Hypoperfusion - evoked compensatory vasodilation R 2 1 Individual susceptibility to hypoperfusion and reductions in exercise performance 1 when perfusion pressure is reduced : evidence for vasodilator phenotypes 2

26 The primary objective of this study was to determine whether cardiovascular 27 compensatory response phenotypes exist in the face of a reduced perfusion pressure 28 challenge to exercising muscle oxygen delivery (O2D), and whether these responses might 29 be exercise intensity (EI) dependent. Ten healthy male subjects (19.5±0.4 years) completed 30 two trials of progressive forearm isometric handgrip exercise to exhaustion (24.5 N 31 increments every 3.5 minutes) in each of forearm above and below heart level (forearm 32 arterial perfusion pressure (FAPP) difference of 29.5±0.97 mmHg). Forearm blood flow 33 (FBF (ml/min); brachial artery Doppler and echo ultrasound), mean arterial blood pressure 34 (MAP (mmHg); finger photoplethysmography), and exercising forearm venous effluent 35 (ante-cubital vein catheter) measurements at the end of each EI revealed distinct 36 cardiovascular response groups: n=6 with compensatory vasodilation vs. n=4 without 37 compensatory vasodilation. Compensatory vasodilators were able to blunt the perfusion 38 pressure-evoked reduction in submaximal O2D in the arm above heart condition whereas 39 non-vasodilators did not (-22.5±13.6 vs. -65.4±14.1 ml O2/min, P<0.05) and, in 40 combination with being able to increase O2 extraction, defended submaximal VO2 and 41 experienced less of an accumulated submaximal O2D deficit (-80.7±24.7 vs. -219.1±36.0 42 ml O2/min, P<0.05). As a result, the compensatory vasodilators experienced less of a 43 compromise to peak EI than non-vasodilators (-24.5±3.5 N vs. -52.1±8.9 N, P<0.05). In 44 conclusion, in the forearm exercise model studied, vasodilatory response phenotypes exist 45 which determine individual susceptibility to hypoperfusion and the degree to which aerobic 46 metabolism and exercise performance are compromised. 47