Exploring the Magnesium-deficient Weanling Rat as an Animal Model for the Sudden Infant Death Syndrome: Physical, Biochemical, Electrocardiographic, and Gross Pathologic Changes

Abstract

SummaryAn 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 (0-Mg) that fasted for 24 hr. The plasma magnesium concentration of 0-Mg rats with no known seizures was 0.36 +. 0.02 (27); the plasma magnesium value increased during fasting to 0.96 & 0.06 ( 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 OMg rats with no known seizures. The weights in grams of four rats from each of these two groups were, respectively: body weights, 53.9 rt 0.05 and 53. 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. Specul...

Effects of hypomagnesemia on reactivity of bovine and ovine platelets: possible relevance to infantile apnea and sudden infant death syndrome.

“…Similarity of vascular lesions in Mg-deficient calves to atherosclerosis in humans was noted over 50 years ago [3]. Postmortem findings in human victims of unex pected sudden death [4,5] and in cattle which died in hypomagnesemic tetany [6,7] were also similar to lesions produced in hearts and lungs of rabbits by ex perimentally induced clumping of platelets [8][9][10].…”

“…Acting synergistically, these compounds, which have strong bronchoconstrictor and vasoconstrictor activity, could have an important role in the pathogenesis and clinical expression and be a major factor for the lethal event in susceptible hypomag nesemic animals. If Mg deficiency is a major contribut ing cause of SIDS [5], then it is not unreasonable to speculate that abnormal activation of platelets may also be involved in SIDS.…”

“…Lungs of hypomagnesemic lambs which died spontaneously in tetany (Fig. 1) and lambs in which intravascular clumping of platelets was induced by collagen injected intravenously [23] were markedly similar to lungs of an 11-week-old human infant diag nosed as a victim of SIDS [5]. Clinical experience with idiopathic apnea neonatorum [24] revealed no record of hospital readmission for recurrent apnea or death in 61 infants receiving Mg therapy (0.4 mEq intramuscularly as the sulfate or 1.0 mEq orally as the chloride/kg body weight/day) a minimum of 5 days.…”

Magnesium deficiency and stress

“…During the experiment [18] in rats with magnesium deficiency, an insignificant increase in the level of corticosterone in blood plasma, increased irritability and aggressive behavior, as well as higher mortality rate were observed in comparison with the control group. It is generally believed that, in response to psychological stress, individuals with type A behavior experience an increased release of catecholamines and cortisol, and therefore a decrease in magnesium levels and an increase of the risk of cardiovascular events compared to the behavior of type B [20].…”

Magnesium therapy in premature neonates with apnea neonatorum.

“…Emesis, nasogastric suction, and frequent stooling can cause major gastrointestinal losses of Mg [6,7,16]. Finally, the cardiorespiratory cri ses experienced by the sickest infants resem bled the seizure-shock episodes of Mg deficient weanling animals in terms of physical, bio chemical, and electrocardiographic changes [19]; and the structural changes of RDS resem ble the changes found in the lungs of these animals [20]. It is difficult to diagnose Mg deficiency in the sick neonate.…”