Assessment of cardiac sympathetic regulation by respiratory-related arterial pressure variability in the rat

Abstract

1. Mechanical ventilation evokes a corresponding arterial pressure variability (APV) which is decreased by beta-adrenoceptor antagonism. Therefore, in this study we set out to determine whether the respiratory-related APV can be used to assess cardiac sympathetic tone. 2. Computer-generated broad-band mechanical ventilation (0-3 Hz) was applied to Sprague-Dawley rats that had been anaesthetized with ketamine and paralysed with pancuronium. APV and its relationship to lung volume variability (LVV-APV) was systematically quantified with auto- or cross-spectral frequency domain analysis. 3. APV and LVV-APV transfer magnitudes between 0.5 and 1.5 Hz showed dose-dependent suppression by propranolol from 0.01 to 1 mg kg-1, while the static value of arterial pressure remained unchanged. Stroke volume variability, assessed by the use of a pulse contour method, exhibited a similar pattern of suppression by propranolol. In contrast, heart rate variability was not lowered with propranolol. 4. The effect of propranolol on respiratory-related APV persisted even in the presence of combined alpha-adrenoceptor and muscarinic receptor blockade by phentolamine and atropine. 5. The frequency range of 0.5-1.0 Hz was optimal for LVV-APV transfer magnitude to correlate with cardiac sympathetic tone. 6. We conclude that respiratory-related APV may provide a valid assessment of cardiac sympathetic regulation which is independent of parasympathetic and vascular sympathetic influences in ketamine-anaesthetized and positive pressure-ventilated rats.

Figure 1. Irregular mechanical ventilation technique

The ventilatory rate was fixed at 1.5 Hz before and after each test period. During the test period, the ventilatory rate varied randomly from 0 to 3 Hz, with a mean value of 1.5 Hz, and the lung volume (LV) was essentially unchanged. Note the irregular fluctuations in arterial pressure (AP) and stroke volume (SV) signals during the test period, and their return to baseline status after the test period. In contrast, the fluctuation in heart rate (HR) was minimal (bpm, beats min⁻¹).

Figure 2. Effect of propranolol on respiratory-related APV

A, time domain illustration of lung volume (LV) and arterial pressure (AP) signals before (a) and 5 min after (b) i.v. administration of propranolol (1 mg kg⁻¹). B, frequency domain analysis of the effect of propranolol (Pro; 0.01–1 mg kg⁻¹i.v.) on LVV, APV and LVV-APV transfer magnitude following pretreatment with saline. Values are presented as means ±s.e.m., n = 8 rats. *P < 0.05 vs. corresponding value of the preceding treatment by Duncan's multiple range test.

Figure 3. Effect of propranolol on respiratory-related APV following systemic α-adrenoceptor and muscarinic receptor blockade

Frequency domain analysis of the effect of propranolol (Pro; 0.01–1 mg kg⁻¹i.v.) on LVV, APV and LVV-APV transfer magnitude following combined pretreatment with phentolamine (Phe; 2.5 mg kg⁻¹i.v.) and atropine (Atr; 0.3 mg kg⁻¹i.v.). Values are presented as means ±s.e.m., n = 8. *P < 0.05 vs. corresponding value with the preceding treatment by Duncan's multiple range test.

Figure 4. Correlation between heart rate and transfer magnitude of LVV and APV

Relationship between the static value of HR and the transfer magnitude of LVV and APV as measured within the frequency range of 0.5–1.0 Hz in response to incremental doses of propranolol (0.01, 0.1, 1 mg kg⁻¹i.v.) following pretreatment with saline or combined phentolamine (Phe; 2.5 mg kg⁻¹i.v.) and atropine (Atr; 0.3 mg kg⁻¹i.v.). Values are presented as means ±s.e.m., n = 8.

Figure 5. Effect of propranolol on respiratory-related stroke volume and HR variability

A, time domain illustration of lung volume (LV), stroke volume (SV) and HR signals before (a) and 5 min after (b) i.v. administration of propranolol (1 mg kg⁻¹). B, frequency domain analysis of the effect of propranolol (Pro; 0.01–1 mg kg⁻¹i.v.) on the transfer magnitude of LVV and stroke volume variability, and the transfer magnitude of LVV and HRV following pretreatment with saline. Values are presented as means ±s.e.m., n = 8. *P < 0.05vs. corresponding value of the preceding treatment by Duncan's multiple range test.