Myocyte cytoskeletal disorganization and right heart failure in hypoxia-induced neonatal pulmonary hypertension.

Previous studies have demonstrated that environmentally or genetically induced changes in the intracellular proteins that compose the cytoskeleton can contribute to heart failure. Because neonatal right ventricular myocytes are immature and are in the process of significant cytoskeletal change, we hypothesized that they may be particularly susceptible to pressure stress. Newborn calves exposed to hypobaric hypoxia (barometric pressure = 430 mmHg) for 14 days developed severe pulmonary hypertension (pulmonary arterial pressure = 101 +/- 6 vs. 27 +/- 1 mmHg) and right heart failure compared with age-matched controls. Light microscopy showed partial loss of myocardial striations in the failing neonatal right but not left ventricles and in neither ventricle of adolescent cattle dying of altitude-induced right heart failure. In neonatal calves, immunohistochemical analysis of the cytoskeletal proteins (vinculin, metavinculin, desmin, vimentin, and cadherin) showed selectively, within the failing right ventricles, patchy areas characterized by loss and disorganization of costameres and intercalated discs. Within myocytes from the failing ventricles, vinculin and desmin were observed to redistribute diffusely within the cytosol, metavinculin appeared in disorganized clumps, and vimentin immunoreactivity was markedly decreased. Western blot analysis of the failing right ventricular myocardium showed, compared with control, vinculin and desmin to be little changed in total content but redistributed from insoluble (structural) to soluble (cytosolic) fractions; metavinculin total content was markedly decreased, tubulin content increased, particularly in the structural fraction, and cadherin total content and distribution were unchanged. We conclude that hypoxic pulmonary hypertensive-induced neonatal right ventricular failure is associated with disorganization of the cytoskeletal architecture.

Coarctation index: identification of recurrent coarctation in infants with hypoplastic left heart syndrome after the Norwood procedure.

Assessment of recurrent coarctation after the Norwood procedure by routine measures is complicated by the unusual physiology caused by the presence of a modified Blalock-Tausig shunt with distal aortic arch obstruction. We present a new index that uses 2-dimensional measurement of the reconstructed aortic arch, which is highly sensitive and specific in identifying recurrent coarctation after the Norwood procedure in children with hypoplastic left heart syndrome.

Insights into catheter/Doppler discrepancies in congenital aortic stenosis.

Despite inherent discrepancies between Doppler and catheter gradients in aortic stenosis, the simplified Bernoulli equation is still the accepted noninvasive technique to quantitate severity. The Reynolds number is a dimensionless parameter that characterizes the nature of flow as being viscous, turbulent, or transitional. Recently, in vivo and animal studies have successfully used a Reynolds number-based approach to reconcile Doppler-estimated and catheter-measured discrepancies. At the midrange of Reynolds number, pressure recovery effects are most evident, resulting in "overestimation" of catheter gradients by Doppler. At the lower range of the Reynolds number viscous effects are important, whereas at a higher range, turbulent factors are dominant; both result in a tendency toward agreement. We recorded 18 peak instantaneous gradients from dual left ventricular catheters (15 to 95 mm Hg), while simultaneously recording Doppler velocities before and after intervention in 11 pediatric patients (ages 0.5 to 16 years, mean 4.5). Doppler correlated but overestimated catheter-measured peak instantaneous gradients (y = 0.84x + 18.4, r = 0.8, SEE +/- 15.2 mm Hg, mean percent difference 29.9 +/- 36) over the range of catheter gradients measured. Accounting for the Reynolds number successfully collapsed data onto a single curve. Our study confirms in a clinical setting the importance of applying fluid dynamic principles such as the Reynolds number to explain apparent discrepancies between catheter and Doppler gradients. These principles provide a foundation for developing clinically appropriate correction factors.