ABSTRACT
OBJECTIVES: The rapid induction of heat shock proteins (HSPs) by cardiac overload has been shown using in vivo models and it is assumed that HSPs are involved in myocardial protection against cardiac overload. However, the mechanisms for the induction of heat shock response by cardiac overload remain unclear. We examined whether increased preload as mechanical stress directly induces heat shock gene expression. METHODS: Rat hearts were isolated and perfused with Krebs-Henseleit buffer by the Langendorff method. Whole-cell extracts were prepared for gel mobility shift assay using oligonucleotides containing the heat shock element. We examined the induction of the DNA-binding activity of heat shock transcription factor (HSF), by which the transcription of heat shock genes is mainly regulated, during increased preload of left ventricle (LV) or perfusion with the buffer containing epinephrine, norepinephrine, angiotensin II, or vasopressin. RESULTS: In preloaded hearts, with LVEDP of both 30 and 50 mmHg, the DNA-binding activity of HSF1 was detected at 10 min, and increased at 20 and 60 min. At any time point, the activity with LVEDP of 50 mmHg was stronger than that with LVEDP of 30 mmHg. However, none of these hypertensive agents activated the DNA-binding activities of HSF. In afterloaded hearts, with the perfusion of norepinephrine, the activation of HSF was not induced. CONCLUSION: Our findings demonstrate that increased preload as mechanical stress directly induces the activation of HSF1 in the LV-overloaded heart.
Subject(s)
DNA-Binding Proteins/metabolism , Gene Expression Regulation , Ventricular Dysfunction, Left/metabolism , Angiotensin II/pharmacology , Animals , Cardiomegaly/metabolism , DNA-Binding Proteins/genetics , Epinephrine/pharmacology , Gene Expression Regulation/drug effects , Heat Shock Transcription Factors , Heat-Shock Proteins/metabolism , Hemodynamics , Male , Norepinephrine/pharmacology , Organ Culture Techniques , Rats , Rats, Sprague-Dawley , Stress, Mechanical , Transcription Factors/metabolism , Vasopressins/pharmacologyABSTRACT
BACKGROUND: The aim of this study was to report midterm valve replacement (VR) results with the Carbo-Medics valve (Sulzer Carbomedics, Austin, TX). METHODS: From 1991 to 1999, 468 patients aged 13 to 76 years (mean 56 years) underwent VR with CarboMedics valve: 239 aortic (A), 167 mitral (M), and 62 A+M or double valve replacement (DVR). Mean follow-up time was 4.4 years; follow-up was 99.1% complete for 2,016 patient-years (PY). The anticoagulation level was targeted to an international normalized ratio of 1.47 to 2.8. RESULTS: The hospital mortality rate was 1.2%. Actuarial analysis for the entire group at 7 years for survival was 87%+/-2.3%. Freedom from valve-related death was 94%+/-1.9%. Freedom from thromboembolic and bleeding events, respectively, were as follows: for AVR, 82%+/-4.9% (2.4%/PY) and 88%+/-2.9% (1.6%/PY); for MVR, 95%+/-2.1% (0.8%/PY) and 91%+/-3.1% (1.3%/PY); and for DVR, 96%+/-3.2% (0.7%/PY) and 85%+/-9.7% (1.0%/PY). Actuarial freedom from reoperation was 98%+/-1.4%. CONCLUSIONS: The CarboMedics valve can be implanted with satisfactory early mortality and a low incidence of valve-related events even under low-intensity anticoagulation, as shown in a Japanese population.
