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Biomedical subjects

R D Kirkpatrick

Publications and source records attributed to R D Kirkpatrick.

29 records · Page 2Linked to original sources

Method for studying arterial wave transmission effects on left ventricular function.

A technique for studying the real-time effects of arterial wave reflections on the performance of the isolated left ventricle was investigated. Real-time arterial loading of an isolated ferret heart with an asymmetric T-tube wave transmission model was obtained with the use of a multiprocessor computer control system and a volume control linear motor pump. The multiprocessor computer system was programmed to compute the instantaneous aortic flow from the instantaneous ventricular pressure. The time integral of the flow was used as a command to the linear motor pump to control the instantaneous ventricular volume. This loading system allowed the imposition of a wide variety of vascular impedances on the ventricle by changing the parameters of the asymmetric T-tube model.

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Short-time-scale left ventricular systolic dynamics. Evidence for a common mechanism in both left ventricular chamber and heart muscle mechanics.

Based on the premise that short-time-scale, small-amplitude pressure/volume/outflow behavior of the left ventricular chamber was dominated by dynamic processes originating in cardiac myofilaments, a prototype model was built to predict pressure responses to volume perturbations. In the model, chamber pressure was taken to be the product of the number of generators in a pressure-bearing state and their average volumetric distortion, as in the muscle theory of A.F. Huxley, in which force was equal to the number of attached crossbridges and their average lineal distortion. Further, as in the muscle theory, pressure generators were assumed to cycle between two states, the pressure-bearing state and the non-pressure-bearing state. Experiments were performed in the isolated ferret heart, where variable volume decrements (0.01-0.12 ml) were removed at two commanded flow rates (flow clamps, -7 and -14 ml/sec). Pressure responses to volume removals were analyzed. Although the prototype model accounted for most features of the pressure responses, subtle but systematic discrepancies were observed. The presence or absence of flow and the magnitude of flow affected estimates of model parameters. However, estimates of parameters did not differ when the model was fitted to flow clamps with similar magnitudes of flows but different volume changes. Thus, prototype model inadequacies were attributed to misrepresentations of flow-related effects but not of volume-related effects. Based on these discrepancies, an improved model was built that added to the simple two-state cycling scheme, a pathway to a third state. This path was followed only in response to volume change. The improved model eliminated the deficiencies of the prototype model and was adequate in accounting for all observations. Since the template for the improved model was taken from the cycling crossbridge theory of muscle contraction, it was concluded that, in spite of the complexities of geometry, architecture, and regional heterogeneity of function and structure, crossbridge mechanisms dominated the short-time-scale dynamics of left ventricular chamber behavior.

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Left ventricular function depends on previous beat ejection but not previous beat pressure load.

Previous beat contraction history, in which the performance of the left ventricle on any one beat is influenced by the mechanical events of the previous beat, may be important in the beat-to-beat regulation of left ventricular performance in the intact cardiovascular system. Prior studies of this phenomenon have established that mechanical events of the previous beat influence the function of the current beat, but it is not known whether the important mechanical influence is exerted by previous beat ejection or previous beat pressure. In addition, the magnitude of the effect of previous beat contraction history on left ventricular performance is unknown. To make these determinations, we performed experiments in six isolated rabbit left ventricle preparations buffer perfused at 30 degrees C. Left ventricular pressure and volume were controlled precisely with a servo-controlled linear motor system. After steady-state ejecting conditions were established by clamping left ventricular ejection pressure at 60% of peak isovolumic pressure, single test beats, which were pressure clamped at 40%, 60%, 80%, and 100% of peak isovolumic pressure, were introduced and followed by an isovolumic reference beat. As the level of pressure clamp decreased from 100% to 40%, developed pressure on the isovolumic beat following the single test beats increased from 139 +/- 15 (mean +/- SD) to 151 +/- 13 mm Hg. Similarly, peak positive left ventricular dP/dt increased from 1,718 +/- 209 to 1,864 +/- 181 mm Hg.sec-1 (both p less than 0.01). Multiple regression analysis showed that this increase in left ventricular function was related to previous beat ejection but not to previous beat pressure load or relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

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Time-domain formulation of asymmetric T-tube model of arterial system.

