Nasal Strips and EIPH in the Exercising Thoroughbred Racehorse

The following is the abstract of the article discussed in the subsequent letter:

	ABSTRACT

Goetz, Thomas E., Murli Manohar, Aslam S. Hassan, and Gordon J. Baker. Nasal strips do not affect pulmonary gas exchange, anaerobic metabolism, or EIPH in exercising Thoroughbreds. J Appl Physiol 91: 2378-2385, 2001.The present study was carried out to examine whether nasal strip application would improve the exercise-induced arterial hypoxemia and hypercapnia, diminish anaerobic metabolism, and modify the incidence of exercise-induced pulmonary hemorrhage (EIPH) in horses. Two sets of experiments, control and nasal strip experiments, were carried out on seven healthy, sound, exercise-trained Thoroughbred horses in random order, 7 days apart. Simultaneous measurements of core temperature, arterial and mixed venous blood gases/pH, and blood lactate and ammonia concentrations were made at rest, during submaximal and near-maximal exercise, and during recovery. In both treatments, whereas submaximal exercise caused hyperventilation, near-maximal exercise induced significant arterial hypoxemia, desaturation of Hb, hypercapnia, and acidosis. However, O₂ content increased significantly with exercise in both treatments, while the mixed venous blood O₂ content decreased as O₂ extraction increased. In both treatments, plasma ammonia and blood lactate concentrations increased significantly with exercise. Statistically significant differences between the control and the nasal strip experiments could not be discerned, however. Also, all horses experienced EIPH in both treatments. Thus our data indicated that application of an external nasal dilator strip neither improved the exercise-induced arterial hypoxemia and hypercapnia nor diminished anaerobic metabolism or the incidence of EIPH in Thoroughbred horses performing strenuous exercise.

	LETTER

Nasal Strips and EIPH in the Exercising Thoroughbred Racehorse

To the Editor: Regarding the recently published article by Goetz et al. (5), we wish to raise several points that bring into question the validity of the title, conclusions, and key presentation features of that paper.

1) The methodologies utilized did not permit quantification of the variables stated in the title [i.e., pulmonary gas exchange, anaerobic metabolism, and exercise-induced pulmonary hemorrhage (EIPH)]. Thus the title and its conclusive nature cannot be supported by the data.

2) At least one key paper (published in the peer-reviewed literature) that addressed very similar issues (and actually measured pulmonary gas exchange and quantified EIPH by bronchoalveolar lavage) but came to completely different conclusions was not referenced (12). It is surprising that Goetz and coauthors were not aware of that publication, as evidenced by this statement in their paper (5): "To our knowledge, there have been no scientific reports evaluating the use of an equine nasal dilator strip on blood gases, indexes of anaerobic metabolism, and/or the incidence of EIPH in racehorses." Over the past 2 years, in addition to the Journal of Equine Veterinary Science article (12), various components of this and subsequent pertinent work have been presented in abstract form (2, 3, 6-8) as well as presented (annual meeting of American Association of Equine Practitioners, Ref. 4) and published as reviews (e.g., Refs. 1 and 4). In addition, this work has received frequent and high-profile visibility in the form of journal editorials and feature articles in the popular press since October 1999.

3) Evaluation of EIPH by endoscopic examination for fresh blood is viewed by many as highly subjective and cannot discriminate with precision among different severities of bleeding. To detect the presence of blood in alveoli and small airways, bronchoalveolar lavage is the technique of choice because it provides an accurate reflection of the cytological population in the terminal airways and alveolar spaces (9, 10). As demonstrated by Poole et al. (12), application of the nasal strip during high-speed (but submaximal) running does not abolish but does significantly reduce EIPH. Perusal of that publication provides a compelling justification for employing bronchoalveolar lavage to assess EIPH quantitatively in the Goetz et al. (5) study. Indeed, with any condition that has a multifactorial etiology, it is doubtful whether a single manipulation could abolish the pathophysiology. It is also pertinent that Goetz et al. (5) state that "statistically significant differences in the above-described parameters [among which is EIPH] were not observed in strenuously exercising horses after application of the external nasal dilator strip [which] raises doubts regarding meaningful benefits to its use in racehorses." How exactly was the presence of fresh blood in the airways assessed statistically? No attempt was made to scale the quantity of blood in the airways, which is clearly possible (but possibly subjective) using this technique (11). It would be tragic if a technique (i.e., the nasal strip) with the demonstrated potential to reduce EIPH severity (12) and possibly lung damage was not utilized because of an evaluation (5) that was not capable of discriminating between mild and severe pulmonary hemorrhage.

