The Negative Chronotropic Effect in Rat Heart Stimulated by Ultrasonic Pulses: Role of Sex and Age

Abstract

Objectives: The goal of this study is to investigate the role of sex and age of the negative chronotropic effect after exposure of 3.5-MHz pulsed ultrasound (US) to the rat heart.

Methods: Forty F344 rats were exposed transthoracically to ultrasonic pulses at a duty factor of approximately 1.0% at 2.0-MPa peak rarefactional pressure amplitude. The transthoracic ultrasonic bursts were delivered consecutively in five 10-s intervals, that is, 10 s of 6-Hz pulse repetition frequency (PRF), 10 s of 5-Hz PRF, 10 s of 4-Hz PRF, 10 s of 5-Hz PRF, and 10 s of 6-Hz, for a 50-s total exposure duration. The rats were divided into 8 groups (n = 5 each): US young male, control young male, US young female, control young female, US old male, control old male, US old female, and control old female.

Results: Two-way ANOVA for repeated measures was used to compare heart rate, cardiac output, arterial pressure, and other hemodynamic values (baseline) before and after US stimulation. Sex versus age versus US interaction was detected for heart rate. Cardiac output showed an age effect, and ejection fraction showed age and US effects. The arterial pressure showed a sex effect. A negative chronotropic effect (∼30% decrease in heart rate) was observed for young female rats. An hypothesis is that the US effect is weight (menopause) dependent, because the young (premenopausal) female rats weighed approximately 40 to 60% less than other groups of rats.

Conclusions: It is likely that the ovarian hormones are responsible for different US-induced cardiac bioeffects in different ages and sexes.

Keywords: age; biological effects; chronotropic effect; heart; sex; ultrasound.

Figure 1

Time line for the 3.5-MHz transthoracic high-amplitude ultrasound stimulation. Baseline data were acquired prior to the initial ultrasound exposure. Post-exposure data were acquired at 3 min and 15 min after ultrasound ceased. The ultrasonic exposure consisted of one sequence of 10 s each (each with a different PRF).The total duration of the stimulation protocol was 50 s. Duty factor (DF) is approximate because the pulse duration was 2 ms.

Figure 2

Transducer pressure response at ~2 MPa.

Figure 3

2 × 2 × 2 factorial design with sex ( male versus female) as on factor, age (young versus old) as another factor and ultrasound (on versus off).

Figure 4

Normalized values of; A) heart rate, B) cardiac output, C) ejection fraction, D) end-diastolic volume, E) end-systolic volume and F) arterial pressure at 3 min (right side) and 15 min (left side) after US application for all 8 groups.