Circulation In Heart Failure Research Articles

Pulmonary pressure-flow responses to exercise in heart failure treated with angiotensin receptor neprilysin inhibitor

BackgroundThe role of the angiotensin receptor neprilysin inhibitor (ARNI) in cardiac function, particularly its impact on pulmonary circulation, remains underexplored. Recent studies have described abnormal mean pulmonary artery pressure (mPAP)-cardiac output (CO) responses as having the potential to assess the disease state. The aim of this study was to assess the effects of ARNI on pulmonary circulation in heart failure. We measured echocardiographic parameters post 6-min walk (6 MW) and compared the changes with baseline and follow-up. Our hypothesis was that pulmonary pressure-flow relationship of the pulmonary circulation obtained by 6 MW stress echocardiography would be improved with treatment. MethodsWe prospectively enrolled 39 heart failure patients and conducted the 6 MW test indoors. Post-6 MW echocardiography measured echocardiographic variables, and CO was derived from electric cardiometry. Individualized ARNI doses were optimized, with follow-up echocardiographic evaluations after 1 year. ResultsLeft ventricular (LV) volume were significantly reduced (160.7 ± 49.6 mL vs 136.0 ± 54.3 mL, P < 0.001), and LV ejection fraction was significantly improved (37.6 ± 11.3% vs 44.9 ± 11.5%, P < 0.001). Among the 31 patients who underwent 6 MW stress echocardiographic study at baseline and 1 year later, 6 MW distance increased after treatment (380 m vs 430 m, P = 0.003). The ΔmPAP/ΔCO by 6 MW stress decreased with treatment (6.9 mmHg/L/min vs 2.8 mmHg/L/min, P = 0.002). The left atrial volume index was associated with the response group receiving ARNI treatment for pulmonary circulation. ConclusionsInitiation of ARNI was associated with improvement of left ventricular size and LVEF. Additionally, the 6 MW distance increased and the ΔmPAP/ΔCO was improved to within normal range with treatment.

Evaluation of renal circulation in heart failure using superb microvascular imaging, a microvascular flow imaging system.

Renal circulation evaluation is essential in understanding the cardiorenal relationship in heart failure (HF), and there is a growing interest in imaging techniques that visualize renal circulation. This study aimed to assess the effectiveness of superb microvascular imaging (SMI) in evaluating renal circulation in HF patients. The study included 71 HF patients undergoing cardiac catheterization. Prior to catheterization, renal ultrasound examinations were performed. A control group of 18 subjects without HF was also included. SMI was used to measure the vascular index (VI), which was calculated as the percentage of blood flow signal area in the region of interest. The intrarenal perfusion index (IRPI) was determined as a fluctuation index of VI, reflecting variations in the number of blood cells moving through renal tissue during the cardiac cycle. Using the upper 95% confidence interval of IRPI (0.6) from the control group, HF patients were classified into two groups. Patients with IRPI > 0.6 showed a more congestive profile. Right atrial pressure and biphasic or monophasic Doppler intrarenal flow pattern were independent determinants of IRPI > 0.6. In addition, IRPI remained a significant predictor of estimated glomerular filtration rate (eGFR). The parameter IRPI as variations in SMI signal during the cardiac cycle may be a useful evaluation method for renal perfusion impairment in HF.

ALTERATIONS IN THE PERIPHERAL CIRCULATION IN HEART FAILURE: CURRENT VIEW ON ENDOTHELIAL DYSFUNCTION AND PHARMACOLOGICAL IMPLICATIONS INVOLVING ITS PATHOPHYSIOLOGICAL ASPECTS

