Hypothermia reduces ischemia- and stimulation-induced myocardial interstitial norepinephrine and acetylcholine releases

Abstract

though hypothermia is one of the most powerful modulators that can reduce ischemic injury, the effects of hypothermia on the function of the cardiac autonomic nerves in vivo are not well understood. We examined the effects of hypothermia on the myocardial interstitial norepinephrine (NE) and ACh releases in response to acute myocardial ischemia and to efferent sympathetic or vagal nerve stimulation in anesthetized cats. We induced acute myocardial ischemia by coronary artery occlusion. Compared with normothermia (n ϭ 8), hypothermia at 33°C (n ϭ 6) suppressed the ischemia-induced NE release [63 nM (SD 39) vs. 18 nM (SD 25), P Ͻ 0.01] and ACh release [11.6 nM (SD 7.6) vs. 2.4 nM (SD 1.3), P Ͻ 0.01] in the ischemic region. Under hypothermia, the coronary occlusion increased the ACh level from 0.67 nM (SD 0.44) to 6.0 nM (SD 6.0) (P Ͻ 0.05) and decreased the NE level from 0.63 nM (SD 0.19) to 0.40 nM (SD 0.25) (P Ͻ 0.05) in the nonischemic region. Hypothermia attenuated the nerve stimulation-induced NE release from 1.05 nM (SD 0.85) to 0.73 nM (SD 0.73) (P Ͻ 0.05, n ϭ 6) and ACh release from 10.2 nM (SD 5.1) to 7.1 nM (SD 3.4) (P Ͻ 0.05, n ϭ 5). In conclusion, hypothermia attenuated the ischemia-induced NE and ACh releases in the ischemic region. Moreover, hypothermia also attenuated the nerve stimulationinduced NE and ACh releases. The Bezold-Jarisch reflex evoked by the left anterior descending coronary artery occlusion, however, did not appear to be affected under hypothermia. vagal nerve; sympathetic nerve; cardiac microdialysis; cats HYPOTHERMIA IS ONE OF THE most powerful modulators that can reduce ischemic injury in the central nervous system, heart, and other organs. The general consensus is that hypothermia induces a hypometabolic state in tissues and balances energy supply and demand (25). With respect to the myocardial ischemia, the size of a myocardial infarction correlates with temperature (6), and mild hypothermia can protect the myocardium against acute ischemic injury (9). The effects of hypothermia on the function of the cardiac autonomic nerves in terms of neurotransmitter releases, however, are not fully understood. Because autonomic neurotransmitters such as norepinephrine (NE) and ACh directly impinge on the myocardium, they would be implicated in the cardioprotection by hypothermia.In previous studies from our laboratory, Kitagawa et al. (16) demonstrated that hypothermia attenuated the nonexocytotic NE release induced pharmacologically by ouabain, tyramine, or cyanide. Kitagawa et al. (15) also demonstrated that hypothermia attenuated the exocytotic NE release in response to vena cava occlusion or to local administration of high K ϩ . The effects of hypothermia on the ischemia-induced myocardial interstitial NE release, however, were not examined in those studies. In addition, the effects of hypothermia on the ischemia-induced myocardial interstitial ACh release have never been examined. Because both sympathetic and parasympathetic nerves control the heart, simultaneous monitoring of the m...

Characterization of blood pressure and endothelial function in TRPV4-deficient mice with l -NAME- and angiotensin II-induced hypertension

“…We next determined the main vasodilator factor(s) (NO vs. EDHFs) that are affected by Ang II infusion. In U46619preconstricted mesenteric arteries from untreated WT mice, L-NAME markedly inhibited ACh-induced dilation, an effect that was more pronounced at lower (probably more physiological) concentrations of ACh (Kawada et al 1985;Shinoe et al 2005) (dilation at 10 À7 mol/L, 11 AE 4% vs. 41 AE 6% in controls, n = 5, P < 0.05; Fig. 4A), confirming previous results that NO is a major vasodilator factor in this isolated vessel preparation (Chataigneau et al 1999;Zhang et al 2009).…”

“…In U46619‐preconstricted mesenteric arteries from untreated WT mice, l ‐NAME markedly inhibited ACh‐induced dilation, an effect that was more pronounced at lower (probably more physiological) concentrations of ACh (Kawada et al. ; Shinoe et al. ) (dilation at 10 −7 mol/L, 11 ± 4% vs. 41 ± 6% in controls, n = 5, P < 0.05; Fig.…”

“…Accumulating evidence suggests that transient receptor potential (TRP) vanilloid 4 (V4), a member of the TRP superfamily, is an endothelial Ca 2+ entry channel involved in NO-and/or EDH-mediated vasodilation in response to flow and receptor agonists in several rodent conduit and resistant arteries (K€ ohler et al 2006;Hartmannsgruber et al 2007;Loot et al 2008;Earley et al 2009;Zhang et al 2009;Mendoza et al 2010;Adapala et al 2011;Rath et al 2012;Sonkusare et al 2012;Ma et al 2013). TRPV4 channels are also expressed in endothelial cells of human coronary arterioles (HCAs) and contribute to flow-induced dilation of coronary arterioles from subjects with coronary artery disease (CAD) (Bubolz et al 2012;Zheng et al 2013).…”

“…This study was designed to further explore the role of TRPV4 in the regulation of blood pressure using conscious TRPV4 À/À mice given two different hypertensive challenges, including N G -nitro-L-arginine methyl ester (L-NAME), a NO synthase (NOS) inhibitor, and angiotensin (Ang) II (Ribeiro et al 1992;Rajagopalan et al 1996;Mattson 1998;Jung et al 2003). There is evidence that TRPV4 is more closely linked to EDHF-mediated dilation in small resistance arteries (K€ ohler et al 2006;Earley et al 2009;Zhang et al 2009;Mendoza et al 2010;Rath et al 2012;Sonkusare et al 2012), and that EDHF may serve as a compensatory mechanism for impaired NO-mediated dilation in the presence of cardiovascular diseases or risk factors (F el etou and Vanhoutte 2004). As Ang II reduces vascular NO bioavailability and impairs endothelium-dependent dilation via a ROS-mediated mechanism and this endothelial dysfunction has been implicated in various vascular diseases (Rajagopalan et al 1996;Touyz and Schiffrin 2000;Jung et al 2003;Garrido and Griendling 2009), we also examined the potential role of TRPV4 in Ang II-induced impairment of endotheliummediated dilation.…”

Therapeutic hypothermia and controlled normothermia in the intensive care unit: Practical considerations, side effects, and cooling methods*

“…Conflicting observations have been reported from studies in children undergoing cardiac surgical procedures; one study reported increased catecholamine levels when patients were cooled to 26°C (172); however, another study reported no significant changes in catecolamine levels during surface cooling to 28°C, nor during circulatory arrest and cooling until 18°C (173). In addition, some animal studies suggest that hypothermia reduces ischemiainduced catecholamine release from hypoperfused tissues, while catecholamine secretion from noninjured tissues may increase (174). Thus, catecholamine levels may increase during mild-to-moderate hypothermia, but this phenomenon may be linked to a shivering/stress response and to rewarming rather than to hypothermia per se.…”