Naoshi Arakawa

Plasma brain natriuretic peptide concentrations predict survival after acute myocardial infarction.

OBJECTIVES This study sought to examine whether plasma brain natriuretic peptide levels can predict prognosis after myocardial infarction. BACKGROUND It has been suggested that concentrations of plasma brain natriuretic peptide reflect left ventricular function. Although the prognosis after myocardial infarction depends on residual left ventricular function, it is not known whether plasma levels of brain natriuretic peptide after the onset of myocardial infarction can be used to predict long-term outcome. METHODS Plasma brain natriuretic peptide and atrial natriuretic peptide levels as well as invasive hemodynamic variables were measured in 70 patients with acute myocardial infarction (53 men, 17 women; mean age 65 years). Measurements were obtained on admission (mean 6 h after onset) and on day 2 after onset. Mean follow-up period was 18 months. RESULTS Plasma brain natriuretic peptide levels measured on admission and day 2 correlated significantly with hemodynamic variables, which are influenced by left ventricular function. However, plasma atrial natriuretic peptide levels correlated with none of the hemodynamic variables measured on admission; and of those measured on day 2, plasma atrial natriuretic peptide levels correlated only with left atrial filling pressure. During the follow-up period (mean 18 +/- 7 months), 11 patients died of cardiac causes. By Kaplan-Meier analysis, it was found that patients with plasma brain natriuretic peptide levels higher than the median level, both on admission and on day 2, had significantly higher mortality rates than those with the submedian level (on admission, p < 0.01; on day 2, p < 0.05). However, only the plasma atrial natriuretic peptide level obtained immediately after admission was significantly related to survival (p < 0.01). By Cox proportional hazards model analysis of the noninvasive variables, it was found that plasma brain natriuretic peptide concentration was more closely related to survival after myocardial infarction (p = 0.0001). CONCLUSIONS Increased plasma brain natriuretic peptide concentrations in the early or subacute phase of myocardial infarction are a powerful noninvasive indicator of poor prognosis, possibly reflecting residual left ventricular function after myocardial infarction.

Potent and Long-Lasting Vasodilatory Effects of Adrenomedullin in Humans Comparisons Between Normal Subjects and Patients With Chronic Heart Failure

BACKGROUND Adrenomedullin (ADM) is a recently discovered hypotensive peptide that has been isolated from human pheochromocytoma cells. Observations that ADM is produced from cardiovascular tissue and is found in plasma suggest that it may be important in the regulation of regional vascular resistance. METHODS AND RESULTS Limb vascular responses to ADM were examined in 10 healthy subjects and compared with those in 18 patients with chronic heart failure (CHF). The peptide increased forearm blood flow (FBF) from 2.7 +/- 0.3 to 11.8 +/- 0.9 mL.min-1.100 mL-1 in the control group and from 2.4 +/- 0.3 to 6.5 +/- 0.7 mL.min-1.100 mL-1 in the CHF group. The ADM-induced FBF increase was significantly impaired in the CHF group (P < .01). After cessation of the infusion, an increased FBF level was sustained for > 60 minutes in the control group, whereas in the CHF group the response returned to the baseline in < 30 minutes. The ADM infusion increased forearm skin blood flow in both groups (P < .05), whereas the skin blood flow response was impaired in the CHF group (P < .01). The role of nitric oxide in ADM-induced vasorelaxation was also studied in 11 healthy subjects and 6 patients with CHF. FBF and skin blood flow responses during ADM administration were significantly attenuated by NG-monomethyl-L-arginine administration in healthy control subjects (P < .05), whereas both flow responses remained the same in the CHF group. CONCLUSIONS These observations demonstrate that ADM exerts a potent and long-lasting vasodilatory effect on skeletal muscle arteries with involvement of nitric oxide-dependent mechanisms in normal human peripheral vasculature and that these vascular effects are significantly attenuated in patients with CHF, in part because of impaired production of nitric oxide in the forearm resistance vessels.