Introduction. Despite the significant advances in the pharmacotherapy of cardiovascular diseases, the increasing prevalence of heart failure (HF) and its poor prognosis constitute one of the leading medical problems worldwide. The complex pathophysiology of HF involves the alterations in the peripheral circulation, particularly the development of endothelial dysfunction (ED). The deepening of understanding the pathology of ED and the spectrum of pharmacological implications, involving its certain pathophysiological aspects, could favor the optimization of the personalized approach to the management of such challenging HF patients.&#x0D; Aim: to provide a literature review of the current data on the alterations in peripheral circulation in HF with the focus on ED, and to outline possible pharmacological implications involving certain pathophysiological aspects of ED in HF patients.&#x0D; Material and methods. The thematic scientific papers, published predominantly during the last decade, constituted the study material. The research methodology involved bibliosemantic method and structural and logical analysis.&#x0D; Results and discussion. Currently, the ED considered as a stage of a specific continuum, which is initiated in the form of «activation» of the endothelium, and moves through the stage of its actual «dysfunction» to the stage of endothelial «damage». Taking into account the important pathogenetic and prognostic significance of ED in HF, the endothelium is considered as a target of various pharmacological influences, including renin-angiotensin-aldosterone inhibitors and statins. Among the modern approaches to pharmacological treatment of HF, the correction of reduced nitric oxide (NO) bioavailability by modulating the «NO-soluble guanylate cyclase-cyclic guanosine monophosphate» signaling pathway is a perspective option in terms of preventing the occurrence and progression of ED.&#x0D; Conclusion. The deepening of knowledge about the pathophysiological features of ED in HF allows both to improve the understanding of the pharmacodynamic effects of already approved cardiovascular drugs, and to outline the perspectives for pharmacological direct or indirect impact on endothelium.

Brain TACE (Tumor Necrosis Factor-α-Converting Enzyme) Contributes to Sympathetic Excitation in Heart Failure Rats.

TNF-α (tumor necrosis factor-α) is initially synthesized as a transmembrane protein that is cleaved by TACE (TNF-α-converting enzyme) to release soluble TNF-α. The elevated level of TNF-α in the brain and circulation in heart failure (HF) suggests an increase in the TACE-mediated ectodomain shedding process. The present study sought to determine whether TACE is upregulated in cardiovascular/autonomic brain regions like subfornical organ and hypothalamic paraventricular nucleus in rats with ischemia-induced HF and whether TACE plays a role in TNF-α-driven sympathetic excitation. We found that TACE was expressed throughout the subfornical organ and paraventricular nucleus, with significantly higher levels in HF than in sham-operated (Sham) rats. Intracerebroventricular injection of recombinant TACE induced a mild increase in blood pressure, heart rate, and renal sympathetic nerve activity that peaked at 15 to 20 minutes in both Sham and HF rats. HF rats had a secondary prolonged increase in these variables that was prevented by the TNF-α inhibitor SPD304. Intracerebroventricular administration of the TACE inhibitor TNF-alpha protease inhibitor 1 decreased blood pressure, heart rate, and renal sympathetic nerve activity in Sham and HF rats, with an exaggerated reduction in heart rate and renal sympathetic nerve activity in the HF rats. Direct microinjection of TACE or TNF-alpha protease inhibitor 1 into paraventricular nucleus or subfornical organ of Sham and HF rats elicited blood pressure, heart rate, and renal sympathetic nerve activity responses similar to intracerebroventricular TACE or TNF-alpha protease inhibitor 1. Intracerebroventricular infusion of Ang II (angiotensin II) and IL (interleukin)-1β increased TACE expression in subfornical organ and paraventricular nucleus of normal rats. These data suggest that a TACE-mediated increase in soluble TNF-α in the brain contributes to sympathetic excitation in HF.

RV Contractile Function and its Coupling to Pulmonary Circulation in Heart Failure With Preserved Ejection Fraction: Stratification of Clinical Phenotypes and Outcomes

