This study compares two cardioplegic solutions—HTK and Del Nido—for their impact on cerebral inflammation in a porcine cardiopulmonary bypass model. Results showed that while both solutions produced comparable hypoxia and inflammation markers overall, HTK led to more pronounced hyponatremia, hypochloremia, and increased IL-1β mRNA in certain brain regions. Del Nido cardioplegia provided more stable electrolyte levels and less cerebral inflammation.