Abstract
We have previously reported that the negative inotropic effects of hyperthermia (42 °C) on left ventricular (LV) mechanoenergetics using the excised, cross-circulated rat heart model. Here, we investigated the role of TRPV1 on LV mechanoenergetics in hyperthermia. We analyzed the LV end-systolic pressure–volume relation (ESPVR) and the linear relation between the myocardial oxygen consumption per beat (VO2) and the systolic pressure–volume area (PVA; a total mechanical energy per beat) during infusion of capsazepine (CPZ) in hyperthermia, or capsaicin (Cap) under 300 bpm pacing. LV ESP decreased in each LV volume and the resultant downward-shift of LV ESPVR was suppressed by CPZ infusion in hyperthermia-hearts. In Cap-treated hearts, LV ESPVR shifted downward from the control ESPVR, similar to hyperthermia-hearts. The slopes of VO2–PVA relationship were unchanged. The VO2 intercepts in hyperthermia-hearts did not decrease because of decreased E–C coupling VO2, and inversely increased basal metabolic VO2, which was suppressed by CPZ, though the VO2 intercepts in Cap-treated hearts significantly decreased. The levels of phosphorylated phospholamban at serine 16 decreased significantly in hyperthermia-hearts, as well as Cap-treated hearts. These results indicate that a Cap-induced decrease in the LV contractility, like in cases of hyperthermia, are due to the down-regulation of the total calcium handling in E–C coupling, suggesting that negative inotropic effect in hyperthermia-heart is, at least in part, mediated through TRPV1 signaling pathway.
Highlights
Myocardial temperature sensitivity affects cardiac contractility following energy metabolism
We investigated the role of Transient receptor potential vanilloid 1 (TRPV1) in hyperthermia by treatment with CPZ or Cap on left ventricular (LV) myocardial mechanoenergetics using the excised, crosscirculated rat heart model to reveal whether TRPV1 acts as molecular micro-thermometers in cardiomyocytes
Inhibition of hyperthermia‐induced negative inotropic effect by CPZ We previously reported that LV end-systolic pressure (ESP) decreased and LV end-systolic pressure–volume relation (ESPVR) shifted downward in hyperthermia conditions at 42 °C [5]
Summary
Myocardial temperature sensitivity affects cardiac contractility following energy metabolism. The cardiac Troponin I is frequently elevated in patients with heat-related illnesses during a heat wave, which indicates myocardial damage [1]. Others studies, including our own, have previously reported that elevated cardiac temperature decreases left ventricular (LV) contractility and energy consumption, mechanoenergetics, in cardiac muscle strip and hearts isolated from rats, rabbits, or dogs [2,3,4,5,6]. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel that may be activated by a wide variety of exogenous and endogenous physical and chemical stimuli, such as pH, capsaicin (Cap), or temperatures above 43 °C (109 °F). Cap-sensitive sensory nerves are widely distributed in the cardiovascular
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