Relationship between Plasma Level of Brain Natriuretic Peptide and Myocardial Infarct Size

To investigate the clinical significance of plasma brain natriuretic peptide (BNP) measurement in patients with acute myocardial infarction (MI), circulating levels of BNP, atrial natriuretic peptide, creatine kinase (CK), and hemodynamic parameters were serially determined in 24 patients with a first episode of acute MI. Plasma BNP (mean +/- SEM) gradually increased and peaked 21 h after the onset (from 13.7 +/- 2.2 to 23.0 +/- 3.3 fmol/ml; p < 0.001). A significant correlation was found between the increase in plasma BNP level and both the peak CK level (r = 0.83; p < 0.05) and the MI size (r = 0.74; p < 0.05). The increase in plasma BNP in the acute phase was found to be a significant predictor of left ventricular (LV) function evaluated in the convalescent phase (LV ejection fraction, r = -0.63; p < 0.05, LV end-diastolic pressure, r = 0.56; p < 0.05). In conclusion, in patients with acute MI, increases in plasma BNP concentration during the early phase reflect MI size, and thereby may predict later LV function.

Effect of angiotensin-converting enzyme inhibitors on endothelium-dependent peripheral vasodilation in patients with chronic heart failure

OBJECTIVES This study was performed to determine whether acute inhibition of angiotensin-converting enzyme restores impaired endothelium-dependent vasorelaxation in patients with chronic heart failure. BACKGROUND Recent reports have demonstrated that endothelium-dependent vasodilation induced by cholinergic stimuli is attenuated in the peripheral vascular bed of patients with chronic heart failure. METHODS We examined the effects of local intraarterial infusion of enalaprilat (0.6 micrograms/min per 100 ml tissue volume) on responses initiated by acetylcholine or sodium nitroprusside in the forearm vascular bed in 8 normal subjects, 12 patients with mild heart failure (New York Heart Association functional classes I and II) and 10 patients with more advanced heart failure (functional classes III and IV). Forearm blood flow was measured by means of venous occlusion plethysmography. RESULTS Although enalaprilat alone did not affect basal forearm blood flow, it significantly augmented the increase in forearm blood flow induced by acetylcholine in normal subjects (p < 0.01) and in those with mild heart failure (p < 0.05). However, the effect was not found in patients with more advanced heart failure. Coinfusion of enalaprilat did not enhance sodium nitroprusside-induced vasodilation in any of the groups. To explore the mechanism of the inhibitors effect, an additional 20 patients with mild heart failure (functional class II) were pretreated with a cyclooxygenase inhibitor, acetylsalicylic acid (n = 10) or an inhibitor of nitric oxide synthesis, NG-monomethyl-L-arginine (n = 10), followed by administration of acetylcholine with or without enalaprilat. Acetylsalicylic acid reduced the converting enzyme inhibitors effect, whereas NG-monomethyl-L-arginine failed to block the augmentation of blood flow. CONCLUSIONS These results suggest that inhibition of angiotensin-converting enzyme potentiates endothelium-dependent vasodilation induced by cholinergic stimuli, presumably through modulation of prostaglandin metabolism, in the peripheral vasculature of patients with mild chronic heart failure.

Vasodilatory effects of B-type natriuretic peptide are impaired in patients with chronic heart failure ☆ ☆☆ ★ ★★

