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Administration of inotropic agents for safe intravenous epoprostenol therapy in patients with primary pulmonary hypertension
The 8th Annual Scientific Meeting
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JHFS
S187
O-129
O-131
Effect of Mibefradil, a T-Type Calcium-channel Blocker in Pigs with Heart Failure: Comparison with Amlodipine, An L-Type Calciumchannel Blocker ISHIKAWA KIMITO1, OHTSUKA SADANORI2, YAMAGUCHI IWAO2 1 Department of Cardiology, Tsukuba Medical Center Hospital, 2Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba
Dose Torasemide Have An Aldosterone Receptor Antagonist ?
Mibefradil, a T-type calcium-channel blocker (CCB) is an arterial vasodilator with negative chronotropic effect. We compared its hemodynamic effects with those of amlodipine, an L-type CCB in pigs with heart failure due to myocardial infarction. Methods: Myocardial infarction was produced in pigs by placing a nylon tube in the left circumflex (LCx) coronary artery. Three months after the tube placement, the pigs were allocated to either of mibefradil-group (n ⫽ 5) and amlodipine-group (n ⫽ 5) and underwent thoracotomy. Aortic pressure, aortic flow, and the left anterior descending (LAD) coronary flow were measured. Left ventricular (LV) pressure-volume relation was also analyzed with a conductance and a micromanometer catheter. The hemodynamic measurements were performed before and 20-minutes after the intravenous administration of mibefradil (0.3mg/kg) and amlodipine (0.3mg/kg). Results: There were no differences in baseline values between the mibefradil- and the amlodipine- groups. Aortic pressure decreased and aortic flow increased after amlodipine infusion (P ⬍ 0.05), but did not change after mibefradil infusion. The LAD flow similarly increased with mibefradil and amlodipine infusions. LV end-systolic-elastance (Ees) decreased after amlodipine infusion (8.2 ⫾ 1.8 vs. 4.2 ⫾ 2.6 mmHg/ml) (P ⬍ 0.05), but did not change with mibefradil infusion (7.7 ⫾ 3.6 vs. 7.6 ⫾ 1.8 mmHg/ml). Conclusion: A T-type CCB mibefradil increased coronary flow and was not associated with negative inotropic effects. Thus, mibefradil is suggested to be more useful than amlodipine in patient with ischemic heart failure.
Background: We reported that mineralocorticoid receptor antagonist spironolactone inhibits the transcardiac extraction of aldosterone (ALD) in patients with congestive heart failure (CHF). In the TORIC study, torasemide had more beneficial effect on mortality and morbidity of CHF patients than furosemide. However, the mechanism of the beneficial effect of torasemide remains unknown. Method: To evaluate whether the torasemide has an ALD receptor antagonist, we studied 50 CHF patients who had been randomly administered furosemide (n ⫽ 25) or torasemide (n ⫽ 25). Results: There was no difference of patients characteristics, other treatments, left ventricular ejection fraction, and plasma levels of BNP in the aortic root (AO) between the two groups. In the furosemide group, plasma ALD was significantly lower in the coronary sinus (CS) than in the AO (96 ⫾ 11 vs. 75 ⫾ 12 pg/mL, p ⬍ 0.001), suggesting that ALD is extracted through the heart. In contrast, there was no difference of plasma ALD between the AO and CS in the torasemide group (83 ⫾ 11 vs. 78 ⫾ 12 pg/mL, p ⫽ 0.17), suggesting that the extraction of ALD through the heart is inhibited by torasemide. In addition, there was a significant negative correlation between dose of torasemide and the transcardiac gradient (AoCS) of ALD in the torasemide group (r ⫽ -0.56, p ⬍ 0.01). Conclusion: These findings suggest that torasemide has an ALD receptor antagonist in the failing heart in patients with CHF.
