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B K Slinker

Publications and source records attributed to B K Slinker.

47 records · Page 3Linked to original sources

Systolic direct ventricular interaction affects left ventricular contraction and relaxation in the intact dog circulation.

Changes in right ventricular systolic function directly influence left ventricular systolic function. Most of our knowledge of this systolic direct ventricular interaction comes from studies of isolated hearts, which suggest that changes in right ventricular size only affect left ventricular systolic function at low pressures and volumes. However, almost nothing is known about systolic direct ventricular interaction in a heart functioning in situ as a part of the intact circulation. We used sudden constriction of the pulmonary artery to assess the immediate effect of a change in right ventricular pressure and contraction pattern on left ventricular contraction and relaxation on the beat following the pulmonary artery constriction in anesthetized open-chest dogs. By focusing on this first beat, we were able to avoid the confounding effect of series ventricular interaction, which changes left ventricular filling and, thus, indirectly influences left ventricular function. At baseline left ventricular end-diastolic pressure of 9.6 +/- 2.1 mm Hg (mean +/- SD), sudden pulmonary artery constriction increased left ventricular peak systolic pressure by 3 +/- 2 mm Hg (2% change), left ventricular stroke volume by 2 +/- 2 ml (8% change), and monoexponential time constant of left ventricular pressure fall during relaxation by 9 +/- 6 msec (22% change). This increased left ventricular relaxation time constant was associated with altered regional segment length changes in the posterior and anterior left ventricular free walls during relaxation. We conclude that systolic direct ventricular interaction affects left ventricular systolic function and relaxation under normal conditions in the intact circulation.

Animals↗

Similar normalized Emax and O2 consumption-pressure-volume area relation in rabbit and dog.

The end-systolic pressure-volume relation (ESPVR), a measure of ventricular contractile state, and systolic pressure-volume area (PVA), a primary determinant of cardiac oxygen consumption per beat (VO2), have been derived from the pressure-volume diagram of the cross-circulated dog left ventricle. The slope of the PVA-VO2 relation represents the efficiency of chemomechanical energy transduction of the contractile machinery. To see whether these relationships were similar in other animals, we studied the isovolumic ESPVR and the VO2-PVA relation in nine excised, cross-circulated rabbit left ventricles. The base-line ESPVR was linear (r = 0.94-0.99) with the slope (Emax) and volume-axis intercept (V0) equal to 83.4 +/- 18.3 mmHg/ml and 0.43 +/- 0.17 ml, respectively. When normalized for left ventricular weight, Emax (4.1 +/- 1.1 mmHg.ml-1.100 g) and V0 (8.9 +/- 3.7 ml/100 g) were similar to values reported for the dog left ventricle. The correlation between PVA and VO2 was linear (r = 0.93-1.00), and the slope (1.90 X 10(-5) +/- 0.44 X 10(-5) ml O2.mmHg-1.ml-1) and VO2-axis intercept (0.040 +/- 0.009 ml O2.beat-1.100 g-1) were similar to values found in the dog left ventricle. Hence, despite the greatly different heart size, the base-line contractile state and chemomechanical energy conversion efficiency of the excised, cross-circulated rabbit left ventricle are similar to those of the dog left ventricle.

Animals↗

Accuracy of volume measurement of rabbit left ventricle by balloon method.

Although the intraventricular balloon method has been commonly used to measure left ventricular volume of the isolated heart preparation of various animals, the accuracy of the method has not been examined in the ventricle of small animals such as the rabbit. To assess the accuracy of the intraventricular balloon method in measuring left ventricular volume, we measured the space between the balloon inflated in the left ventricle and the endocardial surface in eight Formalin-fixed rabbit left ventricles. The space was only 0.05-0.12 ml (1.5-3.6% of total left ventricular volume) at intraballoon pressures of 40-160 mmHg. However, it increased to 0.37 ml (14.6% of total ventricular volume) with a decrease in pressure to 5 mmHg. We conclude that the intraventricular balloon method accurately measures left ventricular volume in the rabbit, especially in the high pressure range.

Animals↗

Multiple linear regression is a useful alternative to traditional analyses of variance.

