Cardiac hypertrophy in response to systolic pressure overloading frequently results in contractile dysfunction, the cause for which has been unknown. Since, in contrast, the same degree and duration of hypertrophy in response to systolic volume overloading does not result in contractile dysfunction, we postulated that the contractile dysfunction of pressure hypertrophied myocardium might result from a direct effect of stress as opposed to strain loading on an intracellular structure of the hypertrophied cardiocyte. The specific hypothesis tested here is that the microtubule component of the cytoskeleton is such an intracellular structure, which, forming in excess, impedes sarcomere motion. The feline right ventricle was either pressure overloaded by pulmonary artery banding or volume overloaded by atrial septotomy. The quantity of microtubules was estimated from immunoblots and immunofluorescent micrographs, and their mechanical effects were assessed by measuring sarcomere motion during microtubule depolymerization. We show here that stress loading increases the microtubule component of the cardiac muscle cell cytoskeleton; this apparently is responsible for the entirety of the cellular contractile dysfunction seen in our model of pressure-hypertrophied myocardium. No such effects were seen in right ventricular cardiocytes from normal or volume-overloaded cats or in left ventricular cardiocytes from any group of cats. Importantly, the linked microtubule and contractile abnormalities are persistent and thus may be found to have significance for the deterioration of initially compensatory cardiac hypertrophy into the congestive heart failure state.

Background Intensive statins are superior to moderate statins in reducing morbidity and mortality after an acute myocardial infarction (AMI). While studies have documented rates of statin prescription as a quality performance measure, variations in hospitals’ rates of initiating, intensifying and maximizing statin therapy after AMI are unknown. Methods and Results We assessed statins at admission and discharge among 4340 AMI patients from 24 US hospitals (2005–08). Hierarchical models estimated site variation in statin initiation in naïve patients, intensification in those on sub-maximal therapy, and discharge on maximal therapy (defined as a statin with expected LDL-C lowering ≥50%), after adjusting for patient factors including LDL-C. Site variation was explored with a median rate ratio (MRR), which estimates the relative difference in risk ratios of 2 hypothetically identical patients at 2 different hospitals. Among statin naïve patients, 87% without a contraindication were prescribed a statin, with no variability across sites (MRR 1.02). Among patients who arrived on sub-maximal statins, 26% had their statin therapy intensified with modest site variability (MRR 1.47). Among all patients without a contraindication, 23% were discharged on maximal statin therapy with substantial hospital variability (MRR 2.79). Conclusions In a large, multicenter AMI cohort, nearly 90% of patients were started on statins during hospitalization, with no variability across sites. However, rates of statin intensification and maximization were low and varied substantially across hospitals. Given that more intense statin therapy is associated with better outcomes, changing the existing performance measures to include the intensity of statin therapy may improve care.

This report identifies a rapid increase in the expression of cardiac Na(+)-Ca2+ exchanger mRNA in response to an acute pressure overload. This enhanced exchanger expression appeared within 1 h after the onset of right ventricular pressure overload in the cat and was sustained during cardiac overloading for at least 4 h. Maintenance of this right ventricular pressure overload for 48 h evoked an increase in the production of exchanger protein. Because of our previous finding that load imposition on the heart initiates cell growth and our hypothesis that this is in response to the enhanced entry of cellular cations, we then examined the effect of Na+ influx into cultured adult cardiac myocytes, or cardiocytes, in terms of early anabolic responses. Pressure overload of the heart and cardiocyte Na+ influx were found to produce a common, rapid result in terms of both enhanced Na(+)-Ca2+ exchanger expression and accelerated synthesis of general and contractile proteins, the hallmarks of cardiac hypertrophy.

No abstract