Effects Of Systemic Hypothermia Research Articles

Effect of Systemic Hypothermia on Reactions of Pial Arteries to Acute Massive Blood Loss in Anesthetized Rats

Effect of Systemic Hypothermia on Reactions of Pial Arteries to Acute Massive Blood Loss in Anesthetized Rats

Effectiveness of Antiplatelet Drugs Under Therapeutic Hypothermia: A Comprehensive Review.

Out-of-hospital cardiac arrest is among the most frequent causes of death worldwide. Immediate intervention, as well as dual antiplatelet therapy consisting of acetylsalicylic acid and a P2Y12 inhibitor is often recommended. In line with the growing number of reports on cardiac arrest treatment, therapeutic hypothermia (TH) has been proposed for unconscious patients to improve neurological outcomes. Nevertheless, studies report controversial and often discrepant results on the effect of hypothermia on blood coagulability and platelet reactivity. In this review, we summarize the knowledge on platelet function under diverse hypothermic conditions. Additionally, we review the current literature on the effect of systemic hypothermia on pharmacokinetic and pharmacodynamic properties of antiplatelet agents. It has been shown that TH can alter the effectiveness of antiplatelet agents, including P2Y12 inhibitors, through multiple mechanisms, hence, special attention should be paid while implementing antiplatelet therapy in patients under TH conditions.

Induced Hypothermia: Implications for Free Flap Survival.

Plastic surgeons may not be aware that the new advanced cardiac life support (ACLS) guidelines released in 2010 include induced hypothermia as an adjuvant treatment to improve neurologic outcomes following cardiac arrest [1]. Induced hypothermia (IH) is thought to mitigate ischemic damage by lowering metabolic demand and preventing noxious byproducts of resuscitation. IH is recommended for patients who experience the return of spontaneous circulation after cardiac arrest, but remain unconscious [2]. The hypothermia protocol involves the reduction of body temperature to 32℃–34℃ for 12 to 24 hours, followed by slow rewarming [1,2]. However, the use of induced hypothermia in microvascular free tissue transfer has not been studied. We present the case of a patient who underwent IH following free-flap reconstruction of a head and neck cancer defect. A 69-year-old male with a history of coronary artery disease and three-vessel coronary artery bypass grafting presented with recurrent basal cell carcinoma of the left ear canal. He underwent total auriculectomy and lateral temporal bone resection, and the defect was reconstructed with a left vertical rectus abdominis myocutaneous free flap. On the second postoperative day, the patient was found unresponsive in pulseless electrical activity cardiac arrest. The ACLS protocol was initiated, including mechanical ventilation and vasopressors for hemodynamic support. The patient was successfully resuscitated but suffered a second cardiac arrest with ventricular fibrillations. He was resuscitated again but remained unresponsive. Hypothermia was induced, with the patient cooled to 32℃ for 48 hours (Fig. 1). The free flap remained well perfused with an audible Doppler signal during the cardiac arrests, vasopressor therapy, hypothermic cooling, and the remainder of his hospitalization (Fig. 2). Unfortunately, the patient had no meaningful neurologic recovery and magnetic resonance imaging showed diffuse hypoxic brain injury. Therefore, the family elected to withdraw care on postoperative day 10. Fig. 1 Temperature curve showing induced hypothermia to 32℃–34℃, from postoperative day three until postoperative day five. Fig. 2 A 69-year-old male underwent composite resection of the left auriculotemporal area and temporal bone for recurrent basal cell carcinoma, and the defect was reconstructed with a left vertical rectus abdominis myocutaneous free flap. The effects of systemic hypothermia on free tissue transfer are not fully understood. Limited animal and human studies have demonstrated conflicting results. Some data have suggested that hypothermia causes decreased perfusion, vasospasm, and thrombosis, while other animal experiments have shown a protective effect of mild hypothermia on free flaps [3,4,5]. Clotting enzymes, platelets, and leukocytes function less effectively in a hypothermic setting; however, no reports have been published on the effect of severe hypothermia (<34℃) on free flap survival in humans. This is the first reported case of induced hypothermia after free tissue transfer. Plastic surgeons should be aware of ongoing changes to the ACLS algorithm and its impact on perioperative care. In this case, a free tissue transfer remained viable despite induced hypothermia and vasopressors, which is a single data point suggesting that free flaps can tolerate such interventions. However, further research is needed to clarify the effects of hypothermia on free tissue transfer.

