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CLINICAL STUDIES

Elevated endothelin concentrations are associated with reduced coronary vasomotor responses in patients with chest pain and normal coronary arteriograms

Ian D. Cox, MRCP^*, Hans E. Bøtker, MD, Jens P. Bagger, MD, Helle S. Sonne, MD, Bent Ø Kristensen, MD and Juan Carlos Kaski, MD, FACC^*

^* Department of Cardiological Sciences, St. George’s Hospital Medical School, London, United Kingdom
Department of Cardiology, Skejby University Hospital, Aarhus, Denmark
Department of Cardiology, Hammersmith Hospital, London, United Kingdom

Manuscript received August 13, 1998; revised manuscript received March 17, 1999, accepted April 22, 1999.

Reprint requests and correspondence: Dr. J.C. Kaski, Department of Cardiological Sciences, St. George’s Hospital Medical School, Cranmer Terrace, London, SW17 0RE, United Kingdom
jkaski{at}sghms.ac.uk

OBJECTIVES

The purpose of this study was to investigate the relationship between arterial and coronary sinus endothelin (ET) concentrations and coronary vasomotor responses during rapid atrial pacing in patients with chest pain and normal coronary arteriograms (CPNA).

BACKGROUND

Plasma ET concentrations are significantly higher in CPNA patients than in healthy control subjects.

METHODS

We investigated 19 carefully characterized CPNA patients (14 women; mean age 53 ± 9 years) of whom 10 had positive electrocardiographic responses to exercise. The percentage fall in coronary vascular resistance (%d.CVR) after 10 min of rapid atrial pacing was determined using a thermodilution pacing catheter. Plasma ET concentrations were measured by radioimmunoassay on simultaneously drawn arterial and coronary sinus samples.

RESULTS

No significant differences in ET concentrations were observed between men and women, but a strong statistical trend suggested that %d.CVR was lower in women than men (27[23 to 31]% vs. 34[29 to 45]%—median[interquartile range]; p = 0.07). Simple regression analysis including only the women (n = 14) suggested a significant relationship between baseline arterial ET concentrations and %d.CVR (R² = 0.34; p = 0.06). Furthermore, stepwise multivariate regression analysis of the group as a whole indicated that both gender (p = 0.03) and baseline arterial ET concentration (p = 0.02) were independently predictive of %d.CVR (R² = 0.44; overall p = 0.02); this relationship predicts that women with high ET levels would have the lowest %d.CVR during pacing.

CONCLUSIONS

These data support the hypothesis that elevated ET activity may be associated with reduced coronary flow responses during rapid atrial pacing in CPNA patients.

Abbreviations and Acronyms   CPNA = chest pain with normal coronary arteriogram   CSBF = coronary sinus blood flow   eECG = exercise electrocardiogram   ET = endothelin   %d.CVR = percentage fall in coronary vascular resistance during pacing

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