Hypothermia Device Research Articles

A novel intracoronary hypothermia device reduces myocardial reperfusion injury in pigs.

Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury. This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH. The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Peltier Elements-based Human Brain Hypothermia Treatment

Cooling and hypothermia of the brain is an important and effective way to save the lives of many patients suffering from diseases such as strokes, epilepsy, incurable diseases, and others due to general accidents. Brain cells are also weak and sensitive to changes and fluctuations in human temperature. In this work, a hypothermia device was designed and practically implemented to reduce the brain and body temperature. It mainly consists of temperature sensors for measuring water and patient temperature, a Helmet made of plastic tubes with a thermal coefficient suitable for absorbing heat, cold water is circulated inside the tubes to cool the head, and the cooling is done through Peltier elements in the device. The Arduino microcontroller controls the system. The experimental results showed a decreasing in brain temperature to 36.5 °C within a cooling time of 12 minutes. The effectiveness of the proposed system was also validated by comparing the findings with the previous system in terms of temperature and cooling time.

Pre-hospital mild therapeutic hypothermia for patients with severe traumatic brain injury

ABSTRACT Background We aimed to assess the effects of pre-hospital mild therapeutic hypothermia (MTH) on patients with severe traumatic brain injury (sTBI). Methods Eighty-six patients with sTBI were prospectively enrolled into the pre-hospital MTH group and the late MTH group (initiated in hospital). Patients in the pre-hospital MTH group were maintained at a tympanic temperature of 33°C–35°C before admission and continued to be treated with a therapeutic hypothermia device for 4 days. Patients in the late MTH group were treated with the same MTH parameters. Intracranial pressure (ICP), complications and Glasgow Outcome Scale (GOS) scores were monitored. Results ICP was significantly lower for patients in the pre-hospital MTH group 24, 48, and 72 h after treatment (17.38 ± 4.88 mmHg, 18.40 ± 4.50 mmHg, and 16.40 ± 4.13 mmHg, respectively) than that in the late MTH group (20.63 ± 3.00 mmHg, 21.80 ± 6.00 mmHg, and 18.81 ± 4.50 mmHg) (P < .05). The favorable prognosis (GOS scores 4–5) rate in the pre-hospital MTH group was higher tha n the late MTH group (65.1% vs. 37.2%, respectively; P < .05) without complications . Conclusion Pre-hospital MTH for patients with STBI can reduce ICP and improve neurological outcomes.

Novel Focal Therapeutic Hypothermia Device for Treatment of Acute Neurologic Injury: Large Animal Safety and Efficacy Trial.

Objective Therapeutic hypothermia is a potentially powerful and controversial clinical tool for neuroprotection following acute neurologic pathology, particularly vascular injury. Indeed, therapeutic hypothermia remains a standard of care for postcardiac arrest ischemia and acute neonatal hypoxic-ischemic encephalopathy, improving both survival and outcomes. Although therapeutic hypothermia remains promising for cellular and systems-based neuronal protection in other neurologic injury states, the systemic side effects have limited clinical utility, confounded analysis of potential neurologic benefits, and precluded the completion of meaningful clinical trials. Methods To address such limitations, we developed and tested a novel, minimally invasive, neurocritical care device that employs continuous circulation of cold saline through the pharyngeal region to deliver focal cerebrovascular cooling. We conducted a preclinical safety and efficacy trial in six adult porcine animals to assess the validity and functionality of the NeuroSave device, and assess cooling potential following middle cerebral artery occlusion ( n = 2). Results NeuroSave consistently lowered brain parenchymal temperature by a median of 9°C relative to core temperature within 60 minutes of initiation, including in ischemic cerebral parenchyma. The core body temperature experienced a maximal reduction of 2°C, or 5% of body temperature, with no associated adverse effects identified. Conclusion The present study uses a large animal preclinical model to demonstrate the safety and efficacy of a novel, noninvasive device for the induction of robust and systemically safe hypothermia within the brain.

Selective Brain Hypothermia in Acute Ischemic Stroke: Reperfusion Without Reperfusion Injury.

