Pediatric tracheal disruption repaired via median sternotomy.
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Biomedical subjects
Bradley C Linden
Publications and source records attributed to Bradley C Linden.
Chronic intrauterine pulmonary hypertension compromises fetal pulmonary artery smooth muscle cell O2 sensing.
To test the hypothesis that chronic intrauterine pulmonary hypertension (PHTN) compromises pulmonary artery (PA) smooth muscle cell (SMC) O2 sensing, fluorescence microscopy was used to study the effect of an acute increase in Po2 on the cytosolic Ca2+ concentration ([Ca2+]i) of chronically hypoxic subconfluent monolayers of PA SMC in primary culture. PA SMCs were derived from fetal lambs with PHTN due to intrauterine ligation of the ductus arteriosus. Acute normoxia decreased [Ca2+]i in control but not PHTN PA SMC. In control PA SMC, [Ca2+]i increased after Ca2+-sensitive (KCa) and voltage-sensitive (Kv) K+ channel blockade and decreased after diltiazem treatment. In PHTN PA SMC, KCa blockade had no effect, whereas Kv blockade and diltiazem increased [Ca2+]i. Inhibition of sarcoplasmic reticulum Ca2+ ATPase activity caused a greater increase in [Ca2+]i in controls compared with PHTN PA SMC. Conversely, ryanodine caused a greater increase of [Ca2+]i in PHTN compared with control PA SMC. KCa channel mRNA is decreased and Kv channel mRNA is unchanged in PHTN PA SMC compared with controls. We conclude that PHTN compromises PA SMC O2 sensing, alters intracellular Ca2+ homeostasis, and changes the predominant ion channel that determines basal [Ca2+]i from KCa to Kv.
Animals↗
Paravalvular leaks around prosthetic valves implanted in the mitral position: technical refinements of the ovine model.
BACKGROUND AND AIM OF THE STUDY: Currently, the sheep model is preferred for preclinical in-vivo evaluation of prosthetic heart valves implanted in the mitral position. In sheep, the anatomy and tissue characteristics in, and around, the native mitral valve's posterior commissure (12:00-3:00 quadrant) makes valve implantation technically challenging. As the majority of non-infectious paravalvular leaks occurred in this quadrant, the surgical technique was modified to offer greater exposure of the annulus in this region and permit more accurate placement of sutures. METHODS: A total of 223 valve implantations (138 bioprostheses, 85 mechanical valves) performed between 1991 and 1998 using the sheep model was retrospectively reviewed. No evidence of endocarditis was found, indicating that etiology of the leaks was due to surgical technique. The incidence of paravalvular leak in the 12:00-3:00 quadrant was compared with that in all other quadrants, both before and after the surgical technique change. RESULTS: The incidence of paravalvular leak was 33% (28/85) for mechanical valves and 13.8% (19/138) for bioprosthetic valves. Leaks in the 12:00-3:00 quadrant accounted for 82% (14/17) of those occurring before the surgery change, and only 43% (13/30) afterwards. Before the change, the incidence of paravalvular leak was 20.3% (14/69) in the 12:00-3:00 position, and 4.3% (3/69) in the non-12:00-3:00 quadrants. After the change, incidence in the 12:00-3:00 position fell to 8.4% (13/154; p < 0.05), but that in other quadrants was not significantly affected. Analysis by valve type showed that leak incidence in the 12:00-3:00 quadrant fell from 20.3% (12/59) to 3.8% (3/79) in the bioprosthesis group (p < 0.05), and from 20.0% (2/10) to 13.3% (10/75) in the mechanical valve group (p = 0.56). In all other quadrants there was no statistically significant change in either groups. CONCLUSION: Technical refinement of surgery has led to a reduced incidence of paravalvular leak in the 12:00-3:00 quadrant, thereby providing a standard by which to compare prostheses implanted in the mitral position. These data should also assist in improving prosthetic heart valve design by enabling device-related complications to be distinguished from model-related complications.
Animals↗
Contribution of the K(Ca) channel to membrane potential and O2 sensitivity is decreased in an ovine PPHN model.
Ca2+-sensitive K+ (K(Ca)) channels play an important role in mediating perinatal pulmonary vasodilation. We hypothesized that lung K(Ca) channel function may be decreased in persistent pulmonary hypertension of the newborn (PPHN). To test this hypothesis, pulmonary artery smooth muscle cells (PASMC) were isolated from fetal lambs with severe pulmonary hypertension induced by ligation of the ductus arteriosus in fetal lambs at 125-128 days gestation. Fetal lambs were killed after pulmonary hypertension had been maintained for at least 7 days. Age-matched, sham-operated animals were used as controls. PASMC K+ currents and membrane potentials were recorded using amphotericin B-perforated patch-clamp techniques. The increase in whole cell current normally seen in response to normoxia was decreased (333.9 +/- 63.6% in control vs. 133.1 +/- 16.0% in hypertensive fetuses). The contribution of the K(Ca) channel to the whole cell current was diminished in hypertensive, compared with control, fetal PASMC. In PASMC from hypertensive fetuses, a change from hypoxia to normoxia caused no change in membrane potential compared with a -14.6 +/- 2.8 mV decrease in membrane potential in PASMC from control animals. In PASMC from animals with pulmonary hypertension, 4-aminopyridine (4-AP) caused a larger depolarization than iberiotoxin, whereas in PASMC from control animals, iberiotoxin caused a larger depolarization than 4-AP. These data confirm the hypothesis that the contribution of the K(Ca) channel to membrane potential and O2 sensitivity is decreased in an ovine model of PPHN, and this may contribute to the abnormal perinatal pulmonary vasoreactivity associated with PPHN.
4-Aminopyridine↗
Laparoscopic stapled left lateral segment liver resection--technique and results.
Because of the favorable anatomy of the left lateral segment of the liver, a totally laparoscopic approach to resection is feasible. Herein we describe a technique for laparoscopic stapled resection of the left lateral segment of the liver, including the necessary anatomic criteria for a safe operation and data on clinical outcome. Five patients at our center underwent laparoscopic exploration, ultrasound examination, and resection of segments II and III. After complete mobilization of the left lateral segment and minimal portal dissection, the totally laparoscopic resections were performed with two endoscopic staple loads (4.5 mm x 60 mm) applied sequentially across the portal pedicle and the left hepatic vein. The mean operative time was 182 minutes (range 130 to 240 minutes), blood loss was 41 ml (range 25 to 50 ml), and length of hospital stay was 2.2 days (range 1 to 3 days). All three patients with malignancy had negative surgical margins. All five patients returned to normal activity or work by 1 week postoperatively. There were no complications. Patients with isolated malignant and benign diseases of the left lateral segment of the liver are candidates for totally laparoscopic resection, if evaluation demonstrates a normal liver character and hepatic parenchymal thickness less than 3 cm overlying the ligamentum venosum groove. Such patients benefit from the minimally invasive approach, with no compromise in the surgical result as compared to the open approach.
Adult↗