32 bradykinin antagonism appears to blunt the antihypertensive effect of CEI therapy. We have previously reported that plasma renin activity is not increased in this LV damage model.
In summary, the documented inhibition of the early increase in ventricular mass by CEI compounds in the DC shock model appears to be related to the preservation of bradykinin. Future analysis of the impact of nitric oxide synthase inhibition and prostaglandin synthase inhibition will further clarify the mechanism of action of bradykinin in this setting.
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Acknowledgments |
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This study was supported in part by Program Project Grant PO-132427 from the National Heart, Lung, and Blood Institute and a Minnesota American Heart Association Research Fellowship Award.
Received August 8, 1994; revision received November 17, 1994; accepted November 26, 1994.
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References |
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TopAbstractIntroductionMethods Results Discussion References |
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1. Mehta J, Runge W, Cohn JW, Carlyle P. Myocardial damage after repetitive direct current shock in the dog: correlation between left ventricular end-diastolic pressure and extent of myocardial necrosis. J Lab Clin Med. 1978;91:272-279. [Medline] [Order article via Infotrieve]
2. McDonald KM, Francis GS, Carlyle PF, Hauer K, Matthews J, Hunter DW, Cohn JN. Hemodynamic, left ventricular structural and humoral changes after discrete myocardial damage in the dog. J Am Coll Cardiol. 1992;19:460-467. [Abstract]
3. McDonald KM, Zhang J, Yoshiyama M, Francis GS, Ugurbil K, Cohn JN. Abnormal myocardial bioenergetics in canine asymptomatic left ventricular dysfunction. J Am Coll Cardiol. 1994;23:786-793. [Abstract]
4. McDonald KM, Carlyle PF, Mathews J, Hauer K, Elbers T, Hunter D, Cohn JN. Early ventricular remodeling after myocardial damage and its attenuation by converting enzyme inhibition. Trans Assoc Am Physicians. 1990;103:229-235. [Medline] [Order article via Infotrieve]
5.
McDonald KM, Garr MD, Carlyle PF, Francis GS, Hauer K, Hunter
DW, Parrish T, Stillman A, Cohn JN. The relative effects of
alpha1 adrenoceptor blockade, converting enzyme inhibitor
therapy and angiotensin II subtype I receptor blockade on ventricular
remodeling in the dog. Circulation. 1994;90:3034-3036.
6.
Farhy RD, Carretero OA, Ho K-L, Scicli G. Role of kinins and
nitric oxide in the effects of angiotensin converting enzyme inhibitors
on neointima formation. Circ Res. 1993;72:1202-1210.
7. Linz W, Schölkens BA. A specific ß2-bradykinin receptor antagonist HOE 140 abolishes the antihypertrophic effect of ramipril. Br J Pharmacol. 1992;105:771-772. [Medline] [Order article via Infotrieve]
8.
Pfeffer MA, Braunwald E. Ventricular remodeling after
myocardial infarction: experimental observations and clinical
implications. Circulation. 1990;81:1161-1172.
9. Anversa P, Sonnenblick EH. Ischemic cardiomyopathy: pathophysiologic mechanisms. Prog Cardiovasc Dis. 1990;33:49-70. [Medline] [Order article via Infotrieve]
10.
Beltrami CA, Finato N, Roco M, Feruglio GA, Puricelli C,
Cigola E, Quaini F, Sonnenblick EH, Olivetti G, Anversa P. Structural
basis of end-stage failure in ischemic cardiomyopathy in humans.
Circulation. 1994;89:151-163.
11.
McKay RG, Pfeffer MA, Pasternak RC, Markis JE, Come PC, Nakao
S, Alderman JD, Ferguson JJ, Safian RD, Grossman W. Left ventricular
remodeling after myocardial infarction: a corollary to infarct
expansion. Circulation. 1986;74:693-702.
12.
St John Sutton M, Pfeffer MA, Plapport T, Rouleau J-L,
Moyé LA, Dagenais GR, Lamas GA, Klein M, Sussex B, Goldman S,
Menapace EJ, Parker JO, Lewis S, Sestier F, Gordon DF, McEwan P,
Bernstein V, Braunwald E, for the SAVE Investigators. Quantitative
two-dimensional echocardiographic measurements are major predictors of
adverse cardiovascular events after acute myocardial infarction: the
protective effects of captopril. Circulation. 1994;89:68-75.
13. Sharpe N, Smith H, Murphy J, Hannon S. Treatment of patients with symptomless left ventricular dysfunction after myocardial infarction. Eur Heart J. 1990;11(suppl B):147-150.