Therapeutic Hypothermia in Brain Injuries and Related Diseases

Mild or moderate hypothermia is a useful therapeutic method for improving the outcome for patients who have suffered brain injuries including traumatic brain injury and strokes, as well as secondary damages such as neuroinflammation and edema. The feasibility and safety of therapeutic hypothermia have been evaluated in experimental settings and clinical trials. Because the efficacy of therapeutic hypothermia, however, is dependent on the cooling method, application time, duration, and strategies, a continuous effort for obtaining optimal standard protocols of controlling temperature and the documentation of hypothermic devices and drugs are required. Here, we discuss the most recent hypothermia applications in brain injury and related diseases, and review the latest patents in hypothermic devices and cannabinoid-based hypothermia-inducing drugs. Ultimately, we conclude that a localized hypothermia may overcome the limitations, risks, and side effects of systemic hypothermia, and the combination of local hypothermia and drug treatment may improve clinical benefits.

The effects of systemic hypothermia on a murine model of thoracic aortic ischemia reperfusion

Hypothermia is widely used to mediate ischemia-reperfusion injury associated with repair of the thoracoabdominal aorta. Experiments were designed in a murine model of thoracic aortic ischemia-reperfusion (TAR) to evaluate the effect of moderate systemic hypothermia on neurologic function, spinal cord morphology, and indices of inflammation in critical organs. C57BL/6 mice were subjected to TAR under hypothermic (34 degrees C) or normothermic (38 degrees C) conditions, followed by 24 or 48 hours of normothermic reperfusion. Neurologic functions were assessed during reperfusion. Spinal cords were examined at 24 and 48 hours after reperfusion, and the degree of injury qualified by counting the number of viable motor neurons within the anterior horns. Keratinocyte chemokine, interleukin-6, and myeloperoxidase levels were measured from lung, liver, and kidney at 24 and 48 hours. Normothermic TAR resulted in a dense neurologic deficit in all mice throughout the reperfusion period. Mice subjected to TAR under hypothermic conditions had transient, mild neurologic deficit during the initial periods of reperfusion. Between 24 and 48 hours, delayed paralysis developed in half of these mice, whereas the other half remained neurologically intact. Spinal cord histology showed a graded degree of injury that correlated with neurologic function. There was no correlation between markers of inflammation in various organs and neurologic outcomes following TAR. Systemic moderate hypothermia was protective against immediate paralysis after TAR in all cases and was associated with delayed paralysis in 50% of mice. This study suggests that delayed-onset paralysis may be the result of a local insult, rather than a systemic inflammatory event, precipitating spinal cord injury.

Effect of systemic hypothermia on local soft tissue trauma-induced microcirculatory and cellular dysfunction in mice*

Changes in body temperature occur as a systemic reaction to severe trauma; however, its role in the manifestation of injury remains unclear. Thermoregulatory responses vary considerably from fever to hypothermia. Although hypothermic trauma patients seem to have a worse prognosis, there is the question whether hypothermia per se or the severity of trauma producing the hypothermia is responsible for aggravated injury and increased mortality rate. The present study unravels how moderate to severe systemic hypothermia modulates local microcirculatory dysfunction and cellular injury in local soft tissue trauma. Prospective, experimental study. Research laboratory at a university. C57BL/6J mice. A model involving standardized drop weight device-induced tissue trauma and high-resolution multifluorescence microscopy in the dorsal skinfold chamber was used to show arteriolar vasoconstriction, reduction of blood flow, nutritive perfusion failure, and apoptotic cell death at 1 hr after trauma. During the 8-hr posttrauma observation period, microcirculation, but not apoptosis, restituted to almost baseline level. Concomitant systemic hypothermia of either 34 degrees C or 30 degrees C did not affect late manifestation of apoptotic cell death but aggravated initial microcirculatory dysfunction and inhibited recovery during the 8-hr follow-up period. Our study provides evidence that systemic hypothermia may aggravate soft tissue trauma-associated microcirculatory dysfunction. These experimental results clearly support clinical efforts to prevent hypothermia in the acutely traumatized patient.