An asymmetric T-tube model of the arterial system with complex terminal loads was formulated in the time domain. The model was formulated to allow it to be fitted to the aortic pressure waveform, the aortic flow waveform, or simultaneously to both the aortic and descending aortic flow waveforms. Pressure and flow measurements were taken in anesthetized open-chest dogs under basal, vasoconstricted, and vasodilated states. It was found that the T-tube model fitted the data well in all formulations and in all vasoactive states. However, all parameters were estimated accurately in all vasoactive states only with the formulation that fitted to both aortic and descending aortic flow simultaneously. The T-tube model was compared with the three-element windkessel model with regard to the respective models' ability to recreate specific aspects of the pressure waveform and with regard to the estimates of global arterial parameters. The T-tube model recremated those features of the pressure waveform, such as diastolic waves, that the windkessel model could not. Also, the T-tube model systematically estimated lower global arterial compliance and higher characteristic impedance than the windkessel. It was argued that the T-tube model accurately represented important wave transmission features of the arterial loading system. The model is recommended for use in characterizing the arterial load and for merging with representations of the left ventricle in studies of left ventricle-systemic arterial interaction.

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Late-systolic pumping properties of the left ventricle. Deviation from elastance-resistance behavior.

Elastance-resistance [E(t)-R] representations of the left ventricle (LV) were evaluated for their ability to reproduce instantaneous pressure [P(t)] and outflow [Q(t)]. Experiments were performed in open-chest rats. P(t) and Q(t) were measured during steady-state ejecting beats and during a beat in which the aorta was suddenly clamped. The degree of clamping varied from partial to total occlusion. The total occlusion beat was considered an isovolumic beat that generated an isovolumic pressure [Piso(t)] with a characteristic time to maximal Piso(t) [Tpisomax]. In ejecting beats, 34% of stroke volume was delivered after Tpisomax. P(t) and Q(t) from the steady-state ejecting beats and Piso(t) from the clamped beat were then used to estimate parameters of an E(t)-R model. Components of P(t) and Q(t) not accounted for by E(t)-R were identified and termed extra-pressure [Pext(t)] and extra-outflow [Qext(t)]. Pext(t) and Qext(t) were near-zero valued until Tpisomax; then they became systematically positive and finally negative valued after end ejection. During partial aortic occlusion, P(t) was elevated and Q(t) was reduced. However, the time of ejection was extended, and the fraction of stroke volume delivered after Tpisomax increased as P(t) was made higher. Partial occlusion also prolonged the positive phase of Pext(t) and Qext(t). Elements possessing "active" and "deactive" properties were added to the E(t)-R model in an attempt to account for Pext(t) and Qext(t) during partial occlusion. Optional forms of these elements were considered. These expanded E(t)-R models were fitted to basal ejecting data and then asked to predict data from a partial occlusion beat. All expanded models failed to adequately predict the partial occlusion pressure and/or outflow. It was concluded that 1) late ejection was quantitatively important to LV pumping, 2) behavior during late ejection was inconsistent with E(t)-R, and 3) ad hoc modification of E(t)-R models was not likely to yield LV pumping models that could satisfactorily reproduce instantaneous P(t) and Q(t) behavior over the entire ejection period.

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Taurine: effect on myocardial relaxation.

