Is vertical vein ligation necessary in repair of total anomalous pulmonary venous connection?

BACKGROUND: In the repair of total anomalous venous connection, vertical vein ligation is recommended to eliminate left-to-right shunting. However, the small left heart chambers may not always tolerate the immediate increase in blood flow after combined repair and vein ligation. METHODS: A retrospective review of 23 infants and children undergoing correction of total anomalous pulmonary venous connection was undertaken to determine whether vertical vein ligation is a necessary component of successful surgical repair. In 14 patients this vein was ligated, whereas in 9 it was left patent. Six patients who underwent ligation and 5 who did not had pulmonary venous obstruction before operation. RESULTS: The operative mortality rate was 36% (5 of 14 patients) for the ligated group compared with 0% (0 of 9 patients) for the nonligated group (p = 0.06). All deaths occurred in patients with preoperative obstruction and a low mean left atrial pressure, and four of the deaths were directly attributable to left heart failure. Follow-up echocardiography in patients in whom the vertical vein was not ligated revealed adequate cardiac function and no residual left-to-right flow through the previously patent venous conduit. CONCLUSION: Vertical vein ligation during the repair of total anomalous pulmonary venous connection is not routinely necessary and actually may be undesirable in patients with preoperative obstruction, in whom the left heart chambers are particularly small.

Myosin light chain kinase phosphorylation in nitrovasodilator induced swine carotid artery relaxation.

Nitrovasodilators are hypothesized to induce smooth muscle relaxation by their metabolism to nitric oxide, which then activates soluble guanylyl cyclase, increases [cGMP], and activates cGMP-dependent protein kinase. cGMP-dependent phosphorylation is then proposed to decrease intracellular [Ca2+] ([Ca2+]i) and to reduce the Ca(2+)-sensitivity of contraction. We hypothesized that one component of decreased Ca(2+)-sensitivity, reduced Ca(2+)-sensitivity of MLC phosphorylation, was due to phosphorylation of myosin light chain kinase (MLCK) on the peptide site A. In the swine carotid artery, histamine (10 microM) stimulation increased aequorin-estimated [Ca2+]i, MLCK site A phosphorylation, MLC phosphorylation, and force. Subsequent addition of 100 microM nitroglycerin (NTG) or 100 microM sodium nitroprusside (NP) to histamine-stimulated tissues increased [cGMP], decreased both MLC phosphorylation and force, but did not significantly alter [cAMP], [Ca2+]i, or MLCK site A phosphorylation. Addition of NTG and NP alone to unstimulated tissues increased MLCK site A phosphorylation, but did not alter [Ca2+]i. In tissues preincubated with NP, subsequent histamine contraction was slowed compared with controls, however, this slowed rate of contraction appeared to result from an attenuation of histamine-dependent increases in [Ca2+]i. These data suggest that, in swine carotid artery, nitrovasodilators can decrease the Ca(2+)-sensitivity of MLC phosphorylation without increasing MLCK site A phosphorylation. Nitrovasodilators, per se, can induce site A MLCK phosphorylation, potentially by cGMP dependent activation of cAMP-dependent protein kinase.

Association of hypertrophic maxillary frenulum with hypoplastic left heart syndrome.

We report a previously unrecognized association between a hypertrophic frenulum separating the alveolar portion of the maxillary palatine suture with hypoplastic left heart syndrome in one fetus and seven children. A hypertrophic frenulum was not found in 25 pediatric cardiology patients without hypoplastic left heart syndrome. This finding may provide a marker for suspecting hypoplastic left heart syndrome in the neonate.

Cyclic nucleotide dependent relaxation in vascular smooth muscle.