ObjectivesThis study sought to investigate how right ventricular (RV) contractile function and its coupling with pulmonary circulation (PC) stratify clinical phenotypes and outcome in heart failure preserved ejection fraction (HFpEF) patients. BackgroundPulmonary hypertension and RV dysfunction are key hemodynamic abnormalities in HFpEF. MethodsThree hundred eighty seven HFpEF patients (mean age 64 ± 12 years, 59% females, left ventricular ejection fraction 59 ± 7%) underwent RV and pulmonary hemodynamic evaluation by echocardiography (entire population) and right heart catheterization (219 patients). Patients were investigated by tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) relationship and stratified according to TAPSE/PASP ratio tertiles (1: <0.35; 2: 0.35 to 0.57; 3: >0.57). Specifically, TAPSE/PASP ratio was taken as a noninvasive index of RV to PC coupling based on the correlation with invasively evaluated RV systolic elastance/arterial elastance (r = 0.35; p < 0.0001). ResultsGroups had similar prevalence of comorbidities except for a higher prevalence of atrial fibrillation and kidney dysfunction in tertile 1. Progressively increasing levels of natriuretic peptides, worse systemic and pulmonary hemodynamics, abnormal exercise aerobic capacity and ventilatory inefficiency were observed from the highest to lowest TAPSE/PASP tertile. TASPE/PASP correlated with pulmonary artery compliance (r = 0.69; p < 0.0001). Remarkably, the tertile 1 group distributed along the worse portion of the curve at lower pulmonary artery compliance and higher pulmonary vascular resistances. In addition, the TAPSE/PASP ratio emerged as an independent predictor of worse outcomes. ConclusionsA thorough assessment of RV-PC coupling and RV contractile function stratify HFpEF phenotypes at different level of risk. These observations shift the interest toward therapeutic strategies that may benefit the right heart as primary unmet need in the complex pathophysiology of the HFpEF syndrome.

Pro-atrial natriuretic peptide1-126 is processed in the human circulation to a mature GC-A activating peptide with therapeutic potential in heart failure

Purpose: Atrial natriuretic peptide (ANP), a stimulator of cGMP through its receptor, GC-A, circulates in various molecular forms in humans. Importantly, mature ANP1-28 and Urodilatin, which is ANP1-28 plus 4 additional N-terminus added amino acids, are used as drugs for acute decompensated heart failure (HF). GC-A activation in the heart is characterized by anti-hypertrophic and anti-fibrotic responses in vivo and in vitro. To date it remains unclear if the precursor; proANP1-126 is processed by convertase corin into active forms in the circulation of normal and HF with the possibility that if converted could serve as a long-acting ANP like peptide for HF. Studies report that corin is reduced in the circulation in HF and thus proANP processing might be impaired. Methods: Fresh serum was obtained from normals (n=13) and patients with NYHA III to IV HF (n=14). Samples were incubated with or without Histidine-tagged exogenous proANP1-126 in the C-terminus to facilitate isolation of processed forms which were isolated by immunoprecipitation and detected by Western Blot (WB), and then sequenced. GC-A or GC-B expressing HEK293 cells were treated with/without mature ANP1-28, proANP1-126, the isolated peptides from proANP1-126 in serum, and the cGMP activity determined by specific assay was measured so as to test biological activity of processed ANP. In addition, cGMP activity and TGF beta-1 stimulated Collagen type I (Col I) mRNA expression measured by qPCR in human cardiac fibroblasts (CFs) in which corin protein exist were examined with or without treatment with ANP1-28 or proANP1-126. Results: ProANP1-126 was processed into ANP1-28 in normal serum; processed ANP1-28 appeared at 5 min and then decreased but remained present at 180 min. In HF serum proANP1-126 was processed at the same rate as in normals The processed peptide from proANP1-126 as well as unprocessed proANP1-126 stimulated cGMP production in GC-A cells, but processed peptide had significantly higher cGMP stimulation than unprocessed proANP1-126. In addition, proANP1-126 had equivalent cGMP activating and Col I mRNA inhibiting actions compared to ANP in CFs. Conclusions: Exogenous proANP1-126 is processed into biologically active GC-A peptides in both normal and HF human serum. ProANP1-126 and its processed form possess significant cGMP activating and anti-fibrotic actions in vitro in human CFs. Importantly, proANP1-126 appears to have a longer half-life than mature ANP1-28 ex vivo, suggesting the emerging concept that proANP1-126 may have a therapeutic opportunity as a long acting GC-A agonist for HF.