O-130
O-132
Effect of Spironolactone on Chamber Stiffness and Diastolic Function Associated with Regression of Myocardial Fibrosis in Dilated Cardiomyopathy IZAWA HIDEO1, YOSUKE MURASE1, HIROYUKI ASANO1, TOMOKO KATO1, AKIRA YAMADA1, SATORU OHSHIMA1, AKIKO NODA3, KOHZO NAGATA3, MITSUHIRO YOKOTA2, TOYOAKI MUROHARA1 1 Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 2Department of Cardiovascular Genome Science, Nagoya University School of Medicine, Nagoya, Japan, 3Nagoya University School of Health Science, Nagoya, Japan
Administration of Inotropic Agents for Safe Intravenous Epoprostenol Therapy in Patients with Primary Pulmonary Hypertension
We investigated whether spironolactone-induced regression of myocardial fibrosis is associated with improvement of left ventricular (LV) diastolic function in dilated cardiomyopathy (DCM). Methods and Results: Tissue Doppler echocardiography, LV catheterization and biopsies were performed in 10 DCM patients before and after 12 months of treatment with spironolactone. The biochemical index of coupling between the synthesis (PIP) and degradation (CITP) of collagen type-I revealed the presence of 2 subgroups: 5 with PIP/CITP ⬍ 40 (GroupA) and 5 with PIP/CITP ⬎ 40 (GroupB). After the treatment, collagen volume fraction (CVF), LV chamber stiffness, and diastolic strain-rate were significantly improved in GroupB accompanied with a reduction of PIP/CITP, but not in GroupA (Table). CVF correlated with PIP/CITP (r ⫽ 0.70). Conclusions: Spironolactone improves LV diastolic function and chamber stiffness accompanied with regression of fibrosis in patients with higher PIP/CITP. Group A
Group B
Baseline
After Treatment
Baseline
After Treatment
LV diastolic strain-rate (/s)
0.71 ± 0.27
0.72 ± 0.13
0.46 ± 0.10
0.71 ± 0.27*†
LV chamber stiffness (mmHg/ml)
0.10 ± 0.01
0.10 ± 0.01
0.12 ± 0.01†
0.11 ± 0.01*†
EF (%)
35 ± 4
37 ± 5
36 ± 6
BNP (ng/mL)
82 ± 23
62 ± 11
135 ± 30†
65 ± 19*
PIP/CITP
18.1 ± 5.1
17.4 ± 5.0
49.1 ± 5.2†
29.5 ± 1.9*†
CVF (%)
3.5 ± 2.0
3.9 ± 1.4
7.0 ± 0.6†
5.1 ± 2.2*†
*P<0.05 vs. baseline; †P<0.05 vs. Group A.
40 ± 8
SAKAI HIROSHI, TUTAMOTO TAKAYOSHI, ISHIKAWA CHITOSE, HORIE MINORU Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Shiga, Japan
MIYAJI KATSUMASA, NAKAMURA KAZUFUMI, NAGASE SATOSHI, SAITO HIRONORI, KUSANO KENGO, TETSURO EMORI, OHE TOHRU Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine and Dentistry Purpose: Continuous intravenous epoprostenol therapy is effective for patients with primary pulmonary hypertension. However, it often causes unstable hemodynamics early after start of intravenous epoprostenol therapy. The aim of this study was to investigate the importance of administration of inotropic agents for safe intravenous epoprostenol therapy. Methods: Continuous intravenous epoprostenol was introduced in 21 patients with primary pulmonary hypertension. Before administration of epoprostenol, we evaluated the hemodynamic parameters by cardiac catheterization and the plasma brain natriuretic peptide level. Results: A total of 16 (76%) of the 21 patients, required administration of inotropic agents when intravenous epoprostenol therapy was started because of unstable hemodynamics or symptoms of right cardiac failure. The New York Heart Association functional class, mean right atrial pressure and plasma brain natriuretic peptide level in those patients were significantly higher than those in the patients who did not require administration of inotropic agents. There was no significant difference between other hemodynamic parameters in patients who required and those who did not require administration of inotropic agents. Conclusions: Administration of inotropic agents should be considered when intravenous epoprostenol therapy would start for patients with primary pulmonary hypertension, especially for patients with severe primary pulmonary hypertension who have high New York Heart association functional class, high right atrial pressure and a high level of plasma brain natriuretic peptide.
