Effects of pre-, peri-, and postmyocardial infarction treatment with omapatrilat in rats: survival, arrhythmias, ventricular function, and remodeling

2003 ◽  
Vol 285 (1) ◽  
pp. H398-H405 ◽  
Author(s):  
Nathalie Lapointe ◽  
Quang Trinh Nguyen ◽  
Jean-François Desjardins ◽  
Francois Marcotte ◽  
Ali Pourdjabbar ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ventricular Arrhythmias ◽  
Left Ventricular ◽  
Treatment Control ◽  
Postmyocardial Infarction ◽  
Vasopeptidase Inhibitor ◽  
Lv Remodeling ◽  
Cardiac Hemodynamics ◽  
The Subject ◽  
Early Benefit

We showed previously that the vasopeptidase inhibitor (VPI) omapatrilat improves peri-myocardial infarction (MI) survival, but the mechanisms involved and whether these effects are sustained remained to be determined, and are the subject of this study. Rats ( n = 272) received omapatrilat (20 mg · kg-1 · day-1) starting 7 days before MI and continued peri- and post-MI, or no treatment (control). One group of rats had continuous ambulatory ECG and blood pressure recordings started 6 h before MI and continued until 24 h after MI, when survival was evaluated, and the rats were killed, and MI size was evaluated. A second group had left ventricular (LV) remodeling evaluated by echocardiography at 30 days and, at 38 days, had cardiac hemodynamics and morphology done and survival evaluated. Survival 24 h after MI ( n = 255) improved with omapatrilat (60% vs. 46% for control; P = 0.0378). Over the next 37 days, there was no further improvement with omapatrilat but the early benefit was sustained. Omapatrilat reduced MI size 24 h after MI (36 ± 2 vs. 42 ± 2 mm2 for controls; P = 0.034). Omapatrilat reduced ventricular arrhythmia score 1–12 h after MI. Omapatrilat decreased blood pressure, but not during the first 24 h after MI. Omapatrilat reduced LV diastolic and systolic dimensions and LV and right ventricular weights compared with control large MI, indicating a decrease in reactive hypertrophy. Improvement in cardiac remodeling was accompanied by improved cardiac hemodynamics. Thus this study indicates that pre-, peri-, and post-MI treatment with the VPI omapatrilat is beneficial in survival, ventricular arrhythmias, LV remodeling, and cardiac function.

Effects of pre-, peri-, and postmyocardial infarction treatment with losartan in rats: effect of dose on survival, ventricular arrhythmias, function, and remodeling

2005 ◽  
Vol 288 (4) ◽  
pp. H1997-H2005 ◽  
Author(s):  
Ali Pourdjabbar ◽  
Thomas G. Parker ◽  
Quang Trinh Nguyen ◽  
Jean-Francois Desjardins ◽  
Nathalie Lapointe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ventricular Arrhythmias ◽  
Angiotensin Receptor Blockers ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Lv Function ◽  
High Dose ◽  
Postmyocardial Infarction ◽  
Lv Remodeling ◽  
Cardiac Hemodynamics

Angiotensin receptor blockers (ARBs) reduce adverse left ventricular (LV) remodeling and improve LV function and survival when started postmyocardial infarction (MI). ARBs also reduce ventricular arrhythmias during ischemia-reperfusion injury when started pre-MI. No information exists regarding their efficacy and safety when started pre-MI and continued peri- and post-MI. We evaluated whether the ARB losartan improves the outcome when started pre-MI and continued peri- and post-MI. Male Wistar rats ( n = 502) were treated for 7 days pre-MI with losartan at a high dose (30 mg·kg−1·day−1), progressively increasing dose (3 mg·kg−1·day−1 increased to 10 mg·kg−1·day−1 10 days and 30 mg·kg−1·day−1 20 days post-MI), or no treatment. Ambulatory systolic blood pressure and Holter monitoring were performed for 24 h post-MI. Echocardiography was done 30 days post-MI, and LV remodeling, cardiac hemodynamics, and fetal gene expression were assessed 38 days post-MI. High-dose losartan reduced 24-h post-MI survival compared with the progressive dose and control (21.9% vs. 36.6% and 38.1%, P = 0.033 and P = 0.009, respectively). This was associated with greater hypotension in the high dose and no change in ventricular arrhythmias in all groups. In 24-h post-MI survivors, the progressive dose group had reduced mortality from 24 h to 38 days (8.5% vs. 28.6% for control vs. 38.9% for high dose, P = 0.032 and P = 0.01, respectively). Survivors of both losartan groups demonstrated improved LV remodeling, cardiac hemodynamics, preserved GLUT-4, and reduced cardiac fetal gene expression. Pretreatment with ARBs does not reduce 24-h post-MI ventricular arrhythmias or survival, and high doses increase mortality by causing excessive hypotension. In 24-h post-MI survivors, progressively increasing doses of losartan have multiple beneficial effects, including improved survival.

