Vascular endothelial growth factor expression in canine peripheral vein bypass grafts.

PURPOSE: Autologous veins used as arterial bypass grafts undergo initial loss of the endothelial cell (EC) lining, which is followed by reendothelialization. We characterized the expression of the EC-specific angiogenic mitogen, vascular endothelial growth factor (VEGF), in vascular grafts to help elucidate the molecular and cellular events after bypass procedures. METHODS: Cephalic vein-femoral artery interposition grafts were placed in mongrel dogs. Vein grafts and arteries were harvested at either 48 hours or 4 weeks after bypass, the total RNA was isolated, and the VEGF mRNA expression was evaluated by Northern blot analysis. Tissue segments from each time period were evaluated by immunohistochemical analysis using anti-VEGF antibodies. RESULTS: VEGF mRNA expression in vein grafts as compared with control veins was increased 2.5-fold 48 hours after bypass grafting (p = 0.02) but returned to initial control levels in grafts removed at 4 weeks. Distal arterial segments, which included the anastomotic site without attached vein graft, had a 21.4-fold increase in VEGF expression at 48 hours (p = 0.02) and a 6.6-fold increase at 4 weeks (p < 0.01) as compared with control arterial segments. Vessels subjected to arteriotomy or ischemia alone also demonstrated increased VEGF expression. Immunohistochemical analysis revealed VEGF protein within ECs and smooth muscle cells of the venous bypass graft, with maximal levels observed within intimal hyperplasia at the arterial anastomosis. CONCLUSIONS: After arterial reconstruction procedures using venous conduits, VEGF is significantly increased at 48 hours in the vein graft and arterial anastomosis. VEGF expression in the vein graft normalizes within 4 weeks but remains significantly elevated in the adjacent arterial segment. Increased VEGF production after arterial grafting may facilitate reendothelialization, thus partially accounting for optimal patency rates achieved with autologous vein grafts.

Infrapopliteal bypasses to severely calcified, unclampable outflow arteries: two-year results.

PURPOSE: Although severe, circumferential calcification of distal outflow vessels is frequently encountered, its effect on bypass graft patency rates has not been well established. METHODS: Using a computerized vascular registry database, we conducted a retrospective review of 1957 bypass grafts with distal anastomoses to infrapopliteal vessels performed at a single institution between 1990 and 1995. Of these cases, 101 procedures involved outflow arteries classified by the operating surgeon as severely calcified and unclampable (requiring intraluminal occluders for vascular control), whereas in 105 cases the outflow arteries had no calcification present at the distal anastomotic site. The remaining cases had varying intermediate degrees of calcification and were not analyzed. Indication for bypass procedure was limb-threatening ischemia in 90% of severe calcification cases and in 84% of cases without calcification. Atherosclerotic risk factors were similar except for the presence of diabetes (92% vs 74%, p < 0.001), creatinine level > 2.0 mg/dl (21% vs 8%, p < 0.01), and dialysis dependency (17% vs 3%, p < 0.001), all of which were more prevalent in the severe calcification group. Infrapopliteal distal anastomotic location and type of conduit ( > 90% autogenous vein) were comparable between groups. RESULTS: Primary patency, secondary patency, and foot salvage rates at 24 months were 60%, 65%, and 77% for the severe calcification group and 74%, 82%, and 93% for the no calcification group, respectively. With secondary procedures comprising 26% of cases in each group, data from the 150 primary procedures were reanalyzed separately. In this primary procedure group, 24-month primary patency, secondary patency, and foot salvage rates were 66%, 69%, and 77% for the severe calcification group and 84%, 90%, and 96% for the no calcification group, respectively. Although patency and salvage rates were consistently lower for the severe calcification group in all analyses, these differences did not achieve significance by log-rank life-table analysis at 2-year follow-up. Perioperative 30-day mortality (0.99% severe calcification vs 0.95% no calcification) and 24-month survival rates (84% severe calcification vs 83% no calcification) were also similar between groups. CONCLUSION: These data suggest that effective techniques exist to perform infrapopliteal bypasses to severely calcified, unclampable outflow arteries with results comparable with those obtained with clampable, uncalcified vessels. The finding of severe, circumferential calcification of outflow target arteries should not dissuade vascular surgeons from distal bypass for limb salvage indications.

