It is common medical knowledge that after 5 minutes of cardiac arrest the prospects of successful resuscitation without neurological impairment become progressively bleak. But there is less consensus on the mechanisms of such injury. One strong candidate is what is called the “no-reflow” phenomenon. No-reflow refers to the impairment of perfusion of the brain after circulation is restored. A number of researchers (e.g., Ames, Fisher) have demonstrated the existence of the no-reflow phenomenon in cerebral ischemia by perfusing the brain with carbon black after various periods of ischemia. Areas that are perfusable thus turn black, while non-perfusable areas of no-reflow do not.
In a remarkable 1992 paper by De Le Torre et al., the researchers report that the no-reflow phenomenon is only observed in the presence of agonal or post-mortem cardiopulmonary failure. Perfusion impairment was not observed in brains of rats that maintained stable cardiopulmonary function during, and received intravenous carbon black after, up to 30 minutes of cerebral ischemia. Clearly, these results are hard to reconcile with traditional explanations of no-reflow (e.g., blood rheology changes, edema-induced changes in the vessel lumen) and the authors offer little guidance in the discussion section of the paper on how to explain the finding that co-existence of stable cardiopulmonary function and global cerebral ischemia does not produce post-ischemic vessel filling defects after restoring blood flow to the brain. Unless blood flow to the brain was not completely eliminated in the animals in which stable cardiopulmonary function was maintained it is difficult to imagine a mechanism of no-reflow that makes sense.
It may be that reperfusion of blood that has been circulating continuously throughout the body during the period of cerebral ischemia accounts for improved perfusability of ischemic brains as compared to those reperfused after whole-body ischemia (i.e., cardiac arrest). Maintaining cardiopulmonary function during cerebral ischemia could improve subsequent perfusion of ischemic tissues by preventing red cell aggregation in the blood and/or inflammatory responses (e.g., neutrophil activation) initiated by reduction in, or lack of, blood flow. If this would be the case, the adverse effects of ischemia in the brain would be offset by the maintenance of physiological blood flow in the rest of the body.
The findings in this paper do not offer encouragement for the practice of human cryopreservation because cryonics patients invariably experience cardiopulmonary failure prior to stabilization intervention. Classic cryonics interventions such as administration of streptokinase and heparin do not seem to be very effective in reversing cerebral perfusion impairment, which raises some important questions about the phenomenon of post-mortem blood coagulation. The only effective intervention in animal research remains rapid hemodilution and high perfusion pressures, which is not easy to implement in typical cryonics casework. But why this intervention works in the light of the findings above remains something of a mystery. Other interventions to prevent no-reflow after cardiac arrest in cryonics patients are currently being investigated and detailed reports will be forthcoming in the future.