3D.05 TREATMENT OF HYPERTENSION WITH PERINDOPRIL PLUS INDAPAMIDE LEADS TO REVERSE CORONARY MICROVASCULAR REMODELLING AND IMPROVED BLOOD FLOW P. Camici1, D. Neglia3, E. Fommei3, A. Varela-Carver1, M. Mancini2, S. Ghione3, M. Lombardi3, H. Parker1, G. Damati2, L. Donato3. 1Imperial College, London, United Kingdom, 2Universita’ La Sapienza, Roma, Italy, 3CNR Institute of Clinical Physiology, Pisa, Italy Rationale: The heart of patients with arterial hypertension (HT) is characterized by structural and functional abnormalities of the microcirculation which cause coronary microvascular dysfunction (CMD) and may contribute to myocardial ischemia. Aim of the present study was to ascertain whether treatment with a fixed combination of perindoprilþindapamide (PþI) in patients withHTimprovesCMDas assessed by measuring myocardial blood flow (MBF) noninvasively with positron emission tomography (PET). The human study was complemented by further experiments in spontaneously hypertensive rats (SHR) to ascertain whether treatment with the same drug regimen can reverse anatomical remodelling of the coronary arterioles while improving coronary flow (CF). Methods and Results: In 20 HT patients with left ventricular hypertrophy, blood pressure (BP), left ventricular mass index (LVMI) and resting and hyperemic MBF were measured at baseline and after 6 months of therapy with PþI. In SHR, BP was measured at baseline and after 8 weeks of treatment with placebo or PþI. After sacrifice, baseline and hyperemic CF (Langendorff) and histomorphometry of intramural coronary arterioles were measured. In patients, PþI decreased BP (16110/965 to 13612/816 mmHg; p<0.0001) and LVMI (9316 to 8517 g/m2; p<0.01) whilst baseline (0.690.13 to 0.880.36 ml/min/g; p<0.05) and hyperemic MBF (1.420.32 to 1.940.99 ml/min/g; p<0.05) were increased. In SHR treated with PþI (n¼11), BP was 9318/5518 compared to 21518/ 16117 mmHg in the placebo (n¼6) group (p<0.001) whilst the ratio of hyperemic/baseline CF was 3.971.15 and 1.910.19 respectively (p<0.001). The medial area of intramural arterioles was 1613410 in the PþI group and 104992152mm2 in the placebo (p<0.001). Conclusions: In patients, treatment with PþI reduced BP and LVMI and improved MBF, suggesting reversal of both myocardial and microvascular remodelling. The SHR data provide translational evidence that the improvement of CF observed after treatment with PþI is due to reverse remodelling of intramural arterioles.
TREATMENT OF HYPERTENSION WITH PERINDOPRIL PLUS INDAPAMIDE LEADS TO REVERSE CORONARY MICROVASCULAR REMODELLING AND IMPROVED BLOOD FLOW
FOMMEI, ENZA;
2010-01-01
Abstract
3D.05 TREATMENT OF HYPERTENSION WITH PERINDOPRIL PLUS INDAPAMIDE LEADS TO REVERSE CORONARY MICROVASCULAR REMODELLING AND IMPROVED BLOOD FLOW P. Camici1, D. Neglia3, E. Fommei3, A. Varela-Carver1, M. Mancini2, S. Ghione3, M. Lombardi3, H. Parker1, G. Damati2, L. Donato3. 1Imperial College, London, United Kingdom, 2Universita’ La Sapienza, Roma, Italy, 3CNR Institute of Clinical Physiology, Pisa, Italy Rationale: The heart of patients with arterial hypertension (HT) is characterized by structural and functional abnormalities of the microcirculation which cause coronary microvascular dysfunction (CMD) and may contribute to myocardial ischemia. Aim of the present study was to ascertain whether treatment with a fixed combination of perindoprilþindapamide (PþI) in patients withHTimprovesCMDas assessed by measuring myocardial blood flow (MBF) noninvasively with positron emission tomography (PET). The human study was complemented by further experiments in spontaneously hypertensive rats (SHR) to ascertain whether treatment with the same drug regimen can reverse anatomical remodelling of the coronary arterioles while improving coronary flow (CF). Methods and Results: In 20 HT patients with left ventricular hypertrophy, blood pressure (BP), left ventricular mass index (LVMI) and resting and hyperemic MBF were measured at baseline and after 6 months of therapy with PþI. In SHR, BP was measured at baseline and after 8 weeks of treatment with placebo or PþI. After sacrifice, baseline and hyperemic CF (Langendorff) and histomorphometry of intramural coronary arterioles were measured. In patients, PþI decreased BP (16110/965 to 13612/816 mmHg; p<0.0001) and LVMI (9316 to 8517 g/m2; p<0.01) whilst baseline (0.690.13 to 0.880.36 ml/min/g; p<0.05) and hyperemic MBF (1.420.32 to 1.940.99 ml/min/g; p<0.05) were increased. In SHR treated with PþI (n¼11), BP was 9318/5518 compared to 21518/ 16117 mmHg in the placebo (n¼6) group (p<0.001) whilst the ratio of hyperemic/baseline CF was 3.971.15 and 1.910.19 respectively (p<0.001). The medial area of intramural arterioles was 1613410 in the PþI group and 104992152mm2 in the placebo (p<0.001). Conclusions: In patients, treatment with PþI reduced BP and LVMI and improved MBF, suggesting reversal of both myocardial and microvascular remodelling. The SHR data provide translational evidence that the improvement of CF observed after treatment with PþI is due to reverse remodelling of intramural arterioles.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