Ischemia-dependent efficacy of phosphodiesterase inhibition.

To evaluate the inotropic efficacy of phosphodiesterase inhibition in hearts with and without ischemic injury, 27 sheep were evaluated sonomicrometrically during incremental volume loading on right heart bypass. Contractility was assessed with the preload recruitable stroke work relationship. Active relaxation rate was estimated using the time constant of isovolumic pressure decay (tau). For nonischemic assessment, groups 1 and 2 (n = 6 each) underwent 45 minutes of vented perfusion after which milrinone was administered to group 1; group 2 served as nonischemic controls. There was no detectable increase in preload recruitable stroke work or decrement in tau after milrinone administration. Groups 3 and 4 underwent 15 minutes of 37 degrees C ischemia (aortic cross-clamping) followed by 30 minutes of vented reperfusion. Milrinone was then administered to group 3 (n = 7); group 4 (n = 8) served as ischemically injured controls. Inotropic and lusitropic effects were present (group 3 preload recruitable stroke work: 35.4 +/- 5.8 mJ.beat-1.100 g-1.mL-1 before milrinone to 49.5 +/- 4.4 mJ.beat-1.100 g-1.mL-1 after milrinone [p < 0.05]; group 3 tau: 51.8 +/- 5.5 ms before milrinone to 32.2 +/- 2.5 ms after milrinone [p < 0.02]). Although milrinone restored contractility and increased the rate of active relaxation in the postischemic hearts, there was no detectable inotropic effect in nonischemic hearts. In this model, milrinone augments contractility and relaxation in postischemic myocardium but offers little inotropic benefit in non-ischemically injured hearts.

Perfusion deficits with retrograde warm blood cardioplegia.

Prior studies of cold retrograde cardioplegia have demonstrated the existence of regional deficits in perfusate delivery. To address the hypothesis that these deficits persist with the use of warm perfusate, cardioplegic arrest was induced in 7 swine hearts with retrograde warm blood cardioplegia. Regional perfusion was assessed with the simultaneous infusion of colored 10-microns microspheres. The percentage microsphere recovery (regional microsphere count/total number of microspheres counted x 100) was greatest in the anterior (43% +/- 4%) and lateral (35% +/- 6%) left ventricle. The microsphere recoveries in the posterior left ventricle (7% +/- 1%) and anterior septum (14% +/- 4%) were intermediate, and were statistically lower than those in the anterior left ventricle (p < 0.01). The lateral right ventricle (0.6% +/- 0.2%) and the posterior septum (1.4% +/- 0.9%) exhibited minimal perfusion versus that in the anterior left ventricle (p < 0.01). Less than 1% of the infused microspheres were recovered in the aortic root; 67% were recovered in the right ventricle and are presumed to have bypassed the microcirculation as nonnutritive flow. These data demonstrate that cold retrograde perfusion patterns persist during retrograde warm blood cardioplegia. Limited perfusion of the right ventricle and the posterior septum as well as a large nonnutritive flow were also noted. These perfusion deficits in metabolically active arrested hearts may limit myopreservation at low cardioplegia flow rates.

Recovery of postischemic contractile function is depressed by antegrade warm continuous blood cardioplegia.

To assess the effectiveness of warm antegrade continuous blood cardioplegia in the setting of an acute coronary arterial occlusion, we instrumented 19 Yorkshire swine to quantitate left ventricular global, systolic, diastolic, and regional mechanics. Data were acquired before and after 10 minutes of mid-left anterior descending coronary artery occlusion followed by 60 minutes of aortic crossclamping. Cardiac arrest was induced by the antegrade infusion of 20 ml/kg of warm (37 degrees C) or cold (4 degrees C) oxygenated blood cardioplegic solution followed by either continuous warm (75 ml/min, n = 9) or intermittent cold (10 ml/kg every 20 minutes, n = 10) cardioplegic reinfusions. Left anterior descending coronary artery occlusion was released 20 minutes after aortic crossclamping and resulted in warm-arrested hearts developing a 139% increase in global oxygen consumption compared with values obtained with the left anterior descending coronary artery occluded (p < 0.02). Recovery of global left ventricle contractility, quantitated by the linear preload recruitable stroke-work relationship, was significantly worse after warm cardioplegia (52.4% +/- 5.1% versus 68.0% +/- 5.9%, warm versus cold, p < 0.05). Similarly, left anterior descending coronary artery regional ischemic zone contractility recovered 34.5% +/- 7.3% of control function with cold cardioplegia, whereas warm cardioplegia resulted in -11.36% +/- 7.46% functional recovery indicative of dyssynchronous contraction (p < 0.05). Diastolic compliance, calculated with an exponential end-diastolic pressure-versus-volume relationship, was not changed postischemically in either group. These data suggest that warm antegrade blood cardioplegia may potentiate acute ischemic injury and provide inadequate myocardial protection.

