September 1, 1981Circulation
Determinants of drug response in severe chronic heart failure. 1. Activation of vasoconstrictor forces during vasodilator therapy.
Why the study?
Does the activation of neurohumoral vasoconstrictor forces limit the hemodynamic response to vasodilator therapy in patients with severe chronic heart failure?
Population
40 patients with severe chronic heart failure
Comparison
Vasodilator therapy; a subset of 4 patients… vs Patients stratified by magnitude of rebound…
Design
Cohort
Authors
Discussion
Loading...
Member takes
Implication
Marked rebound vasoconstriction may blunt vasodilator responses in severe HF; hypothesis-generating for combined neurohumoral blockade.
Key Points
- To determine whether reactive neurohumoral vasoconstrictor forces activated during vasodilator therapy limit hemodynamic responses in patients with severe chronic heart failure.
- Quantified reactive vasoconstriction by measuring the magnitude of rebound change (MRC) after nitroprusside withdrawal in 40 patients with severe chronic heart failure.
- Evaluated hemodynamic changes following nitroprusside (4.5 µg/kg/min) and oral isosorbide dinitrate (40 mg) in low-rebound (MRC ≤ 27%, n=22) versus high-rebound (MRC > 27%, n=18) groups.
- Assessed response to nitroprusside and nitrates in a subgroup of 4 patients following pretreatment with intravenous phentolamine (0.3 mg/min).
- Patients with minimal reactive vasoconstriction (MRC ≤ 27%, n=22) showed marked hemodynamic improvements and significant reductions in heart rate with both nitroprusside and isosorbide dinitrate (p < 0.001).
- Patients with marked rebound changes (MRC > 27%, n=18) exhibited significantly smaller changes in cardiac index, systemic vascular resistance, and mean arterial pressure (p < 0.001), with unchanged or increased heart rates.
- Pretreatment with intravenous phentolamine in 4 patients attenuated rebound events and enhanced the hemodynamic response to nitroprusside and nitrates.
Structured PICO
Does the activation of neurohumoral vasoconstrictor forces limit the hemodynamic response to vasodilator therapy in patients with severe chronic heart failure?
P
Population
40 patients with severe chronic heart failure
I
Intervention
Vasodilator therapy (nitroprusside 4.5 microgram/kg/min and isosorbide dinitrate 40 mg orally); a subset of 4 patients received pretreatment with i.v. phentolamine (0.3 mg/min)
C
Comparator
Patients stratified by magnitude of rebound change (MRC) after nitroprusside withdrawal: Group 1 (MRC ≤ 27%, n=22) vs Group 2 (MRC > 27%, n=18)
O
Outcome
Hemodynamic responses (changes in cardiac index, systemic vascular resistance, mean arterial pressure, and heart rate)surrogate
Activation of neurohumoral forces limits the hemodynamic efficacy of vasodilators in severe heart failure, supporting the rationale for combining direct-acting vasodilators with neurohumoral antagonists.
Cite This Study
Packer et al. (1981) studied this question.