Effects of systemic hypothermia and selective brain cooling on ischemic brain damage and swelling.

The present study investigates the neuroprotective effects of temporary mild systemic hypothermia and selective brain cooling against focal cerebral infarction in the rat and the changes of cortical blood flow, and compares these two treatment modalities. In permanent middle cerebral artery (MCA) model, the treatments were induced 15 min following the artery occlusion. The animals were kept at the desired rectal or brain temperature (about 32 degrees C) for 30 min; (each, n = 6) and for 1 hr (each, n = 6), and then allowed to rewarm spontaneously, whereas control animals were kept at normothermia throughout the experiment. The volumes of brain infarction and edema were assessed 24 hr post-occlusion. The blood flow of the dorsolateral cortex was monitored by Laser-Doppler flowmetry (LDF) in the other experiments. Hemispheric infarct volume was attenuated only in the animals treated for 1 hr with systemic hypothermia (49.2%, P < 0.001) and selective brain cooling (26.7%, P < 0.01). The volume of brain swelling was diminished only in the animals treated with systemic hypothermia for 1 hr (23.6%, P < 0.05). LDF examination revealed a sharp drop in blood flow upon MCA occlusion and maintaining in low blood flow throughout the experiment in the control and systemic hypothermia. However, in the selective brain cooling, the reduced blood flow increased from 40% to 70% of baseline value while the brain was rewarmed. The present study indicates that mild systemic hypothermia has much stronger protective effects against focal cerebral infarction and edema than selective brain cooling. The lack of protective effects of selective brain cooling may be caused by post-cooling cerebral hyperemia in the ischemia area.

Normothermic Cardiopulmonary Bypass

Normothermic cardiopuhnonary bypass avoids the detrimental systemic effects of hypothermia. It is a safe and effective technique of systemic perfusion during cardiopulmonaiy bypass. Myocardial preservation is not compromised when electromechanical quiescence is maintained. Cerebral protection is comparable to that of systemic hypothermia. Low vascular resistance is common and easily treated with higher perfusion flows or vasopressors during bypass and facilitates weaning from bypass. Duration of cardiopulmonary bypass is significantly shortened by the absence of systemic cooling and rewarming phases. Clinical outcomes of patients undergoing cardiac, surgery with normothermic bypass compare favorably with those receiving moderate hypothermia.

The effects of hypothermia on amino acid neurotransmitter release from the cerebral cortex

The effects of systemic hypothermia (33.5°C) on the ischemia-evoked release of the neurotransmitter amino acids, glutamate, aspartate, γ-aminobutyric acid (GABA) and glycine into rat cerebral cortical superfusates were evaluated in the rat four vessel occlusion model. Glutamate, aspartate and GABA, but not glycine, levels were enhanced during and following a 20 min period of ischemia. However, when compared with normothermic ischemic animals, no reductions in glutamate, aspartate or GABA levels in the superfusates were apparent either prior to, during or following forebrain ischemic episodes. Indeed, the superfusate levels of aspartate and GABA were transiently increased immediately following ischemia. Glycine levels were significantly depressed, both pre- and post-ischemia, in cortical superfusates from hypothermic animals in comparison with normothermic rats.

Effects of systemic hypothermia on myocardial metabolism and coronary blood flow in the fibrillating heart

Ventricular fibrillation during normothermic cardiopulmonary bypass is deleterious to the myocardium. This study was undertaken to determine if moderate systemic hypothermia would protect the myocardium during ventricular fibrillation. Fourteen mongrel dogs were subjected to 1 hour, 15 minutes of total cardiopulmonary bypass. Ventricular fibrillation was induced by a continuous electrical alternating current applied at the beginning of bypass and lasting for 1 hour. Six animals were maintained at normothermia (Group I), and eight were cooled to 30 degrees C. for 1 hour (Group II). The hypothermic group (Group II) demonstrated lower myocardial oxygen consumption and metabolism, decreased coronary blood flow, and less myocardial lactate production during ventricular fibrillation than did Group I. It is concluded that hypothermia does offer some protection, although not complete, against the deleterious effects of ventricular fibrillation described previously.