In acute ischemic stroke, early recanalization of the occluded artery is crucial for best outcome to be achieved. Recanalization aims at restoring blood flow to the ischemic tissue (reperfusion) and is achieved with pharmacological thrombolytic drugs, endovascular thrombectomy (EVT) devices, or both. The introduction of modern endovascular devices has led to tremendous anatomical and clinical success with rates of substantial reperfusion exceeding 80% and proven clinical benefit in patients with anterior circulation large vessel occlusions (LVOs). However, not every successful reperfusion procedure leads to the desired clinical outcome. In fact, the rate of non-disabled outcome at 3 months with current EVT treatment is ~1 out of 4. A constraint upon better outcomes is that reperfusion, though resolving ischemic stress, may not restore the anatomic structures and metabolic functions of ischemic tissue to their baseline states. In fact, ischemia triggers a complex cascade of destructive mechanisms that can sometimes be exacerbated rather than alleviated by reperfusion therapy. Such reperfusion injury may cause infarct progression, intracranial hemorrhage, and unfavorable outcome. Therapeutic hypothermia has been shown to have a favorable impact on the molecular elaboration of ischemic injury, but systemic hypothermia is limited by slow speed of attaining target temperatures and clinical complications. A novel approach is endovascular delivery of hypothermia to cool the affected brain tissue selectively and rapidly with tight local temperature control, features not available with systemic hypothermia devices. In this perspective article, we discuss the possible benefits of adjunctive selective endovascular brain hypothermia during interventional stroke treatment.

Effects of Different Target Temperatures on Angiogenesis and Neurogenesis Following Resuscitation in a Porcine Model After Cardiac Arrest.

The optimal effective temperature of targeted temperature management (TTM) used to prevent cerebral injury following cardiopulmonary resuscitation (CPR) is undetermined. In this study, we compared the mortality, neurologic deficits, and cerebral protein levels of two target temperatures. Fifty 4-month-old female domestic pigs were randomized to sham, TTM at 33°C ± 0.5°C (T33), TTM at 35°C ± 0.5°C (T35), and normothermic (NT) groups. In the NT and TTM groups, untreated ventricular fibrillation was induced electrically in animals for 10 min, followed by 6 min of CPR. Target core temperatures (Tc) of TTM groups were induced and maintained (6 h) using an endovascular hypothermia device, and rewarmed to 37.5 ± 0.5°C in the next 6 h. Tc of the NT group was maintained at 37.5 ± 0.5°C. The survival outcomes and neurological function were evaluated every 24 h for 72 h. All animals were successfully resuscitated with no significant differences in baseline characteristics or hemodynamic indexes. Survival rates and neurological outcomes were significantly improved in the TTM groups, with T33 showing the most significant effect. Compared with NT-treated animals, TTM-treated animals had higher expressions of angiopoietin-1, transforming growth factor-alpha , vascular endothelial growth factor, metallopeptidase inhibitor (TIMP)-1, TIMP-2, and platelet-derived growth factor-BB. Macrophage migration inhibitory factor and IL-17F levels were markedly upregulated after resuscitation in the NT group but inhibited in the TTM groups. Neuron-specific enolase staining data was also consistent with our conclusion that hypothermia can reduce reperfusion-induced brain injuries. Lower target temperature showed greater protective effects against cerebral injuries after CPR, and the improved neurological outcomes after TTM may be associated with decreased expression of pro-inflammatory cytokines and increased expression of blood-brain barrier and neurogenesis regulatory factors in this porcine model of CA following resuscitation.

Neuroprotection by selective endovascular brain cooling - the TwinFlo™ Catheter.

The neuroprotective effects of hypothermia have been demonstrated in experimental models and clinical trials. Experimental studies indicate that improved efficacy and broadened indications can be achieved with moderate to deep hypothermia. The TwinFlo catheter was designed to provide very rapid, deep and selective brain cooling with faster cooling rates, and temperatures much lower than those which can be achieved by any other hypothermia device and technique. This report describes the experimental in vivo studies and initial clinical experience with the TwinFlo catheter.

