Format

Send to

Choose Destination
Circulation. 2017 Jul 4;136(1):24-34. doi: 10.1161/CIRCULATIONAHA.116.025856. Epub 2017 May 3.

Physiology of Angina and Its Alleviation With Nitroglycerin: Insights From Invasive Catheter Laboratory Measurements During Exercise.

Author information

1
From King's College London British Heart Foundation Centre of Excellence, Rayne Institute, St. Thomas' Hospital, London, United Kingdom (K.N.A., R.W., T.L., M.Z.K., K.D.S., M.L., T.P., S.A., H.E., D.P., M.S.M., S.R.R.); National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom (K.N.A., M.S.M., S.R.R.); Department of Cardiology, Royal North Shore Hospital, Sydney, Australia (K.N.A., K.D.S.); Kolling Institute, Northern Clinical School, University of Sydney, Australia (K.N.A.); Department of Clinical Pharmacology (A.G., P.J.C.) and Division of Imaging Sciences and Biomedical Engineering, Rayne Institute (S.I., S.P.), St Thomas' Hospital, King's College London, London, United Kingdom; Guy's and St Thomas' Hospital NHS Foundation Trust, London, United Kingdom (B.C.); and Division of Cardiovascular and Neuronal Remodelling, University of Leeds, United Kingdom (S.P.). kaleab.asrress@sydney.edu.au.
2
From King's College London British Heart Foundation Centre of Excellence, Rayne Institute, St. Thomas' Hospital, London, United Kingdom (K.N.A., R.W., T.L., M.Z.K., K.D.S., M.L., T.P., S.A., H.E., D.P., M.S.M., S.R.R.); National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom (K.N.A., M.S.M., S.R.R.); Department of Cardiology, Royal North Shore Hospital, Sydney, Australia (K.N.A., K.D.S.); Kolling Institute, Northern Clinical School, University of Sydney, Australia (K.N.A.); Department of Clinical Pharmacology (A.G., P.J.C.) and Division of Imaging Sciences and Biomedical Engineering, Rayne Institute (S.I., S.P.), St Thomas' Hospital, King's College London, London, United Kingdom; Guy's and St Thomas' Hospital NHS Foundation Trust, London, United Kingdom (B.C.); and Division of Cardiovascular and Neuronal Remodelling, University of Leeds, United Kingdom (S.P.).

Abstract

BACKGROUND:

The mechanisms governing exercise-induced angina and its alleviation by the most commonly used antianginal drug, nitroglycerin, are incompletely understood. The purpose of this study was to develop a method by which the effects of antianginal drugs could be evaluated invasively during physiological exercise to gain further understanding of the clinical impact of angina and nitroglycerin.

METHODS:

Forty patients (mean age, 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterization via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual nitroglycerin was administered to half the patients, and all patients continued to exercise for 2 minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity and central aortic pressure were recorded with sensor wires.

RESULTS:

Patients continued to exercise after nitroglycerin administration with less ST-segment depression (P=0.003) and therefore myocardial ischemia. Significant reductions in afterload (aortic pressure, P=0.030) and myocardial oxygen demand were seen (tension-time index, P=0.024; rate-pressure product, P=0.046), as well as an increase in myocardial oxygen supply (Buckberg index, P=0.017). Exercise reduced peripheral arterial wave reflection (P<0.05), which was not further augmented by the administration of nitroglycerin (P=0.648). The observed increases in coronary pressure gradient, stenosis resistance, and flow velocity did not reach statistical significance; however, the diastolic velocity-pressure gradient relation was consistent with a significant increase in relative stenosis severity (k coefficient, P<0.0001), in keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilatation of normal segments, with trends toward reversal with nitroglycerin.

CONCLUSIONS:

The catheterization laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established antianginal drugs. Administration of nitroglycerin causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and to increase supply, thereby attenuating exercise-induced ischemia. Designing antianginal therapies that exploit these mechanisms may provide new therapeutic strategies.

KEYWORDS:

angina pectoris; coronary circulation; exercise; myocardial ischemia; nitroglycerin; physiology

PMID:
28468975
PMCID:
PMC5491223
DOI:
10.1161/CIRCULATIONAHA.116.025856
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center