Optimization of Absolute Coronary Blood Flow Measurements to Assess Microvascular Function: In Vivo Validation of Hyperemia and Higher Infusion Speeds

Lennert Minten; Johan Bennett; Keir McCutcheon; Wouter Oosterlinck; Michiel Algoet; Hisao Otsuki; Kuniaki Takahashi; William F Fearon; Christophe Dubois

doi:10.1161/CIRCINTERVENTIONS.123.013860

Optimization of Absolute Coronary Blood Flow Measurements to Assess Microvascular Function: In Vivo Validation of Hyperemia and Higher Infusion Speeds

Circ Cardiovasc Interv. 2024 Apr 29:e013860. doi: 10.1161/CIRCINTERVENTIONS.123.013860. Online ahead of print.

Authors

Lennert Minten^{1

2}, Johan Bennett^{1

3}, Keir McCutcheon¹, Wouter Oosterlinck^{1

4}, Michiel Algoet^{1

4}, Hisao Otsuki², Kuniaki Takahashi², William F Fearon^{2

5}, Christophe Dubois^{1

3}

Affiliations

¹ Department of Cardiovascular Sciences, Katholieke Universiteit Leuven, Belgium (L.M., J.B., K.M.C., W.O., M.A., C.D.).
² Division of Cardiovascular Medicine, Stanford University, CA (L.M., H.O., K.T., W.F.F.).
³ Departments of Cardiovascular Medicine, UZ Leuven, Belgium. (J.B., C.D.).
⁴ Cardiac Surgery, UZ Leuven, Belgium. (W.O., M.A.).
⁵ VA Palo Alto Health Care System, CA (W.F.F.).

PMID: 38682331
DOI: 10.1161/CIRCINTERVENTIONS.123.013860

Abstract

Background: Reliable assessment of coronary microvascular function is essential. Techniques to measure absolute coronary blood flow are promising but need validation. The objectives of this study were: first, to validate the potential of saline infusion to generate maximum hyperemia in vivo. Second, to validate absolute coronary blood flow measured with continuous coronary thermodilution at high (40-50 mL/min) infusion speeds and asses its safety.

Methods: Fourteen closed-chest sheep underwent absolute coronary blood flow measurements with increasing saline infusion speeds at different dosages under general anesthesia. An additional 7 open-chest sheep underwent these measurements with epicardial Doppler flow probes. Coronary flows were compared with reactive hyperemia after 45 s of coronary occlusion.

Results: Twenty milliliters per minute of saline infusion induced a significantly lower hyperemic coronary flow (140 versus 191 mL/min; P=0.0165), lower coronary flow reserve (1.82 versus 3.21; P≤0.0001), and higher coronary resistance (655 versus 422 woods units; P=0.0053) than coronary occlusion. On the other hand, 30 mL/min of saline infusion resulted in hyperemic coronary flow (196 versus 192 mL/min; P=0.8292), coronary flow reserve (2.77 versus 3.21; P=0.1107), and coronary resistance (415 versus 422 woods units; P=0.9181) that were not different from coronary occlusion. Hyperemic coronary flow was 40.7% with 5 mL/min, 40.8% with 10 mL/min, 73.1% with 20 mL/min, 102.3% with 30 mL/min, 99.0% with 40 mL/min, and 98.0% with 50 mL/min of saline infusion when compared with postocclusive hyperemic flow. There was a significant bias toward flow overestimation (Bland-Altman: bias±SD, -73.09±30.52; 95% limits of agreement, -132.9 to -13.27) with 40 to 50 mL/min of saline. Occasionally, ischemic changes resulted in ventricular fibrillation (9.5% with 50 mL/min) at higher infusion rates.

Conclusions: Continuous saline infusion of 30 mL/min but not 20 mL/min induced maximal hyperemia. Absolute coronary blood flow measured with saline infusion speeds of 40 to 50 mL/min was not accurate and not safe.

Keywords: adenosine; blood pressure; cardiovascular physiological phenomena; coronary circulation; coronary vessels; microcirculation; thermodilution.