Early hemodynamic and biochemical changes in overloaded swine ventricle.

The present study was undertaken to investigate, in an animal model, the relationship between sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity, phospholamban phosphorylation, acylphosphatase activity, and hemodynamic changes that occur in the early phase of pressure overload. In 54 study-group pigs, weighing 40±5 kg each, an aortic stenosis was created with a band of umbilical tape tied around the aorta; 18 sham-operated pigs formed our control group. Eight animals (6 study and 2 control) were randomly assigned to each experimental time (0.5, 3, 6, 12, 24, 48, 72, 96, and 168 hr). All indices of left ventricular function declined significantly, with a peak at 6 hr and a return to baseline at 168 hr. At each observational time, SERCA2a activity, Ca2+ uptake, and acylphosphatase activity rose significantly, with a maximum increase at 6 hr. These changes indicated a higher expression of these proteins; conversely, phospholamban did not show significant changes in its concentration or in its phosphorylation status. Nuclear proto-oncogene c-fos expression rose at 6 hr. A strong inverse correlation was found when Ca2+-ATPase activity, Ca2+-ATPase expression, Ca2+ uptake, and acylphosphatase were compared with indices of systolic function. In our model of induced pressure overload, an initial phase of depressed myocardial contractility was accompanied by an increased sarcoplasmic reticulum function and by higher Ca2+-ATPase and Ca2+ uptake activities mediated by acylphosphatase. This new finding of Ca2+ homeostasis might indicate a compensatory mechanism for mechanical stress. Further studies are needed to confirm our findings.

Neurohormonal and echocardiographic results after CorCap and mitral annuloplasty for dilated cardiomyopathy.

BACKGROUND: Restrictive mitral annuloplasty (RMA) can be an effective treatment for functional mitral regurgitation in congestive heart failure (CHF). Passive cardiac restraint is another surgical approach, but the midterm results are not well characterized. METHODS: Thirty patients with functional mitral regurgitation were prospectively randomized to RMA alone or cardiac restraint with the CorCap Cardiac Support Device (Acorn Cardiovascular Inc, St. Paul, MN) and RMA. Clinical, echocardiographic, New York Heart Association (NYHA) functional class, Short Form 36-Item Health Survey (SF-36) quality of life scores, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) results were analyzed. RESULTS: No hospital deaths or device-related complications occurred. The two groups had comparable morbidity (p = 0.34). Echocardiography showed a trend towards a slightly better functional improvement during follow-up in CorCap plus RMA patients (between groups, p = 0.001). Both groups showed improved results for SF-36, NYHA, and NT-pro.BNP; however, CorCap plus RMA patients had significantly better SF-36 at discharge (p = 0.003), postoperative NYHA (p = 0.05), and NT-pro.BNP (p = 0.001). Survival (p = 0.46), freedom from CHF (p = 0.23), and rehospitalization (p = 0.28) were comparable. Patients in whom CHF developed after postoperative day 1 had higher NT-pro.BNP values (p = 0.001 at all time-points). CONCLUSIONS: Adjunctive application of CorCap with RMA correlated with better NT-pro.BNP at short-term follow-up together with slightly improved echocardiographic and functional results. This deserves further evaluation at midterm and long-term follow-up. Reduction of NT-pro.BNP at follow-up may be suggested as a prognostic index.