Endovascular hypothermia improves post-resuscitation myocardial dysfunction by increasing mitochondrial biogenesis in a pig model of cardiac arrest

The aim of the study was to investigate the effects of endovascular hypothermia on mitochondrial biogenesis in a pig model of prolonged cardiac arrest (CA). Ventricular fibrillation was electrically induced, and animals were left untreated for 10 min; then after 6min of cardiopulmonary resuscitation (CPR), defibrillation was attempted. 25 animals that were successfully resuscitated were randomized into three groups: Sham group (SG, 5, no CA), normal temperature group (NTG, 5 for 12 h observation and 5 for 24 h observation), and endovascular hypothermia group (EHG, 5 for 12 h observation and 5 for 24 h observation). The core temperatures (Tc) in the EHG were maintained at 34 ± 0.5 °C for 6 h by an endovascular hypothermia device (Coolgard 3000), then actively increased at the speed of 0.5 °C per hour during the next 6 h to achieve a normal body temperature, while Tc were maintained at 37.5 ± 0.5 °C in the NTG. Cardiac and mitochondrial functions, the quantification of myocardial mitochondrial DNA (mtDNA), peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), nuclear respiratory factor (NRF)-1, and NRF-2 were examined. Results showed that myocardial and mitochondrial injury and dysfunction increased significantly at 12 h and 24 h after CA. Endovascular hypothermia offered a method to rapidly achieve the target temperature and provide stable target temperature management (TTM). Cardiac outcomes were improved and myocardial injuries were alleviated with endovascular hypothermia. Compared with NTG, endovascular hypothermia significantly increased mitochondrial activity and biogenesis by amplifying mitochondrial biogenesis factors’ expressions, including PGC-1α, NRF-1, and NRF-2. In conclusions, endovascular hypothermia after CA alleviated myocardial and mitochondrial dysfunction, and was associated with increasing mitochondrial biogenesis.

Comparative evaluation of controllability and safety of therapeutic hypothermia in the intensive care of severe traumatic brain injury.

The article presents the results of a comparative study of control and safety of two technologies of therapeutic hypothermia in intensive care in patients with TBI: an estimate of the rate of its induction, control of its maintenance, dynamics of attaining normothermia. A total of 24 patients with a severe TBI divided into 2 groups were examined: I (n=12) –therapeutic hypothermia with "Blanketrol II" (CSZ) with the use of non-invasive technology to achieve the target core body temperature (Tco) of 34-34.50C; II group (n=12) – carrying out therapeutic hypothermia «Blanketrol - II» with the use of an esophageal device for hypothermia to achieve Tco - 34-34,50С. The mean time from the moment of induction to achievement of the target Tco in group I was 9.5±2.39 hours, in group II – 9±2.70 hours (p&gt;0.05). The maintenance period Tco at the level of ≤34.50C in the II group was greater – 10.5±5.78 compared with 6.83±3.95 hours in patients of the I group (p&lt;0.05). Control of the warming process was significantly higher in group II, which was reflected by a lower mean of Tco value at 24, 28 and 32 hours. There were no clinically significant adverse effects in therapeutic hypothermia.

A Human Thermoregulation Simulator for Calibrating Water-Perfused Cooling Pad Systems for Therapeutic Hypothermia

The induction of a mild reduction in body core temperature has been demonstrated to provide neuroprotection for patients who have suffered a medical event resulting in ischemia to the brain or vital organs. Temperatures in the range of 32–34 °C provide the required level of protection and can be produced and maintained by diverse means for periods of days. Rewarming from hypothermia must be conducted slowly to avoid serious adverse consequences and usually is performed under control of the thermal therapeutic device based on a closed-loop feedback strategy based on the patient's core temperature. Given the sensitivity and criticality of this process, it is important that the device control system be able to interact with the human thermoregulation system, which itself is highly nonlinear. The therapeutic hypothermia device must be calibrated periodically to ensure that its performance is accurate and safe for the patient. In general, calibration processes are conducted with the hypothermia device operating on a passive thermal mass that behaves much differently than a living human. This project has developed and demonstrated an active human thermoregulation simulator (HTRS) that embodies major governing thermal functions such as central metabolism, tissue conduction, and convective transport between the core and the skin surface via the flow of blood and that replicates primary dimensions of the torso. When operated at physiological values for metabolism and cardiac output, the temperature gradients created across the body layers and the heat exchange with both an air environment and a clinical water-circulating cooling pad system match that which would occur in a living body. Approximately two-thirds of the heat flow between the core and surface is via convection rather than conduction, highlighting the importance of including the contribution of blood circulation to human thermoregulation in a device designed to calibrate the functioning of a therapeutic hypothermia system. The thermoregulation simulator functions as anticipated for a typical living patient during both body cooling and warming processes. This human thermoregulatory surrogate can be used to calibrate the thermal function of water-perfused cooling pads for a hypothermic temperature management system during both static and transient operation.

