Developing and optimizing a chronic cyanotic swine model.

BACKGROUND: Pulmonary artery (PA)-left atrial (LA) shunt models in piglets have been described, but technical details critical to limit morbidity/mortality and promote study of chronic cyanosis are lacking. Accordingly, we describe our experience with an optimized technique. MATERIALS AND METHODS: In 25 6- to 8-wk-old Yorkshire piglets, a beveled, 8 mm, polytetrafluoroethylene tube graft was anastomosed to the PA and LA. Systemic pressure was maintained at >60 mmHg. Saturation targets were met by adjusting a Teflon band on the graft and distal PA. The target oxygen saturation (SO(2)) was 85% on a 50% fraction of inspired oxygen (FiO(2)). If the SO(2) was <75% on a 50% FiO(2), the graft was constricted to achieve a SO(2) ≥ 90% on a 100% FiO(2) and 75%-80% on a 21% FiO(2). Complications affecting mortality were neutralized with a stepwise strategy to minimize risk. RESULTS: Thrombosis, blood loss, and arrhythmia were determinants of survival. Protocol optimization over time increased survival while assuring chronic cyanosis. Survival approached 90%, with a SO(2) of 80% to 90%, 3 to 5 wk postoperatively. Complications included bleeding, excessive hypoxemia, uncontrolled shunt flow, arrhythmias, and thrombosis. CONCLUSIONS: Refinement of surgical technique, shunt adjustment via graft banding, and thrombotic and arrhythmia prophylaxis are the keys to success with this model.

Spigelian hernia as a cause of small bowel obstruction.

Spigelian hernia is a rare abdominal wall defect usually appearing between the abdominal muscle lateral to the rectus abdominis and through a debilitated spigelian aponeurosis. Spigelian hernias account for 0.12% to 2.4% of all abdominal wall hernias with a 17-24% risk of strangulation. We report the case of a 77-year-old male that presented with small bowel obstruction with incarcerated spigelian hernia which was successfully treated with a Ventralex hernia patch (Bard Access Systems, Inc., Murray Hill, NJ). A small open incision over the incarcerated hernia was a safe and effective method of repairing an incarcerated spigelian hernia in an urgent fashion.

Tuberculous peritonitis: a surgical dilemma.

This is a case report of tuberculous peritonitis (TB), an entity which is difficult to diagnose. When TB is found in extrapulmonary organs it is usually associated with an immunocompromised state, such as that caused by the human immunodeficiency virus (HIV). Medical therapy continues to be the treatment of choice and, if the correct diagnosis is made early, surgery is rarely required.

Hemodynamics and axial strain additively increase matrix remodeling and MMP-9, but not MMP-2, expression in arteries engineered by directed remodeling.

We previously demonstrated the ability to create engineered arteries by carefully controlling the mechanical environment of intact arteries perfused ex vivo, yielding engineered arteries with native appearance and vasoactive response. Increased axial strain was sufficient to increase length up to 20% in 9 days through a growth and remodeling response. The amount of the achievable length increase, however, was highly dependent on the hemodynamic conditions acting through unknown mechanisms. Because matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) activity is increased, and often required, in mechanically induced remodeling in vivo, MMP-2 and MMP-9 expression was investigated to elucidate the hemodynamic mediation of artery length. Carotid arteries from 30 kg pigs were perfused for 9 days ex vivo at either in situ axial strain or with a gradual 50% increase in axial strain, under either arterial or reduced hemodynamics ( approximately 10% of arterial hemodynamics). MMP-2 protein expression increased roughly twofold, while MMP-9 expression increased threefold under either reduced hemodynamics or increased axial strain (p < 0.05). The combination of reduced hemodynamics with increased axial strain demonstrated an additive increase in MMP-9 protein (p < 0.05) with no further change in MMP-2 expression. To investigate the mechanism by which axial strain and hemodynamics could additively increase MMP-9 expression, the expression of nuclear factor kappa B (NF-kappaB) subunits p50 and p65 was evaluated. Axial strain stimulated p65 expression and localization, while hemodynamics increased p50 expression, with both molecules being expressed only when both mechanical stimuli were applied. These data suggest that MMP-9 expression can be simultaneously stimulated by separate mechanical stimuli mediated by p50 and p65 expression, and that by using conditions that maximize MMP-9 expression, we can create an optimal remodeling environment to better direct the growth of engineered arteries and other tissues.

