OBJECTIVES: This study sought to determine the effects of long-term angiotensin-converting enzyme (ACE) inhibition on left ventricular (LV) diastolic filling in postinfarction heart failure. BACKGROUND: Long-term treatment with ACE inhibitors is beneficial in experimental animals and patients with heart failure. Because this treatment typically produces only small improvements in LV systolic function, we hypothesized that improvements in LV diastolic filling might contribute to the overall beneficial effects of ACE inhibitors after myocardial infarction (MI). METHODS: We performed transthoracic echocardiographic-Doppler examinations in rats 1 and 6 weeks after transmural MI or sham operation. Rats with MI were randomized to no treatment (n = 10) or captopril (2 g/liter in drinking water, n = 8) after the baseline echocardiogram. RESULTS: Six weeks after MI, untreated rats had significant LV dilation compared with sham-operated rats (LV diastolic dimension [mean+/-SEM] 10.7 +/- 0.3 vs. 8.5 +/- 0.3 mm, p < 0.05). Rats with untreated MI also had impaired fractional shortening (9 +/- 1% vs. 34 +/- 2%, p < 0.05) and depressed systolic thickening of the noninfarcted posterior wall (3% +/- 3% vs, 65 +/- 9%, p < 0.05). Rats with MI showed progressively restricted LV diastolic filling as assessed by transmitral Doppler recordings. At 6 weeks, peak early filling velocity (E) was increased (97 +/- 3 vs. 77 +/- 2 cm/s, p < 0.05), E wave deceleration was more rapid (23 +/- 3 vs. 12 +/- 1 m/s2, p < 0.05), isovolumetric relaxation time was decreased (18 +/- 1 vs. 24 +/- 1 ms, p < 0.05), and late filling velocity was lower (26 +/- 7 vs. 34 +/- 1 cm/s, p < 0.05) in rats with MI versus sham-operated rats. Compared with rats with untreated MI, rats receiving captopril had similar LV diastolic dimensions (10.5 +/- 0.35 vs. 10.7 +/- 0.35 mm), slightly higher fractional shortening (16 +/- 2% vs. 9 +/- 1%, p < 0.05 [captopril MI vs. untreated MI]) and unchanged posterior wall thickening (49 +/- 12% vs. 37 +/- 3%, p = 0.3). In contrast, captopril almost completely normalized diastolic filling abnormalities (E velocity 82 +/- 5 cm/s, p < 0.05 [captopril MI vs. untreated MI]; E wave deceleration rate 15 +/- 2 m/s2, p < 0.05 [captopril MI vs. untreated MI]; isovolumetric relaxation time 20 +/- 1 ms). CONCLUSIONS: Long-term captopril treatment in rats with a large MI modestly limits LV remodeling and the development of systolic dysfunction but markedly improves the restrictive diastolic filling abnormalities that are seen in untreated rats.
OBJECTIVES: This study sought to determine the effects of long-term angiotensin-converting enzyme (ACE) inhibition on left ventricular (LV) diastolic filling in postinfarction heart failure. BACKGROUND: Long-term treatment with ACE inhibitors is beneficial in experimental animals and patients with heart failure. Because this treatment typically produces only small improvements in LV systolic function, we hypothesized that improvements in LV diastolic filling might contribute to the overall beneficial effects of ACE inhibitors after myocardial infarction (MI). METHODS: We performed transthoracic echocardiographic-Doppler examinations in rats 1 and 6 weeks after transmural MI or sham operation. Rats with MI were randomized to no treatment (n = 10) or captopril (2 g/liter in drinking water, n = 8) after the baseline echocardiogram. RESULTS: Six weeks after MI, untreated rats had significant LV dilation compared with sham-operated rats (LV diastolic dimension [mean+/-SEM] 10.7 +/- 0.3 vs. 8.5 +/- 0.3 mm, p < 0.05). Rats with untreated MI also had impaired fractional shortening (9 +/- 1% vs. 34 +/- 2%, p < 0.05) and depressed systolic thickening of the noninfarcted posterior wall (3% +/- 3% vs, 65 +/- 9%, p < 0.05). Rats with MI showed progressively restricted LV diastolic filling as assessed by transmitral Doppler recordings. At 6 weeks, peak early filling velocity (E) was increased (97 +/- 3 vs. 77 +/- 2 cm/s, p < 0.05), E wave deceleration was more rapid (23 +/- 3 vs. 12 +/- 1 m/s2, p < 0.05), isovolumetric relaxation time was decreased (18 +/- 1 vs. 24 +/- 1 ms, p < 0.05), and late filling velocity was lower (26 +/- 7 vs. 34 +/- 1 cm/s, p < 0.05) in rats with MI versus sham-operated rats. Compared with rats with untreated MI, rats receiving captopril had similar LV diastolic dimensions (10.5 +/- 0.35 vs. 10.7 +/- 0.35 mm), slightly higher fractional shortening (16 +/- 2% vs. 9 +/- 1%, p < 0.05 [captopril MI vs. untreated MI]) and unchanged posterior wall thickening (49 +/- 12% vs. 37 +/- 3%, p = 0.3). In contrast, captopril almost completely normalized diastolic filling abnormalities (E velocity 82 +/- 5 cm/s, p < 0.05 [captopril MI vs. untreated MI]; E wave deceleration rate 15 +/- 2 m/s2, p < 0.05 [captopril MI vs. untreated MI]; isovolumetric relaxation time 20 +/- 1 ms). CONCLUSIONS: Long-term captopril treatment in rats with a large MI modestly limits LV remodeling and the development of systolic dysfunction but markedly improves the restrictive diastolic filling abnormalities that are seen in untreated rats.
Authors: Hartmut Ruetten; Doris Gehring; Katrin Hiss; Ursula Schindler; Martin Gerl; Andreas E Busch; Stefan Schaefer Journal: Br J Pharmacol Date: 2005-11 Impact factor: 8.739