Secretogranin II; a protein increased in the myocardium and circulation in heart failure with cardioprotective properties.

BackgroundSeveral beneficial effects have been demonstrated for secretogranin II (SgII) in non-cardiac tissue. As cardiac production of chromogranin A and B, two related proteins, is increased in heart failure (HF), we hypothesized that SgII could play a role in cardiovascular pathophysiology.Methodology/Principal FindingsSgII production was characterized in a post-myocardial infarction heart failure (HF) mouse model, functional properties explored in experimental models, and circulating levels measured in mice and patients with stable HF of moderate severity. SgII mRNA levels were 10.5 fold upregulated in the left ventricle (LV) of animals with myocardial infarction and HF (p<0.001 vs. sham-operated animals). SgII protein levels were also increased in the LV, but not in other organs investigated. SgII was produced in several cell types in the myocardium and cardiomyocyte synthesis of SgII was potently induced by transforming growth factor-β and norepinephrine stimulation in vitro. Processing of SgII to shorter peptides was enhanced in the failing myocardium due to increased levels of the proteases PC1/3 and PC2 and circulating SgII levels were increased in mice with HF. Examining a pathophysiological role of SgII in the initial phase of post-infarction HF, the SgII fragment secretoneurin reduced myocardial ischemia-reperfusion injury and cardiomyocyte apoptosis by 30% and rapidly increased cardiomyocyte Erk1/2 and Stat3 phosphorylation. SgII levels were also higher in patients with stable, chronic HF compared to age- and gender-matched control subjects: median 0.16 (Q1–3 0.14–0.18) vs. 0.12 (0.10–0.14) nmol/L, p<0.001.ConclusionsWe demonstrate increased myocardial SgII production and processing in the LV in animals with myocardial infarction and HF, which could be beneficial as the SgII fragment secretoneurin protects from ischemia-reperfusion injury and cardiomyocyte apoptosis. Circulating SgII levels are also increased in patients with chronic, stable HF and may represent a new cardiac biomarker.

Increased Levels of Inflammatory Cytokines and Endothelin-1 in Alveolar Macrophages from Patients with Chronic Heart Failure

BackgroundPathophysiological interactions between heart and lungs in heart failure (HF) are well recognized. We investigated whether expression of different factors known to be increased in the myocardium and/or the circulation in HF is also increased in alveolar macrophages in HF.Methodology/Principal FindingsLung function, hemodynamic parameters, gene expression in alveolar macrophages, and plasma levels in the pulmonary and femoral arteries of HF patients (n = 20) were compared to control subjects (n = 16). Our principal findings were: (1) Lung function was significantly lower in HF patients compared to controls (P<0.05). (2) mRNA levels of ET-1, tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) were increased in alveolar macrophages from HF patients. (3) Plasma levels of ET-1, TNFα, IL-6 and MCP-1 were significantly increased in HF patients, whereas our data indicate a net pulmonary release of MCP-1 into the circulation in HF.Conclusions/SignificanceSeveral important cytokines and ET-1 are induced in alveolar macrophages in human HF. Further studies should clarify whether increased synthesis of these factors affects pulmonary remodeling and, directly or indirectly, adversely affects the failing myocardium.

A New Signal From B-Type Natriuretic Peptide in ST-Elevation Myocardial Infarction

A New Signal From B-Type Natriuretic Peptide in ST-Elevation Myocardial Infarction

The central circulation in congestive heart failure non-invasively evaluated with dynamic positron emission tomography

