AJP - Heart Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 288: H244-H249, 2005. First published September 9, 2004; doi:10.1152/ajpheart.00042.2004
0363-6135/05 $8.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
288/1/H244    most recent
00042.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Trueblood, N. A.
Right arrow Articles by Colucci, W. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Trueblood, N. A.
Right arrow Articles by Colucci, W. S.

Biphasic temporal pattern in exercise capacity after myocardial infarction in the rat: relationship to left ventricular remodeling

Nathan A. Trueblood,1 Patrick R. Inscore,1 Daniel Brenner,2 Daniel Lugassy,1 Carl S. Apstein,2 Douglas B. Sawyer,1,3 and Wilson S. Colucci1,3

1Myocardial Biology Unit and 2Cardiac Muscle Research Laboratory, Boston University School of Medicine; and 3Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, Boston, Massachusetts

Submitted 15 January 2004 ; accepted in final form 5 September 2004


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
After myocardial infarction (MI), there is progressive left ventricular (LV) remodeling and impaired exercise capacity. We tested the hypothesis that LV remodeling results in structural and functional changes that determine exercise impairment post-MI. Rats underwent coronary artery ligation (n = 12) or sham (n = 11) surgery followed by serial exercise tests and echocardiography for 16 wk post-MI. LV pressure-volume relationships were determined using a blood-perfused Langendorff preparation. Exercise capacity was 60% of shams immediately post-MI (P < 0.05) followed by a recovery to near normal during weeks 5–8. Thereafter, there was a progressive decline in exercise capacity to ±40% of shams (P < 0.01). At both 8 and 16 wk post-MI, fractional shortening (FS) was reduced and end-diastolic diameter (EDD) was increased (P < 0.01). However, neither FS nor EDD correlated with exercise at 8 or 16 wk (r2 < 0.12, P > 0.30). LV septal wall thickness was increased at both 8 (P = 0.17 vs. shams) and 16 wk (P = 0.035 vs. shams) post-MI and correlated with exercise at both times (r2 ≥ 0.50 and P ≤ 0.02 at 8 and 16 wk). Neither end-diastolic volume nor maximum LV developed pressure at 16 wk correlated with exercise capacity. Exercise capacity follows a biphasic time course post-MI. An immediate decrease is followed by an early recovery phase that is associated with compensatory LV hypertrophy. Subsequently, there is a progressive decrease in exercise capacity that is independent of further changes in LV volume or contractile function.

cardiac hypertrophy; exercise capacity; cardiac function; echocardiography

AFTER A MYOCARDIAL INFARCTION (MI), there is progressive left ventricular (LV) remodeling that is characterized by LV chamber dilation and contractile dysfunction (17, 19). Maximal exercise capacity also decreases post-MI (1, 13, 18, 22). Both the extent of LV remodeling and the impairment in exercise capacity correlate with clinical outcomes in patients with chronic heart failure (5, 7). However, relatively little is known about the relationship between LV remodeling and exercise capacity post-MI. It is possible that LV remodeling is an important determinant of the exercise impairment that occurs after MI. For example, in patients with chronic heart failure due to systolic dysfunction the changes in LV volume, fractional shortening and mass are predictive of exercise capacity (7). On the other hand, exercise capacity often correlates poorly or not at all with central hemodynamics, systolic function, or ventricular volumes in cross-sectional studies (8, 9, 13, 22, 23). Thus the role of LV remodeling in the determination of exercise impairment post-MI is not clear.

We tested the hypothesis that LV remodeling, as reflected by changes in LV structure and function, is a major determinant of exercise impairment post-MI. As an approach to this thesis, we measured maximal exercise capacity on a treadmill at weekly intervals for 16 wk in rats after MI caused by coronary ligation. Correlations were measured between exercise capacity and 1) echocardiographic measurements of LV size and function at 8 and 16 wk post-MI and 2) systolic and diastolic pressure-volume relationships measured by the isovolumic Langendorff method at 16 wk post-MI.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Animals. Male Wistar rats weighing 225–250 g were housed in a temperature-controlled environment, exposed to a 12:12-h light-dark cycle, and given a standard diet of rat chow and water ad libitum. Experimental protocols were approved by the Institutional Animal Care and Use Committee at Boston University.

