Renal and hormonal effects of phosphodiesterase III inhibition in congestive heart failure
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1Division of Cardiology, Ohio State University Medical School and Hospital, Columbus.
Insights
Phosphodiesterase (PDE) III inhibitors like milrinone increased cardiac output in heart failure patients but did not improve kidney function or neurohormonal markers. Blood flow preferentially shifted to skeletal muscles, potentially at the kidney's expense.
Area of Science:
- Cardiology
- Pharmacology
- Renal Physiology
Background:
- Congestive heart failure (CHF) often presents with renal and neurohormonal abnormalities.
- Therapeutic interventions for CHF require evaluation of regional blood flow and functional changes.
- Phosphodiesterase (PDE) III inhibitors increase cardiac output and decrease systemic vascular resistance.
Purpose of the Study:
- To evaluate the effects of milrinone, a PDE III inhibitor, on renal and neurohormonal parameters in patients with CHF.
- To assess regional blood flow changes, particularly in the kidney and skeletal muscle, during PDE III inhibition therapy.
Main Methods:
- A study involving 13 patients diagnosed with congestive heart failure.
- Milrinone therapy administered for a duration of one month.
- Measurement of cardiac output, systemic vascular resistance, renal blood flow, glomerular filtration rate, forearm blood flow, and neurohormonal parameters.
Main Results:
- Milrinone therapy did not significantly increase renal blood flow or glomerular filtration rate.
- No favorable changes were observed in neurohormonal parameters after one month of milrinone treatment.
- Forearm blood flow increased proportionally with cardiac output, indicating a preferential increase in skeletal muscle perfusion.
Conclusions:
- PDE III inhibition with milrinone may lead to a preferential increase in skeletal muscle blood flow.
- This observed effect could represent a relative shunting of blood away from the kidneys.
- Alternatively, renal cellular mechanisms might be activated by PDE III inhibition, counteracting expected benefits on renal function.
Abstract:
Evaluation of the impact of therapeutic interventions in congestive heart failure (CHF) with compounds such as the phosphodiesterase (PDE) III inhibitors must include the determination of regional blood flow and functional changes. Thus, whereas PDE III inhibitors produce a significant increase in cardiac output and reduction of systemic vascular resistance, it is necessary to understand their effects on the kidney and neurohormonal parameters. The evaluation of these effects must take into consideration both the baseline renal and neurohormonal abnormalities in CHF, and the cellular actions of PDE III inhibition, which include an increase in cyclic adenosine monophosphate and cytosolic calcium. In a group of 13 patients with CHF, milrinone therapy for 1 month did not increase renal blood flow or glomerular filtration rate, or favorably affect neurohormonal parameters. However, forearm blood flow increased proportionately with cardiac output. Therefore PDE III inhibition produces a preferential increase in skeletal muscle blood flow, which may be a relative shunting of blood from the kidney. Alternatively, PDE III inhibition may activate renal cellular mechanisms that offset the anticipated favorable response to the increase of cardiac output produced by milrinone.