Abstract

In the repair of complex congenital heart defects or in surgery of the aortic arch, normal circulation may be temporarily halted to ensure a clean, bloodless operation field. The brain is the organ most vulnerable to ischemic injury during this no-flow period, and the mortality and morbidity of these procedures today consists mostly of neurological complications. Hypothermia decreases the need for oxygen and other metabolites, and cooling the patient with an extracorporeal heart-lung machine can provide enough time to perform the necessary surgical procedures during a circulatory standstill. This procedure is referred to as hypothermic circulatory arrest (HCA). Sometimes the cerebral circulation can be maintained even if the rest of the body undergoes circulatory arrest, and this strategy, involving separate catheterization of brain-destined vessels, is referred to as selective cerebral perfusion (SCP).

In this work, four separate brain protection strategies were evaluated. Two studies were performed on a surviving porcine model (I, II) to evaluate neurological recovery as well as cerebral metabolism and histopathology, and two were acute in design (III, IV), employing the modern technology of intravital microscopy to examine cerebral microcirculation.

The first study (I) showed that the administration of hypertonic saline dextran (HSD) led to a decrease in intracranial pressure, improved brain metabolism, better neurological recovery and less histopathological injury of the brain tissue in association with HCA. In the second study (II) a novel pharmacological molecule, levosimendan, reduced the intracranial pressure during the operation, but no improvement in terms of cerebral metabolism, neurological recovery or histopathological brain injury was observed after HCA. In the third study (III), real-time intravital microscopy showed that in association with HCA, a leukocyte depleting filter (LDF) attached to the cardiopulmonary bypass circuit reduces the number of activated leukocytes in cerebral microcirculation. In the fourth study (IV), cerebral metabolism and microcirculation were similar during SCP independent of the acid-base management strategy.

The results of this work suggest that HSD could be assessed in human trials, that levosimendan needs further studies to optimize its potential, that the LDF functions as designed and that the differences between the α- and the pH-stat acid-base management strategies with SCP did not differ in moderate hypothermia.