Surgical procedure. The animals were randomized to coronary artery ligation (MI) or a sham operation without ligation (sham) as previously described (12, 20). Rats were anesthetized with pentobarbital sodium (45 mg/kg, intraperitoneal injection), intubated, and ventilated with a rodent ventilator (model 386, Harvard Apparatus). The heart was exposed by a left lateral thoracotomy, and the pericardial sac was removed. The left main coronary artery was visualized and ligated with a 5-0 silk suture. Ligation of the coronary artery was confirmed by noting the pallor of the LV wall. To obtain a range of infarction sizes, the location of the coronary ligation varied between 1 and 4 mm distal to its origin between the pulmonary trunk and left atrial appendage. Without exception, distal ligations resulted in small infarct sizes (as determined by histology) and proximal ligations resulted in large infarctions. The chest wall, individual muscles, and skin were sutured separately, and the animal was allowed to recover. Sham-operated rats underwent the same surgical procedures except for the coronary artery ligation.

Exercise protocol. Maximum exercise capacity was measured using a rodent treadmill equipped with an electric motivator grid (Columbus Instruments) as previously described (12). Animals were familiarized with running on the treadmill before surgery. The treadmill was set at a constant incline of 15°. The initial speed was 15 m/min and was increased by 1 m/min every minute. Exercise capacity was measured once per week for the entire 16-wk study. Total exercise time was recorded as the elapsed time to exhaustion and then converted to distance. Exhaustion was determined by an observer blinded to surgery group (sham or MI) and was defined as the point at which the animals could not keep pace with the treadmill and no longer avoided the electrical stimulus.

Echocardiography. At 8 and 16 wk post-MI, two-dimensional and M-mode echocardiographic measurements were obtained on nonexercise days. Animals were lightly anesthetized with pentobarbital sodium (20 mg/kg ip), and their chests were shaved. All echocardiographic measurements were obtained using a Hewlett-Packard Sonos 5500 equipped with a 12-MHz vector array probe. End-diastolic diameter (EDD) and end-systolic diameter (ESD) were measured digitally from the frames with the largest and smallest dimensions. The precise phase of the cardiac cycle was confirmed with a simultaneously recorded electrocardiogram. Dimensions were averaged from three cardiac cycles to obtain the value used for each animal. Fractional shortening (FS) was calculated as (EDD – ESD)/EDD.

Pressure-volume relationships in isolated hearts. At the 16-wk endpoint, animals were killed, and their hearts were rapidly isolated. LV diastolic and systolic pressure-volume relationships were obtained by the isovolumic Langendorff method as previously described (12, 20). After the hearts were isolated, the aortic root was canulated, and the coronary arteries were perfused at a constant pressure of 80 mmHg. The perfusate consisted of Krebs-Henseleit buffer supplemented with bovine red blood cells (adjusted to a final hematocrit of 40%) and albumin. LV pressures were monitored via a polyvinyl chloride balloon attached to a small cannula that was inserted through the left atrium into the LV. After pressure-volume assessment, the hearts were arrested in diastole by infusion of potassium chloride and perfusion fixed with formalin at an end-diastolic pressure of 10 mmHg.

Infarct size determination. Infarct size was measured from paraffin-embedded histological sections taken of the formalin-fixed tissue after pressure-volume relationship assessment (19, 20). Four equally spaced short-axis sections were taken to obtain representative samples from the entire vertical length of the LV. The internal and external total LV circumferences and the infarcted portions of the circumference were measured for each of these four sections. The percentage of the LV circumference that consisted of infarcted tissue was then averaged for each section, and each of the four sections were then averaged together, as originally described by Pfeffer et al. (17, 19).

