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

¹Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892; ²Inotek Pharmaceuticals Corporation, Beverly, Massachusetts 01915; ³Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary H-1082; ⁴Critical Care Division, Department of Internal Medicine, University Hospital, Lausanne 1005, Switzerland; ⁵Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; ⁶Department of Surgery, University of Medicine and Dentistry- New Jersey Medical School, Newark, New Jersey 07103; ⁷Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083; and ⁸Institute of Human Physiology and Clinical Experimental Research, Budapest, Hungary H-1082

Submitted 3 May 2004 ; accepted in final form 25 June 2004

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.

systolic dysfunction; diastolic dysfunction

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