Synergistic Adaptations to Exercise in the Systemic and Coronary Circulations That Underlie the Warm-Up Angina Phenomenon

Abstract

Background-The mechanisms of reduced angina on second exertion in patients with coronary arterial disease, also known as the warm-up angina phenomenon, are poorly understood. Adaptations within the coronary and systemic circulations have been suggested but never demonstrated in vivo. In this study we measured central and coronary hemodynamics during serial exercise. Methods and Results-Sixteen patients (15 male, 61Ϯ4.3 years) with a positive exercise ECG and exertional angina completed the protocol. During cardiac catheterization via radial access, they performed 2 consecutive exertions (Ex1, Ex2) using a supine cycle ergometer. Throughout exertions, distal coronary pressure and flow velocity were recorded in the culprit vessel using a dual sensor wire while central aortic pressure was recorded using a second wire. Patients achieved a similar workload in Ex2 but with less ischemia than in Ex1 (PϽ0.01). A 33% decline in aortic pressure augmentation in Ex2 (PϽ0.0001) coincided with a reduction in tension time index, a major determinant of left ventricular afterload (PϽ0.001). Coronary stenosis resistance was unchanged. A sustained reduction in coronary microvascular resistance resulted in augmented coronary flow velocity on second exertion (both PϽ0.001). These changes were accompanied by a 21% increase in the energy of the early diastolic coronary backward-traveling expansion, or suction, wave on second exercise (PϽ0.05), indicating improved microvascular conductance and enhanced left ventricular relaxation. Conclusions-On repeat exercise in patients with effort angina, synergistic changes in the systemic and coronary circulations combine to improve vascular-ventricular coupling and enhance myocardial perfusion, thereby potentially contributing to the warm-up angina phenomenon. (Circulation. 2012;126:2565-2574.)

Deleterious Effects of Cold Air Inhalation on Coronary Physiological Indices in Patients With Obstructive Coronary Artery Disease

“…Despite increased myocardial oxygen demand and reduced diastolic time fraction,17 ischemia is minimized because of parallel adaptive reductions in afterload and MVR of 50% and 30%, respectively. The acute reduction in afterload enables a relatively efficient ejection time that is associated with enhanced ventricular relaxation,26 and in our study was evidenced by the 200% increase in the backward expansion wave.…”

“…Doctors should inform patients with obstructive coronary stenoses about the following: (1) to avoid sudden vigorous exertion, as asymptomatic ischemia can manifest before angina occurs; (2) to avoid exertion in cold air where possible, or at least to wrap up warmly (ideally involving coverage of the cheeks, mouth, and forehead); (3) that their exercise tolerance may be less in cold air; (4) indoor warm‐up exercise before exertion in cold air might attenuate these deleterious effects (by augmenting the reduction in MVR and increase in backward expansion wave intensity during the second period of exertion17). In addition, angiotensin‐converting enzyme inhibitors may attenuate coronary sympathetic vasoconstriction of resistance vessels,42 and glyceryl trinitrate may enhance diastolic ventricular relaxation,43 which may significantly reduce ischemia burden and possibly mortality with cold air 44…”

“…An adapted supine ergometer (Ergosana, Schiller, Germany) was attached to the cardiac catheterization laboratory table 17. Exercise started at 50 W, with 20‐W increments every minute.…”

“…Exercise in room temperature was used as our control. The exercise periods were performed in randomized order to minimize potential warm‐up effects of prior exercise 17. There was a minimum of 15 minutes rest between exercise periods to allow hemodynamics to return to baseline.…”

“…Aortic pulse wave analysis (from central arterial pressure waveforms): Augmentation index (a central measure of afterload), rate pressure product (a measure of myocardial oxygen consumption),17 and diastolic time fraction were calculated as previously described 17…”