Exploring the magnesium-deficient weanling rat as an animal model for the sudden infant death syndrome: physical, biochemical, electrocardiographic, and gross pathologic changes.

Summary: An hypothesis has been proposed that a relative or absolute deficiency of magnesium in the rapidly growing infant might be a major cause of the sudden infant death syndrome (SIDS, crib death). We studied the magnesium-deficient weanling rat as an animal model for the human infant, exploring physical, biochemical, and gross pathologic changes during the sudden seizure episode of magnesium deficiency, as compared with during fatal strychine seizures. In addition, the electrocardiographic changes were examined during this episode of magnesium deficiency. No audiogenic seizures could be elicited on day 7 in any of five rats with acute magnesium deficiency (O-Mg) that fasted for 24 hr. The plasma magnesium concentration of O-Mg rats with no known seizures was 0.36 ±0.02 (27); the plasma magnesium value increased during fasting to 0.96 ±06 (P <0.001). Apparently new findings in the blood chemistries associated with the seizure-shock episode of magnesium deficiency include a sharp increase in plasma osmolality, hematocrit, blood sugar, blood urea nitrogen, uric acid, and the activity of SGOT, SGPT, LDH, and creatine kinase. Electrocardiograms were taken in rats that weighed 28-32 g at the onset of the study. During the seizure-shock episode, there was sinus arrest, and the ventricular rate precipitously dropped to about one-third of the normal rate. The ventricular complexes were sometimes initiated from two electrical foci. Apnea persisted and bradycardia was rapidly progressive in rats that died. Other rats made rapid, spontaneous recoveries; the heart rate and rhythm improving as animals resumed respirations. Spiked electrical complexes sometimes developed during the early recovery period. The tracings normalized within 18 hr. Pronounced intrathoracic pathologic changes were found in rats after a fatal tetanic and apneic episode. In these animals there was some variation in the severity of pathologic change. The most severe pathology was usually found in the smallest and youngest animals and usually included scattered petechiae on the pleura, the thymus, and the pericardium; expanded lungs that were plumcolored in areas extending from the hilus and in scattered patches throughout; edema and congestion on the cut surface; and foamy fluid, sometimes blood-tinged, in the bronchi. The right atrium and the right ventricle were usually distended with dark, fluid blood. The urinary bladder was always contracted and empty. When weighed with fluid contents, both the heart and lungs of the 0-Mg rats that died of seizures weighed more than those of 0- Mg rats with no known seizures. The weights in grams of four rats from each of these two groups were, respectively: body weights, 53.9 ± 0.05 and 53.8 ±0.08; lungs, 0.831 ±0.038 and 0.585 ±0.05 (P <0.001); and hearts, 0.636 ±0.042 and 0.40 ±0.03 (P <0.005). In contrast to rats dying of magnesium deficiency, rats that died of seizures due to strychnine were only mildly cyanotic. Their lungs were only slightly inflamed, with occasional petechiae. Their body weights and the weights of their lungs and hearts were not significantly different than the weights of four controls. Speculation: The sudden, potentially fatal episode occuring in the very young magnesium-deficient rat and in SIDS victims appears to be a form of shock similar to anaphylactic shock, but without a sensitizing agent. Pathologic changes are not due to the violence of seizures alone, but could well be caused by biochemical events associated with the shock state.