Although not without controversy, the mechanisms inducing contraction of vascular smooth muscle are relatively well defined. There is a stimulus-induced increase in myoplasmic [Ca2+] with activation of myosin light chain kinase by the Ca(2+)-calmodulin complex, phosphorylation of the 20-kDa regulatory light chain of myosin, with subsequent cross-bridge cycling and force development. Ca(2+)-dependent phosphorylation of the myosin regulatory light chain appears to be the primary mechanism responsible for regulating stress in vascular smooth muscle. The relationship between myoplasmic [Ca2+] and myosin phosphorylation (i.e., the calcium sensitivity of phosphorylation) is regulated. It is higher with agonist stimulation than in tissues depolarized with high potassium solutions or after skinning procedures. The relationship between myosin phosphorylation and stress appears to be invariant with physiologic stimulation. This suggests that cross-bridge phosphorylation normally determines contraction. The mechanisms of relaxation are less well defined. In the most simple scheme, reduction of myoplasmic [Ca2+] with a fall in myosin light chain kinase activity would suffice to account for dephosphorylation of the regulatory light chain and relaxation. However, other mechanisms have been implicated in cyclic nucleotide dependent relaxation in vascular and other smooth muscle tissues. The current hypotheses of the mechanism of cyclic nucleotide dependent relaxation in vascular smooth muscle are reviewed.

Mechanisms of increased sensitivity to A2 adenosine receptor stimulation in immature rabbit aortic rings.

Adenosine receptor-mediated vasodilation is increased in immature vessels compared to mature vessels. To determine the mechanism of this increased sensitivity, isolated vascular rings from mature and immature rabbits were studied to evaluate the contribution of the endothelium and the contribution of adenosine-dependent 3',5'-cyclic monophosphate (cAMP) to adenosine receptor-mediated relaxation. Dose responses were measured in endothelial-intact and nonendothelialized aortic rings using 5'-(N-ethylcarboxamido)-adenosine (NECA), a nonhydrolyzable adenosine agonist. Immature rings were more sensitive to NECA than mature rings as demonstrated by a lower ED50 and steeper slope of the dose-response curve. There was no effect on endothelial removal in immature rings while there was a significant decrease in response in mature rings. Despite being more sensitive to NECA, immature rings had less increase in cAMP (percent change from basal level) at maximal vasodilation than mature rings although cAMP did not change in either age at the ED50. The lack of change with endothelial removal in immature vessels suggests that the endothelium is not involved in the increased sensitivity of immature rings to NECA. The cAMP data suggests that other mechanisms for vasodilation are important at the ED50 for NECA in both ages. Maximal vasodilation with NECA on the other hand was associated with increases in cAMP although they were lower in the immature rings.

Nitrovasodilators relax arterial smooth muscle by decreasing [Ca2+]i and uncoupling stress from myosin phosphorylation.

Elevations in guanosine 3',5'-cyclic monophosphate concentration ([cGMP]) are proposed to induce arterial smooth muscle relaxation by either 1) decreasing myoplasmic [Ca2+] ([Ca2+]i), 2) decreasing the [Ca2+]i sensitivity of phosphorylation, or 3) uncoupling force from myosin phosphorylation. We evaluated the importance of each of these mechanisms by measuring changes in [cGMP], aequorin- and fura-2-estimated [Ca2+]i, myosin light chain phosphorylation, and stress in histamine-stimulated swine carotid arteries. In tissues submaximally stimulated with 3 microM histamine, nitroprusside (NP) induced a proportional decrease in myoplasmic [Ca2+] and myosin phosphorylation, suggesting that the relaxation was at least partially induced by decreases in [Ca2+]i without a change in the [Ca2+]i sensitivity of phosphorylation. In tissues maximally stimulated with 10 microM histamine, NP and nitroglycerin produced significant relaxations that were not associated with significant sustained reductions in [Ca2+]i or myosin phosphorylation. With both submaximal and maximal histamine stimulation, nitrovasodilators produced more substantial relaxation than that expected from the nitrovasodilator-induced reduction in myosin phosphorylation. These results suggest that nitrovasodilators relax histamine-stimulated swine arterial smooth muscle by at least two mechanisms: 1) reducing [Ca2+]i, an effect observed in submaximally stimulated tissues, and 2) uncoupling of stress from myosin phosphorylation.

Cyclic AMP relaxes swine arterial smooth muscle predominantly by decreasing cell Ca2+ concentration.

