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LETTERS TO THE EDITOR
Department of Exercise Science
The University of Iowa
Iowa City, Iowa
e-mail: harald-stauss{at}uiowa.edu
Department of Physical Education
Cornell College
Mt. Vernon, Iowa
Departments of Internal Medicine and Physiology and Biophysics
and the Cardiovascular Center
The University of Iowa
and The Veterans Affairs Medical Center
Iowa City, Iowa
Departments of Internal Medicine and Physiology and Biophysics
and the Cardiovascular Center
The University of Iowa
Iowa City, Iowa
Departments of Psychology, Pharmacology, and Exercise Science and the Cardiovascular Center
The University of Iowa
Iowa City, Iowa
ABSTRACT
The following is the abstract of the article discussed in the subsequent letter:
The function of the arterial baroreflex has traditionally been assessed by measurement of reflex changes in heart rate (HR) or sympathetic nerve activity resulting from experimenter-induced manipulation of arterial blood pressure (the Oxford method, also termed the pharmacological method). However, logistical and flexibility limitations of this technique have promoted the development of new methods for assessing baroreflex function such as the evaluation of changes in spontaneous arterial pressure and HR. Although this new spontaneous method has been validated in dogs and humans, it has not been rigorously tested in rats. In the present study, the method of correlating spontaneous changes in systolic blood pressure and HR was evaluated in resting, normotensive Sprague-Dawley rats. This technique was found to be neither reliable nor valid under the conditions employed in the present protocol. We also tested a variation of the spontaneous method that evaluates particular sequences of data during which arterial pressure and pulse interval are changing in the same direction for at least three consecutive heart beats (the sequence method). The sequence method did not provide extra reliability or validity over the spontaneous method. We conclude that due to the restricted range of variability obtained by measuring spontaneous blood pressure fluctuations, the spontaneous and sequence techniques do not provide data that are comparable to the traditional method of assessing HR changes triggered by arterial blood pressure increases and decreases induced by vasoactive drugs. However, it is possible that surgical stress obscured the relationship between blood pressure and HR, and therefore additional studies are needed to determine whether the spontaneous and sequence methods can be applied to rats during different behavioral states.
The purpose of this letter is to clarify that the negative conclusion by Moffitt et al. (5) regarding the sequence method is due to the computational algorithm applied in their study. In addition, we demonstrate how applying the algorithm originally outlined by Bertinieri et al. (1) to the original data files from the study of Moffitt et al. (5) confirms the validity of the sequence method as a measure of baroreceptor-heart rate reflex sensitivity.
The sequence method, as first described by Bertinieri et al. (1), identifies sequences of four or more heart beats, where blood pressure and pulse interval change in the same direction. Moffitt et al. (5) pooled all pairs of systolic blood pressure and corresponding pulse intervals from all sequences and calculated one single linear regression line. In contrast, the sequence technique as first described by Bertinieri et al. (1), and as used by us and others (4, 6, 8–10), requires the calculation of a linear regression for each individual sequence. The average of the slopes of all individual regression lines is then used as an index of baroreceptor-heart rate reflex sensitivity.
In five rats, recordings were obtained on two consecutive days under baseline conditions and during cardiac autonomic blockade by using atropine, propranolol, and the combination of both (for details, see Ref. 5). The sampling rate was 1,000 Hz although the METHODS inadvertently referred to the sampling rate as 200 Hz. The freely available HemoLab software (http://www.intergate.com/
harald/HemoLab/HemoLab.html) was used to calculate baroreceptor-heart rate reflex sensitivity by using the sequence technique according to Bertinieri et al. (1). Figure 1 shows the correlation between the baroreflex sensitivities on days 1 and 2. The squared correlation coefficient R2 was 0.942 (R = 0.971), indicating an excellent correlation between the baroreceptor-heart rate reflex sensitivities on both days. The average reflex sensitivity on day 1 was 0.90 ± 0.09 ms/mmHg and on day 2 was 1.29 ± 0.28 ms/mmHg (means ± SE, P = 0.11). This tendency to higher gains on day 2 may be related to recovery from surgery and anesthesia.
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1-adrenergic receptor blockade.
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1-adrenergic receptor blockade (propranolol) did not alter baroreflex sensitivity as estimated by the sequence technique (P = 0.83). The lack of a reduction in baroreflex sensitivity during 1-adrenergic receptor blockade may be seen as an indication that the sequence technique is more sensitive to fast parasympathetic modulation of heart rate compared with the slower sympathetic modulation of sinus node function. It may be possible to overcome this apparent limitation by only selecting longer sequences (e.g., 7 heart beats or more) and longer recording durations or by introducing a time delay between blood pressure and pulse interval during identification of the baroreflex sequences. Another possibility is that the lack of a reduction in baroreflex sensitivity during 1-adrenergic receptor blockade is due to the randomization of the experimental protocol. Four of the five propranolol experiments were done on day 1 (24 h after surgery) when baroreflex sensitivity was still low even under control conditions. Thus 1-adrenergic receptor blockade did not further reduce baroreflex sensitivity. In conclusion, although the spontaneous method of calculating baroreceptor-heart rate reflex sensitivity (pooling of heart beats) is not reliable in rats, the sequence method (based on the gains of individual sequences and the number of sequences) appears to be highly reliable and valid.
REFERENCES
This article has been cited by other articles:
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  G. R. Borges, H. C. Salgado, C. A. A. Silva, M. A. Rossi, C. M. Prado, and R. Fazan Jr. Changes in hemodynamic and neurohumoral control cause cardiac damage in one-kidney, one-clip hypertensive mice Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2008; 295(6): R1904 - R1913. [Abstract] [Full Text] [PDF]
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V. A. Braga, M. A. Burmeister, R. V. Sharma, and R. L. Davisson Cardiovascular responses to peripheral chemoreflex activation and comparison of different methods to evaluate baroreflex gain in conscious mice using telemetry Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1168 - R1174. [Abstract] [Full Text] [PDF]
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 R. Fazan Jr, D. A. Huber, C. A. A. Silva, V. J. Dias da Silva, M. C. O. Salgado, and H. C. Salgado Sildenafil acts on the central nervous system increasing sympathetic activity J Appl Physiol, June 1, 2008; 104(6): 1683 - 1689. [Abstract] [Full Text] [PDF]
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 Y. Feng, X. Yue, H. Xia, S. M. Bindom, P. J. Hickman, C. M. Filipeanu, G. Wu, and E. Lazartigues Angiotensin-Converting Enzyme 2 Overexpression in the Subfornical Organ Prevents the Angiotensin II-Mediated Pressor and Drinking Responses and Is Associated With Angiotensin II Type 1 Receptor Downregulation Circ. Res., March 28, 2008; 102(6): 729 - 736. [Abstract] [Full Text] [PDF]
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