scholarly journals Left Ventricular Mass Index Is Associated With Cognitive Function in Middle-Age

2020 ◽  
Vol 13 (8) ◽  
Author(s):  
Alexander C. Razavi, ◽  
Camilo Fernandez ◽  
Jiang He ◽  
Tanika N. Kelly ◽  
Marie Krousel-Wood ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Cognitive Function ◽  
Systolic Blood Pressure ◽  
Middle Age ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Left Ventricular ◽  
Lv Mass ◽  
Lv Remodeling

Background: Elevated cardiovascular disease risk factor burden is a recognized contributor to poorer cognitive function; however, the physiological mechanisms underlying this association are not well understood. We sought to assess the potential mediation effect of left ventricular (LV) remodeling on the association between lifetime systolic blood pressure and cognitive function in a community-based cohort of middle-aged adults. Methods: Nine hundred sixty participants of the Bogalusa Heart Study (59.2% women, 33.8% black, aged 48.4±5.1 years) received 2-dimensional echocardiography to quantify relative wall thickness, LV mass, and diastolic and systolic LV function; and a standardized neurocognitive battery to assess memory, executive functioning, and language processing. Multivariable linear regression assessed the association of cardiac structure and function with a global composite cognitive function score, adjusting for traditional cardiovascular disease risk factors. Mediation analysis assessed the effect of LV mass index on the association between lifetime systolic blood pressure burden and cognitive function. Results: There were 233 (24.3%) and 136 (14.2%) individuals with concentric LV remodeling and concentric LV hypertrophy, respectively. Each g/m 2.7 increment in LV mass index was associated with a 0.03 standardized unit decrement in global cognitive function ( P =0.03). Individuals with concentric LV remodeling and isolated diastolic dysfunction had the poorest cognitive function, and a greater ratio between early mitral inflow velocity and early diastolic mitral annular velocity (E/e’) was associated with poorer cognitive function, even after adjustment for LV mass index (B=−0.12; P =0.03). A total of 18.8% of the association between lifetime systolic blood pressure burden and midlife cognitive function was accounted for by LV mass index. Conclusions: Cardiac remodeling partially mediates the association between lifespan systolic blood pressure burden and adult cognition in individuals without dementia or clinical cardiovascular disease. Slowing or reversing the progression of cardiac remodeling in middle-age may be a novel therapeutic approach to prevent cognitive decline.

scholarly journals First-in-man experience with ultrasound renal denervation for treatment of recurrent ventricular arrhythmias

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D.N Millenaar ◽  
F Mahfoud ◽  
V Pavlicek ◽  
L Lauder ◽  
M Boehm ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Catheter Ablation ◽  
Ejection Fraction ◽  
Ventricular Arrhythmias ◽  
Ischemic Cardiomyopathy ◽  
Renal Denervation ◽  
Left Ventricular ◽  
Funding Source ◽  
Ultrasound Energy

