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Reversal of a calcium-mediated vasoconstrictor component in patients with congestive heart failure
1Department of Medicine, New York Hospital, Cornell University Medical Center, New York.
Insights
Calcium influx inhibition improves blood flow in congestive heart failure (CHF) patients. Blocking calcium entry into vascular smooth muscle cells offers a potential therapeutic strategy for improving circulation in CHF.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
Background:
- Calcium influx into vascular smooth muscle cells is a key factor in vasoconstriction.
- This mechanism's role in congestive heart failure (CHF) remains under-explored.
Purpose of the Study:
- To investigate the direct effects of inhibiting calcium influx in vascular smooth muscle.
- To assess the therapeutic potential of nicardipine in patients with CHF.
Main Methods:
- Utilized an isolated forearm model in 11 patients diagnosed with CHF.
- Administered the soluble dihydropyridine, nicardipine, in a dose-dependent manner.
Main Results:
- Nicardipine significantly increased forearm blood flow and reduced vascular resistance.
- No significant systemic hemodynamic effects were observed.
- Patients with lower baseline forearm blood flow showed the most substantial improvements (r = -0.729, p < 0.01).
- A reduction in forearm oxygen extraction indicated a favorable metabolic effect.
Conclusions:
- Intracellular calcium in vascular smooth muscle is a critical determinant of vasoconstriction in CHF patients.
- Inhibition of calcium influx represents a promising therapeutic approach for managing vasoconstriction in CHF.
Abstract:
The influx of calcium into vascular smooth muscle cells is a major determinant of vasoconstriction, yet this concept has not been explored in congestive heart failure (CHF). We therefore used an "isolated" forearm model to assess the direct effects of the inhibition of calcium influx into vascular smooth muscle in 11 patients who had CHF, with use of the soluble dihydropyridine, nicardipine. Nicardipine produced a dose-dependent increase of forearm blood flow and a reduction of resistance, without producing a systemic hemodynamic effect. Patients with the lowest baseline forearm blood flow levels had the greatest percentage increases in forearm blood flow (r = -0.729, p less than 0.01), and a favorable metabolic effect was documented by a reduction in oxygen extraction across the forearm. This study demonstrated the importance of vascular smooth muscle intracellular calcium as a determinant of vasoconstriction in patients who have CHF.