This study quantifies the effect of afterload and preload changes and of temperature on interbeat interval variability of the intact isolated heart. Ventricular pressure pulse records were obtained from isolated working rat hearts. The variability of interbeat intervals (BIs) was quantified by C90, the central 90% range of the BIs during 10 min periods; predominant frequencies were searched for by power spectral analysis. At 37 degrees C the BI lengths oscillated pseudo-randomly with BI variability C90< or =4 ms. Alternating signs of consecutive BI differences were predominant, and no peaks. were seen in the power spectra. Changes in end-diastolic and aortic pressure had little effect. From 37 degrees C down to 27 degrees C the variability increased about sevenfold, run phase length became randomly distributed, and individual, time-variant peaks occurred in the power spectra. BI variability vanished during atrial pacing. We conclude that: (1) effective mutual synchronization with minimal fluctuation happens within the sino-atrial node of intact rat hearts at body temperature, and synchronization is not affected even by extreme changes in pre- and afterload, (2) the sino-atrial node is the sole source of BI variability in the intact isolated rat heart, (3) low temperature hampers this functional organization which can be reestablished by sinus node accelerating agents (isoprenaline, theophylline), (4) decreasing frequency by N6-Cyclopentyladenosine at normothermia also increases BI variability but less pronouncedly than hypothermia does.

Myocardial relaxation has received much attention as an important property in normal and pathologic hearts [1], especially as a sensitive indicator of beginning ("diastolic") heart failure [2,3] and myocardial hypoxia [4][5][6]. The time constant of the exponential part of diastolic left ventricular pressure (LVP) fall has become a widespread index of isovolumic relaxation. The beginning of isovolumic relaxation (tϭ0) is usually assumed at the time of peak negative pressure fall velocity, min LVdP/dt. The time when previous end-diastolic pressure is re-encountered is chosen as the end point of isovolumic relaxation. The time course of LVP during that relaxation interval is usually fitted to the exponential: , 2 by *ϭ 0 ϩb t*, wherein t* is the central point (i.e., half the length) of the time interval of isovolumic pressure fall; ∞ , asymptotic at t→∞ in model Eq. 3; BI, interbeat interval; C 90 , central 90% range of a set of data (i.e., the shortest possible interval which covers at least 90% of the data).

is still in use. It was extended by coestimating the actual pressure asymptote empirically [2], yielding the most popular three-parametric monoexponential regression with coestimated (variable) asymptote. Others prefer the semilogarithmic τ estimate, assuming that fixing a zero asymptote may compensate for misestimation caused by the nonexponentiality of the actual pressure decay [3]. Goodness-of-fit was improved in canine [4] and human hearts [5] by substituting the exponential with a logistic model that is given by the following regression equation with fixed γ = 0.5:Japanese Journal of Physiology Vol. 54, No. 4, 2004 347 Myocardial relaxation is crucial to prepare the ventricle for diastolic refill. The time constant, τ, of the decelerative part of the left ventricular isovolumic pressure decay is widely used as a lusitropic index, i.e., to quantify the phase of ventricular relaxation.A multitude of models and numerical methods developed during the past decades to estimate time constants of the isovolumic pressure decay, including different selections of the regression interval and digitizing rates, have brought discredit on this lusitropic parameter by yielding inconsistent and noncomparable results. Abstract:The decelerative part of the left ventricular isovolumic pressure decay is an important phase to make the heart ready for diastolic refill (lusitropy). Its widely used characterization by an exponential regression with zero pressure asymptote or coestimated asymptote provides empirically biased time constant estimates because of significant deviations of the pressure decay from exponentiality. We systematically analyzed the regression residua of these pressure decays in isolated ejecting rat, guinea pig, and ferret hearts. A four-parametric logistic (tangens hyperbolicus) function, together with a superimposed acustomechanic oscillation, yields normally distributed residua with standard regression error typically less than one per cent of the initial pressure; this is the first model with proved unbiased and statistically complete regressive extraction of the information provided by the time course of pressure decay. Equal values of the lusitropic parameters (logistic time constant and pressure asymptote) were estimated even after the oscillatory component was removed from the regression model. Reliable estimates of the frequency, but not of the amplitude, can be obtained by fitting the oscillation model to the residua provided by the logistic; this two-step method is statistically weaker than the full onestep model, but it reduces computational effort.In conclusion, the four-parametric logistic, but not a three-parametric exponential or logistic model, suffices to obtain unbiased lusitropic parameters characterizing the left ventricular isovolumic pressure decay of small animal hearts.

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In isolated ejecting rat and guinea pig hearts, the sensitivity of the time constant tau of left ventricular isovolumic pressure fall, the maximum pressure fall velocity min LVdP/dt, and the relaxation time to different hemodynamic conditions, temperature, and isoprenaline were investigated. Tau was obtained by fitting the isovolumic pressure fall three-parametrically to the exponential p(t) = p infinity + (p0-p infinity) exp (-t/tau) which was found to be superior to semilogarithmic estimation. The influence of different working conditions on the relaxation parameters was tested by a rank correlation test and quantified by calculating standardized regression coefficients. Hemodynamic conditions were altered by changing left ventricular end-diastolic pressure (increasing inflow to the heart) and peak pressure (max LVP, varying aortic outflow resistance), and by atrial pacing (variation of interbeat interval). Lusitropic sensitivity was investigated by changing temperature and by applying isoprenaline. All regression parameters were only moderately sensitive to changes in end-diastolic pressure, max LVP, or heart rate, with the exception of a considerable afterload dependence of min LVdP/dt in rat hearts. This dependence, however, can be overcome to a large extent by dividing min LVdP/dt by mean aortic pressure. Isoprenaline strongly influenced all relaxation parameters, and so did temperature, except for relaxation time in guinea pig hearts. We conclude that tau serves as a reliable relaxation parameter, also in the hearts of small animals with heart rates up to 450 beats/min. In isolated hearts, min LVdP/dt, corrected for afterload dependence, is also suitable as a complementary index of the early relaxation phase.