Carotid Body Denervation Markedly Improves Survival in Rats With Hypertensive Heart Failure
Kana Fujii1, Keita Saku2, Takuya Kishi3
1Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University,Maidashi, Higashi-ku, Fukuoka, Japan.
Insights
Carotid body denervation (CBD) reduced sympathetic activity, improving blood pressure and heart function in rats with hypertensive heart failure. This intervention significantly enhanced survival rates.
Area of Science:
- Cardiovascular Research
- Nephrology
- Surgical Innovation
Background:
- Hypertension is a primary driver of heart failure, with excessive sympathetic nervous system activity worsening patient prognosis.
- Carotid body denervation (CBD) has demonstrated potential in reducing sympathetic nerve activity in animal models of hypertension and heart failure.
Purpose of the Study:
- To investigate whether bilateral carotid body denervation (CBD) can mitigate the progression of hypertensive heart failure.
- To assess the impact of CBD on survival rates in a rat model of hypertensive heart failure.
Main Methods:
- Dahl salt-sensitive rats were randomly assigned to CBD or sham-operation (SHAM) groups and fed a high-salt diet.
- Key parameters monitored included 24-hour urinary norepinephrine excretion, blood pressure, cardiac function (percent fractional shortening), pressure-natriuresis relationship, hemodynamics, and histology.
Main Results:
- CBD significantly reduced sympathetic activity (urinary norepinephrine) and blood pressure.
- The procedure preserved cardiac function (fractional shortening) and reduced cardiac remodeling (hypertrophy and fibrosis).
- Carotid body denervation markedly improved survival rates by 64.8%.
Conclusions:
- Bilateral carotid body denervation effectively attenuated hypertension and the progression of heart failure in this rat model.
- The beneficial effects are likely mediated through sympathoinhibition, leading to significantly improved survival.
Background:
Hypertension is a major cause of heart failure. Excessive sympathoexcitation in patients with heart failure leads to poor prognosis. Since carotid body denervation (CBD) has been shown to reduce sympathetic nerve activity in animal models of hypertension and heart failure, we examined if bilateral CBD attenuates the progression of hypertensive heart failure and improves survival.
Methods:
We randomly allocated Dahl salt-sensitive rats fed a high-salt diet from 6 weeks of age into CBD (n = 31) and sham-operation (SHAM; n = 50) groups, and conducted CBD or SHAM at 7 weeks of age. We examined the time course of 24-hour urinary norepinephrine (uNE) excretion, blood pressure (BP) and the percent fractional shortening assessed by echocardiography, and estimated the pressure-natriuresis relationship at 14 weeks of age. Finally, we assessed hemodynamics, histological findings, and survival at 16 weeks of age.
Results:
Compared to SHAM, CBD significantly reduced 24-hour uNE at 12, 14, and 16 weeks of age, shifted the pressure-natriuresis relationship leftward without changing its slope, and attenuated the increase in BP. CBD preserved percent fractional shortening (34.2 ± 1.2 vs. 29.1 ± 1.3%, P < 0.01) and lowered left ventricular end-diastolic pressure (5.0 ± 0.9 vs. 9.0 ± 1.4 mm Hg, P < 0.05). Furthermore, CBD significantly attenuated myocardial hypertrophy (P < 0.01) and fibrosis (P < 0.01). Consequently, CBD markedly improved survival (relative risk reduction: 64.8%).
Conclusions:
CBD attenuated the progression of hypertension and worsening of heart failure possibly through sympathoinhibition, and markedly improved survival in a rat model of hypertensive heart failure.
