Pulmonary arterial medial smooth muscle thickness in sudden infant death syndrome: an analysis of subsets of 73 cases

Abstract

Previous studies addressing pulmonary artery morphology have compared cases of sudden infant death syndrome (SIDS) to controls but none have compared demographic profiles, exposure to potentially hypoxic risk factors and other pathologic variables in SIDS cases grouped according to pulmonary artery medial smooth muscle thickness. Aims: To compare the relative medial thickness (RMT) in alveolar wall arteries (AW) in SIDS cases with that in age-matched controls and 2. Compare demographic, clinical, and pathologic characteristics among three subsets of SIDS cases based upon alveolar wall (AW) RMT. Retrospective morphometric planimetry of all muscularized arteries in standardized right apical lung sections in 73 SIDS cases divided into three groups based on increasing AW RMT as well as 19 controls age-matched to 19 of the SIDS cases. SIDS and age-matched control cases did not differ with respect to AW RMT or other demographic variables.The SIDS group with the thickest AW RMT had significantly more males and premature birth than the other groups, but the groups did not differ for known clinical risk factors that would potentially expose them to hypoxia. Pathologic variables, including pulmonary inflammation, gastric aspiration, intra-alveolar siderophages, cardiac valve circumferences, and heart and liver weights, were not different between groups. Age was not significantly correlated with RMT of alveolar wall and pre-acinar arteries but was significant at p = .018 for small intra-acinar arteries. The groups were different for RMT of small pre-acinar and intra-acinar arteries, which increased with increasing AW RMT. Statistical differences should not necessarily be equated with clinical importance, however future research incorporating more quantified historical data is recommended.

A “Wear and Tear” Hypothesis to Explain Sudden Infant Death Syndrome

“…Sympathetic activation/catecholamine release in response to hypoxia/hypercapnia is mediated by carotid body glomus cells acutely (143) and by peripheral chemoreceptor organs [e.g., adrenal medulla and oxygen sensing pulmonary neuroendocrine cells (PNEC)] (144). Lungs from infants dying of SIDS have demonstrated hyperplasia of PNEC with reduced myelination of its vagal afferents impairing oxygen sensing (145) as well as increased airway (146) and thick pulmonary arteries in males (147). …”

Abnormal Muscularization of Intra-acinar Pulmonary Arteries in Two Cases Presenting as Sudden Infant Death

“…Muscularization of normally nonmuscularized peripheral vessels is the result of the release of endothelial vasoconstrictors, growth factors, matrix proteins and adhesion molecules as a cellular response to hypoxia. 10,13 Although our cases fell under the spectrum of Sudden Unexpected Death in Infancy (SUDI), there shared some unusual findings: both died in hospital after a short history of unexplained respiratory deterioration: Case 1 had been increasingly breathlessness with grunting for 2 days, and then presenting with shortness of breath and tachycardia and subcostal recession before arrest; Case 2 suddenly struggled to breathe and died shortly after admission. Hypoxia-induced smooth muscle proliferation in pulmonary arteries requires several days, 10 so at first sight it seems unlikely that the short-lived respiratory symptoms in our cases had any influence in the muscularization of the intraacinar arteries.…”

“…Williams et al 9 study on 15 consecutive SIDS and controls showed an extension of muscle in arteries not usually muscularized, as well as an increase in the percentage of medial wall thickness in some SIDS participants, therefore corroborating Naeye's results. 8 Krous et al, 10 retrospectively, compared the relative medial thickness in alveolar wall arteries, pre-acinar and intraacinar arteries as well as the demographic, clinical and pathological features in 19 SIDS cases with 19 agematched controls. All cases and controls in their study 10 were >28 days of age, while our cases were 12 and 28 days old.…”

“…8 Krous et al, 10 retrospectively, compared the relative medial thickness in alveolar wall arteries, pre-acinar and intraacinar arteries as well as the demographic, clinical and pathological features in 19 SIDS cases with 19 agematched controls. All cases and controls in their study 10 were >28 days of age, while our cases were 12 and 28 days old. With reference to the intra-acinar arteries morphometry, Krous et al 10 showed that age was inversely correlated to the relative medial thickness for small intra-acinar arteries (p ¼ .018) and that increasing relative medial thickness of pre-acinar and intra-acinar arteries correlated with increasing relative medial thickness of alveolar wall arteries, suggesting that increasing muscularization is seen in all categories of vessels with a stimulus sufficient to produce it in alveolar wall arteries.…”

“…With reference to the intra-acinar arteries morphometry, Krous et al 10 showed that age was inversely correlated to the relative medial thickness for small intra-acinar arteries (p ¼ .018) and that increasing relative medial thickness of pre-acinar and intra-acinar arteries correlated with increasing relative medial thickness of alveolar wall arteries, suggesting that increasing muscularization is seen in all categories of vessels with a stimulus sufficient to produce it in alveolar wall arteries. Although SIDS and control groups in Krous et al 10 study did not differ for known clinical risk factors that would potentially expose them to hypoxia, the increased thickness of alveolar wall arteries had significantly more males and premature birth than the other groups. Interestingly, the heart's weight in SIDS cases from Krous' study 10 was normal, a significant difference with our 2 cases, where it was above the expected for the age (see Table 1).…”