Calibration of Baroreflex Equilibrium Diagram Based on Exogenous Pressor Agents in Chronic Heart Failure Rats

Q: What is the clinical evidence from this study?

Population: Chronic heart failure (post-myocardial infarction rat model) (n=15). Intervention: Intravenous bolus injections of phenylephrine and norepinephrine vs. Normal control rats (NC, n=9) and saline control injections. Primary outcome: Maximum slope of the arterial pressure dose-effect curve in response to phenylephrine (p=<0.01).

Q: What does this research mean for the field?

Rats with chronic heart failure exhibit significantly reduced arterial pressure responsiveness to exogenous phenylephrine and norepinephrine compared to normal control rats. Novelty: ClaimNovelty.METHODOLOGICAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To calibrate the sympathetic nerve activity axis of the baroreflex equilibrium diagram in chronic heart failure rats using arterial pressure responses to exogenous pressor agents.

Toru Kawada; Meihua Li; Yusuke Sata; Can Zheng; Michael J. Turner; Shuji Shimizu; Masaru Sugimachi

doi:10.4137/cmc.s18759

January 1, 2015Clinical Medicine Insights CardiologyOpen Access

Calibration of Baroreflex Equilibrium Diagram Based on Exogenous Pressor Agents in Chronic Heart Failure Rats

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Key result

Phenylephrine and norepinephrine produced significantly smaller maximum dose-effect arterial pressure slopes in chronic heart failure rats than in normal control rats (57.3 vs 80.9 mmHg/decade; P<0.01).

Why the study?

Does chronic heart failure attenuate the arterial pressure response to exogenous phenylephrine and norepinephrine and alter the calibrated baroreflex equilibrium diagram in rats?

Key Points

To calibrate the sympathetic nerve activity axis of the baroreflex equilibrium diagram in chronic heart failure rats using arterial pressure responses to exogenous pressor agents.
Administered intravenous bolus injections of phenylephrine (0.2–50 μg/kg) and norepinephrine (0.02–5 μg/kg) to normal control rats (n = 9) and rats with chronic heart failure (n = 6).
Calculated the chronic heart failure to normal control ratio of the maximum dose-response slope to calibrate the sympathetic nerve activity axis.
The maximum slope of the dose-effect curve was significantly smaller in the chronic heart failure group than in normal controls for phenylephrine (57.3 ± 5.2 vs 80.9 ± 6.3 mmHg/decade; P < 0.01) and norepinephrine (60.2 ± 7.8 vs 80.4 ± 5.9 mmHg/decade; P < 0.01).
The calibrated baroreflex equilibrium diagram demonstrated increased maximum and operating-point sympathetic nerve activity in heart failure rats, but the magnitude was smaller than expected from excess plasma norepinephrine concentrations.

Structured PICO

Does chronic heart failure attenuate the arterial pressure response to exogenous phenylephrine and norepinephrine and alter the calibrated baroreflex equilibrium diagram in rats?

P

Population

15 male Sprague-Dawley rats (6 with chronic heart failure 8 weeks post-myocardial infarction and 9 normal controls) undergoing acute open-loop baroreflex experiments under urethane and alpha-chloralose anesthesia.

I

Intervention

Intravenous bolus injections of phenylephrine (0.2, 0.5, 1, 2, 5, 10, 20, and 50 μg/kg) followed after a 30-minute recovery period by norepinephrine (0.02, 0.05, 0.1, 0.2, 0.5, 1, 2, and 5 μg/kg) in chronic heart failure rats.

C

Comparator

Normal control rats receiving identical intravenous bolus injection protocols of phenylephrine and norepinephrine (with 0.5 mL saline control injections prior to pressor protocols).

O

Outcome

Maximum slope of the dose-effect curve of peak arterial pressure response to phenylephrine and norepinephrine (in mmHg/decade) used to calibrate the sympathetic nerve activity (SNA) axis of the baroreflex equilibrium diagram.surrogate

Main Result

Absolute Event Rate: 57.3% vs 80.9%

p-value: p=<0.01

Calibrating the baroreflex equilibrium diagram using attenuated pressor responses in chronic heart failure rats reveals increased operating-point sympathetic nerve activity, though less than expected from elevated plasma norepinephrine levels.

Limitations

The norepinephrine protocol was always performed after the phenylephrine protocol, which may have introduced an aftereffect of alpha-1-adrenergic activation.
Arterial pressure did not completely return to baseline levels at higher doses of phenylephrine or norepinephrine, making the drug effect somewhat cumulative.
The experiment was performed under anesthetic conditions, so results may not directly extrapolate to conscious conditions.
Systemic administration of pressor agents induced relatively homogenous vasoconstriction, ignoring regional differences in sympathetic tone.
The norepinephrine protocol was always performed after the phenylephrine protocol, potentially causing an aftereffect from high-dose alpha-1-adrenergic activation.
Arterial pressure did not completely return to baseline at higher doses of phenylephrine or norepinephrine, resulting in a partially cumulative drug effect.
Experiments were conducted under anesthesia, limiting direct extrapolation to conscious baroreflex regulation.
Systemic administration of pressor agents causes relatively homogenous vasoconstriction, which does not account for regional differences in sympathetic tone.

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Implication

Attenuated pressor responses in heart failure rats suggest baroreflex shifts; hypothesis-generating and does not yet inform clinical vasopressor dosing.

Abstract

A baroreflex equilibrium diagram describes the relation between input pressure and sympathetic nerve activity (SNA) and that between SNA and arterial pressure (AP). To calibrate the SNA axis (abscissa) of the baroreflex equilibrium diagram, the AP response to intravenous bolus injections of phenylephrine (0.2-50 μg/kg) or norepinephrine (NE, 0.02-5 μg/kg) was examined in normal control rats (NC, n = 9) and rats with chronic heart failure (CHF, n = 6). The maximum slope of the dose-effect curve was significantly smaller in the CHF group than in the NC group (57.3 ± 5.2 vs 80.9 ± 6.3 mmHg/decade for phenylephrine, 60.2 ± 7.8 vs 80.4 ± 5.9 mmHg/decade for NE; P < 0.01). The CHF/NC ratio of the maximum slope was used to calibrate SNA. While the calibrated baroreflex equilibrium diagram showed increased maximum SNA and operating-point SNA in CHF rats compared with NC rats, the magnitude of increase was smaller than that expected from the excess plasma NE concentration in CHF rats. Plasma NE concentration in the CHF group could be disproportionally high relative to SNA.

Discussion

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Cite This Study

Kawada et al. (2015) studied Chronic heart failure (post-myocardial infarction rat model) (n=15). Intravenous bolus injections of phenylephrine and norepinephrine vs. Normal control rats (NC, n=9) and saline control injections was evaluated on Maximum slope of the arterial pressure dose-effect curve in response to phenylephrine (p=<0.01). Phenylephrine and norepinephrine produced significantly smaller maximum dose-effect arterial pressure slopes in chronic heart failure rats than in normal control rats (57.3 vs 80.9 mmHg/decade; P<0.01).

synapsesocial.com/papers/6a7a2d12fbd9051d3b0e25fe https://doi.org/10.4137/cmc.s18759

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Calibration of Baroreflex Equilibrium Diagram Based on Exogenous Pressor Agents in Chronic Heart Failure Rats

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Calibration of Baroreflex Equilibrium Diagram Based on Exogenous Pressor Agents in Chronic Heart Failure Rats

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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