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1 Laboratory of Physiologic Studies, National Institute on Alcohol Abuse & Alcoholism, National Institutes of Health, Bethesda, MD, USA; Inotek Pharmaceuticals Corporation, Beverly, MA, USA; Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
2 Inotek Pharmaceuticals Corporation, Beverly, MA, USA
3 Department of Internal Medicine, University Hospital, Lausanne, Lausanne, Switzerland
4 Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
5 Department of Surgery, University of Medicine and Dentistry-New Jersey Medical School, Newark, New Jersey, NJ, USA; Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
6 Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary
7 Inotek Pharmaceuticals Corporation, Beverly, MA, USA; Department of Surgery, University of Medicine and Dentistry-New Jersey Medical School, Newark, New Jersey, NJ, USA; Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary
* To whom correspondence should be addressed. E-mail: pacher{at}mail.nih.gov.
Aging is associated with profound changes in 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 4-5-month (young) and 24-26-month-old (old) Fischer 344 male rats, using the Millar pressure-volume (PV) conductance catheter system. We evaluated systolic and diastolic function in vivo at different preloads, including preload recruitable stroke work (PRSW), +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 end-diastolic pressure-volume relation (EDPVR), an index of left ventricular stiffness, was also calculated. Aging was associated with decrease in left ventricular systolic pressure, +dP/dt, -dP/dt, +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 Fisher rats. Pressurevolume analysis is a sensitive method to determine cardiac function in rats.
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