Left ventricular pressure-volume relationship in a rat model of advanced aging-associated heart failure.

Aging is associated with profound changes in the structure and function of the heart. A fundamental understanding of these processes, using relevant animal models, is required for effective prevention and treatment of cardiovascular disease in the elderly. Here, we studied cardiac performance in 4- to 5-mo-old (young) and 24- to 26-mo-old (old) Fischer 344 male rats using the Millar pressure-volume (P-V) conductance catheter system. We evaluated systolic and diastolic function in vivo at different preloads, including preload recruitable stroke work (PRSW), maximal slope of the systolic pressure increment (+dP/dt), and its relation to end-diastolic volume (+dP/dt-EDV) as well as the time constant of left ventricular pressure decay, as an index of relaxation. The slope of the end-diastolic P-V relation (EDPVR), an index of left ventricular stiffness, was also calculated. Aging was associated with decrease in left ventricular systolic pressure, +dP/dt, maximal slope of the diastolic pressure decrement, +dP/dt-EDV, PRSW, ejection fraction, stroke volume, cardiac and stroke work indexes, and efficiency. In contrast, total peripheral resistance, left ventricular end-diastolic volume, left ventricular end-diastolic pressure, and EDPVR were greater in aging than in young animals. Taken together, these data suggest that advanced aging is characterized by decreased systolic performance accompanied by delayed relaxation and increased diastolic stiffness of the heart in male Fischer 344 rats. P-V analysis is a sensitive method to determine cardiac function in rats

A new, potent poly(ADP-ribose) polymerase inhibitor improves cardiac and vascular dysfunction associated with advanced aging

Increased production of reactive oxygen and nitrogen species has recently been implicated in the pathogenesis of cardiac and endothelial dysfunction associated with atherosclerosis, hypertension, and aging. Oxidant-induced cell injury triggers the activation of nuclear enzyme poly(ADP-ribose) polymerase (PARP), which in turn contributes to cardiac and vascular dysfunction in various pathophysiological conditions including diabetes, reperfusion injury, circulatory shock, and aging. Here, we investigated the effect of a new PARP inhibitor, INO-1001, on cardiac and endothelial dysfunction associated with advanced aging using Millar's new Aria pressure-volume conductance system and isolated aortic rings. Young adult (3 months old) and aging (24 months old) Fischer rats were treated for 2 months with vehicle, or the potent PARP inhibitor INO-1001. In the vehicle-treated aging animals, there was a marked reduction of both systolic and diastolic cardiac function and loss of endothelial relaxant responsiveness of aortic rings to acetylcholine. Treatment with INO-1001 improved cardiac performance in aging animals and also acetylcholine-induced, nitric oxide-mediated vascular relaxation. Thus, pharmacological inhibition of PARP may represent a novel approach to improve cardiac and vascular dysfunction associated with aging

A genetic analysis of ambulatory cardiorespiratory coupling.

This study assessed the heritability of ambulatory heart period, respiratory sinus arrhythmia (RSA), and respiration rate and tested the hypothesis that the well-established correlation between these variables is determined by common genetic factors. In 780 healthy twins and siblings, 24-h ambulatory recordings of ECG and thorax impedance were made. Genetic analyses showed considerable heritability for heart period (37%-48%), RSA (40%-55%), and respiration rate (27%-81%) at all daily periods. Significant genetic correlations were found throughout. Common genes explained large portions of the covariance between heart period and RSA and between respiration rate and RSA. During the afternoon and night, the covariance between respiration rate and RSA was completely determined by common genes. This overlap in genes can be exploited to increase the power of linkage studies to detect genetic variation influencing cardiovascular disease risk. Copyright © 2005 Society for Psychophysiological Research

Frequency components of systolic blood pressure variability reflect vasomotor and cardiac sympathetic functions in conscious rats

In this study, after confirming the suppression of autonomic nervous function by isoflurane anesthesia using autonomic antagonists, we pharmacologically investigated the involvement of vasomotor and cardiac sympathetic functions in systolic blood pressure variability (SBPV) frequency components in conscious rats at rest and during exposure to low-ambient temperature (LT-exposure, 9°C for 90 min). Under unanesthesia, phentolamine administration (α-adrenoceptor antagonist, 10 mg/kg) decreased the mid-frequency component (MF 0.33–0.73 Hz) and inversely increased the high-frequency component (HF 1.3–2.5 Hz). The increased HF was suppressed by subsequent treatment with atenolol (β-adrenoceptor antagonist, 10 mg/kg), but not with atropine (muscarinic receptor antagonist, 10 mg/kg). Moreover, phentolamine administration after atenolol decreased MF, but did not increase HF. LT-exposure increased MF and HF; however, phentolamine pretreatment suppressed the increased MF during LT-exposure, and atenolol pretreatment dose-dependently decreased the increased HF. These results suggest that MF and HF of SBPV may reflect α-adrenoceptor-mediated vasomotor function and β-adrenoceptor-mediated cardiac sympathetic function, respectively, in the conscious state

The association between neuroticism and heart rate variability is not fully explained by cardiovascular disease and depression

Neuroticism is associated with cardiovascular disease, autonomic reactivity, and depression. Here we address the extent to which neuroticism accounts for the excess heart disease risk associated with depression and test whether cardiac autonomic tone plays a role as mediator. Subjects were derived from a nationally representative sample (n = 1,255: mean age 54.5, SD = 11.5). Higher neuroticism was associated with reduced heart rate variability equally under rest and stress. The baseline structural equation model revealed significant paths from neuroticism to heart rate variability, cardiovascular disease and depression, and between depression and cardiovascular disease, controlling for age, sex, height, weight, and BMI. Dropping both the neuroticism to heart rate variability, and neuroticism to heart disease paths significantly reduced the model fit (p < .001 in each case). We conclude that neuroticism has independent associations with both autonomic reactivity and cardiovascular disease, over and above its associations with depression and other related variables