Effects of Hypercapnia on Myocardial Blood Flow in Healthy Human Subjects

Abstract Background: Elevation of end-tidal partial pressure of CO2 (PETCO2) increases cerebral and myocardial blood flow (MBF), suggesting that it may be a suitable alternative to pharmacological stress or exercise for myocardial perfusion imaging. The purpose of this study was to document the pharmacodynamics of CO2 on MBF using prospective end-tidal targeting to precisely control arterial PCO2 and use positron emission tomography (PET) to measure the outcome variable, MBF Methods: 10 healthy males underwent serial (82)Rb PET/CT imaging. Imaging was performed at rest, and under 6 min hypercapnic plateaus (PETCO2=baseline, 50, 55, 60, and repeated 60 mmHg, baseline). MBF was measured using (82)Rb injected 3 min after the beginning of hypercapnia, using a one-tissue-compartment model with flow-dependent extraction correction. Results were compared to those during an adenosine stress test (140 μg/kg/min) Results: Baseline PETCO2 was 38.9±0.8 (standard deviation, SD) mmHg (range 35 to 43 mmHg). All PETCO2 targets were sustained with SD<1.5 mmHg. Heart rate, systolic blood pressure, rate pressure product (RPP), and respiratory frequency (f) increased with progressive hypercapnia. MBF increased significantly at each level of hypercapnia to 1.92 fold above baseline (0.86±0.24 vs 0.45±0.08 mL/min/g, P = 0.002) at PETCO2 of 60 mmHg. MBF following administration of adenosine was significantly greater than that during maximal hypercapnic stimuli (2.00 vs 0.86 mL/min/g, p<0.0001). Conclusion: This is the first study to assess the response of MBF to different levels of hypercapnia in healthy humans with PET. MBF increases with increasing level of hypercapnia; at PETCO2 60 mmHg, MBF doubled compared to baseline.