Depression of heart rate in fish at critically high temperatures is due to atrioventricular block

Abstract

29At critically high temperature, cardiac output in fish collapses due to depression of heart rate 30 (bradycardia). However, the cause of bradycardia remains unresolved. Here we provide a 31 mechanistic explanation for the temperature induced bradycardia. To this end rainbow trout 32 (Oncorhynchus mykiss; acclimated at +12°C) were exposed to acute warming, while cardiac 33 function was followed from electrocardiograms. From +12℃ to +25.3℃, electrical excitation 34 between different parts of the heart was coordinated but above +25.3℃ atrial and ventricular 35 beating rates became partly dissociated due to 2:1 atrioventricular (AV) block. With further 36 warming atrial rate increased to the peak value of 188 ± 22 bpm at +27℃, while the rate of the 37 ventricle reached the peak value of 124 ± 10 bpm at +25.3 ℃ and thereafter dropped to 111 ± 38 15 bpm at +27℃. In single ventricular myocytes, warming from +12°C to +25°C attenuated 39 electrical excitability as evidenced by increases in rheobase current and critical depolarization 40 required to trigger action potential. The depression of excitability was caused by temperature 41 induced decrease in input resistance (sarcolemmal K + leak via the outward IK1 current) of 42 resting myocytes and decrease in inward charge transfer by the Na + current (INa) of active 43 myocytes. Collectively these findings show that at critically high temperatures AV block causes 44 ventricular bradycardia which is an outcome from the increased excitation threshold of the 45 ventricle due to changes in passive (resting ion leak) and active (inward charge movement) 46 electrical properties of ventricular myocytes. The sequence of events from the level of ion 47 channels to the cardiac function in vivo provides a mechanistic explanation for the depression 48 of cardiac output in fish at critically high temperature. 49 50 rheobase 52 53 List of abbreviations:54 55 AP Action potential 56 APD50 Action potential duration at 50% of repolarization 57 CD Critical depolarization 58 Cm Membrane capacitance 59 ECG Electrocardiogram 60 EE Electrical excitability 61 fH Heart rate 62 fHA Beating rate of atrium 63 fHV Beating rate of ventricle 64 Ith Threshold current 65 Rin Input resistance 66 3 TBP Breakpoint temperature 67 Vth Threshold potential 68 Vrest Resting membrane potential 69 70 71 72 73 Physical performance of fish is dependent on the oxygen supply to the tissues, which is largely 74 determined by the quantity of blood delivered to them. The volume of blood circulated through 75 the body in a unit of time is cardiac output which is the product of heart rate (fH), or the number 76 of heart beats per minute, and stroke volume, or the volume of blood pumped by the ventricle 77 in one contraction. In fish, acute warming initially increases cardiac output but at temperatures 78 slightly below the critical thermal maximum of the animal cardiac output first plateaus and then 79 sharply collapses (Stevens et al., 1972). The temperature induced collapse of cardiac output is 80 caused by depressio...

Adrenergic tone benefits cardiac performance and warming tolerance in two teleost fishes that lack a coronary circulation

“…This suggests that adrenergic stimulation has a beneficial and potentially protective influence on in vivo heart function during acute warming, which was also shown by Gilbert and co-workers in rainbow trout (2019). Moreover, as suggested by these authors (2019), adrenergic stimulation may rectify the imbalances in ion (Na + and K + ) flux rate dynamics which underlie the failure of myocardial action potential conduction and cardiac excitability, thus preventing AV block and/or arrhythmias which are associated with the declining heart rate at high temperatures (Aho and Vornanen 2001 ; Vornanen 2017 ; Haverinen and Vornanen 2020 ). Indeed, the higher prevalence of arrhythmias after β-adrenergic blockade in both species observed here may reflect an accentuation of AV block at higher temperatures, which warrants further exploration.…”

“…This is consistent with our previous observation in adult rainbow trout (Ekström et al 2014 , 2019 ), but contrasts with observations in juvenile trout where atropine reduced CT max and the temperature at which heart rate peaked (Gilbert et al 2019 ). Gilbert and colleagues (2019) speculated that cholinergic slowing of action potential generation in the cardiac pacemaker may serve to synchronize the pacemaker rate with the functional depolarisation rate of the ventricle, thus avoiding the AV block that may occur at higher temperatures (Haverinen and Vornanen 2020 ). However, we found no indications (0% occurrence) of AV block following cholinergic blockade in either species.…”

“…Acute warming typically results in elevated heart rate and cardiac output, but at temperatures approaching the upper thermal tolerance limit (here defined by the critical thermal maximum, CT max , in turn defined as the temperature at which the animal loses equilibrium (Beitinger et al 2000)), a plateau and subsequent reduction in heart rate and cardiac output is often observed (Ekström et al 2014;Ekström et al 2016a;Heath and Hughes 1973;Hughes and Roberts 1970;Gollock et al 2006). This decline in heart rate has been interpreted as cardiac failure in fish approaching CT max , and likely has multiple underlying reasons (see Eliason and Anttila 2017;Ekström et al 2016a;Iftikar and Hickey 2013;Haverinen and Vornanen 2020;Vornanen 2020). First, the venous oxygen tension declines as temperature rises (i.e., venous hypoxemia), which results in a reduced partial pressure gradient for oxygen diffusion into the spongy myocardium.…”

“…Second, the increase in heart rate with rising temperatures may constrain luminal oxygenation further by reducing the time for oxygen diffusion as diastole shortens, along with increased myocardial diffusion distances as end-diastolic filling and distension decline (see Eliason and Anttila 2017). Finally, the specific tendency for heart rate to decline at high temperatures immediately prior to CT max has recently been attributed to compromised ventricular myocardial excitability and action potential conduction capacity causing a functional atrioventricular (AV) block; e.g., as observed in roach (Rutilus rutilus), rainbow trout (Oncorhynchus mykiss) and brown trout (Salmo trutta) (Haverinen and Vornanen 2020;Badr et al 2016;Haverinen et al 2016;Vornanen 2020). The cellular mechanism behind this is an ensuing imbalance of Na + and K + ionic transmembrane flux rate dynamics due to deteriorating ion channel functionality (predominately Na + channels) as temperature increases (Vornanen 2016(Vornanen , 2017(Vornanen , 2020.…”

Responses of aquaculture fish to climate change‐induced extreme temperatures: A review

“…Both acute and chronic thermal changes disrupt cardiac rhythm because of alteration in ionic balance (Vornanen, 2016). For example, higher temperature stress limits reduce cardiac function in Atlantic salmon, Salmo salar (Anttila et al, 2014; Gamperl et al, 2020), sparid, Chrysoblephus laticeps (Skeeles et al, 2020), rainbow trout, Oncorhynchus mykiss (Haverinen & Vornanen, 2020), and decrease blood flow to brain, liver, kidney, and intestine in rainbow trout, O. mykiss (Barron et al, 1987). Low thermal stress also reduces the cardiac performance in largemouth bass, Micropterus salmoides (Cooke et al, 2003), and sculpin, Myoxocephalus scorpius (Filatova, Abramochkin, & Shiels, 2019).…”