cardiovascular-agents and Hypothermia

Acute ischemic stroke (AIS) is a significant cause of death and disability in the United States. It has been 10 years since tissue plasminogen activator became the first medication approved by the US Food and Drug Administration for treatment for AIS. However, this treatment simply reopens arteries. The identification of deleterious cellular reactions that occur secondary to cerebral ischemia has led investigators to search for neuroprotection strategies to complement reperfusion. More than 100 human trials, including a handful of phase III trials, had failed to produce an efficacious neuroprotective agent. In 2006, the first positive trial of neuroprotection was published: the SAINT I (Stroke-Acute Ischemic NXY Treatment) study. In February 2008, the SAINT II study was published, indicating that NXY-059 was not effective for AIS treatment.

Topics: Acute Disease; Benzenesulfonates; Brain Ischemia; Cardiovascular Agents; Clinical Trials as Topic; GABA Agonists; Humans; Hypothermia; N-Methylaspartate; Narcotic Antagonists; Neuroprotective Agents; Stroke; Tissue Plasminogen Activator

Hypothermia is a promising clinical therapy for acute injuries, including neural damage, but it also faces practical limitations due to the complexities of the equipment and procedures required. This study investigates the use of the A1 adenosine receptor (A1AR) agonist N6-cyclohexyladenosine (CHA) as a more accessible method to induce steady, torpor-like hypothermic states. Additionally, this study investigates the protective potential of CHA against LPS-induced sepsis and neuroinflammation. Our results reveal that CHA can successfully induce a hypothermic state by activating a neuronal circuit similar to the one that induces physiological torpor. This state is characterized by maintaining a steady core body temperature below 28 °C. We further found that this torpor-like state effectively mitigates neuroinflammation and preserves the integrity of the blood-brain barrier during sepsis, thereby limiting the infiltration of inflammatory factors into the central nervous system. Instead of being a direct effect of CHA, this protective effect is attributed to inhibiting pro-inflammatory responses in macrophages and reducing oxidative stress damage in endothelial cells under systemic hypothermia. These results suggest that A1AR agonists such as CHA could potentially be potent neuroprotective agents against neuroinflammation. They also shed light on possible future directions for the application of hypothermia-based therapies in the treatment of sepsis and other neuroinflammatory conditions.

Topics: Adenosine A1 Receptor Agonists; Cardiovascular Agents; Endothelial Cells; Humans; Hypothermia; Neuroinflammatory Diseases; Purinergic P1 Receptor Agonists; Torpor

Topics: Adult; Anuria; Bradycardia; Cardiovascular Agents; Cold Temperature; Coma; Combined Modality Therapy; Drug Overdose; Electric Countershock; Emergencies; Extracorporeal Membrane Oxygenation; Female; Frostbite; Humans; Hypotension; Hypothermia; Intermittent Positive-Pressure Ventilation; Psychotropic Drugs; Resuscitation; Suicide, Attempted; Ventricular Fibrillation

Topics: Adrenalectomy; Adrenergic Agents; Animals; Autonomic Nerve Block; Body Temperature; Cardiovascular Agents; Dogs; Ergoloid Mesylates; Ergot Alkaloids; Hyperglycemia; Hypothermia; Oxytocics

Topics: Cardiovascular Agents; Curare; Hibernation; Hypothermia; Hypothermia, Induced; Tetanus; Tetanus Toxoid

Topics: Cardiovascular Agents; Diphenylacetic Acids; Humans; Hypothermia; Muscle Relaxants, Central; Ventricular Fibrillation

Topics: Antihypertensive Agents; Body Temperature; Cardiovascular Agents; Heart; Hypothermia; Muscle Relaxants, Central