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Efficacy of dibutyryl cyclic AMP in heart failure unresponsive to catecholamines
S Matsui1, E Murakami, N Takekoshi
1Department of Cardiology, Kanazawa Medical University, Japan.
Insights
Dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) improved heart function in patients with severe heart failure unresponsive to other treatments. This cyclic AMP derivative demonstrated significant vasodilating and inotropic effects, offering a potential new therapy.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Heart failure is a complex condition often requiring multifaceted treatment approaches.
- Patients with severe, catecholamine-refractory heart failure present significant therapeutic challenges.
Observation:
- Dibutyryl adenosine 3",5"-cyclic monophosphate (DBcAMP) was administered to eight patients with advanced heart failure.
- Hemodynamic parameters were assessed before and after intravenous DBcAMP infusion.
Findings:
- DBcAMP significantly increased cardiac index (CI) and left ventricular stroke work index (LVSWI).
- A significant decrease in total systemic vascular resistance index (TSVRI) was observed, indicating vasodilation.
- Left ventricular function improved in a majority of patients, with some showing clinical improvement and survival.
Implications:
- DBcAMP exhibits potent vasodilating and mild positive inotropic effects.
- This suggests DBcAMP may be a valuable therapeutic option for refractory heart failure.
- Further research into DBcAMP's role in advanced heart failure management is warranted.
Abstract:
The efficacy of dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) was evaluated in eight patients with heart failure unresponsive to catecholamine therapy. Seven patients who were hemodynamically at Forrester's hemodynamic subset stage H-IV and had a left ventricular stroke work index (LVSWI) of less than 20 g-m/m2 despite administration of unloading drugs and catecholamines were studied both hemodynamically and clinically. Another patient with dilated cardiomyopathy, in whom invasive hemodynamic monitoring could not be carried out, was studied clinically. The DBcAMP was administered intravenously at a mean (+/- SD) of 0.05 +/- 0.036 mg/kg/min, and hemodynamic measurements were made 63 +/- 37 min after administration. The cardiac index (CI) increased from 1.92 +/- 0.22 to 2.49 +/- 0.59 L/min/m2, and LVSWI from 14 +/- 4.0 to 18 +/- 5.1 g-m/m2, both significantly (CI, P less than 0.01; LVSWI, P less than 0.025). The total systemic vascular resistance index (TSVRI) decreased significantly from 2,746 +/- 427.2 to 2,218 +/- 582.6 dan.sec.cm-5.m2 ( P less than 0.01). The increase in CI was accompanied by a proportional decrease in TSVRI in all patients. Left ventricular function, which was estimated by the relation between pulmonary arterial end-diastolic pressure and LVSWI, was improved in five of seven patients after administration of DBcAMP. Two patients in whom DBcAMP was given intermittently improved clinically and survived. The authors conclude that DBcAMP has powerful vasodilating and mild positive inotropic effects and hence can be useful for treating heart failure unresponsive to catecholamines.