The incidence of diastolic heart failure increases dramatically with age. We investigated the impact of long-term exercise training on age-related diastolic dysfunction. Old (25-month-old) male Fischer 344 rats were studied after 12 weeks of treadmill exercise training or sedentary cage life (N=7, in each group). We determined cardiac performance using a pressure-volume conductance catheter and magnetic resonance imaging. Collagen volume fraction (CVF) and myocardial collagen solubility by pepsin as an index of advanced glycation end products (AGEs) crosslinked collagen were measured. The maximal slope of systolic pressure increment (+dP/dt) and the slope of end-systolic pressure-volume relation were higher, and end diastolic volume (EDV), delta EDV (the percentage of the EDV increment-to-baseline EDV) and the slope of end-diastolic pressure-volume relation were lower in training group. The maximal slope of diastolic pressure decrement (-dP/dt) and time constant of LV pressure decay (tau) had no difference. AGEs cross-linked collagen, not CVF was reduced by exercise training. Long-term exercise training appears to attenuate age-related deterioration in cardiac systolic function and myocardial stiffness and could be reduce in pathologic AGEs cross-linked collagen in myocardium.
*Aging ; Animals ; Blood Pressure ; Collagen/*metabolism ; Glycosylation End Products, Advanced/metabolism ; Heart Failure, Diastolic/metabolism/*physiopathology ; Magnetic Resonance Imaging ; Male ; Myocardium/*metabolism ; Physical Conditioning, Animal ; Rats ; Rats, Inbred F344 ; Solubility ; Stroke Volume/physiology

OBJECTIVETo study the effects of different doses of tetramethylpyrazine on injury and calcium overload in myocardial cells of diastole heart failure rat model.

METHODDiastole heart failure model was established by the coarctation of abdominal aorta. 4 weeks after operation, forty rats with DHF were divided into four groups randomly as follows, model (physiological saline 2 mL), tetramethylpyrazine (40 mg x kg(-1) x d(-1)), tetramethylpyrazine (20 mg x kg(-1) x d(-1)), tetramethylpyrazine (10 mg x kg(-1) x d(-1)), with 10 rats for each group (n = 10), and 10 sham operation rats was taken as control (physiological saline, 2 mL). After 4 weeks administration, cardiac function was determined by catheter. The changes of myocardial ultrastructure were investigated by means of transmission electron microscope. [Ca2+ ]i was measured by laser scanning confocal microscope [LSCM]. Ca(2+) -ATPase activity of mitochondrion was measured by the method of enzymatic reaction chromatometry.

RESULTCompared with the control group, the rats of operation group have no significant changes on left ventricular systolic pressure (LVSP) and maximal rising rate of ventricular pressure (+dp/dt(max)), but left ventricular end diastolic pressure (LVEDP) increased markedly, maximal delining rate of ventricular pressure (-dp/dt(max)) decreased significantly, left ventricular relax time constant quantity (T) markedly extended, myocardial pathology injured markedly, [Ca2+]i in cardiocyte increased markedly and the Ca(2+) -ATPase activity of myocardial mitochondria decreased significantly in the model group. After 4 weeks administration, compared with the model group, LVEDP decreased significantly, -dp/dt(max) increased markedly, T markedly shortened, myocardial ultrastructure damage were significantly reduced, fluorescent value decreased and Ca(2+) -ATPase activity of mitochondrion increased significantly in TMP low-dose group and mid-dose group.

CONCLUSIONLow dosage of TMP can reduced myocardial pathology injury, increased Ca(2+)-ATPase activity of myocardial mitochondria, improve cardiac function and [Ca2+]i in cardiocyte and antagonise calcium overload of rats with DHF.

Animals ; Calcium ; metabolism ; Calcium-Transporting ATPases ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Heart Failure, Diastolic ; drug therapy ; metabolism ; physiopathology ; Humans ; Male ; Myocardium ; metabolism ; Pyrazines ; administration & dosage ; Random Allocation ; Rats ; Rats, Wistar ; Ventricular Pressure ; drug effects

OBJECTIVETo study the effects of different doses of berberine on hemodynamic parameters and calcium ion concentration ([Ca2+]i) of diastole heart failure rat models.

METHODThe mouse models of diastole heart failure were made by the imcomplete ligation of abdominal aorta. Forty Wistar heart failure rats were divided randomly into four groups, with 10 for each group (n = 10). Heart failure rats were treated according to different doses drugs as follows: Model (natrii chloride 2 mL), berberine (63 mg x kg(-1) x d(-1)), berberine (42 mg x kg(-1) x d(-1)), berberine (21 mg x kg(-1) x d(-1)) ig, for each of the four groups respectively, 4 weeks after coarctation of ascending aorta operation; and 10 age matched sham operation group was taken as control (natrii chloridi, 2 mL). After administration four weeks, cardiac function was determined by catheter. Isolate single cardiomyocytes of rat which were loaded with Ca(2+)-sensitive fluorescent indicator Fluo-3/AM. [Ca2+]i represented by fluorescent intensity [FI] was measured by laser scanning cofocal microscope [LSCM].

RESULTThe rats of operation group have no significant changes with those of the control on left ventricular systolic pressure (LVSP) and maximal rising rate of ventricular pressure (+dp/dt(max)), left ventricular end diastolic pressure (LVEDP) was much higher in operation group (P < 0.01), but maximal falling rate of ventricular pressure (-dp/dt(max)) was depressed (P < 0.01), left ventricular relax time constant quantity (T) was markedly extended (P < 0.01). [Ca2+]i level in carkiac muscle cell was elevated markedly (P < 0.05). Compared with operation group, high dose of Ber can decrease LEVDP, improve (-dp/dt(max)) (P < 0.01), decurtate left ventricular relax time constant quantity (P < 0.01) and decrease [Ca2+]i level better than those of middle and low dose group (P < 0.01).

CONCLUSIONBerberine is an effective new potent drug for conspicuous symptom relief of heart failure with positive dose dependency and step down [Ca2+]i of myocardial cell.

Animals ; Berberine ; pharmacology ; therapeutic use ; Blood Pressure ; drug effects ; Calcium ; metabolism ; Dose-Response Relationship, Drug ; Female ; Heart Failure, Diastolic ; drug therapy ; metabolism ; pathology ; physiopathology ; Heart Ventricles ; drug effects ; physiopathology ; Hemodynamics ; drug effects ; Male ; Myocytes, Cardiac ; drug effects ; metabolism ; Rats ; Rats, Wistar ; Ventricular Pressure ; drug effects