Effects of Hypercapnia on Myocardial Blood Flow in Healthy Human Subjects.

Abstract

Elevation of the end-tidal partial pressure of CO₂ (P_ETco₂) increases cerebral and myocardial blood flow (MBF), suggesting that it may be a suitable alternative to pharmacologic stress or exercise for myocardial perfusion imaging. The purpose of this study was to document the pharmacodynamics of CO₂ for MBF using prospective end-tidal targeting to precisely control arterial Pco₂ and PET to measure the outcome variable, MBF. <b>Methods:</b> Ten healthy men underwent serial ⁸²Rb PET/CT imaging. Imaging was performed at rest and during 6-min hypercapnic plateaus (baseline; P_ETco₂ at 50, 55, and 60 mm Hg; repeat of P_ETco₂ at 60 mm Hg; and repeat of baseline). MBF was measured using ⁸²Rb injected 3 min after the beginning of hypercapnia and a 1-tissue-compartment model with flow-dependent extraction correction. Results were compared with those obtained during an adenosine stress test (140 μg/kg/min). <b>Results:</b> Baseline P_ETco₂ was 38.9 ± 0.8 (mean ± SD) mm Hg (range, 35-43 mm Hg). All P_ETco₂ targets were sustained, with SDs of less than 1.5 mm Hg. Heart rate, systolic blood pressure, rate × pressure product, and respiratory frequency increased with progressive hypercapnia. MBF increased significantly at each level of hypercapnia to 1.92-fold over baseline (0.86 ± 0.24 vs. 0.45 ± 0.08 mL/min/g; <i>P</i> = 0.002) at a P_ETco₂ of 60 mm Hg. MBF after the administration of adenosine was significantly greater than that with the maximal hypercapnic stimulus (2.00 vs. 0.86 mL/min/g; <i>P</i> < 0.0001). <b>Conclusion:</b> To our knowledge, this study is the first to assess the response of MBF to different levels of hypercapnia in healthy humans with PET. MBF increased with increasing levels of hypercapnia; MBF at a P_ETco₂ of 60 mm Hg was double that at baseline.