Positron emission tomography (PET) with [15O]-H2O-PET (WAT-PET) or [11C]-acetate (AC-PET) quantifies myocardial perfusion and oxidative metabolism, but routine clinical use is hampered by the need for additional investigations to assess cardiac performance. To apply classical tracer kinetics to dynamic PET could provide important haemodynamic parameters. First-pass PET data were used with indicator dilution techniques to measure stroke volume index (SVI). Early pulmonary retention of [11C]-acetate was converted to standard uptake values (SUV) (Lung(AC-SUV)). Regional lung water (rLW) content was computed from the WAT-PET scan at equilibrium. PET was compared with radionuclide angiography and echocardiography in patients with ischaemic cardiomyopathy with New York Heart Association class II (n = 10) or III (n = 18) congestive heart failure. Elderly male volunteers without heart disease (n = 11) underwent AC-PET as controls. SVI with both tracers correlated in patients (r = 0.91, P<0.001, estimated standard error = 4 ml m(-2)) and with left ventricular ejection fraction (both tracers r>0.6, P<0.001). SVI was significantly different between all groups (ANOVA: P<0.001). Lung(AC-SUV) correlated with rLW (r = 0.78, P<0.001) and both were elevated in severe heart failure (P<0.05 for both). Elevated Lung(AC-SUV) was associated with a restrictive left ventricular (LV) filling pattern by Doppler echocardiography. Dynamic PET with first-pass analysis and tracers of myocardial perfusion enables quantification of the haemodynamic consequences of LV systolic and diastolic dysfunctions in ischaemic cardiomyopathy and could be useful in the evaluation of the central circulation in heart failure.

Biventricular pacing for weaning from extracorporeal circulation in heart failure

Resynchronization of the intra- and interventricular conduction by biventricular pacing has been suggested in patients with end-stage heart failure. We present a case in which extracorporeal circulation could only be weaned after placement of an additional left ventricular pacing wire. Biventricular stimulation led to normal motion of the anterior wall and a previously bulging interventricular septum; this improved the hemodynamic situation significantly.

Vasorelaxing effects of atrial and brain natriuretic peptides on coronary circulation in heart failure.

Natriuretic peptide (NP) receptor has been postulated to be downregulated under a high concentration of atrial NP (ANP) in congestive heart failure (CHF), but limited information is available on how the vascular functional responsiveness to NPs is altered in coronary circulation during CHF. We assessed the relaxant effects of ANP, brain NP (BNP), and other vasodilators in isolated coronary arteries obtained from dogs with and without severe CHF induced by rapid right ventricular pacing. In CHF dogs, plasma ANP and cGMP concentrations were elevated compared with control dogs. In CHF arteries the relaxant effects of ANP and BNP (10(-8) and 10(-7) mol/l) were suppressed compared with control arteries. Nitroglycerin, nitric oxide, 8-bromo-cGMP, and beraprost sodium produced similar concentration-response curves in both arteries. The addition of 10(-7) mol/l ANP increased the level of tissue cGMP in control arteries, but not in CHF arteries. We conclude that there was a specific reduction in the relaxant effects of ANP and BNP in isolated coronary arteries in severe CHF dogs, which suggests the possibility of the downregulation of NP receptors coupled to guanylate cyclase.

Effects of amlodipine on sympathetic nerve traffic and baroreflex control of circulation in heart failure.

Short-acting calcium antagonists exert a sympathoexcitation that in heart failure further enhances an already elevated sympathetic activity. Whether this is also the case for long-acting formulations is not yet established, despite the prognostic importance of sympathetic activation in heart failure. It is also undetermined whether in this condition long-acting calcium antagonists favorably affect a mechanism potentially responsible for the sympathetic activation, ie, the baroreflex impairment. In 28 heart failure patients (NYHA functional class II) under conventional treatment we measured plasma norepinephrine and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during arterial baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Measurements were performed at baseline and after 8 weeks of daily oral amlodipine administration (10 mg/d, 14 patients) or before and after an 8-week period without calcium antagonist administration (14 patients). Amlodipine caused a small and insignificant blood pressure reduction. Heart rate, left ventricular ejection fraction, and plasma renin and aldosterone concentrations were not affected. This was the case also for plasma norepinephrine (from 2.43+/-0.41 to 2.50+/-0.34 nmol/L, mean+/-SEM), muscle sympathetic nerve activity (from 54.4+/-5.9 to 51.0+/-4.3 bursts/min), and arterial baroreflex responses. No change in the above-mentioned variables was seen in the control group. Thus, in mild heart failure amlodipine treatment does not adversely affect sympathetic activity and baroreflex control of the heart and sympathetic tone. This implies that in this condition long-acting calcium antagonists can be administered without untoward neurohumoral effects anytime conventional treatment needs to be complemented by drugs causing additional vasodilatation.