Abstract Background/Introduction Ventricular arrhythmias (VA) are common in patients with chronic heart failure (CHF) and can be refractory to drugs and catheter ablation. Promising results of sympathomodulatory treatment have been reported in these patients. Purpose This first in man study aims at investigating catheter-based renal denervation (RDN) using ultrasound energy for treatment of refractory VA in patients with CHF. Methods Four patients (age 65±10 years, all male, left ventricular ejection fraction 36±7%, global longitudinal strain (GLS) −10±3%) with CHF (n=1 ischemic cardiomyopathy, n=3 non-ischemic cardiomyopathy) and refractory VA were treated with RDN using ultrasound energy. All patients had undergone endo- or epicardial catheter ablation for recurrent ventricular tachycardia (VT) or fibrillation (VF) in the past and were on at least 2 antiarrhythmic drugs. Computer tomography angiography was performed at baseline, duplex ultrasound of renal arteries, ambulatory blood pressure monitoring (ABPM) and ICD interrogations were performed before, 1 day and 3 months post RDN. Results Bilateral RDN using an ultrasound-based catheter were performed with at least 2 sonications in each main branch of the left and right renal artery. In this analysis, mean follow-up time was 113±12 days. All RDN procedures were performed without any complications. No renal artery stenoses during follow-up. Arrhythmic burden (measured as VT/VF episodes) within 3 months before RDN requiring ICD therapy was reduced from 3 [1.5–54.5] episodes of anti-tachycardia pacing (ATP) and 0.5 [0–1.25] adequate ICD shocks to 1 [0.75–1] episode of ATP. There were no adequate ICD shocks after 3 months. Mean 24-hour ABP before RDN was 94±8/65±9 mmHg with no change in BP following 3 months (SBP 92±1 mmHg, DBP 62±6 mmHg after 3 months). There was no change in left ventricular GLS (−10±3% before, −9±4% after RDN) or ejection fraction (36±7% before and after RDN). Conclusions RDN using ultrasound energy in patients with CHF and refractory VA was safely performed with no changes in blood pressure and reduced the arrhythmic burden after 3 months follow-up. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): ReCor Medical Inc.

ANG II type 1A receptor signaling causes unfavorable scar dynamics in the postinfarct heart

2007 ◽  
Vol 292 (2) ◽  
pp. H946-H953 ◽  
Author(s):  
Yiwen Li ◽  
Genzou Takemura ◽  
Hideshi Okada ◽  
Shusaku Miyata ◽  
Hiromitsu Kanamori ◽  
...  
Keyword(s):  
Granulation Tissue ◽  
Growth Factor Receptor ◽  
Wall Stress ◽  
Scar Tissue ◽  
Left Ventricular ◽  
Tissue Cell ◽  
Ang Ii ◽  
Postmyocardial Infarction ◽  
Lv Remodeling ◽  
Infarcted Tissue

Blockade of ANG II type 1A receptor (AT1A) is known to attenuate postinfarction [postmyocardial infarction (post-MI)] heart failure, accompanying reduction in fibrosis of the noninfarcted area. In the present study, we investigated the influence of AT1A blockade on the infarcted tissue itself. Consistent with earlier reports, AT1A knockout (AT1AKO) mice showed significantly attenuated left ventricular (LV) remodeling (dilatation) and dysfunction compared with wild-type (WT) mice. Morphometry revealed that the infarcted wall was thicker and had a smaller circumferential length in AT1AKO than WT hearts. In addition, significantly greater numbers of cells were present within infarcts in AT1AKO hearts 4 wk post-MI; most notably, there was an abundance of vessels and myofibroblasts. One week post-MI, the incidence of apoptosis among granulation tissue cells was fewer (3.3 ± 0.4 vs. 4.4 ± 0.5% in WT, P < 0.05), whereas vessel proliferation was higher in AT1AKO hearts, which likely explains the later abundance of cells within the scar tissue. Insulin-like growth factor receptor-I was upregulated and its downstream signal protein kinase B (Akt) was significantly activated in infarcted AT1AKO hearts compared with WT hearts. Inactivation of Akt with wortmannin partially but significantly prevented the benefits observed in AT1AKO. Collectively, in AT1AKO hearts, Akt-mediated granulation tissue cell proliferation and preservation resulting from antiapoptosis likely contributed to an abundant cell population that altered the infarct scar structure, thereby reducing wall stress and attenuating LV dilatation and dysfunction at the chronic stage. In conclusion, altered structural dynamics of infarct scar and increasing myocardial fibrosis may be responsible for the deleterious effects of AT1A signaling following MI.

scholarly journals Hemodynamic and Non-Hemodynamic Components of Cardiac Remodeling in Primary Aldosteronism

2021 ◽  
Vol 12 ◽  
Author(s):  
Chien-Ting Pan ◽  
Xue-Ming Wu ◽  
Cheng-Hsuan Tsai ◽  
Yi-Yao Chang ◽  
Zheng-Wei Chen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Multivariate Analysis ◽  
Cardiac Remodeling ◽  
Primary Aldosteronism ◽  
Left Ventricular Mass Index ◽  
Left Ventricular ◽  
Plasma Aldosterone Concentration ◽  
Lv Remodeling ◽  
Aldosterone Producing Adenoma ◽  
Aldosterone To Renin Ratio