Data analysis. All values are shown as means ± SE. Differences between two independent variables were assessed using an unpaired t-test and changes within groups at two time points were assessed using paired t-tests. P values ≤0.05 were considered statistically significant. ANOVA for repeated measures, followed by Student-Newman-Keuls post tests, was used for serial exercise data.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
Infarct size and mortality. MI size ranged from 4% to 38% of the LV, with an average of 26 ± 3%. Survival in sham-operated animals was 100% (n = 11). In the infarcted animals, survival was 60% at 24 h postsurgery (n = 12 survivors). There was one death at 6 wk post-MI. All results presented are for the animals surviving the full 16 wk (sham, n = 11; MI, n = 10–11). Lung and liver wet-to-dry weight ratios were not different between the two groups [P = not significant (NS)].

Exercise capacity. After surgery, the maximal exercise capacity of the MI group showed an immediate decrease to {approx}60% of sham exercise capacity (P ≤ 0.01 vs. shams; Fig. 1). The exercise capacity of the MI group remained between 60% and 70% of the sham group levels for the first 4 wk postsurgery (P < 0.05 vs. shams). During weeks 5–9, however, exercise capacity in the post-MI group recovered to {approx}90% of that in the sham group (P = NS vs. shams). Subsequently, there was a progressive decrease between weeks 10 and 16 in the MI group. At 16 wk, exercise capacity had decreased to 42% of that in the sham group (P < 0.01 vs. shams).



View larger version (23K):
[in this window]
[in a new window]
  		Fig. 1. Changes in maximal exercise capacity (distance run) over time in rats after myocardial infarction (MI; solid circles, n = 11) or a sham operation without ligation of the coronary artery (open circles, n = 11). Maximal exercise capacity was measured using a progressive treadmill protocol to exhaustion as per METHODS. #P < 0.05.

 
MI size is an important determinant of LV remodeling and post-MI exercise capacity (2). To determine whether MI had an effect on post-MI exercise capacity, exercise capacity was compared in animals with infarcts above and below the group mean infarct size (22%). We found that these post hoc-derived groups had qualitatively similar temporal patterns of exercise limitation post-MI; both were significantly different from the sham group at the beginning and end of the 16-wk study, and both groups came to within 1SD of the exercise distance of shams at week 8. However, the decreased sample size of these groups segregated according to infarct size limits the statistical power of between MI size group comparisons.

In vivo LV function by echocardiography. In infarcted rats, LV EDD increased an average of 26% at 8 wk post-MI (P ≤ 0.001 vs. shams) but did not change between weeks 8 and 16 (Fig. 2). LV FS decreased {approx}40% in the MI group at 8 wk (P ≤ 0.001 vs. shams) but exhibited no further change between weeks 8 and 16 (Fig. 2). Compared with shams, there was a nonsignificant increase (12 ± 6%) in septal wall thickness in the MI group at 8 wk (P = 0.17 vs. shams), a trend that reached significance by 16 wk post-MI (24 ± 6%, P < 0.05 vs. shams; Fig. 2).



View larger version (33K):
[in this window]
[in a new window]
  		Fig. 2. Left ventricular (LV) end-diastolic diameter (A), LV fractional shortening (B), septal wall thickness (C), and exercise distance (D) measured at 8 and 16 wk post-MI; n = 11 in both groups. Fractional shortening was calculated from echocardiographic measurements of end-diastolic and end-systolic diameter, as described in METHODS. *P < 0.001; #P < 0.01.

 
In the infarcted animals, neither FS nor EDD correlated with exercise capacity at 8 or 16 wk (Fig. 3, A–D). There was, however, a significant positive relationship between septal wall thickness and exercise capacity at both 8 and 16 wk (Fig. 3, E and F).