Stridor in neonates with hypoxic-ischaemic encephalopathy subject to selective cerebral or whole body hypothermia

Abstract Introduction Hypothermia treatment has improved the prognosis of asphyxiated neonates. Widely used, it has demonstrated to be safe without severe side effects. The aim of this article is to review the incidence of stridor amongst asphyxiated newborns treated with hypothermia in our unit. Methods Retrospective chart review of our patients. Results Stridor was presented in 7/75 (9.3%) of patients during hypothermia. Three received whole body hypothermia, 3 selective cerebral, and in one case both techniques were used. All cases required increased respiratory support. Conclusions Different mechanisms may be responsible for the appearance of stridor in patients with hypoxic-ischaemic encephalopathy (HIE). In our series the incidence of stridor was similar for the two hypothermia devices. To better understand these possible side effects of hypothermia, further prospective studies (which should include laryngoscopy) are needed.

Estridor en neonatos con encefalopatía hipóxico-isquémica sometidos a tratamiento con hipotermia cerebral selectiva o corporal total

IntroductionHypothermia treatment has improved the prognosis of asphyxiated neonates. Widely used, it has demonstrated to be safe without severe side effects. The aim of this article is to review the incidence of stridor amongst asphyxiated newborns treated with hypothermia in our unit. MethodsRetrospective chart review of our patients. ResultsStridor was presented in 7/75 (9.3%) of patients during hypothermia. Three received whole body hypothermia, 3 selective cerebral, and in one case both techniques were used. All cases required increased respiratory support. ConclusionsDifferent mechanisms may be responsible for the appearance of stridor in patients with hypoxic-ischaemic encephalopathy (HIE). In our series the incidence of stridor was similar for the two hypothermia devices. To better understand these possible side effects of hypothermia, further prospective studies (which should include laryngoscopy) are needed.

Transporting neonates with hypoxic-ischemic encephalopathy utilizing active hypothermia

The objective of this report was to evaluate a servo-controlled active hypothermia device used during the transport of neonates with HIE. Retrospective review of all cases of therapeutic hypothermia, both passive and active, using a servo-controlled device in a single regional referral neonatal intensive care unit from 2009-2013 RESULTS: An ambulance (43%), fixed wing aircraft (25%), or helicopter (32%) transported 28 neonates with active hypothermia. The servo-controlled device captured core temperatures in all 28 neonates, resulting in 2,985 minutes of data. All neonates attained a core temperature between 33-34 °C by 33 minutes of the transport. Once the neonates attained a core temperature, the average temperature for the remainder of the transport was 33 ± 0.2 °C. The neonates maintained the core temperature regardless of the type of transport vehicle. Servo-controlled hypothermia enables rapid attainment of targeted temperatures and maintains the temperature throughout the transport process in both ground and air transport.

Multi-scale modeling on human intravascular cooling to induce brain hypothermia via circle of Willis

Therapeutic hypothermia has been the most effective therapy to treat serious cardiovascular and cerebrovascular diseases. Among them, intravascular cooling is identified as a most efficient approach to induce brain hypothermia. However until now, some key parameters and temperature management method for intravascular cooling are still not well addressed because of the complexity of human thermoregulation mechanism. Aiming at predicting temperature variation of tissues and organs in a more accurate way during therapeutic hypothermia, this study is dedicated to integrate the blood flow model in the circle of Willis together with the compartmental model for characterizing the heat and blood transport throughout the whole human body. According to the theoretical evaluation, the new model could well simulate the temperature response of the whole human body especially the brain under various cooling. Effects of different intervention site and cooling power to the hypothermia performance are discussed, which shows that carotid artery intervention is a more suitable therapeutic hypothermia method in comparison with femoral artery or femoral vein intervention. These results could help design controlling software for intravascular therapeutic hypothermia device in the near future.