14. Pfeffer MA, Lamas GA, Vaughan DE, Parisi AF, Braunwald E. Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med. 1988;319:80-86. [Abstract]
15. Belichard P, Savard P, Cardinal R, Nadeau R, Gosselin H, Paradis P, Rouleau JL. Markedly different effects on ventricular remodeling result in a decrease in inducibility of ventricular arrhythmias. J Am Coll Cardiol. 1994;23:505-513. [Abstract]
16.
Raya TE, Gay RG, Aguirre M, Goldman S. Importance of
venodilatation in prevention of left ventricular dilatation after
chronic large myocardial infarction in rats: a comparison of captopril
and hydralazine. Circ Res. 1989;64:330-337.
17.
Aceto JF, Baker KM. (SAR1) angiotensin II
receptor-mediated stimulation of protein synthesis in chick heart
cells. Am J Physiol. 1990;258:H806-H813.
18.
Morgan HE, Baker KM. Cardiac hypertrophy: mechanical, neural,
and endocrine dependence. Circulation. 1991;83:13-25.
19. Brilla CG. Angiotensin II type 2 receptor-mediated stimulation of collagen synthesis in human cardiac fibroblasts. Circulation. 1992;86(suppl I):I-89. Abstract.
20.
Weber KT, Brilla CG. Pathological hypertrophy and cardiac
interstitium: fibrosis and the renin-angiotensin-aldosterone system.
Circulation. 1991;83:1849-1865.
21. Raya TE, Fonker SJ, Lee RW, Daugherty S, Goldman S, Wong PC, Timmermans PBMWM, Morkin E. Hemodynamic effects of direct angiotensin II blockade compared to converting enzyme inhibition in a rat model of heart failure. Am J Hypertens. 1991;4:334S-340S. [Medline] [Order article via Infotrieve]
22.
Schieffer B, Wirger A, Meybrunn M, Seitz S, Holtz T,
Reide UN, Drexler H. Comparative effects of chronic
angiotensin-converting enzyme inhibitor and angiotensin II type I
receptor blockade on cardiac remodeling after myocardial infarction in
the rat. Circulation. 1994;89:2273-2282.
23. Garg VC, Hassid A. Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest. 1989;83:1774-1777.
24. deBlois D, Lombardi DM, Garvin MA, Schwartz SM. Inhibition by ramipril of intimal hyperplasia in the denuded rat carotid is reversed by Hoe 140, a kinin B2 receptor antagonist. Circulation. 1992;86(suppl I):I-226. Abstract.
25. McDonald KM, Francis GS, Matthews J, Hunter DW, Cohn JN. Chronic oral nitrate therapy prevents long-term ventricular remodeling in the dog. J Am Coll Cardiol. 1993;21:514-522. [Abstract]
26. Olivetti G, Ricci R, Beghi C, Giuderi R, Anversa P. Response of the border zone to myocardial infarction in the rat. Am J Pathol. 1986;125:476-483. [Abstract]
27. McDonald KM, Toher C, Parrish T, Stillman A, Cohn J. The effect of ramipril on right ventricular remodeling following left ventricular damage. Cardiovasc Drugs Ther. 1993;7:404. Abstract.
28.
Gohlke P, Linz W, Schölkens BA, Kuwer I, Bartenbach S,
Schnell A, Unger T. Angiotensin-converting enzyme inhibition improves
cardiac function: role of bradykinin.
Hypertension. 1994;23:411-418.
29. Bao G, Gohlke P, Unger TH. Role of bradykinin in chronic antihypertensive actions of ramipril in different hypertension models. J Cardiovasc Pharmacol. 1992;20(suppl 9):S96-S99.
30.
Benetos A, Gavras H, Stewart JM, Vavrek RJ, Hatinoglou S,
Gavras I. Vasodepressor role of endogenous bradykinin assessed by a
bradykinin antagonist. Hypertension. 1986;8:971-974.
31.
Danckwardt L, Shimizu I, Bönner G, Rettig R, Unger TH.
Converting enzyme inhibition in kinin-deficient Brown Norway rats.
Hypertension. 1990;16:429-435.
32. Carbonell LF, Carretero OA, Stewart JM, Scicli AG. Effect of a kinin antagonist on the acute antihypertensive activity of enalapril in severe hypertension. Hypertension. 1988;11:239-243.[Abstract]
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|
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|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
J. N. Cohn Structural Basis for Heart Failure : Ventricular Remodeling and Its Pharmacological Inhibition Circulation, May 15, 1995; 91(10): 2504 - 2507. [Full Text]
|
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