Differential effects of epsilon-aminocaproic acid and aprotinin on matrix metalloproteinase release in patients following cardiopulmonary bypass.

This study examined whether differential effects of 2 agents commonly used for hemostatic purposes during cardiac surgery, aprotinin and epsilon-aminocaproic acid (EACA), exist with respect to elevations in proinflammatory interleukins (ILs) and matrix metalloproteinases (MMPs) in patients undergoing coronary artery bypass surgery. Sixty patients were prospectively randomized to receive either aprotinin (1 x 10 KIU; n = 30) or EACA (5 g IV; n = 30), and blood samples were obtained for IL and MMP levels just before induction of anesthesia (Baseline), 10 minutes after separation from cardiopulmonary bypass (Post), and 6 hours after surgery (6 hours). IL-6 was increased at Post in the EACA group and increased further at 6 hours.

Specific temporal profile of matrix metalloproteinase release occurs in patients after myocardial infarction: relation to left ventricular remodeling.

Background: Changes in matrix metalloproteinase (MMP) and tissue inhibitors of MMPs (TIMPs) contribute to left ventricular (LV) remodeling after myocardial infarction (MI). We tested the hypothesis that a specific plasma MMP/TIMP profile would emerge after MI and be associated with the degree of LV dilation.

Methods And Results: LV end-diastolic volume and MMP/TIMP plasma profiles were determined in 53 age-matched control subjects and 32 post-MI patients from day 1 through 180 after MI.

Differential effects of protein kinase C isoform activation in endothelin-mediated myocyte contractile dysfunction with cardioplegic arrest and reperfusion.

Background: Increased myocardial interstitial levels of endothelin (ET) occur during cardioplegic arrest (CA) and may contribute to contractile dysfunction. Endothelin receptor transduction involves the protein kinase-C (PKC) family comprised of multiple isoforms with diverse functions. Which PKC isoforms may be involved in ET-induced contractile dysfunction after CA remains unknown.

Matrix metalloproteinases/tissue inhibitors of metalloproteinases: relationship between changes in proteolytic determinants of matrix composition and structural, functional, and clinical manifestations of hypertensive heart disease.

Background: Chronic hypertension may cause left ventricular (LV) remodeling, alterations in cardiac function, and the development of chronic heart failure (CHF). Changes in the composition of the extracellular matrix (ECM) known to occur in hypertension are believed to be causally related to these structural, functional, and clinical outcomes. However, whether the determinants of ECM composition, such as the balance between ECM proteases (matrix metalloproteinases [MMPs]) and their tissue inhibitors [TIMPs]), are altered in hypertensive heart disease is unknown.

Myocardial interstitial matrix metalloproteinase activity is altered by mechanical changes in LV load: interaction with the angiotensin type 1 receptor.

LV myocardial remodeling is a structural hallmark of hypertensive hypertrophy, but molecular mechanisms driving this process are not well understood. The matrix metalloproteinases (MMPs) can cause myocardial remodeling in chronic disease states, but how MMP activity is altered with a mechanical load remains unknown. The present study quantified interstitial MMP activity after a discrete increase in LV load and dissected out the contributory role of the angiotensin II Type 1 receptor (AT1R).