ObjectivesPatients with primary aldosteronism (PA) have cardiac remodeling due to hemodynamic and non-hemodynamic causes. However, component analysis of cardiac remodeling and reversal in PA patients is lacking. We investigated components of cardiac remodeling and reversal after adrenalectomy in patients with aldosterone-producing adenoma (APA).MethodsThis study prospectively enrolled 304 APA patients who received adrenalectomy and 271 with essential hypertension (EH). Clinical, biochemical and echocardiographic data were collected in both groups and 1 year after surgery in the APA patients. The hemodynamic and non-hemodynamic components of left ventricular (LV) remodeling were represented by predicted left ventricular mass index (LVMI) (pLVMI) and inappropriately excessive LVMI (ieLVMI, defined as LVMI-pLVMI).ResultsAfter propensity score matching, 213 APA and 213 EH patients were selected. APA patients had higher hemodynamic (pLVMI) and non-hemodynamic (ieLVMI) components of LV remodeling than EH patients. In multivariate analysis, baseline pLVMI was correlated with systolic blood pressure (SBP) and serum potassium, whereas ieLVMI was correlated with log plasma aldosterone concentration but not blood pressure. Post-operative echocardiography was available in 207 patents and showed significant decreases in both pLVMI and ieLVMI after adrenalectomy. In multivariate analysis, ΔpLVMI was correlated with SBP, ΔSBP, and pre-operative pLVMI, whereas ΔieLVMI was correlated with Δlog aldosterone-to-renin ratio (ARR) and pre-operative ieLVMI.ConclusionsThis study concluded that extensive cardiac remodeling in APA patients occurs through hemodynamic and non-hemodynamic causes. Adrenalectomy can improve both hemodynamic and non-hemodynamic components of LV remodeling. Regressions of pLVMI and ieLVMI were correlated with decreases in blood pressure and ARR, respectively.

scholarly journals Differences in resting and ambulatory blood pressure data in coarctation of aorta vs idiopathic hypertension

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Egbe ◽  
K Banala ◽  
R Vojjini
Keyword(s):  
Blood Pressure ◽  
Clinical Decision Making ◽  
Arterial Compliance ◽  
Pressure Overload ◽  
Clinical Decision ◽  
Left Ventricular ◽  
Coarctation Of Aorta ◽  
Masked Hypertension ◽  
Lv Remodeling ◽  
Blood Pressure Data

Abstract Background Ambulatory systolic blood pressure (SBP) is more sensitive than resting-SBP in detecting hypertension in patients with coarctation of aorta (COA) and patients with idiopathic hypertension. A recent study showed that compared to patients with idiopathic hypertension with similar resting-SBP, COA patients had lower arterial compliance, and hence experienced higher SBP per unit increase in stroke volume during exercise. The purpose of this study was to compare resting vs ambulatory-SBP relationship between COA patients and non-COA patients (with and without hypertension), and to determine if ambulatory-SBP had better correlation with left ventricular (LV) remodeling as compared to resting-SBP. Methods Case-control study of 106 COA patients and 106 patients with idiopathic hypertension (ControlHTN+ group) matched by age, sex, body mass index and resting-SBP. Resting/ambulatory BP relationship in COA patients and patients with idiopathic hypertension were also compared to that of 19 patients without hypertension (ControlHTN- group). LV remodeling was assessed using LV mass index, e', and E/e'. Results Although the COA and ControlHTN+ groups had similar resting-SBP (by design), the COA group had a higher ambulatory-SBP and a higher prevalence of masked hypertension (30% vs 12%, p&lt;0.001). There was a stronger correlation between ambulatory-SBP (as compared to resting-SBP) and LVMI (r=0.36 vs r=0.55, p=0.042), and average E/e' (r=0.42 vs r=0.59, p=0.046), in the COA group but not the ControlHTN+ group. There was no difference in the resting/ambulatory BP relationship between ControlHTN+ and ControlHTN- groups, but both groups were significantly different from the COA group. Conclusion These results highlight the unique differences in disease pathophysiology between hypertension in patients with COA and those with idiopathic hypertension, and also suggest that ambulatory-SBP may be a more accurate measure of LV pressure overload in COA patients. This underscores the potential limitations of relying on resting-SBP alone for clinical decision making. Funding Acknowledgement Type of funding source: None

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