Evidence for Impaired Endothelium Dependent Vasodilation in Experimental Left Ventricular Dysfunction

Kaye, David M.; Jennings, Garry; Angus, James A.

doi:10.1111/j.1440-1681.1994.tb02574.x

Cited by 13 publications

(6 citation statements)

References 33 publications

(44 reference statements)

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“…Numerous studies have consistently demonstrated the presence of an attenuated response to endothelium-dependent vasodilators, most typically acetylcholine, in the peripheral and coronary circulation in human and experimental models of heart failure. [1][2][3][4][5][6] Furthermore, these observations have been confirmed by use of a more physiological stimulus such as exercise and the hyperemia induced by ischemia. 7,8 Although the evidence for reduced endothelial function in congestive heart failure (CHF) is compelling, the mechanisms responsible for this phenomenon remain unclear.…”

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confidence: 50%

In Vivo and In Vitro Evidence for Impaired Arginine Transport in Human Heart Failure

et al. 2000

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Background-The clinical features of congestive heart failure (CHF) result from a complex interaction between reduced ventricular function, neurohormonal activation, and impaired endothelial function. Although endothelial dysfunction has been well documented, the mechanisms that contribute to this abnormality remain unknown. Recent studies, however, indicate a potential therapeutic role for supplemental L-arginine, suggesting the presence of an underlying disorder of L-arginine metabolism. Methods and Results-We used 2 complementary approaches to assess L-arginine transport in control subjects and patients with CHF. During a steady-state intra-arterial infusion of [ 3 H]L-arginine (100 nCi/min), forearm clearance of [ 3 H]L-arginine was significantly reduced in CHF patients compared with forearm kinetics in control subjects (64Ϯ2 versus 133Ϯ14 mL/min, Pϭ0.002). In conjunction with this, [ 3 H]L-arginine uptake by peripheral blood mononuclear cells (PBMCs) was also substantially reduced in heart failure patients compared with controls (V max 10.1Ϯ1.3 versus 49.8Ϯ7.1 pmol/10 5 cells per 5 minutes, PϽ0.001). In association with this finding, we observed a 76% (PϽ0.01) reduction in mRNA expression for the cationic amino acid transporter CAT-1, as assessed by ribonuclease protection assay. Conclusions-These data document both in vivo and in vitro evidence for a marked depression of L-arginine transport in human CHF and therefore provide an explanation for the restorative actions of supplemental L-arginine on vascular function in

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confidence: 50%

In Vivo and In Vitro Evidence for Impaired Arginine Transport in Human Heart Failure

et al. 2000

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“…8,24 Alternatively, impaired vasodilator capacity may also reflect a reduction in the absolute cross‐sectional area (ie, number of resistance vessels) of the microcirculation, given that this limitation to flow may only become evident at maximal vasodilatation. 30–31 Consistent with this possibility, recent studies in myocardial biopsy samples from patients undergoing cardiac surgery showed reduced microvascular density in obesity, 32 the latter being associated with HFPEF.…”

Section: Discussionmentioning

confidence: 84%

Impaired Myocardial Oxygen Availability Contributes to Abnormal Exercise Hemodynamics in Heart Failure With Preserved Ejection Fraction

Empel

Mariani

Borlaug

et al. 2014

JAHA

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BackgroundHypertension is a frequent risk factor for the development of heart failure with preserved ejection fraction (HFPEF). Progressive extracellular matrix accumulation has been presumed to be the fundamental pathophysiologic mechanism that leads to the transition to impaired diastolic reserve. However, the contribution of other mechanisms affecting active and passive components of diastolic function has not been comprehensively assessed. In this study, we investigated the potential role of impaired myocardial oxygen delivery in the pathophysiology of HFPEF.Methods and ResultsPatients with HFPEF, those with controlled hypertension, and healthy controls underwent simultaneous right‐heart catheterization, echocardiography, and paired arterial and coronary sinus blood gas sampling at rest and during supine‐cycle ergometry. Despite a lower workload (HFPEF vs control, hypertension: 43±8 versus 114±12, 87±14 W; P<0.001 and P<0.05, respectively), peak exercise pulmonary capillary wedge pressure was markedly higher in HFPEF patients compared with healthy and hypertensive controls (32±2 versus 16±1 and 17±1 mm Hg, both P<0.001). During exercise, the transcardiac oxygen gradient increased significantly in all groups; however, the peak transcardiac oxygen gradient was significantly lower in HFPEF patients (P<0.05). In addition, the left ventricular–work corrected transcardiac oxygen gradient remained significantly lower in HFPEF patients compared with controls (P<0.001).ConclusionThe current study provides unique data suggesting that the abnormal diastolic reserve observed during exertion in HFPEF patients may, in part, be explained by impaired myocardial oxygen delivery due possibly to microvascular dysfunction. Further studies are required to confirm the structural and functional basis of these findings and to investigate the influence of potential therapies on this abnormality.

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“…It is well understood that endothelium-dependent vasodilation is impaired in CHF [25][26][27][28]. Hambrecht and colleagues [28] showed that an improvement in endothelial function in heart failure patients may be associated with an increase in exercise capacity.…”

Section: Arterial Mechanicsmentioning

confidence: 97%

Exercise training increases arterial compliance in patients with congestive heart failure

2001

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Systemic arterial compliance (SAC) makes an important contribution to cardiac afterload, and thus is a significant determinant of left ventricular work. Previous studies have suggested that arterial compliance may be reduced in patients with congestive heart failure (CHF), and that SAC is increased after a 4-week exercise training programme in healthy, sedentary individuals. The present study aimed to investigate the effects of an 8-week exercise training programme on arterial mechanical properties, left ventricular performance and quality of life in CHF patients. A total of 21 patients with NYHA class II or III CHF (mean+/-S.D. age 55+/-13 years) were randomly allocated to either an 8-week exercise training group or a "usual lifestyle" control group. SAC, as determined non-invasively using applanation tonometry and Doppler aortic velocimetry, increased from 0.57+/-0.11 to 0.77+/-0.14 arbitrary compliance units (mean+/-S.E.M.; P=0.01) in the exercise group, while no change occurred in the control group. Left ventricular structure and function was assessed by echocardiography, and these parameters were unchanged over the 8-week study period. Exercise training significantly increased exercise capacity, measured by a 6-min walking test (474+/-27 to 547+/-34 m; P=0.008). Quality of life, as assessed using the Minnesota Living with Heart Failure Evaluation, demonstrated a decrease in heart failure symptoms from 46+/-7 to 24+/-5 units (P=0.01) following the exercise training programme. These data show that exercise training improves SAC in patients with CHF. The accompanying improvement in exercise capacity may be due, in part, to an improvement in arterial function.

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Evidence for Impaired Endothelium Dependent Vasodilation in Experimental Left Ventricular Dysfunction

Cited by 13 publications

References 33 publications

In Vivo and In Vitro Evidence for Impaired Arginine Transport in Human Heart Failure

In Vivo and In Vitro Evidence for Impaired Arginine Transport in Human Heart Failure

Impaired Myocardial Oxygen Availability Contributes to Abnormal Exercise Hemodynamics in Heart Failure With Preserved Ejection Fraction

Exercise training increases arterial compliance in patients with congestive heart failure

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