Moderate Hypothermia Modifies Coronary Hemodynamics and Endothelium‐Dependent Vasodilation in a Porcine Model of Temperature Management

Abstract

Background Hypothermia has been associated with therapeutic benefits including reduced mortality and better neurologic outcomes in survivors of cardiac arrest. However, undesirable side effects have been reported in patients undergoing coronary interventions. Using a large animal model of temperature management, we aimed to describe how temperature interferes with the coronary vasculature. Methods and Results Coronary hemodynamics and endothelial function were studied in 12 pigs at various core temperatures. Left circumflex coronary artery was challenged with intracoronary nitroglycerin, bradykinin, and adenosine at normothermia (38°C) and mild hypothermia (34°C), followed by either rewarming (38°C; n=6) or moderate hypothermia (Mo HT ; 32°C, n=6). Invasive coronary hemodynamics by Doppler wire revealed a slower coronary blood velocity at 32°C in the Mo HT protocol (normothermia 20.2±11.2 cm/s versus mild hypothermia 18.7±4.3 cm/s versus Mo HT 11.3±5.3 cm/s, P =0.007). Mo HT time point was also associated with high values of hyperemic microvascular resistance (>3 mm Hg/cm per second) (normothermia 2.0±0.6 mm Hg/cm per second versus mild hypothermia 2.0±0.8 mm Hg/cm per second versus Mo HT 3.4±1.6 mm Hg/cm per second, P =0.273). Assessment of coronary vasodilation by quantitative coronary analysis showed increased endothelium‐dependent (bradykinin) vasodilation at 32°C when compared with normothermia (normothermia 6.96% change versus mild hypothermia 9.01% change versus Mo HT 25.42% change, P =0.044). Results from coronary reactivity in vitro were in agreement with angiography data and established that endothelium‐dependent relaxation in Mo HT completely relies on NO production. Conclusions In this porcine model of temperature management, 34°C hypothermia and rewarming (38°C) did not affect coronary hemodynamics or endothelial function. However, 32°C hypothermia altered coronary vasculature physiology by slowing coronary blood flow, increasing microvascular resistance, and exacerbating endothelium‐dependent vasodilatory response.

Early warm compress treatment can promote recanalization of vascular embolisms and reduce tissue necrosis after polymethyl methacrylate injection

“…Therefore, some clinical studies have adopted the method of warm massage during the first 30 min after hyaluronidase injection (the specific temperature is unknown), followed by local cooling with a gauze pad soaked with antibiotic saline solution 22 . Hypothermia slowed the blood flow and increased the resistance of the microvasculature; however, it did not affect the blood reserve capacity and vascular endothelial function 27 . This treatment achieved good therapeutic effects.…”

Therapeutic hypothermia augments the restorative effects of PKC-β and Nox2 inhibition on an in vitro model of human blood–brain barrier

“…Considering that various therapeutic agents such as Rho kinase inhibitor (Gibson et al 2014 ), anti-oxidant compounds (catalase, vitamin C and E) (Allen and Bayraktutan 2009 ), NADPH oxidase inhibitor (Abdullah and Bayraktutan 2014 ), anti-TNF-α (Abdullah et al 2015 ), and calcium inhibitor (Rakkar and Bayraktutan 2016 ) protected BBB integrity and function against ischaemic/reperfusion, hyperglycaemic, or TNF-α injury in our previous studies and those studies utilised similar experimental settings, such positive control was not utilised in the present study. Moreover, given that exposure to therapeutic hypothermia in clinical settings equally affects both damaged and normal cells, we have investigated whether and how hypothermia modulates the parameters studied in the current study in cells maintained under normoglycaemic conditions (Bobi et al 2020 ). However, PKC-β or Nox2 pathways are targeted only in pathological conditions such as hyperglycaemic injury, their effects in physiological settings have not been probed.…”

Bradykinin‐mediated estrogen‐dependent depressor response by direct activation of female‐specific distribution of myelinated Ah‐type baroreceptor neurons in rats

“…Bradykinin (BK), a well‐known inflammatory mediator 21 released from tissue damages, plays a role in renal protection 22 and cardiovascular function as a key substance in the kallikrein‐kinin system (KKS), 23 such as vasodilation and hypotension applied locally 24 or systemically. 25 This depressor response is supported by centrally application of BK directly into the nucleus ambiguous and NTS leading to the bradycardia 26 and hypotension, 27 while the pressor responses is produced by microinjection of BK directly into the paratrigeminal nucleus. 28 Based upon the molecular weight of BK (1.06 KDa), however, it is hard to believe that BK itself can easily pass through the blood‐brain barrier (BBB) 29 and modulate cardiovascular/vagal responses centrally, even though it can significantly increase the permeability of the BBB by activating B 2 R located on endothelial cells of capillary.…”

“…Bradykinin (BK), a well‐known inflammatory mediator 21 released from tissue damages, plays a role in renal protection 22 and cardiovascular function as a key substance in the kallikrein‐kinin system (KKS), 23 such as vasodilation and hypotension applied locally 24 or systemically 25 . This depressor response is supported by centrally application of BK directly into the nucleus ambiguous and NTS leading to the bradycardia 26 and hypotension, 27 while the pressor responses is produced by microinjection of BK directly into the paratrigeminal nucleus 28 .…”