Metabolism and Hypothermia

Metabolism and Hypothermia

Hypothermia while being a common problem associated with all operations, remains an inseparable aspect of cardiopulmonary bypass that has a profound impact on most enzyme systems, and the coagulation cascade.

Activated clotting time, prothrombin times and partial thromboplastin times are prolonged and platelets become nonfunctional as the body temperature is lowered (usually to 32-34° C).

Cellular potassium uptake is increased and may result in hypokalemia unless appropriately treated during the rewarming phase of cardiopulmonary bypass.

Hypothermia has demonstrated therapeutic benefits during cardiac surgery.  It will allow for lower perfusion indices (subsequently less blood trauma), improved myocardial protection, tissue and organ preservation, and reduced oxygen consumption, implying a reduction in basal metabolic rate.

This reduction in metabolic requirement can be summarized as being approximately 50% for every drop in core body temperature of 7° (Celsius).  It should be noted that conversion of the patients’ heart beat to normal sinus rhythm may not be possible until the body core temperature is rewarmed to 34° Celsius.

Mechanism of Neuroprotection

The earliest rationale for the effects of hypothermia as a neuroprotectant focused on the slowing of cellular metabolism resulting from a drop in body temperature.

Accordingly, most early hypotheses suggested that hypothermia reduces the harmful effects of ischemia by decreasing the body’s need for oxygen.^[3] The initial emphasis on cellular metabolism explains why the early studies almost exclusively focused on the application of deep hypothermia, as these researchers believed that the therapeutic effects of hypothermia correlated directly with the extent of temperature decline.^[17]

More recent data suggests that even a modest reduction in temperature can function as a neuroprotectant ^[18], suggesting the possibility that hypothermia affects pathways that extend beyond a decrease in cellular metabolism.

One plausible hypothesis centers around the series of reactions that occur following oxygen deprivation, particularly those concerning ion homeostasis. In the special case of infants suffering perinatal asphyxia it appears that apoptosis is a prominent cause of cell death and that hypothermia therapy for neonatal encephalopathy interrupts the apoptotic pathway.

Cellular Death

In general, cell death is not directly caused by oxygen deprivation, but occurs indirectly as a result of the cascade of subsequent events. Cells need oxygen to create ATP, a molecule used by cells to store energy, and cells need ATP to regulate intracellular ion levels.

ATP is used to fuel both the importation of ions necessary for cellular function and the removal of ions that are harmful to cellular function. Without oxygen, cells cannot manufacture the necessary ATP to regulate ion levels and thus cannot prevent the intracellular environment from approaching the ion concentration of the outside environment.

It is not oxygen deprivation itself that precipitates cell death, but rather without oxygen the cell can not make the ATP it needs to regulate ion concentrations and maintain homeostasis.^[3]

Notably, even a small drop in temperature encourages cell membrane stability during periods of oxygen deprivation. For this reason, a drop in body temperature helps prevent an influx of unwanted ions during an ischemic insult. By making the cell membrane more impermeable, hypothermia helps prevent the cascade of reactions set off by oxygen deprivation.

Even moderate dips in temperature strengthen the cellular membrane, helping to minimize any disruption to the cellular environment. It is by moderating the disruption of homeostasis caused by a blockage of blood flow that many now postulate results in hypothermia’s ability to minimize the trauma resultant from ischemic injuries.^[3]

Therapeutic hypothermia may also help to reduce reperfusion injury, damage caused by oxidative stress when the blood supply is restored to a tissue after a period of ischemia. Various inflammatory immune responses occur during reperfusion.

These inflammatory responses cause increased intracranial pressure, which leads to cell injury and in some situations, cell death. Hypothermia has been shown to help moderate intracranial pressure and therefore to minimize the harmful effects of a patient’s inflammatory immune responses during reperfusion.

The oxidation that occurs during reperfusion also increases free radical production. Since hypothermia reduces both intracranial pressure and free radical production, this might be yet another mechanism of action for hypothermia’s therapeutic effect.^[3]

References

Therapeutic hypothermia:  Wikipedia

Brodie JE, Johnson RB. The Manual of Clinical Perfusion. Augusta, GA. Glendale Medical Corporation; 1994.