Status of digitalis in therapy of acute and chronic heart failure

Although supported by more than 200 years of experience and anecdotal clinical evidence, the efficacy of digitalis in the management of heart failure has been questioned until the past decade. The idea to improve contractility of the diseased myocardium with an inotropic agent is fundamental in the management of left ventricular dysfunction. The majority of clinical trials published since 1980, most of which examined patients with mild to moderate heart failure, indicate that digitalis alone or in combination with vasodilators may improve the clinical outcome particular in those patients with more advanced symptoms and poorer left ventricular function. Aside from its action as an inotropic drug the pharmacology and the mechanisms by which digitalis influence the diseased myocardium and peripheral circulation in heart failure has gained more complexity within the last years, raising the idea of other mechanisms that might be involved in its action. Particular for ACE inhibition multiple clinical trials have conclusively demonstrated its impact on survival and morbidity in congestive heart failure. Improvement of clinical outcome as measured in terms of fewer hospitalizations and improvement of symptoms in patients receiving digitalis seems to be comparable to patients receiving beta-blockers additional to diuretics and ACE inhibitors, an entirely different approach to the treatment of heart failure. Despite initial improvement of hemodynamics it now appears that there is no survival benefit found for digitalis in the management of heart failure.

Effects of chronic ACE inhibition on sympathetic nerve traffic and baroreflex control of circulation in heart failure.

In congestive heart failure ACE inhibitors chronically reduce plasma norepinephrine. No information exists, however, on whether and to what extent this reduction reflects a true chronic inhibition of sympathetic outflow and which mechanisms may be responsible. In 24 patients aged 60.3+/-2.0 years (mean+/-SEM) affected by congestive heart failure (New York Heart Association class II) and treated with diuretics and digitalis, we measured mean arterial pressure (Finapres), plasma renin activity and angiotensin II levels (radioimmunoassay), plasma norepinephrine (high-performance liquid chromatography), and muscle sympathetic nerve activity (microneurography at a peroneal nerve) at rest and during baroreceptor stimulation and deactivation caused by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. In 12 patients measurements were repeated after a 2-month addition of the ACE inhibitor benazepril (10 mg/d P.O.), while in the remaining 12 patients they were performed again after 2 months without any treatment modifications. Benazepril did not alter mean arterial pressure, markedly increased plasma renin activity, reduced plasma angiotensin II, and caused a nonsignificant reduction in plasma norepinephrine. In contrast, muscle sympathetic nerve traffic was significantly reduced (-30.5+/-5.3%, P<.01). This reduction was accompanied by no change in the sympathoexcitatory responses to baroreceptor deactivation but by a marked enhancement of the sympathoinhibitory responses to baroreceptor stimulation (103.5+/-3.4%). These results provide the first direct evidence that in congestive heart failure chronic ACE inhibitor treatment is accompanied by a marked reduction in central sympathetic outflow. This reduction may depend on a persistent restoration of baroreflex restraint on the sympathetic neural drive.

Neural control of the circulation in heart failure and coronary ischaemia: introduction.

1. A large gap in our knowledge of the reflex control of the circulation still exists in the setting of chronic heart failure. This symposium will provide state-of-the-art experimental data on the reflex regulation of the circulation in heart failure and myocardial ischaemia. 2. Alterations in arterial baroreflex and cardiopulmonary reflexes contribute to the increase in sympathetic tone in this disease state. Additionally, changes in neurohormones, such as angiotensin, are thought to contribute. 3. Coronary ischaemia is associated with activation of both vagal and sympathetic reflexes of cardiac origin. The balance between activation of these two reflexes will determine the ultimate change in sympathetic outflow. 4. Sensory endings in the myocardium are exquisitely sensitive to local mediators, such as prostaglandins, oxygen-derived free radicals, adenosine and bradykinin.

