Combined angiotensin II receptor antagonism and angiotensin-converting enzyme inhibition further attenuates postinfarction left ventricular remodeling.

BACKGROUND: ACE inhibition (ACEI) attenuates post-myocardial infarction (MI) LV remodeling, but the effects of angiotensin II type 1 receptor (AT(1)) antagonism alone or in combination with ACEI are unclear. Accordingly, we investigated the effects of AT(1) antagonism, ACEI, and their combination in a well-characterized ovine postinfarction model. METHODS AND RESULTS: Beginning 2 days after transmural anteroapical MI, 62 sheep were treated with 1 of 5 treatment regimens: no therapy (control, n=12), standard-dose ACEI (sACEI; ramipril 10 mg/d, n=14), high-dose ACEI (hACEI; ramipril 20 mg/d, n=8), AT(1) blockade (losartan 50 mg/d, n=13), and combination therapy with sACEI+AT(1) blockade (CT; ramipril 10 mg/d+losartan 50 mg/d, n=15). MRI was performed before and 8 weeks after MI to quantify changes in LV end-diastolic and end-systolic volume indices (DeltaEDVI, DeltaESVI) and ejection fraction (DeltaEF). Change in regional percent intramyocardial circumferential shortening in noninfarcted segments adjacent to the infarct (Adj Delta%S) was measured by tagged MRI. CT resulted in the most marked blunting of LV remodeling: DeltaESVI (+1.0+/-0.4, +0.7+/-0.4, +0.6+/-0.3, +0.9+/-0.5, and +0.4+/-0.2* mL/kg); DeltaEDVI (+0.9+/-0.4, +0.7+/-0.5, +0.6+/-0.5, +0.9+/-0.5, and +0.4+/-0.3 mL/kg); DeltaEF (-24+/-7, -18+/-6, -14+/-7, -18+/-10, and -11+/-9* %); and Adj Delta%S (-8+/-4, -7+/-3, -5+/-3, -5+/-3, and -2+/-3* %) for Control, sACEI, hACEI, AT(1) blockade, and CT, respectively (*P<0.04 versus sACEI, AT(1) blockade, and control; P<0.05 versus control; P<0.002 versus AT(1) blockade and control). EDVI and ESVI at 8 weeks after MI were smallest with CT (P<0.02 versus all). CONCLUSIONS: Combination therapy with sACEI+AT(1) blockade shows promise in attenuating postinfarction LV remodeling but was not clearly superior to hACEI in the present study.

Systemic consequences of oxidative stress following aortic surgery correlate with the degree of antioxidant defenses.

The purpose of this study was to correlate the preoperative level of antioxidant defenses, measured by the plasma total antioxidant capacity (TAC), to the degree of postoperative systemic inflammatory response, measured by the severity of pulmonary injury following elective aortic surgery. Twenty-four patients had TAC measured preoperatively and 24 hr postoperatively. Chest radiography and arterial blood gases were obtained preoperatively and serially during the first 24 hr after surgery. Using objective radiologic criteria and blood gas analysis, the degree of pulmonary edema and pulmonary dysfunction were quantified. All patients showed evidence of pulmonary dysfunction in the first 24 hr following surgery. Fifteen of the 24 patients showed radiographic evidence of noncardiogenic pulmonary edema in the immediate postoperative period. In this group, the TAC was lower than in those without pulmonary edema immediately following surgery (p = 0.03). Preoperative TAC was associated with the degree of pulmonary edema in the postoperative period (r = -0.372, p = 0.067). These results suggest that preoperative antioxidant supplementation may favorably impact the severity of systemic inflammatory response following ischemia and reperfusion injury.

Awake aortic aneurysm repair in patients with severe pulmonary disease.

BACKGROUND: We report the use of retroperitoneal aortic aneurysm repair utilizing exclusive regional anesthesia (no intubation or inhalation anesthetic) in high pulmonary risk patients. METHODS: Six patients were retrospectively reviewed. Pulmonary disease was diagnosed by clinical history and pulmonary function tests. Patients received intravenous sedation and regional anesthesia. Retroperitoneal aortoiliac aneurysm repair was performed. RESULTS: All patients used inhaled steroids and albuterol. Three required theophylline and home oxygen. FEV1 = 23% +/- 5% predicted, FVC = 34% +/- 5% predicted, and PO2 = 62 +/- 2 mm Hg. Operative time was 247 +/- 25 minutes. Blood loss was 840 +/- 479 mL. Five of six patients (83%) tolerated awake aneurysm repair and had intensive care unit stays of 2.4 +/- 0.6 days, and postoperative hospital stays of 8.2 +/- 1.8 days. One patient was converted to general anesthesia and had a prolonged hospital stay. CONCLUSIONS: With thorough patient communication, awake retroperitoneal aortic aneurysm repair can be safely performed in select patients with severe pulmonary disease.

Mechanical analysis of midline sternotomy wound closure.

OBJECTIVE: Unstable median sternotomy closure can lead to postoperative morbidity. This study tests the hypothesis that separation of the sternotomy site occurs when physiologic forces act on the closure. METHODS: Median sternotomy was performed in 4 human cadavers (2 male) and closed with 7 interrupted stainless steel wires. The chest wall was instrumented to apply 4 types of distracting force: (1) lateral, (2) anterior-posterior, (3) rostral-caudal, and (4) a simulated Valsalva force. Forces were applied in each direction and were limited to physiologic levels (< 400 N). Four sets of sonomicrometry crystals were placed equidistantly along the sternum to measure separation at the closure site. RESULTS: Sternal separation occurred as a result of the wires cutting through the bone. Less force was needed to achieve 2.0-mm distraction in the lateral direction (220 +/- 40 N) than in the anterior-posterior (263 +/- 74 N) and rostral-caudal (325 +/- 30 N) directions. More separation occurred at the lower end of the sternum than the upper. During lateral distraction, xiphoid and manubrial displacement averaged 1.85 +/- 0.14 and 0.35 +/- 0.12 mm, respectively. Anterior-posterior distraction caused 1.99 +/- 0.04-mm xiphoid displacement and 0.26 +/- 0.12-mm manubrial displacement. During a simulated Valsalva force, more separation occurred in the lateral (2.14 +/- 0.11 mm) than in the anterior-posterior (0.46 +/- 0.29 mm) or rostral-caudal (0.25 +/- 0.15 mm) directions. CONCLUSIONS: These data suggest that sternal dehiscence can occur under physiologic loads and that improved sternal stability may be readily achieved via mechanical reinforcement near the xiphoid. Closure techniques designed to minimize wire migration into the sternum should also be developed.