•
JHFS
S187
O-129
O-131
Effect of Mibefradil, a T-Type Calcium-channel Blocker in Pigs with Heart Failure: Comparison with Amlodipine, An L-Type Calciumchannel Blocker ISHIKAWA KIMITO1, OHTSUKA SADANORI2, YAMAGUCHI IWAO2 1 Department of Cardiology, Tsukuba Medical Center Hospital, 2Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba
Dose Torasemide Have An Aldosterone Receptor Antagonist ?
Mibefradil, a T-type calcium-channel blocker (CCB) is an arterial vasodilator with negative chronotropic effect. We compared its hemodynamic effects with those of amlodipine, an L-type CCB in pigs with heart failure due to myocardial infarction. Methods: Myocardial infarction was produced in pigs by placing a nylon tube in the left circumflex (LCx) coronary artery. Three months after the tube placement, the pigs were allocated to either of mibefradil-group (n ⫽ 5) and amlodipine-group (n ⫽ 5) and underwent thoracotomy. Aortic pressure, aortic flow, and the left anterior descending (LAD) coronary flow were measured. Left ventricular (LV) pressure-volume relation was also analyzed with a conductance and a micromanometer catheter. The hemodynamic measurements were performed before and 20-minutes after the intravenous administration of mibefradil (0.3mg/kg) and amlodipine (0.3mg/kg). Results: There were no differences in baseline values between the mibefradil- and the amlodipine- groups. Aortic pressure decreased and aortic flow increased after amlodipine infusion (P ⬍ 0.05), but did not change after mibefradil infusion. The LAD flow similarly increased with mibefradil and amlodipine infusions. LV end-systolic-elastance (Ees) decreased after amlodipine infusion (8.2 ⫾ 1.8 vs. 4.2 ⫾ 2.6 mmHg/ml) (P ⬍ 0.05), but did not change with mibefradil infusion (7.7 ⫾ 3.6 vs. 7.6 ⫾ 1.8 mmHg/ml). Conclusion: A T-type CCB mibefradil increased coronary flow and was not associated with negative inotropic effects. Thus, mibefradil is suggested to be more useful than amlodipine in patient with ischemic heart failure.
Background: We reported that mineralocorticoid receptor antagonist spironolactone inhibits the transcardiac extraction of aldosterone (ALD) in patients with congestive heart failure (CHF). In the TORIC study, torasemide had more beneficial effect on mortality and morbidity of CHF patients than furosemide. However, the mechanism of the beneficial effect of torasemide remains unknown. Method: To evaluate whether the torasemide has an ALD receptor antagonist, we studied 50 CHF patients who had been randomly administered furosemide (n ⫽ 25) or torasemide (n ⫽ 25). Results: There was no difference of patients characteristics, other treatments, left ventricular ejection fraction, and plasma levels of BNP in the aortic root (AO) between the two groups. In the furosemide group, plasma ALD was significantly lower in the coronary sinus (CS) than in the AO (96 ⫾ 11 vs. 75 ⫾ 12 pg/mL, p ⬍ 0.001), suggesting that ALD is extracted through the heart. In contrast, there was no difference of plasma ALD between the AO and CS in the torasemide group (83 ⫾ 11 vs. 78 ⫾ 12 pg/mL, p ⫽ 0.17), suggesting that the extraction of ALD through the heart is inhibited by torasemide. In addition, there was a significant negative correlation between dose of torasemide and the transcardiac gradient (AoCS) of ALD in the torasemide group (r ⫽ -0.56, p ⬍ 0.01). Conclusion: These findings suggest that torasemide has an ALD receptor antagonist in the failing heart in patients with CHF.
