Study Set Content:
Death-receptor mediated apoptotic signaling pathway can be triggered by (), and is one focus of cardio toxicity research.
cytokines
The tightly regulated cellular “housekeeping” process responsible or the degradation of damaged and dysfunctional cellular organelles and protein aggregates
Autophagy
Selective autophagy o mitochondria which is triggered by mitochondrial permeability transition pore opening and loss of mitochondrial membrane potential.
Mitophagy
refers to the general process by which the ventricular myocardium changes in structure and function. • This process is often referred to as “remodeling.”
Myocardial adaptation
In response to pathologic stimuli, such as exposure to environmental toxicants, myocardial remodeling is adaptive in the () term, but is maladaptive in the () term, and often results in further myocardial dysfunction.
short,long
The central feature of myocardial remodeling is an increase in ()mass associated with a change in the shape of the ventricle. • There are both physiologic hypertrophy and pathologic hypertrophy of the heart.
myocardial
is considered an adaptive response, which is an adjustment of cardiac function or an increased demand of cardiac output. Cardiac hypertrophy actually increases the risk or malignant arrhythmia and heart failure
Physiologic hypertrophy
disease
Pathologic hypertrophy
Activation of each of the components is sufficient to induce myocardial hypertrophic growth • Extrinsic and intrinsic stresses activate signaling transduction pathways leading to fetal gene program activation, enhanced protein synthesis of adult cardiomyocytes, and the eventual ()
hypertrophic phenotype.
triggered by inflammatory cytokines. • Can also be triggered by neurohormonal factors, such as atrial natriuretic peptide (ANP), which leads to dilated cardiomyopathy and deterioration of cardiac function
Myocardial apoptosis
may cause dilated cardiomyopathy or heart failure without an intermediate hypertrophic stage
Toxicologic exposures
is that the length of QT interval observed from a typical electrocardiogram is prolonged
QT prolongation
Clinically, long QT syndrome is defined when the QT interval is longer than
460 ms
– occurs with an average increase in QT interval by approximately 200 ms (a normalQ interval is about 300 ms). The development of multiple reentrant circuits within the heart causes ventricular arrhythmia, or TdP, leading to sudden cardiac death. Drugs causing TdP are considered severe cardiac toxic agents. Several drugs that were removed from the market due to their TdP effect include the cyclooxygenase-2 (COX-2) inhibitors rofecoxib (Vioxx) and valdecoxib (Bextra). o Drug-induced QT prolongation o Hypokalemia o Myocardial ischemic injury o Cardiac hypertrophy o Myocardial fibrosis o Heart failure
Torsade’s de pointes (TdP) –
Elevation of specific isoform CK-MB in the serum is a specific marker of acute myocardial infarction
Creatine kinase
Elevation of serum ()is likely reflective of the extent of myocardial damage, although not specific to cardiac muscle
Myoglobin
Cardiac neurohormone secreted by the ventricular myocardium in response to volume and pressure over-load, and the release of BNP is a valuable indicator of heart failure
B-type natriuretic peptide
are constituents of the myofilaments and expressed exclusively in cardiomyocytes. It is thus of absolute myocardial tissue specificity
Cardiac troponins T and I
is an important diagnostic marker as well as a drug used to alleviate congestive heart failure symptoms in cardiac decompensation. Has value for preclinical models of heart failure across species
B-type natriuretic peptide
Routinely used clinical and preclinical myocardial injury marker
Creatine kinase
