Obstructive sleep apnea leads to transient uncoupling of coronary blood flow and myocardial work in humans

Abstract

Study objectives: Obstructive Sleep Apnea (OSA) is associated with a poor prognosis in patients with coronary artery disease. We hypothesized that abnormalities of coronary blood flow (CBF) associated with obstructive apneas may predispose patients to ischemia. We aimed to determine CBF during respiratory events in patients with OSA.

Setting: University Hospital.

Patients: Ten subjects undergoing elective percutaneous coronary intervention

Design: We measured CBF and myocardial work (rate-pressure product [RPP]) in a non-culprit coronary artery in patients sleeping in the cardiac catheterization laboratory. Hemodynamic responses were matched to spontaneously occurring respiratory events.

Measurements and results: Events comprised a mixture of obstructive apneas, central apneas and hypopneas. RPP increased at the termination of each type of respiratory event. Following the rise in RPP, there was a delay, identified with breakpoint analysis, before CBF began to increase (P<0.001) that differed in duration with event type: 8 sec for obstructive apnea, 5 sec for central apnea, and 4 sec for hypopnea. The delay in CBF with obstructive apnea was associated with an increase in coronary vascular resistance of 16% +/- 4% (P < 0.05). Stepwise multilinear regression analysis showed the increase in CBF was predicted by the rise in RPP (R=0.52, P<0.001) and presence of arousal from sleep (R=0.30, P<0.05), but not the degree of O2 desaturation.

Conclusion: Following obstructive apneas there is a transient uncoupling of CBF from myocardial work and an increase in CVR. This disturbed flow-metabolic coupling may lead to nocturnal myocardial ischemia in patients with both OSA and coronary artery disease.

Figure 1

Change in CBF and RPP from 15 sec before to 15 sec after the end of OA, CA, and HP. Data represent mean ± SEM for pooled results of 5 patients with OA, 5 patients with CA, and 6 patients with HP. Note the dissociation between CBF and RPP with obstructive apnea.

Figure 2

Bilinear regression curves demonstrating the relationship between CBF and RPP. Data represent mean values for pooled results of 5 patients with OA, 5 patients with CA, and 6 patients with HP. For OA, the increase in CBF follows the increase in RPP with a delay of 8 sec, then the slope of rise is more steep (P < 0.001 for difference of intercept, slope, and coincidence). For CA and HP, the increase in CBF follows the increase in RPP with a delay of 5 and 4 sec, respectively, then increases at the same rate. (P < 0.001 for difference in intercept and coincidence. P = NS for difference of slope.)

Figure 3

Change in CVR from 15 sec before to 15 sec after the end of OA, CA, and HP. Data represents mean ± SEM for pooled results of 5 patients with OA, 5 patients with CA, and 6 patients with HP. With OA, CVR increases post apnea, peaking 16% ± 4% above baseline 3 sec following the end of the apnea (* P < 0.05). There is no significant increase in CVR with CAs or HPs.

Figure 4

Illustrative clinical recordings from a single patient for (A) obstructive apnea and (B) central apnea. The average and instant peak velocity represents the coronary blood flow. Following obstructive apnea (A) note the delay (~ 10 sec) between the termination of the obstructive apnea event (1) and the peak coronary blood flow response (2). Note the lesser delay (~ 4 sec) after termination of central apnea (B).