View larger version (33K):
[in this window]
[in a new window]
  		Fig. 3. Relationships between maximal exercise capacity and fractional shortening (A and B), LV end-diastolic diameter (C and D), and septal wall thickness (E and F) measured 8 and 16 wk post-MI. Eight-week data points are light shaded squares, and 16-wk data points are dark shaded squares. In E, the 8- and 16-wk data points are connected for each individual; n = 11 in both groups.

 
Ex vivo LV function in isolated hearts. The end-diastolic pressure-volume relationship was shifted rightward in infarcted hearts (P < 0.0001; Fig. 4). The LV end-diastolic volume at 5 mmHg was doubled in post-MI rats (0.63 ± 0.05 ml in post-MI vs. 0.30 ± 0.04 ml in shams, P < 0.0001). The LV developed pressure-volume relationship was shifted right and downward in infarcted animals (P < 0.01; Fig. 4). Maximum LV developed pressure was decreased in infarcted hearts (124 ± 7 mmHg in post-MI hearts vs. 136 ± 5 mmHg in sham hearts, P = 0.08). Neither LV end-diastolic volume at 5 mmHg nor LV maximum developed pressure correlated with exercise capacity in the infarcted animals (Fig. 5).



View larger version (23K):
[in this window]
[in a new window]
  		Fig. 4. LV pressure-volume end-diastolic (top) and end-systolic relationships (bottom) measured in isolated hearts using the isovolumic, balloon in LV Langendorff method. There were 10 hearts in each group. *P < 0.0001; #P < 0.01.

 


View larger version (21K):
[in this window]
[in a new window]
  		Fig. 5. Relationships between maximal exercise capacity and LV end-diastolic volume (A) or LV maximal developed pressure (B) as measured in the isolated hearts at 16 wk post-MI, as per Fig. 4; n = 10.

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
The goal of this study was to test the hypothesis that LV remodeling is a determinant of exercise impairment post-MI. There were two major findings. First, the time course of exercise impairment was biphasic. Maximum exercise capacity decreased immediately post-MI but improved to levels approaching those in sham-operated animals between weeks 5 and 9. Subsequently, there was a progressive decrease from week 10 through the end of the study on week 16, at which time exercise capacity had decreased markedly to only {approx}40% of that in the sham group. The second new finding was that septal wall hypertrophy predicted exercise capacity at both 8 and 16 wk, whereas neither LV dilation nor contractile function, measured in vivo or ex vivo, correlated with exercise capacity.

Time course of exercise impairment post-MI. Relatively little is known about the temporal changes in exercise capacity post-MI. An important feature of the present study is that exercise capacity was measured serially in the same animals for 16 wk post-MI. Most previous studies of exercise capacity in post-MI rats have measured exercise function at only a single time point (25) or have used a cross-sectional design in which different cohorts of animals were studied at each time point (2). Using a cross-sectional approach, Bech et al. (2) found that the time course of exercise impairment post-MI in rats was related to infarct size. In animals with small infarcts (<20%) exercise capacity was reduced at weeks 1, 3, and 7 but normal at weeks 9 and 13. In rats with larger infarcts (>20%), exercise capacity was consistently reduced at all times (2). In contrast, we found that the time course of exercise impairment post-MI in animals with small or large MIs showed a similar temporal pattern.

Exercise capacity and LV remodeling. A surprising finding was that exercise impairment did not correlate with LV dilation or systolic dysfunction. By 8 wk post-MI, there was evidence of LV remodeling with both chamber dilation and decreased systolic function. However, neither LV volume nor fractional shortening correlated with exercise capacity, which was normalized at 8 wk. Although LV volume and fractional shortening remained constant between 8 and 16 wk, there was a marked progressive deterioration in exercise capacity. Thus exercise impairment did not correlate with these commonly used measures of LV remodeling post-MI.