	REFERENCES

1.   Erickson, HH, Kindig CA, and Poole DC. Exercise-induced pulmonary hemorrhage: a new concept for prevention. J Equine Vet Sci 20: 164-167, 2000.

2.  Erickson HH, Kindig CA, Rush BR, and Poole DC. Evaluation of the FLAIR equine nasal strip: a new concept to prevent EIPH. In: Equine Fitness: The Olympic Way. Post Graduate Foundation Proc 329 in Vet. Sci., Univ. of Sydney, 21-25 Feb., 2000, p. xvi.

3.   Erickson, HH, Kindig CA, Rush BR, and Poole DC. Evaluation of the FLAIR equine nasal strip: a new concept to prevent EIPH. World Equine Vet Rev 5: 26, 2000.

4.   Erickson, HH. A review of exercise-induced pulmonary hemorrhage and new concepts for prevention. Proc Am Assoc Equine Pract 46: 193-196, 2000.

5.   Goetz, TE, Manohar M, Hassan AS, and Baker GJ. Nasal strips do not affect pulmonary gas exchange, anaerobic metabolism, or EIPH in exercising Thoroughbreds. J Appl Physiol 90: 2378-2385, 2001[Abstract/Free Full Text].

6.   Kindig, CA, Erickson HH, McDonough P, and Poole DC. Efficacy of nasal strip and furosemide in mitigating equine exercise-induced pulmonary hemorrhage (EIPH). Comp Resp Soc Proc 18: 26, 2000.

7.  Kindig CA, Poole DC, McDonough P, Rush BR, and Erickson HH. External nasal dilator reduces bleeding in racehorses. In: Proc 62nd Ann Conf for Vet, KSUCVM, June 4-7, 2000.

8.   McDonough, P, Kindig CA, Poole DC, Rush BR, and Erickson HH. Equine nasal strip reduces bleeding in racehorses. Comp Resp Soc Proc 18: 28, 2000.

9.   Meyer, TS, Fedde MR, Gaughan EM, Langsetmo I, and Erickson HH. Quantification of exercise-induced pulmonary hemorrhage with bronchoalveolar lavage. Equine Vet J 30: 284-288, 1998[Medline].

10.   Moore, BR, and Cox JH. Diagnostic use of bronchoalveolar lavage in horses. Equine Pract 18: 7-15, 1996.

11.   Pascoe, JR, McCabe AE, Franti CE, and Arthur RM. Efficacy of furosemide in the treatment of exercise-induced pulmonary hemorrhage in Thoroughbred racehorses. Am J Vet Res 46: 2000-2003, 1985[Web of Science][Medline].

12.   Poole, DC, Kindig CA, Fenton G, Ferguson L, Rush BR, and Erickson HH. Effects of external nasal support on pulmonary gas exchange and EIPH in the horse. J Equine Vet Sci 20: 579-585, 2000.

Casey A. Kindig, David C. Poole, Paul McDonough, Howard H. Erickson, Departments of Anatomy, Physiology, and Kinesiology Kansas State University Manhattan, Kansas 66506-5802 E-mail: ckindig{at}ucsd.edu

	REPLY

To the Editor: We gratefully accept the opportunity to respond to the comments of Dr. Kindig and colleagues regarding our recently published manuscript in the Journal of Applied Physiology (1). We respond to each of their three points below.

1) For the following reasons, the statements of Kindig and colleagues regarding the title of our article (1) are inaccurate. 1) The adequacy of pulmonary gas exchange is routinely judged on the basis of arterial O₂ and CO₂ tensions (5); these were carefully quantified (along with those in the simultaneously sampled mixed-venous blood) using standard techniques (5) in our experiments (1). As noted in the results and in Figs. 1 and 2 (1), statistically significant differences in these variables between the control and nasal strip treatments were not found either at rest or during incremental exercise leading to galloping at maximal heart rate. 2) In our study (1), two discrete indexes of anaerobic metabolism, namely, lactate and ammonia production, were quantified by using established chemical assays along with arterial blood pH to document the severity of metabolic acidosis. As seen in Fig. 5 and discussed in the results, statistically significant differences in these data were also not discerned between the control and nasal strip treatments (1). 3) By using established airway endoscopic examination methodology (3, 4) routinely employed in competitive horse racing worldwide, we demonstrated that the occurrence of exercise-induced pulmonary hemorrhage (EIPH) was also unaffected by the application of nasal strips in Thoroughbreds performing maximal exertion. Thus, contrary to the specious statements of Kindig and colleagues in their letter, every aspect of our title accurately represents the findings of our study, obtained through careful usage of established methodologies.

