Physiology of Angina and its Alleviation with Nitroglycerine- Insights from Invasive Catheter Laboratory Measurements During Exercise
Background—The mechanisms governing exercise-induced angina and its alleviation by the most commonly used anti-anginal drug, nitroglycerine (GTN), are incompletely understood. The purpose of this study was to develop a method with which the effects of anti-anginal drugs could be evaluated invasively during physiological exercise to gain further understanding as to the clinical impact of angina and GTN.
Methods—40 Patients (mean 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterisation via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual GTN was administered to half the patients and all patients continued to exercise for two minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity, and central aortic pressure were recorded using sensor wires.
Results—Patients continued to exercise post-GTN 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 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 GTN (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 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 towards reversal with GTN.
Conclusions—The catheter laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established anti-anginal drugs. Administration of GTN causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and increase supply, thereby attenuating exercise induced ischemia. Designing anti-anginal therapies that exploit these mechanisms may provide new therapeutic strategies.
- Received October 9, 2016.
- Revision received April 19, 2017.
- Accepted April 26, 2017.