O-130
O-132
Effect of Spironolactone on Chamber Stiffness and Diastolic Function Associated with Regression of Myocardial Fibrosis in Dilated Cardiomyopathy IZAWA HIDEO1, YOSUKE MURASE1, HIROYUKI ASANO1, TOMOKO KATO1, AKIRA YAMADA1, SATORU OHSHIMA1, AKIKO NODA3, KOHZO NAGATA3, MITSUHIRO YOKOTA2, TOYOAKI MUROHARA1 1 Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 2Department of Cardiovascular Genome Science, Nagoya University School of Medicine, Nagoya, Japan, 3Nagoya University School of Health Science, Nagoya, Japan
Administration of Inotropic Agents for Safe Intravenous Epoprostenol Therapy in Patients with Primary Pulmonary Hypertension
We investigated whether spironolactone-induced regression of myocardial fibrosis is associated with improvement of left ventricular (LV) diastolic function in dilated cardiomyopathy (DCM). Methods and Results: Tissue Doppler echocardiography, LV catheterization and biopsies were performed in 10 DCM patients before and after 12 months of treatment with spironolactone. The biochemical index of coupling between the synthesis (PIP) and degradation (CITP) of collagen type-I revealed the presence of 2 subgroups: 5 with PIP/CITP ⬍ 40 (GroupA) and 5 with PIP/CITP ⬎ 40 (GroupB). After the treatment, collagen volume fraction (CVF), LV chamber stiffness, and diastolic strain-rate were significantly improved in GroupB accompanied with a reduction of PIP/CITP, but not in GroupA (Table). CVF correlated with PIP/CITP (r ⫽ 0.70). Conclusions: Spironolactone improves LV diastolic function and chamber stiffness accompanied with regression of fibrosis in patients with higher PIP/CITP. Group A
Group B
Baseline
After Treatment
Baseline
After Treatment
LV diastolic strain-rate (/s)
0.71 ± 0.27
0.72 ± 0.13
0.46 ± 0.10
0.71 ± 0.27*†
LV chamber stiffness (mmHg/ml)
0.10 ± 0.01
0.10 ± 0.01
0.12 ± 0.01†
0.11 ± 0.01*†
EF (%)
35 ± 4
37 ± 5
36 ± 6
BNP (ng/mL)
82 ± 23
62 ± 11
135 ± 30†
65 ± 19*
PIP/CITP
18.1 ± 5.1
17.4 ± 5.0
49.1 ± 5.2†
29.5 ± 1.9*†
CVF (%)
3.5 ± 2.0
3.9 ± 1.4
7.0 ± 0.6†
5.1 ± 2.2*†
*P<0.05 vs. baseline; †P<0.05 vs. Group A.
40 ± 8
SAKAI HIROSHI, TUTAMOTO TAKAYOSHI, ISHIKAWA CHITOSE, HORIE MINORU Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Shiga, Japan
MIYAJI KATSUMASA, NAKAMURA KAZUFUMI, NAGASE SATOSHI, SAITO HIRONORI, KUSANO KENGO, TETSURO EMORI, OHE TOHRU Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine and Dentistry Purpose: Continuous intravenous epoprostenol therapy is effective for patients with primary pulmonary hypertension. However, it often causes unstable hemodynamics early after start of intravenous epoprostenol therapy. The aim of this study was to investigate the importance of administration of inotropic agents for safe intravenous epoprostenol therapy. Methods: Continuous intravenous epoprostenol was introduced in 21 patients with primary pulmonary hypertension. Before administration of epoprostenol, we evaluated the hemodynamic parameters by cardiac catheterization and the plasma brain natriuretic peptide level. Results: A total of 16 (76%) of the 21 patients, required administration of inotropic agents when intravenous epoprostenol therapy was started because of unstable hemodynamics or symptoms of right cardiac failure. The New York Heart Association functional class, mean right atrial pressure and plasma brain natriuretic peptide level in those patients were significantly higher than those in the patients who did not require administration of inotropic agents. There was no significant difference between other hemodynamic parameters in patients who required and those who did not require administration of inotropic agents. Conclusions: Administration of inotropic agents should be considered when intravenous epoprostenol therapy would start for patients with primary pulmonary hypertension, especially for patients with severe primary pulmonary hypertension who have high New York Heart association functional class, high right atrial pressure and a high level of plasma brain natriuretic peptide.