Changes in the peripheral circulation in heart failure.

Chronic heart failure is associated with neurohumoral activation and alterations of the peripheral circulation and skeletal muscle. Several mechanisms are involved in the impaired peripheral perfusion, including increased sympathetic tone and increased vascular stiffness. Recently, data have suggested an important role of the endothelium for perfusion of skeletal muscle in heart failure. Endothelium-dependent dilation of resistance vessels is blunted in patients with severe chronic heart failure. Conceivably, this abnormality may be involved in the impaired reactive hyperemia seen in patients with chronic heart failure. In conductance vessels, flow-dependent dilation is attenuated in patients with chronic heart failure as compared with normal subjects, indicating endothelial dysfunction of large conduit vessels. Dysfunctional endothelium may contribute to impaired tissue perfusion in heart failure. Beyond an impairment of perfusion, skeletal muscle itself is altered in chronic heart failure. The metabolic abnormalities of skeletal muscle in patients with heart failure do not result from inadequate O2 delivery, but from inadequate O2 utilization by mitochondria, consistent with previous findings that the oxidative capacity of mitochondria in skeletal muscle is reduced. It appears that the impaired muscular endurance in heart failure is related to an enhanced glycolytic metabolism secondary to the reduced oxidative capacity of skeletal muscle. The observed low muscular strength appears to be due to a smaller muscle cross-sectional area. Despite successful heart transplantation, only partial improvement of bioenergetic abnormalities was noted in patients 15 months after heart transplantation.

Peripheral Circulation in Heart Failure

Journal Article Peripheral Circulation in Heart Failure Get access European Heart Journal, Volume 15, Issue suppl_2, September 1994, Pages 89–91, https://doi.org/10.1093/eurheartj/15.suppl_2.89 Published: 11 September 1994

Baroreflex Abnormalities in Congestive Heart Failure

Abnormalities in reflex control of the circulation in heart failure are mediated by afferent and target organ alterations. Depression of afferent function is especially prominent in arterial baroreceptors. This depression is mediated by an augmentation of responses that are dependent on the action of Na+-K+-ATPase.

Effect of angiotensin-converting enzyme inhibitors on the peripheral circulation in heart failure

In patients with chronic heart failure, the increase in blood flow to working muscle is attenuated and oxygen consumption is lower for any given workload of exercise, compared with normal subjects. This impaired metabolic vasodilation during exercise cannot be restored with short-term administration of angiotensin-converting enzyme (ACE) inhibitors. However, long-term ACE inhibition increases blood flow to skeletal muscle, and this increase is closely correlated with improvement in systemic oxygen consumption. The delayed effect of ACE inhibitors may be related to an interference with the vascular tissue renin-angiotensin system and remodeling of the vascular wall. In addition, endothelial-dependent dilation in response to acetylcholine is blunted in the forearm of patients with chronic heart failure, indicating an impaired endothelial function in this setting. There is experimental evidence that long-term ACE inhibition improves endothelial dysfunction; thus, one might speculate that the beneficial long-term effect of ACE inhibitors on peripheral flow may be, in part, related to its ability to restore normal endothelial function. Vasodilators such as hydralazinethat improve blood flow to working muscle after acute administration do not increase skeletal muscle oxygen consumption, indicating that oxygen utilization is not improved. Ultrastructural analysis of skeletal muscle revealed that intrinsic alterations of skeletal muscle exist in patients with chronic heart failure; that is, the oxidatrve capacity of skeletal muscle is impaired in severe heart failure and contributes to the reduced exercise capacity. Evaluation of skeletal muscle biopsies before and after long-term ACE inhibition revealed that the oxidative capacity of skeletal muscle can be increased after long-term therapy, thereby partially reversing the intrinsic alterations of working muscle in patients with chronic heart failure. It is concluded that the beneficial effect of ACE inhibitors is related, in part, to peripheral mechanisms (i.e., the ability of the peripheral vessels to dilate) and by improving peripheral oxygen utilization.