2) We were unaware of the citations listed by Kindig and colleagues in their letter (their Refs. 1-4, 6-8, and 12) because these did not appear in any of the several MEDLINE/PubMed literature searches on nasal strips carried out last year and this year (including those on June 7, 2001) in our laboratory. This may have been because the MEDLINE/PubMed databases cover only the mainstream veterinary medical literature. These references listed by Kindig and colleagues have appeared in obscure periodicals, whose peer review process is questionable. Also, most of these citations (Refs. 2-4 and 6-8 in their letter) were abstracts, which are usually unscrutinized, preliminary communications.

In studying citation 12 from the above letter (which Kindig et al. pointed out as a key paper), even a knowledgeable reader is hampered in independent evaluation because of the unreported statistical power of their analyses, the inappropriate use of a paired t-test to compare treatments in a repeated measures experimental design, and the paucity of baseline/resting data against which all exercise data must be viewed. Also, in citation 12, only submaximal work was studied. The latter distinction vis-à-vis maximal exertion as examined in our study (1) is highly germane to the O₂ uptake comparisons between control and nasal strip experiments. This is because, during maximal exertion performed at the same workload in the control and nasal strip treatments, cardiac output (at maximal heart rate) having reached its maximal value causes O₂ uptake to become solely dependent on the arterial to mixed-venous O₂ content gradient, which, as demonstrated in our Fig. 4 (1), remained unaffected by the application of nasal strips. Finally, we must note that we still remain unaware of their work's "frequent and high-profile visibility in the form of journal editorials and feature articles in the popular press ... ."

3) Kindig and colleagues make it appear that counting red blood cells (RBC) in the bronchoalveolar lavage (BAL) fluid of exercised horses is the panacea for documenting the severity of EIPH. However, the fact is that the validity of RBC counts in BAL fluid to evaluate the severity of EIPH remains highly questionable for reasons elegantly summarized by Dr. Hinchcliff in a recent editorial (2): "There is no clear demonstration that red cell counts provide an accurate or reproducible means of quantifying the severity of EIPH." Thus, contrary to the dubious assertions of Kindig et al., as yet proven methodology is not available to evaluate the severity of EIPH in racehorses. In Dr. Hinchcliff's words (2), "we should consider the results of studies using BAL fluid as the dependent variable with interest, but with healthy skepticism." Therefore, because of the lack of a proven methodology to document the severity of EIPH, we evaluated only the incidence/occurrence of EIPH as noted in our abstract, introduction, methods, and discussion (1).

In closing, we thank Kindig et al. for their interest in our work (1). However, based on our results, we must adamantly disagree with their specious comments/opinions.

	REFERENCES

1.   Goetz, TE, Manohar M, Hassan AS, and Baker GJ. Nasal strips do not affect pulmonary gas exchange, anaerobic metabolism, or EIPH in exercising Thoroughbreds. J Appl Physiol 90: 2378-2385, 2001.

2.   Hinchcliff, KW. Counting red cellsis it the answer to EIPH? Equine Vet J 32: 362-363, 2000[Medline].

3.   LaPointe, JM, Vrins A, and McCarvill E. A survey of exercise-induced pulmonary hemorrhage in Quebec Standardbred racehorses. Equine Vet J 26: 482-485, 1994[Web of Science][Medline].

4.   Sweeney, CR. Exercise-induced pulmonary hemorrhage. Vet Clin North Am Equine Pract 7: 93-104, 1991[Web of Science][Medline].

5.   West, JB. Gas exchange. In: Pulmonary PathophysiologyThe Essentials (5th ed.). Philadelphia, PA: Lippincott Williams & Wilkins, 1995, chapt. 2, p. 17-31.

Thomas E. Goetz, Murli Manohar, Gordon J. Baker, Departments of Veterinary Clinical Medicine and Biosciences University of Illinois College of Veterinary Medicine Urbana, Illinois 61802 E-mail: mmanohar{at}uiuc.edu