Hemodynamic Effect of Amrinone Depends on Pretreatment Vascular Resistance in Patients with Evolving Congestive Heart Failure: Correlation Between Vascular Resistance and Neurohormonal Activity

Background Most patients with congestive heart failure (CHF) develop pulmonary venous hypertension, but right ventricular afterload is frequently further elevated by increased pulmonary vascular resistance. To investigate whether inhalation of a vasodilatory phosphodiesterase-3 inhibitor may reverse this potentially detrimental process, the authors studied the effects of inhaled or intravenous milrinone on pulmonary and systemic hemodynamics in a rat model of CHF. Methods In male Sprague-Dawley rats, CHF was induced by supracoronary aortic banding, whereas sham-operated rats served as controls. Milrinone was administered as an intravenous infusion (0.2-1 microg.kg body weight.min) or by inhalation (0.2-5 mg/ml), and effects on pulmonary and systemic hemodynamics and lung water content were measured. Results In CHF rats, intravenous infusion of milrinone reduced both pulmonary and systemic arterial blood pressure. In contrast, inhalation of milrinone predominantly dilated pulmonary blood vessels, resulting in a reduced pulmonary-to-systemic vascular resistance ratio. Repeated milrinone inhalations in 20-min intervals caused a stable reduction of pulmonary artery pressure. No hemodynamic effects were detected when 0.9% NaCl was administered instead of milrinone or when milrinone was inhaled in sham-operated rats. No indications of potentially adverse effects of milrinone inhalation in CHF, such as left ventricular volume overload, were detected. Moreover, lung edema was significantly reduced by repeated milrinone inhalation. Conclusion If these results can be confirmed in humans, inhalation of nebulized milrinone may present a novel, effective, safe, and pulmonary selective strategy for the treatment of pulmonary venous hypertension in CHF.

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728 The role of cardiac power and systemic vascular resistance in the pathophysiology and diagnosis of patients with acute congestive heart failure

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(03)90467-x ◽

2003 ◽

Vol 2 (1) ◽

pp. 154

Author(s):

G COTTER ◽

E KALUSKI ◽

O MILO ◽

A SCHNEEWEISS ◽

Z VERED ◽

...

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Cardiac Power

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Relationship between endothelin-1 extraction in the peripheral circulation and systemic vascular resistance in patients with severe congestive heart failure

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(98)00573-7 ◽

1999 ◽

Vol 33 (2) ◽

pp. 530-537 ◽

Cited By ~ 20

Author(s):

Takayoshi Tsutamoto ◽

Atsuyuki Wada ◽

Tomoko Hisanaga ◽

Keiko Maeda ◽

Masato Ohnishi ◽

...

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Severe Congestive Heart Failure ◽

Peripheral Circulation ◽

Endothelin 1

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Effects of supplemental oxygen on forearm vasodilation in humans

Journal of Applied Physiology ◽

10.1152/jappl.1997.82.5.1601 ◽

1997 ◽

Vol 82 (5) ◽

pp. 1601-1606 ◽

Cited By ~ 47

Author(s):

Paul Crawford ◽

Peter A. Good ◽

Eric Gutierrez ◽

Joshua H. Feinberg ◽

John P. Boehmer ◽

...

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Vascular Resistance ◽

Peak Flow ◽

Lower Body Negative Pressure ◽

Normal Subjects ◽

Supplemental Oxygen ◽

Lower Body ◽

Minimal Resistance ◽

Minimum Resistance

Crawford, Paul, Peter A. Good, Eric Gutierrez, Joshua H. Feinberg, John P. Boehmer, David H. Silber, and Lawrence I. Sinoway.Effects of supplemental oxygen on forearm vasodilation in humans. J. Appl. Physiol. 82(5): 1601–1606, 1997.—Supplemental O2 reduces cardiac output and raises systemic vascular resistance in congestive heart failure. In this study, 100% O2 was given to normal subjects and peak forearm flow was measured. In experiment 1, 100% O2 reduced blood flow and increased resistance after 10 min of forearm ischemia (flow 56.7 ± 7.9 vs. 47.8 ± 6.7 ml ⋅ min−1 ⋅ 100 ml−1; P < 0.02; vascular resistance 1.7 ± 0.2 vs. 2.4 ± 0.4 mmHg ⋅ min ⋅ 100 ml ⋅ ml−1; P < 0.03). In experiment 2, lower body negative pressure (LBNP; −30 mmHg) and venous congestion (VC) simulated the high sympathetic tone and edema of congestive heart failure. Postischemic forearm flow and resistance were measured under four conditions: room air breathing (RA); LBNP+RA; RA+LBNP+VC; and 100% O2+LBNP+VC. LBNP and VC did not lower peak flow. However, O2raised minimal resistance (2.3 ± 0.4 RA; 2.8 ± 0.5 O2+LBNP+VC, P < 0.04). When O2 alone ( experiment 1) was compared with O2+LBNP+VC ( experiment 2), no effect of LBNP+VC on peak flow or minimum resistance was noted, although the return rate of flow and resistance toward baseline was increased. O2 reduces peak forearm flow even in the presence of LBNP and VC.

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