Compensatory hypertrophy and exercise capacity. In contrast to the lack of correlation with LV dilation and contractile dysfunction, there were robust positive correlations between exercise capacity and septal wall thickness at both 8 and 16 wk post-MI. It is interesting that this relationship persisted at 16 wk, despite the fact that exercise capacity had decreased markedly over the same time period. Because MI in this model is confined to the LV free wall, septal wall thickness reflects hypertrophy of noninfarcted myocardium that is remote from the infarct. Better exercise capacity in animals with more septal hypertrophy suggests that this was an important compensatory response that may have contributed to the early recovery of exercise capacity between 5 and 9 wk post-MI. Likewise, the progressive decrease in exercise capacity after 9 wk occurred despite further septal hypertrophy, which continued to correlate strongly with exercise capacity at 16 wk. These observations suggest that hypertrophy of the remote myocardium exerts a beneficial effect on exercise capacity at both 8 and 16 wk post-MI but that hypertrophy alone is not sufficient to maintain exercise capacity in the face of other ongoing changes between 9 and 16 wk post-MI.

These data do not identify the mechanism responsible for progressive exercise impairment between weeks 9 and 16. There are several possible mechanisms behind the exercise diminution late post-MI in our study, including changes in cardiac/hemodynamic function, skeletal muscle properties, peripheral vascular responsiveness, and/or ventilatory function changes. Because patients with heart failure have attenuated heart rate and blood pressure responses to exercise (9) due to postsynaptic desensitization of {beta}-adrenergic receptors (6), it is possible that there was a progressive adrenergic receptor desensitization late post-MI in the rats in our study. However, it is also possible that changes in skeletal muscles associated with heart failure contributed to the progressive decline in exercise capacity in our rats. Specifically, it has also been shown that skeletal muscles become progressively weaker with heart failure (4), due to changes in calcium handling and force production of myocytes (24), and also due to skeletal muscle cell atrophy (10, 15) and apoptosis (14). Related to these changes in skeletal muscle are alterations in blood flow to the periphery. Specifically, McAllister et al. (16) demonstrated a decrease in the vascular flow capacity to high oxidative muscle fibers, and Ceiler et al. (3) showed decreased nitric oxide production and vascular hyporeactivity in rats post-MI. Accordingly, it is possible that progressive changes in blood flow to skeletal muscles and/or progressive changes in skeletal muscle properties contributed to the post-MI exercise capacity time course seen in our study. Finally, diaphragm strength is reduced (11) and alveolar gas exchange is impaired at rest and during exercise with heart failure (21). In summary, there are a number of changes associated with heart failure. It may be valuable to determine which changes are occurring progressively in association with the changes in exercise capacity post-MI. It is possible that a combination of the changes discussed above are responsible for the progressive exercise intolerance late post-MI.

Limitations. We cannot exclude the possibility that other measures of systolic (e.g., force-frequency relationship) or diastolic function (e.g., filling velocities) might have correlated with exercise performance. A limitation of this study is that the procedure of inducing the range of MI sizes resulted in variation in the location of infarcts, from the hearts with small MIs (infarct only on the apical LV free wall) to the hearts with larger MIs (infarct from apex to base of the LV free wall). It is also possible that larger (e.g., >40%) MIs would yield a different time profile of exercise dysfunction and might exhibit relationships between exercise and LV remodeling that were not evident in this study. Finally, it is possible that further pathological remodeling, which might occur beyond 16 wk, is an important determinant of late changes in exercise capacity.

Summary. These data demonstrate that progressive deterioration in exercise capacity post-MI can occur independent of changes in LV structure and function. Elucidating the noncardiac factors that contribute to exercise impairment in this model may thus improve our understanding of the factors that determine exercise capacity in heart failure. These data further suggest that hypertrophy of the noninfarcted LV serves an important compensatory role that helps to support exercise function. This latter finding raises the intriguing possibility that interventions that increase the extent of compensatory hypertrophy post-MI might improve exercise capacity.


   GRANTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
The authors gratefully acknowledge support from the American Heart Association (Massachusetts Affiliate postdoctoral fellowship; to N. A. Trueblood), a Whitaker Cardiovascular Institute Training Grant (to N. A. Trueblood), and National Heart, Lung, and Blood Institute Grants HL-42539 and HL-52320 (to W. S. Colucci).


   FOOTNOTES
 

Address for reprint requests and other correspondence: N. A. Trueblood, Biology Dept., Earlham College, 801 National Rd. West, Richmond, IN 47374 (E-mail: truebna{at}earlham.edu)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 

  1. Adamopoulos S, Kemp GJ, Thompson CH, Arnolda L, Brunotte F, Stratton JR, Radda GK, Rajagopalan B, Kremastinos DT, and Coats AJ. The time course of haemodynamic, autonomic and skeletal muscle metabolic abnormalities following first extensive myocardial infarction in man. J Mol Cell Cardiol 31: 1913–1926, 1999.[CrossRef][Web of Science][Medline]
  2. Bech OM, Kahr O, Diamant B, and Steiness E. Time course of functional deterioration after coronary artery ligation in rats. Cardiovasc Res 23: 649–654, 1989.[Web of Science][Medline]
  3. Ceiler DL, Nelissen-Vrancken M, De Mey JG, and Smits JF. Role of basal nitric oxide synthesis in vasoconstrictor hyporeactivity in the perfused rat hindlimb after myocardial infarction: effect of captopril. Cardiovasc Res 43: 779–787, 1999.[Abstract/Free Full Text]
  4. Coats AJ. The "muscle hypothesis" of chronic heart failure. J Mol Cell Cardiol 28: 2255–2262, 1996.[CrossRef][Web of Science][Medline]
  5. Cohn JN, Johnson GR, Shabetai R, Loeb H, Tristani F, Rector T, Smith R, and Fletcher R. Ejection fraction, peak exercise oxygen consumption, cardiothoracic ratio, ventricular arrhythmias, and plasma norepinephrine as determinants of prognosis in heart failure. The V-HeFT VA Cooperative Studies Group. Circulation 87: VI5–V16, 1993.[Medline]
  6. Colucci WS, Ribeiro JP, Rocco MB, Quigg RJ, Creager MA, Marsh JD, Gauthier DF, and Hartley LH. Impaired chronotropic response to exercise in patients with congestive heart failure. Role of postsynaptic beta-adrenergic desensitization. Circulation 80: 314–323, 1989.[Abstract/Free Full Text]
  7. Florea VG, Henein MY, Anker SD, Francis DP, Gibson DG, and Coats AJ. Relation of changes over time in ventricular size and function to those in exercise capacity in patients with chronic heart failure. Am Heart J 139: 913–917, 2000.[Web of Science][Medline]
  8. Franciosa JA, Park M, and Levine TB. Lack of correlation between exercise capacity and indexes of resting left ventricular performance in heart failure. Am J Cardiol 47: 33–39, 1981.[CrossRef][Web of Science][Medline]
  9. Francis GS, Goldsmith SR, and Cohn JN. Relationship of exercise capacity to resting left ventricular performance and basal plasma norepinephrine levels in patients with congestive heart failure. Am Heart J 104: 725–731, 1982.[CrossRef][Web of Science][Medline]
  10. Harrington D, Anker SD, Chua TP, Webb-Peploe KM, Ponikowski PP, Poole-Wilson PA, and Coats AJ. Skeletal muscle function and its relation to exercise tolerance in chronic heart failure. J Am Coll Cardiol 30: 1758–1764, 1997.[Abstract]
  11. Hughes PD, Polkey MI, Harrus ML, Coats AJ, Moxham J, and Green M. Diaphragm strength in chronic heart failure. Am J Respir Crit Care Med 160: 529–534, 1999.[Abstract/Free Full Text]
  12. Jain M, Apstein CS, Libonati JR, Ngoy S, Whittaker P, and Eberli FR. Effects of losartan and exercise on post-MI remodeling and contractility. Circulation 96: I-345, 1997.