Chronic hypoxemia increases ventricular brain natriuretic peptide precursors in neonatal swine.

BACKGROUND: Circulating levels of atrial natriuretic peptide and brain natriuretic peptide (BNP) are elevated in patients with cyanotic congenital heart disease and associated with the severity of ventricular dysfunction. We evaluated the effect of chronic hypoxemia on left ventricle pro-atrial natriuretic peptide and pro-BNP, the cytoplasmic precursors of the plasma hormones. METHODS: Forty newborn piglets were randomized to placement of a pulmonary artery to left atrium shunt to create hypoxemia or sham thoracotomy. Animals were studied at 1 or 2 weeks after the procedure (four groups, n = 10 per group). Arterial oxygen tension and hematocrit were obtained. Left ventricular shortening fraction was measured by echocardiography. Left ventricular tissue was harvested and cytoplasm was extracted. Pro-BNP levels were determined by Western blot analysis. Pro-atrial natriuretic peptide levels were determined using enzyme-linked immunosorbent assay. RESULTS: Significant differences among treatment groups were observed for arterial oxygen tension (p < 0.001) and hematocrit (p < 0.001). Pairwise comparisons indicated lower arterial oxygen tension and higher hematocrit for hypoxemic piglets compared with control piglets at 1 and 2 weeks. Left ventricular shortening fraction was not decreased in the hypoxemic animals at any time (p = 0.638). Left ventricular pro-atrial natriuretic peptide decreased in hypoxemic piglets (p = 0.029), whereas left ventricular pro-BNP increased in hypoxemic piglets at 2 weeks (p = 0.002). CONCLUSIONS: Chronic hypoxemia alone, even in the absence of cardiac dysfunction, is sufficient to increase ventricular levels of pro-BNP. This finding may have implications for the interpretation of BNP levels in the clinical management of patients with cyanotic congenital heart disease.

Femororenal arteriovenous graft: a viable option for hemodialysis access.

There has been a significant increase in the number of patients with end-stage renal disease. The limited number of kidney transplants necessitates that most patients become dependent upon chronic dialysis. Due to the numerous complications associated with temporary access catheters, permanent arteriovenous access is more beneficial for long-term vascular access. However, with the restricted availability of sites for permanent vascular access, it is important to have a variety of possibilities. In this case report, we present an alternative choice for an arteriovenous graft, left common femoral artery to left renal vein, in a patient with limited vascular access options.

Chronic hypoxemia increases myocardial cytochrome oxidase.

OBJECTIVE: Cyanotic patients have potentially decreased tissue oxygen tension. Cytochrome oxidase catalyzes the reduction of oxygen and is integral to adenosine triphosphate production. Cytochrome oxidase subunit I, the active site, is encoded by mitochondrial DNA. Using a newborn swine model of chronic hypoxemia, we evaluated ventricular cytochrome oxidase subunit I mRNA and protein expression and assessed cytochrome oxidase activity. METHODS: Thirty-two newborn piglets underwent thoracotomy and placement of a pulmonary artery-to-left atrium shunt or sham operation. Two weeks later, partial pressure of arterial oxygen, hematocrit, and left ventricular shortening fraction values were compared with baseline values. Northern blot hybridization and protein immunoblotting for ventricular cytochrome oxidase subunit I were performed. Cytochrome oxidase kinetic activity was measured. Heme a,a3 content and turnover number were determined. Significance was assessed with a t test. RESULTS: Baseline partial pressure of arterial oxygen and hematocrit values were similar. Hypoxemic piglets had a lower partial pressure of arterial oxygen of 38 +/- 10 mm Hg (P < .001) and higher hematocrit value of 31.4% +/- 2.9% (P < .001) compared with a partial pressure of arterial oxygen of 140 +/- 47 mm Hg and hematocrit value of 24.6% +/- 3.9% after the sham operation. Baseline and postprocedure left ventricular shortening fraction were similar within and between groups. Chronic hypoxemia increased right ventricular and left ventricular cytochrome oxidase I mRNA and protein by more than 1.4-fold. Cytochrome oxidase activity increased significantly in hypoxemia by 2.5-fold compared with that seen after the sham operation. Heme a,a3 content and turnover number increased by 1.5-fold during hypoxemia. CONCLUSIONS: Chronic hypoxemia increases cytochrome oxidase I message, protein expression, and activity. The increase in kinetics was due to increased enzyme content and catalytic activity. This is a possible adaptive mechanism that might preserve organ function during chronic hypoxemia.