BACKGROUND B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) are secreted from the heart and are thought to be equally important factors in the regulation of vascular tone in health and in congestive heart failure (CHF). However, no studies directly compare vasodilator effects of these peptides in healthy subjects and in patients with CHF. METHODS Plethysmography was used to determine the vasodilatory effects of BNP and to compare these to the effects of ANP in patients with CHF (n = 15) and age-matched healthy subjects (n = 16). Graded doses of ANP and BNP (8, 16, 32, and 48 pmol/min per 100 ml of tissue volume for both) were administered randomly into the brachial artery. Forearm blood flow (FBF) was measured, and cyclic GMP (cGMP) spillover was calculated. RESULTS Responses in FBF to both peptides in CHF were significantly lower than those of healthy subjects (BNP p < 0.05; ANP p < 0.01). Similarly, forearm spillover of cGMP was significantly lower in CHF than in healthy subjects (BNP p < 0.05; ANP p < 0.01). When vascular responses in healthy subjects were compared between BNP and ANP, BNP-induced changes in FBF (p < 0.05) and forearm cGMP spillover (p < 0.01) were significantly less than changes induced by ANP. In CHF, though, FBF change and cGMP spillover induced by the two peptides were not significantly different. CONCLUSIONS These results suggest that the metabolism and action of these natriuretic peptides in CHF may differ from the healthy state.

Endothelium-dependent vasodilation is augmented by angiotensin converting enzyme inhibitors in healthy volunteers

Summary: We have examined the effects of local intra-arterial infusion of enalaprilat (an angiotensin converting enzyme inhibitor) on responses initiated by concomitantly infused acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct dilator of smooth muscle) in the forearm arterial beds of healthy volunteers. Although the angiotensin converting enzyme inhibitor alone did not affect basal forearm blood flow or vascular resistance, it significantly augmented the increase in blood flow and reduction in vascular resistance induced by acetylcholine (both p < 0.05). Coinfusion of enalaprilat did not enhance sodium nitroprusside-induced vasodilation. Pretreatment with NG-monomethyl-L-arginine blocked the augmentation of blood flow induced by the angiotensin converting enzyme inhibitor. The effect of enalaprilat was still observed after the administration of acetylsalicylic acid (p < 0.05). These results suggest that angiotensin converting enzyme inhibitors potentiate nonprostanoid endothelium-derived relaxing factor in normal human forearm vasculature.

Vasodilatory effects of C-type natriuretic peptide on forearm resistance vessels are distinct from those of atrial natriuretic peptide in chronic heart failure.

C-type natriuretic peptide (CNP) is a newly identified peptide that is structurally related to atrial natri-uretic peptide (ANP). Although it has been suggested that CNP is released from the endothelium for the regulation of local vascular tone, no data are available concerning the vasodilatory response to CNP in humans. Methods and ResultsStrain-gauge plethysmography was used to determine the vasodilatory effects of intra-arterially infused CNP compared with the effects of ANP infusion in 11 patients with chronic heart failure (CHF) and 11 age-matched healthy controls. Graded doses of CNP and ANP (8, 16, 32, and 48 pmo.minm−1 · dL−1 tissue volume) were administered randomly into the nondominant brachial artery, and forearm blood flow (FBF) was measured. No significant changes in systemic blood pressure and heart rate were found during the study. Both the absolute and percent FBF responses to ANP relative to the baseline value were significantly lower in CHF patients than in healthy controls (P<.01), whereas the responses to CNP were similar. The calculated forearm spillover of cyclic GMP (cGMP) was significantly lower in CHF patients receiving the highest dose of ANP (P<.02), whereas changes in cGMP spillover after the equimolar dose of CNP were significantly higher (P<.02), despite the lesser potency of CNP. ConclusionsIn patients with CHF the peripheral vasodilatory effect of ANP is attenuated, but CNP-induced peripheral vasorelaxation is preserved, with CNP being less potent for equimolar doses.

