We have developed a microcomputer based, patented* diagnostic medical device which reproducibly, simply, and noninvasively quantifies the respiratory sinus arrhythmia (RSA) within a span of 1 minute. Using this technology the RSA is invariably present and accurately quantifiable in all individuals regardless of age. Its amplitude falls predictably approximately 10% per decade. Individuals with a transplanted heart or severe diabetic neuropathy have resting RSA that is normal for age. The shape and amplitude of the RSA during voluntary cardiorespiratory synchronization (VCRS) may reflect the compliance of the heart muscle and its response to rhythmically changing intrathoracic volume, pressure, and the subsequent ebb and flow of venous return. This new technology allows objective quantitative assessment of the biologic age of the heart and also the effect of any drug, disease, or behavior that affects the RSA. Both acute and chronic-cumulative cardiotoxic effects of anthracyclines are readily measured using this device. RSA disappears acutely following intravenous doxorubicin administration, and gradually returns toward pretreatment values during the 30 days following drug administration. An irreversible progressive fall-off of RSA (averaging 7% per 60 mg/m2 dose) also accompanies increasing cumulative doxorubicin dosage. RSA is invariably undetectable in patients with proven doxorubicin-induced cardiomyopathy. Determination of RSA by this new technology permits instantaneous, noninvasive, quantitative evaluation of cardiotoxicity induced by doxorubicin. Phase I will result in the development and production of a manufacturable Sine-o-graph RSA monitor which may be used to measure the RSA and to quantify doxorubicin-induced heart damage.*U.S. patent granted May 28, 1985. Canadian and European patents also granted; Japanese patent pending.National Institute on Aging (NIA)
