With climate change, fish are facing rising temperatures, an increase in the frequency and severity of heat waves and hypoxia, sometimes concurrently. However, only limited studies have examined the combined effects of increases in temperature and hypoxia on fish physiology and survival. We measured the cardiorespiratory physiology of 12°C-acclimated Atlantic salmon when exposed acutely to normoxia [100% air saturation (sat.)] versus 75 and 50% air sat., and then warmed to their critical thermal maximum (CTmax) at 2°C h-1. Fish exposed to 50% air sat. became bradycardic, were unable to increase heart rate (fH) when warmed, and had lower values for metabolic scope and CTmax (21.3 vs 26.1°C in normoxic fish). The effects of 75% air sat. on cardiorespiratory parameters and CTmax were intermediate. We then used atropine (1.2 mg kg-1) and 8-cyclopentyltheophylline (CPT
50 nmol kg-1) to investigate what role(s) cholinergic tone on the heart and cardiac adenosinergic effects, respectively, play in preventing severely hypoxic salmon (40% air sat.) from increasing fH when warmed. CPT had no/limited effects on salmon cardiorespiratory parameters and thermal tolerance. However, atropine increased fH in hypoxic fish and allowed it to rise with temperature, and this resulted in salmon that were much less tolerant to warming. Collectively, these results: (1) show that fish in severely hypoxic environments will be very susceptible to climate change-associated heat waves
and (2) suggest that cholinergic tone on the heart is not removed when severely hypoxic fish are exposed to rising temperatures to protect the heart's pumping capacity.