1. The effects of taurine on cardiac inotropic state and relaxation were studied in the isolated rabbit heart using solutions containing three concentrations of calcium: 0.7, 1.8 and 3.0 mmol/l. 2. Increases in Ca2+ caused increases in inotropic indices, but had no effect on rate constant of relaxation. 3. Taurine had a positive inotropic effect at Ca2+ = 0.7 mmol/l, an equivocal effect at Ca2+ = 1.8 mmol/l and a negative inotropic effect at Ca2+ = 3.0 mmol/l. 4. Taurine had no effect on the rate constant of relaxation at any Ca2+ concentration. 5. Taurine modulates the positive inotropic effect of Ca2+ but neither taurine nor Ca2+ affect the rate constant of relaxation.

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Pressure response to quick volume changes in tetanized isolated ferret hearts.

Observed pressure responses to quick volume changes in the isolated tetanized heart of ferrets were compared with previously reported tension responses to quick length changes in isolated cardiac muscle. Hearts were isolated from ferrets, perfused with ryanodine solution, and stimulated rapidly (50 ms between stimulations) to produce repeated 4-s intervals of tetanus. During each tetanus interval, volume increments of different amplitudes were rapidly removed and then reinfused into the left ventricular chamber. The pressure responses to these volume changes were evaluated for differences between withdrawals and infusions and for dependence on the amplitude of the volume change. It was found for both withdrawal and infusion that the response could be divided into three phases: 1) an immediate phase coincident with volume change, 2) a fast-recovery phase, and 3) a slow-recovery phase. The amplitude of the immediate phase was linearly dependent on the volume change so that a single regression line fit all the data (withdrawal and infusion). The fast recovery phase was 2.5 times faster for infusion than for withdrawal and generated a rebound effect with the pressure going below the initial pressure in the response to infusion. The pressure never went above the initial pressure in the response to withdrawal. The slow-recovery phases in infusion and withdrawal did not differ. These responses in the isolated heart bear striking similarities to tension responses to quick length changes in isolated constantly activated cardiac muscle. We concluded that muscle fiber dynamics were being faithfully transformed to left ventricular (LV) chamber dynamics without appreciable distortion because of the many intervening factors between the wall muscle fiber and the LV chamber.(ABSTRACT TRUNCATED AT 250 WORDS)

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The presence of endotoxin activity in cases of experimentally-induced heartwater in sheep.

The presence of endotoxin was examined in 5 sheep with experimentally-induced heartwater. Two peaks in endotoxin levels were recorded in 4 out of the 5 sheep during the acute stage of the disease. The 1st peak coincided with or occurred shortly after the febrile reaction (over 40 degrees C). The 2nd peak occurred 3-5 days after the 1st, and in 2 sheep this 2nd elevation in endotoxin levels was associated with severe clinical signs (rapid and laboured breathing, cyanosis and recumbency), and 1 of the 2 sheep died on the day of the 2nd elevation. Both endotoxin peaks were of short duration and levels had decreased in the 24-h follow-up samples.

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Validation of optional elastance-resistance left ventricle pump models.

Left ventricular pressure, P(t), and outflow Q(t), data were collected in anesthetized, open-chest rats and dogs. The data were used in a three-tiered validation procedure to evaluate 14 competing forms of elastance [E(t)]-resistance (R) left ventricle (LV) pump models. Competing models arose from considering two forms of parameterization of E(t), time variation versus no time variation in LV unstretched volume (Vd) and dependence versus no dependence of R on P(t) and isovolumic P(t). A descriptive test based on the normalized root-mean-square errors in the fit to P and, separately, in the fit to Q was used to distinguish between models. The best of the competing models was the one that treated Vd as a function of time and R as a constant. Models of this form fitted the data very well and were said to be descriptively valid. The best of the competing models were then asked to predict the observed responses to changes in afterload, preload, and prior-beat history. The models did not predict these conditions well and failed to pass the test for predictive validity. Additionally, the model parameters were judged not to represent their supposed physical homologs and, thus, failed the test for explanative validity. One cause for E(t)-R model failure was an inadequate representation of events at end systole. This deficiency was apparently due to not accounting for deactivation in the model. Other features may also be needed before a comprehensive LV model can be formulated. Identical conclusions were made from data from the rat and the dog.

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