17. October 2008 · Comments Off on Promoting cerebral blood flow in cryonics patients · Categories: Cryonics, Neuroscience · Tags: , , , , , , ,

It has been shown that perfusability of the brain is significantly compromised after long-term (>5 min) ischemic events (the “no reflow” phenomenon). Improving cerebral blood flow after circulatory arrest is one of the fundamental objectives of human cryopreservation stabilization protocol.  To that end, cryonics organizations administer the resuscitation fluid Dextran-40 and the drug Streptokinase to dilute the blood (and inhibit  red cell aggregation / cold aggulination) and  break up blood clots, thereby improving macro and microvascular circulation. Research by Fischer and Ames, who investigated the effects of perfusion pressure, hemodilution, and anticoagulation (i.e., the use of heparin) on post-ischemic brain perfusion, indicated that hemodilution is the most effective component of the post-ischemic perfusion protocol for enhancing brain perfusability. However, a later study by Lin, et al. (1978) reported significant improvement of cerebral function and blood flow with combined dextran and Streptokinase administration after cardiac arrest in dogs.

In their study, the researchers measured regional cerebral blood flow and cardiac output as well as EEG (i.e., brain wave activity) during five hours of post-resuscitation physiological maintenance following 12-16 minutes of cardiac arrest. Animals were divided into three groups as follows:

Group I:   no treatment

Group II: 1 g/kg dextran 40 in 10% saline following arrest and 10 mg/kg/minute during the five hour maintenance period

Group III: combined therapy of dextran-40 and Streptokinase — same dose of dextran as Group II and 5,000 u/kg rapid infusion and 25 u/kg/minute during the five hour maintenance period

The duration of flat EEG was significantly shorter in Group III animals (20 to 45 minutes with a mean of 28.8 +/- 2.8) than in Groups I (20 to 120 minutes with a mean of 59.5 =/- 10.8) or II (20 to 62 minutes with a mean of 46.9 +/- 4.8) and showed a faster recovery pattern than in Group I (significant difference was reached at three hours). Group II also showed a faster EEG recovery than Group I, reaching significance at five hours.

Cerebral blood flow, particularly in the hippocampus and grey matter (the areas most detrimentally affected by ischemia) in Group III was significantly improved as compared to Group I as early as three hours post-arrest, and was greater than that in Group II (significantly better only in the hippocampus). There was no difference in cardiac output found between the treated and untreated groups. All groups suffered a decrease in cardiac output of nearly 50% of baseline level (measured at 3 and 5 hours post-arrest).

Hematocrit — the proportion of blood volume occupied by red blood cells — was measured in each group and was found to be significantly increased during the post-arrest period in Group I, decreased to 25% of the baseline measurement in Group III (at both 3 and 5 hours post-arrest), and unchanged in Group II.

The authors speculate that “the improvement in cerebral circulation at the microvascular level after infusion of low molecular weight dextran was thought to be 1) related to the rapid increase in plasma volume with resultant lowering of hematocrit and reduction in blood viscosity, 2) a direct effect on the RBC [red blood cell] which increases its negativity and reduces the tendency to cellular aggregation.” They also note that though some doubt had been cast by the Fischer and Ames paper on the hypothesis of vascular endothelial cell swelling as a cause of no reflow, they did observe a higher proportion of smaller diameter capillaries in ischemic brains as compared to controls, and that “if capillary narrowing does play a role in microvascular deterioration, then hemodilution and prevention of cellular aggregates such as occurs with dextran would be beneficial in minimizing poor flow in narrow capillaries.”

Taken together, these findings indicate that combined dextran-40 and Streptokinase therapy improve brain perfusion after cardiac arrest — at least for arrest periods of up to 16 minutes.– supporting the choice for these agents in cryonics. One limitation of this study, however, is that the experiments did not include a group which received only Streptokinase. Including a Streptokinase group would have given more  precise data about the individual effects of the two agents in improving post-ischemic cerebral blood flow. Recent clinical trials with clot busting agents in cardiac arrest have failed and some contemporary authors question the phenomenon of post-arrest blood clotting. Perhaps streptokinase is useful in the treatment of circulatory arrest but its efficacy is dependent upon other blood flow improving interventions such as hemodilution. The case for post-ischemic hemodilution (and interventions to reduce RBC aggregation) is strong but the case for antithrombotic therapy in cryonics (and resusctation medicine) remains to be made.

28. November 2007 · Comments Off on Human cryopreservation combinational pharmacotherapy · Categories: Cryonics · Tags: , , , ,

A comprehensive review of cryonics stabilization medications is now published on the Alcor website.

Table of contents:

* Introduction
* General Anesthesia
* Blood Coagulation
* Vasoactive Medications
* Excitotoxity
* Free Radicals
* Nitric Oxide and PARP
* Inflammation
* Antibiotics
* Acidosis
* Hemodilution and Osmotic Therapy
* Coenzyme Q10
* Magnesium
* Na+ /H+ Exchange Inhibition
* Immunosuppressive Drugs
* Gastrointestinal Ischemia
* Depressed Metabolism
* Combining Medications
* Conclusion