Background Chronic congestive heart failure is a complex condition that leads to dysfunction in the peripheral microcirculation. We have previously shown that vascular reactivity is reduced with increasing age. In thi...Background Chronic congestive heart failure is a complex condition that leads to dysfunction in the peripheral microcirculation. We have previously shown that vascular reactivity is reduced with increasing age. In this study, we examined a group of very old patients with severe chronic heart failure to test the hypothesis that vascular function is further compromised by a combination of heart failure and aging. Methods Cutaneous forearm blood flow was measured by laser Doppler flowmetry and compared among three groups： Group 1 （n = 20, mean ±SE： 85.5 ±4 years）, heart failure patients with New York Heart Association class Ⅳ （NYHA Ⅳ） and with a NT-proBNP level ≥5000 ng/L; Group 2 （n = 15, mean ±SE： 76.5 ±2 years）, heart failure patients with NYHA II and NT-proBNP ≤2000 ng/L, and Group 3 （n = 10, mean ±SE： 67.6 ±3.0 years）, healthy controls with no clinical signs of heart failure. The vasodilator response to the iontophoretic administration of acetylcholine （ACh）, acting via an endothelial mechanism, and sodium nitroprusside （SNP）, acting via a smooth muscle cell mechanism, were studied. Results All patients with heart failure had significantly reduced vascular reactivity independent of the mode of stimulation （ACh, SNP or heat） when compared to healthy controls. However, the responses did not differ between the two groups of heart failure patients. Conclusions Cutaneous vascular reactivity is reduced in heart failure patients and does not correlate with the severity of the condition or age of patients.展开更多
Background Brain natriuretic peptide （BNP） is normally present in low levels in the circulation, but it is elevated in parallel with the degree of congestion in heart failure subjects （CHF）. BNP has natriuretic ef...Background Brain natriuretic peptide （BNP） is normally present in low levels in the circulation, but it is elevated in parallel with the degree of congestion in heart failure subjects （CHF）. BNP has natriuretic effects and is a potent vasodilator. It is suggested that BNP could be a therapeutic alternative in CHF. However, we postulated that the high levels of circulating BNP in CHF may downregulate the response of microvascular natriuretic receptors. This was tested by comparing 15 CHF patients （BNP 〉 3000 ng/L） with 10 matched, healthy controls. Methods Cutaneous microvascular blood flow in the forearm was measured by laser Doppler Flowmetry. Local heating （＋44°C, 10 min） was used to evoke a maximum local dilator response. Results Non-invasive iontophoretic administration of either BNP or acetylcholine （ACh）, a known endothelium-dependent dilator, elicited an increase in local flow. The nitric oxide synthase inhibitor, l-N-Arginine- methyl-ester （L-NAME）, blocked the BNP response （in controls）. Interestingly, responses to BNP in CHF patients were reduced to about one third of those seen in healthy controls （increase in flow： 251% in CHF vs. 908% in controls; P 〈 0.001）. In contrast, the vasodilator responses to ACh and to local heating were only somewhat attenuated in CHF patients. Thus, dilator capacity and nitric oxide signalling were not af- fected to the same extent as BNP-mediated dilation, indicating a specific downregulation of the latter response. Conclusions The findings show for the first time that microvascular responses to BNP are markedly reduced in CHF patients. This is consistent with the hypothesis of BNP receptor function is downregulated in CHF.展开更多
文摘Background Chronic congestive heart failure is a complex condition that leads to dysfunction in the peripheral microcirculation. We have previously shown that vascular reactivity is reduced with increasing age. In this study, we examined a group of very old patients with severe chronic heart failure to test the hypothesis that vascular function is further compromised by a combination of heart failure and aging. Methods Cutaneous forearm blood flow was measured by laser Doppler flowmetry and compared among three groups： Group 1 （n = 20, mean ±SE： 85.5 ±4 years）, heart failure patients with New York Heart Association class Ⅳ （NYHA Ⅳ） and with a NT-proBNP level ≥5000 ng/L; Group 2 （n = 15, mean ±SE： 76.5 ±2 years）, heart failure patients with NYHA II and NT-proBNP ≤2000 ng/L, and Group 3 （n = 10, mean ±SE： 67.6 ±3.0 years）, healthy controls with no clinical signs of heart failure. The vasodilator response to the iontophoretic administration of acetylcholine （ACh）, acting via an endothelial mechanism, and sodium nitroprusside （SNP）, acting via a smooth muscle cell mechanism, were studied. Results All patients with heart failure had significantly reduced vascular reactivity independent of the mode of stimulation （ACh, SNP or heat） when compared to healthy controls. However, the responses did not differ between the two groups of heart failure patients. Conclusions Cutaneous vascular reactivity is reduced in heart failure patients and does not correlate with the severity of the condition or age of patients.
文摘Background Brain natriuretic peptide （BNP） is normally present in low levels in the circulation, but it is elevated in parallel with the degree of congestion in heart failure subjects （CHF）. BNP has natriuretic effects and is a potent vasodilator. It is suggested that BNP could be a therapeutic alternative in CHF. However, we postulated that the high levels of circulating BNP in CHF may downregulate the response of microvascular natriuretic receptors. This was tested by comparing 15 CHF patients （BNP 〉 3000 ng/L） with 10 matched, healthy controls. Methods Cutaneous microvascular blood flow in the forearm was measured by laser Doppler Flowmetry. Local heating （＋44°C, 10 min） was used to evoke a maximum local dilator response. Results Non-invasive iontophoretic administration of either BNP or acetylcholine （ACh）, a known endothelium-dependent dilator, elicited an increase in local flow. The nitric oxide synthase inhibitor, l-N-Arginine- methyl-ester （L-NAME）, blocked the BNP response （in controls）. Interestingly, responses to BNP in CHF patients were reduced to about one third of those seen in healthy controls （increase in flow： 251% in CHF vs. 908% in controls; P 〈 0.001）. In contrast, the vasodilator responses to ACh and to local heating were only somewhat attenuated in CHF patients. Thus, dilator capacity and nitric oxide signalling were not af- fected to the same extent as BNP-mediated dilation, indicating a specific downregulation of the latter response. Conclusions The findings show for the first time that microvascular responses to BNP are markedly reduced in CHF patients. This is consistent with the hypothesis of BNP receptor function is downregulated in CHF.