Effects of tumor necrosis factor-α on basal and stimulated endothelium-dependent vasomotion in human resistance vessel

The aim of this study was to determine whether tumor necrosis factor (TNF)-alpha would impair basal and stimulated endothelium-dependent vasomotion in human resistance vessel. Changes in baseline and acetylcholine (ACh)-induced forearm vascular resistance (FVR) were measured plethysmographically before and after a low-dose intraarterial forearm infusion of TNF-alpha according to the following three protocols in healthy volunteers. In the condition without pretreatment, basal FVR was significantly increased by TNF-alpha (from 30.5 +/- 4.8 to 39.9 +/- 5.9 units; p < 0.01), whereas ACh-induced minimal FVR did not differ between pre- and post-TNF-alpha states. In the condition after pretreatment with the cyclooxygenase inhibitor acetylsalicylic acid, although the vascular effects of TNF-alpha on basal FVR appeared to be blocked (37.1 +/- 5.3 vs. 37.6 +/- 5.2; NS), ACh-induced minimal FVR did not differ between pre- and post-TNF-alpha states. In the condition after pretreatment with the nitric oxide (NO) synthase inhibitor N(G)-monomethyl-L-arginine, the vascular effect of TNF-alpha on basal FVR was diminished, and the ACh-induced maximal dilatory response was significantly blunted after TNF-alpha compared with before TNF-alpha (minimal FVR: 30.4 +/- 12.0 vs. 12.3 +/- 4.2 units; p < 0.05). These findings suggest that brief exposure of the human forearm resistance artery to TNF-alpha may increase basal bioavailability of the vasoconstrictor prostaglandin and reduce basal bioavailability of NO. In the stimulated condition, TNF-alpha-induced vascular dysfunction may be overwhelmed by increased NO bioavailability in healthy humans.

Reduced vascular compliance is associated with impaired endothelium-dependent dilatation in the brachial artery of patients with congestive heart failure

BACKGROUND Alterations in elastic properties and vascular structure of conduit vessels are important detrimental factors contributing to increased cardiac load and reduced tissue perfusion in patients with congestive heart failure (CHF). It has been demonstrated that endothelial function in the peripheral vasculature is impaired in this disorder, which may induce abnormal vascular elastic properties and remodeling. However, it remains unknown whether changes in vascular structure or mechanical properties are related to endothelial dysfunction in conduit arteries of patients with CHF. METHODS AND RESULTS Twenty-five CHF patients with nonischemic heart disease and 20 sex/age-matched controls were enrolled. Brachial artery diameter, intima-media thickness (IMT), and vascular stiffness as represented by distensibility and compliance were determined using a high-frequency linear transducer attached to a high-quality ultrasound system. In addition, flow-mediated dilatation (FMD) after 5-minute forearm occlusion and sublingual nitroglycerin-induced dilatation (NTG) were measured in the brachial artery. Brachial arterial diameter was similar between CHF and controls; however, IMT and wall/lumen ratio were significantly greater in CHF patients than in controls (IMT, 0.37+/-0.01 versus 0.31+/-0.01 mm; wall/lumen, 18.7+/-0.8 versus 15.1+/-0.8%: both P<.01). In addition, vascular stiffness parameters were lower in CHF than in controls (distensibility; 1.09+/-0.14 versus 1.60+/-0.15%/kPa, P<.01: compliance; 0.17+/-0.02 versus 0.26+/-0.02 mm(2) kPa, P<.05). FMD and TNG were significantly reduced in CHF (both P<.001). Although stiffness parameters in CHF were not significantly correlated with vascular structure (ie, IMT, wall/lumen) or clinical parameters (ie, age, lipids, glucose, blood pressure), elastic parameters were significantly correlated with FMD (distensibility; r=0.579, P<.005: compliance; r=0.433, P<.05), but not with NTG. CONCLUSION The present study found that, in limb muscle conduit artery in patients with CHF, there are hypertrophic remodeling and endothelial dysfunction-associated alterations in vascular wall elastic properties.

Effect of the Maze Procedure for Atrial Fibrillation on Atrial and Brain Natriuretic Peptide

We studied plasma levels of atrial and brain natriuretic peptides at rest and after exercise before and after intracardiac surgery with and without the maze procedure in patients with chronic heart failure secondary to valvular heart disease. The present study found that an increased response of both cardiac natriuretic peptides is attenuated with resulting water retention after the maze procedure.