Retrograde is superior to antegrade continuous warm blood cardioplegia for acute cardiac ischemia.

BACKGROUND: Theoretically, the efficacy of continuous warm blood cardioplegia may be improved when administered retrogradely (RCWBC) rather than antegradely (ACWBC) in the setting of acute regional ischemia because of enhanced oxygen and substrate delivery to myocardial tissue distal to an acute coronary artery occlusion. METHODS AND RESULTS: Eighteen Yorkshire swine were instrumented for quantification of global left ventricular systolic, diastolic, and regional left anterior descending coronary artery (LAD) zone mechanics before and after 10 minutes of mid-LAD occlusion, followed by 60 minutes of cardiac arrest using continuous warm blood cardioplegia. Initially, 20 ml/kg of 37 degrees C oxygenated blood cardioplegia (hematocrit, 22 +/- 0.6%) was infused antegradely, followed by maintenance of 75 ml/min ACWBC (n = 9) or 60-100 ml/min of RCWBC (n = 9). LAD occlusion was released 20 minutes after cardiac arrest (30 minutes total LAD ischemia), simulating surgical revascularization. Postischemic recovery of global preload recruitable stroke work was nearly complete with RCWBC but significantly depressed with ACWBC (84.9 +/- 9.5% versus 52.4 +/- 5.1%, respectively; p < 0.01). LAD regional stroke work was also well preserved postischemically with RCWBC but showed no functional recovery and systolic bulging after ACWBC (87.4 +/- 13.7% versus -11.36 +/- 7.46% of control values; p < 0.01). Global diastolic stiffness calculated using the beta-coefficient of an exponential end-diastolic pressure-versus-volume relation was unchanged with ACWBC but increased significantly after RCWBC (from 0.027 +/- 0.002 to 0.028 +/- 0.003 mm Hg/ml and from 0.028 +/- 0.003 to 0.036 +/- 0.004 mm Hg/ml, respectively). CONCLUSIONS: These data suggest that with acute regional ischemia, both global and ischemic zone regional systolic function are depressed by ACWBC, whereas RCWBC affords adequate protection of contractile performance. However, a loss of diastolic compliance may result as a consequence of warm retrograde delivery.

Age-dependent sensitivity to unprotected cardiac ischemia: the senescent myocardium.

Six young, sexually mature sheep and seven senescent sheep (aged 0.75 +/- 0.11 years and 7.1 +/- 0.45 years) were instrumented with sonomicrometric crystals and micromanometers to assess global left ventricular mechanics while preload was varied during right heart bypass both before and 30 minutes after 15 minutes of global normothermic ischemia. Left ventricular weight and end-diastolic volume were not significantly different between age groups when indexed to body weight. Contractility was quantitated by the slope of the linear preload-recruitable stroke work relationship and diastolic mechanics by an exponential end-diastolic pressure versus volume function generated over physiologic cardiac workloads. Postischemic systolic functional recovery was markedly worse in the older group (22.7% +/- 10.7% versus 54.2% +/- 9.5%, old versus young, p less than 0.05). However, diastolic stiffness was not changed in either group postischemically. These data demonstrate that the senescent myocardium is less tolerant of ischemia and may require specific intraoperative myocardial management strategies to preserve global pump function.

Pancreaticobronchial fistula causing lung abscess: case report and brief discussion of the literature.

A case report of a patient with an abscess of the lung caused by a pancreaticobronchial fistula is presented. The patient was treated by pulmonary resection and distal pancreatectomy-splenectomy.