Report From the Meeting of the Circulatory System Devices Panel of the Food and Drug Administration Center for Devices and Radiologic Health

The US Food and Drug Administration (FDA) Circulatory System Devices Panel met to discuss the type of data required to effectively evaluate the performance of cardiopulmonary resuscitation (CPR) and hypothermia devices for cardiac arrest patients. Advisory panels make nonbinding recommendations to the FDA. The era of modern CPR began in the 1960s, when mouth-to-mouth ventilation combined with forceful chest compressions were first used together to attempt to resuscitate victims of cardiopulmonary arrest. Unfortunately, despite the promise of a variety of pharmacological, electrical, and mechanical therapies during and after administration of CPR, meaningful improvements in cardiac arrest survival have been difficult to achieve. Earlier generations of CPR devices are designed to assist the rescuer in the performance of CPR. These devices, for example, may compress the chest at a fixed rate and compression depth, or they may provide audible or visual indicators to assist the rescuer with compliance with published CPR guidelines. In general, regulatory guidelines do not require clinical data for these devices as long as they are similar in design and technology to previously marketed “predicate” devices. More than 30 devices for external compression and/or timing assistance during CPR have been cleared for marketing by the FDA. Devices intended to enhance a clinical aspect of CPR, in contrast to devices designed simply to assist the rescuer in the performance of CPR, require clinical data to support approval of the device. These devices, such as those providing interposed abdominal compression, circumferential chest compression, or active compression-decompression, have focused primarily on enhancing hemodynamics during CPR. Despite great interest in improving CPR survival rates, no device intended to enhance hemodynamics during CPR has been approved by the FDA for marketing in the United States. The Circulatory System Devices Panel was asked to discuss and make recommendations about the type of clinical data …

Hypothermia Devices May Improve Outcomes

Hypothermia Devices May Improve Outcomes

Chronic Scrotal Hypothermia

We studied the use of a testicular hypothermia device worn daily for at least 16 weeks in 64 men with subfertile semen and elevated testicular temperature, who had had an infertile marriage for 2 or more years in which the wife was judged fertile. Improvement in 1 or more semen parameters was seen in 42 patients (65.6 per cent). Semen analysis was converted into the motile oval index, a numerical value representing the count, motility and normal morphology. The motile oval index helps to predict pregnancy outcome. Of 21 patients with pre-treatment motile oval indexes greater than 4.8 million per ml. 11 (52.4 per cent) produced pregnancy. Patients with lower starting indexes did not fare as well. Of 20 patients who met the criteria, and who wore the device for less than 2 weeks or not at all and had no other treatment 1 (5.0 per cent) produced pregnancy. Mean hypothermia time to date of missed menses was 4.2 months. Six patients with nonobstructive azoospermia showed no semen change with the testicular hypothermia device.

Chronic Scrotal Hypothermia: Results in 90 Infertile Couples

We studied the use of a testicular hypothermia device worn daily for at least 16 weeks in 64 men with subfertile semen and elevated testicular temperature, who had had an infertile marriage for 2 or more years in which the wife was judged fertile. Improvement in 1 or more semen parameters was seen in 42 patients (65.6 per cent). Semen analysis was converted into the motile oval index, a numerical value representing the count, motility and normal morphology. The motile oval index helps to predict pregnancy outcome. Of 21 patients with pre-treatment motile oval indexes greater than 4.8 million per ml. 11 (52.4 per cent) produced pregnancy. Patients with lower starting indexes did not fare as well. Of 20 patients who met the criteria, and who wore the device for less than 2 weeks or not at all and had no other treatment 1 (5.0 per cent) produced pregnancy. Mean hypothermia time to date of missed menses was 4.2 months. Six patients with nonobstructive azoospermia showed no semen change with the testicular hypothermia device.

Scrotal Hypothermia: New theraphy for poor semen

A relation between experimental elevation of testis temperature and poor semen has been known for over sixty years. Poor semen from elevated temperature due to intrinsic abnormality of testis thermoregulation has been a recent concept. A testicular hypothermia device (THD) was created which when worn by “hard core” infertile males with varicocele, failed variocelectomy, or “subclinical” varicocele resulted in lowering of temperature with improvement in semen in many. Pregnancies have resulted. The device is noninvasive and well tolerated.

Electronic device for hypothermia of the brain

Electronic device for hypothermia of the brain