  13. Lewis BS, Emmott SN, Smyllie J, MacNeill AB, and Lubsen J. Left ventricular systolic and diastolic function, and exercise capacity six to eight weeks after acute myocardial infarction. The DEFIANT Study Group Doppler Flow and Echocardiography in Functional Cardiac Insufficiency: Assessment of Nisoldipine Therapy. Am J Cardiol 72: 149–153, 1993.[CrossRef][Web of Science][Medline]
  14. Libera LD, Zennaro R, Sandri M, Ambrosio GB, and Vescovo G. Apoptosis and atrophy in rat slow skeletal muscles in chronic heart failure. Am J Physiol Cell Physiol 277: C982–C986, 1999.[Abstract/Free Full Text]
  15. Massie BM, Simonini A, Sahgal P, Wells L, and Dudley GA. Relation of systemic and local muscle exercise capacity to skeletal muscle characteristics in men with congestive heart failure. J Am Coll Cardiol 27: 140–145, 1996.[Abstract]
  16. McAllister RM, Laughlin MH, and Musch TI. Effects of chronic heart failure on skeletal muscle vascular transport capacity of rats. Am J Physiol Heart Circ Physiol 264: H689–H691, 1993.[Abstract]
  17. Pfeffer MA and Braunwald E. Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation 81: 1161–1172, 1990.[Abstract/Free Full Text]
  18. Pfeffer MA, Lamas GA, Vaughan DE, Parisi AF, and Braunwald E. Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med 319: 80–86, 1988.[Abstract]
  19. Pfeffer JM, Pfeffer MA, Fletcher PJ, and Braunwald E. Progressive ventricular remodeling in rat with myocardial infarction. Am J Physiol Heart Circ Physiol 260: H1406–H1414, 1991.[Abstract/Free Full Text]
  20. Podesser BK, Siwik DA, Eberli FR, Sam F, Ngoy S, Lambert J, Ngo K, Apstein CS, and Colucci WS. ETA receptor blockade prevents matrix metalloproteinase activation late postmyocardial infarction in the rat. Am J Physiol Heart Circ Physiol 280: H984–H991, 2001.[Abstract/Free Full Text]
  21. Smith AA, Cowburn PJ, Parker ME, Denvir M, Puri S, Patel KR, and Cleland JG. Impaired pulmonary diffusion during exercise in patients with chronic heart failure. Circulation 100: 1406–1410, 1999.[Abstract/Free Full Text]
  22. Sogaard P, Gotzsche CO, Ravkilde J, Norgaard A, and Thygesen K. Exercise capacity in patients with left ventricular dysfunction following acute myocardial infarction: relation to systolic and diastolic function and intervention with captopril. Cardiology 84: 322–330, 1994.[Web of Science][Medline]
  23. Szlachcic J, Massie BM, Kramer BL, Topic N, and Tubau J. Correlates and prognostic implication of exercise capacity in chronic congestive heart failure. Am J Cardiol 55: 1037–1042, 1985.[CrossRef][Web of Science][Medline]
  24. Williams JH and Ward CW. Changes in skeletal muscle sarcoplasmic reticulum function and force production following myocardial infarction in rats. Exp Physiol 83: 85–94, 1998.[Abstract]
  25. Yamaguchi F, Kawana K, Tanonaka K, Kamano I, Igarashi T, Gen E, Fujimoto Y, Maki T, Sanbe A, Nasa Y, and Takeo S. Improvement of exercise capacity of rats with chronic heart failure by long-term treatment with trandolapril. Br J Pharmacol 126: 1585–1592, 1999.[CrossRef][Web of Science][Medline]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
288/1/H244    most recent
00042.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Trueblood, N. A.
Right arrow Articles by Colucci, W. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Trueblood, N. A.
Right arrow Articles by Colucci, W. S.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2005 by the American Physiological Society.