1. Our objective was to evaluate the mechanism of cyclic AMP-dependent arterial smooth muscle relaxation. Cyclic AMP-dependent relaxation has been proposed to result from either (a) a decrease in intracellular [Ca2+] or (b) a decrease in [Ca2+] sensitivity of myosin light chain kinase by protein kinase A-dependent phosphorylation of myosin kinase. 2. We evaluated these proposed mechanisms by examining forskolin-induced changes in aequorin-estimated myoplasmic [Ca2+], [cyclic AMP], myosin phosphorylation and stress generation in agonist-stimulated or KCl-depolarized swine common carotid media tissues. 3. Forskolin, an activator of adenylyl cyclase, increased [cyclic AMP] and reduced [Ca2+], myosin phosphorylation and stress in tissues pre-contracted with phenylephrine or histamine. This relaxation was not associated with an alteration of the [Ca2+] sensitivity of phosphorylation, nor the dependence of stress on phosphorylation. 4. Forskolin pre-treatment attenuated, but did not abolish, agonist-induced increases in [Ca2+] and stress. 5. These results suggest that cyclic AMP-induced relaxation of the agonist-stimulated swine carotid media is primarily caused by cyclic AMP-mediated decreases in myoplasmic [Ca2+].

Progression of cardiac disease in Emery-Dreifuss muscular dystrophy.

Emery-Dreifuss muscular dystrophy (EDMD) is a rare X-linked muscular dystrophy characterized by early contractures, progressive muscle weakness, and atrial arrhythmias. Recent reports suggest that there may be additional cardiac problems in affected males and that carrier females may also show ECG abnormalities. We restudied two large families with EDMD in order to determine the extent of these problems. We examined 10 affected males and interviewed 2 others. The 3 affected males less than 20 years old had no ECG changes. All affected men of 35 years or older had arrhythmias. One had more severe arrhythmias when asleep, indicating the usefulness of continuous 24-h ECG monitoring in the evaluation of males affected with EDMD. Two required pacemakers, 4 had already had a pacemaker placed, and 4 other affected men with pacemakers had died prior to this study. One affected man with a pacemaker developed ventricular bigeminy and another developed congestive heart failure. Thus of 10 affected males with pacemakers, 6 had additional cardiac symptoms and 4 have died. Males with EDMD may survive longer with a ventricular pacemaker, but this may increase the likelihood that they will develop cardiomyopathy and ventricular arrhythmias. Of 34 carrier females examined, 6 had arrhythmias typical of EDMD. Two required a pacemaker. The risk of arrhythmia increased with age. Results from one family should be extrapolated to another with caution, as there appears to be significant interfamilial variation. We suggest careful cardiologic follow-up of EDMD patients and regular cardiac evaluations for older carrier females.

Intrapericardial teratoma causing nonimmune hydrops fetalis and pericardial tamponade: a case report.

A case of fetal anasarca secondary to an intrapericardial teratoma is reported. The clinical, echocardiographic, and histologic features are described, along with a review of intrapericardial lesions.

Internal consistency of echocardiographic estimates of the severity of left ventricular outflow obstruction.

To determine their internal consistency, M-mode and Doppler echocardiography were used to estimate the gradient across the left ventricular outflow tract during 74 evaluations of 50 infants, children, and young adults with congenital valvular (n = 43), subvalvular (n = 6), and supravalvular (n = 1) aortic stenosis. By M-mode the gradient was estimated from the wall-stress formula (left ventricular pressure = 225 x wall thickness/end-systolic diameter) minus systolic blood pressure determined by sphygmomanometry. Doppler (pulsed or continuous wave) methods utilized the Bernoulli formula (gradient = 4 x V2). There was good agreement between the M-mode and Doppler estimates of outflow gradient in most patients (r = 0.69, standard error of the estimate = 26.9). In 46 of 74 comparisons (62%) the two estimates differed by less than 20 mm Hg, and the estimates placed the patient in the same clinical class (mild, moderate, or severe). In 22 patients undergoing cardiac catheterization, there was only a fair correlation between the M-mode (r = 0.50) and Doppler (r = 0.58) gradients and those obtained at catheterization. Each noninvasive technique yielded major overestimates or underestimates of the gradient in several instances. The M-mode and Doppler techniques for estimating the severity of congenital aortic stenosis are complementary. Their combined use minimizes but does not totally eliminate errors of overestimation or underestimation of outflow gradient.