Physiologists often wish to compare the effects of several different treatments on a continuous variable of interest, which requires an analysis of variance. Analysis of variance, as presented in most statistics texts, generally requires that there be no missing data and often that each sample group be the same size. Unfortunately, this requirement is rarely satisfied, and investigators are confronted with the problem of how to analyze data that do not strictly fit the traditional analysis of variance paradigm. One can avoid these pitfalls by recasting the analysis of variance as a multiple linear regression problem. When there are no missing data, the results of a traditional analysis of variance and the corresponding multiple regression problem are identical; when the sample sizes are unequal or there are missing data, one can use a regression formulation to analyze data that cannot be easily handled in a traditional analysis of variance paradigm and thus overcome a practical computational limitation of traditional analysis of variance. In addition to overcoming practical limitations of traditional analysis of variance, the multiple linear regression approach is more efficient because in one run of a statistics routine, not only is the analysis of variance done but also one obtains estimates of the size of the treatment effects (as opposed to just an indication of whether such effects are present or not), and many of the pairwise multiple comparisons are done (they are equivalent to t tests for significance of the regression parameter estimates). Finally, interaction between the different treatment factors is easier to interpret than it is in traditional analysis of variance.

Analysis of Variance↗

Chronic pressure overload hypertrophy decreases direct ventricular interaction.

We studied the relative roles of direct (via the interventricular septum) and series (via the pulmonary circulation) ventricular interaction in hearts with concentric left ventricular hypertrophy by using statistical models to analyze the transient responses in right and left ventricular pressures and dimensions to occlusions of the venae cava and pulmonary artery in five open-chest anesthetized dogs. The left ventricles of these dogs had moderate concentric hypertrophy (31% increase in mass) induced by 3 mo of renovascular hypertension [peak left ventricular pressure = 160 +/- 13 (SD) mmHg]. At end diastole we found that direct interaction was only about one-tenth as important as series interaction in determining left ventricular size with the pericardium around the heart. At end systole we found that direct interaction was about one-fifth as important as the end-systolic pressure-volume relationship in determining left ventricular size. Removing the pericardium decreased the importance of direct interaction. Direct interaction is less important in these hearts than in normal hearts, probably because the septum is thicker and, hence, less distensible. This change in the relative importance of direct ventricular interaction with hypertrophy complicates comparison of pressure-volume relationships between normal and hypertrophied hearts.

Animals↗

Right heart pressure does not equal pericardial pressure in the potassium chloride-arrested canine heart in situ.

Recently proposed concepts of pericardial surface pressure, as opposed to liquid pressure, have advanced our understanding of the relationship between pericardial and heart chamber pressures. However, the subsequent suggestion that right heart intracavitary pressure equals, or nearly equals, pericardial surface pressure is not strictly consistent with the physiology of pericardial constraint. If right heart pressure equals pericardial surface pressure, then transmural right heart pressure equals zero. Because of the difficulty in measuring pericardial pressure directly in the beating heart we designed an experiment in the recently arrested canine heart in situ to measure pericardial pressure indirectly and to test the hypothesis that right heart transmural pressure is zero under reasonably physiologic, static equilibrium conditions. According to a static equilibrium analysis of the pressures acting across the walls of the heart, at a given volume the change in right heart pressure caused by removing the pericardium is equal to the pericardial pressure when the pericardium is intact. We found that this drop in pressure caused by pericardiectomy did not equal right heart pressure and therefore that right heart transmural pressure does not equal zero.

Animals↗

End-systolic and end-diastolic ventricular interaction.

Right ventricular volume affects left ventricular volume via direct interaction across the interventricular septum and series interaction because the right and left hearts are connected in series through the lungs. Because it is difficult to sort out complex physiological mechanisms in the intact circulation, the relative importance of these two effects is unknown. We used statistical analyses of transient changes in left and right ventricular pressures and dimensions following pulmonary artery and venae caval constrictions to separate and quantitate the direct (immediate) from the series (delayed) interaction effects on left ventricular size at end systole and end diastole. With the pericardium closed, direct interaction was one-half as important as series interaction at end diastole and was one-third as important at end systole. With the pericardium removed, direct interaction was one-fifth as important as series interaction at end diastole and one-sixth as important at end systole. These results suggest that differences between transient and steady-state end-systolic pressure-volume relationships are largely explained by direct interaction and that direct end-systolic interaction is important for maintaining balanced right and left heart outputs.

Animals↗

Multiple regression for physiological data analysis: the problem of multicollinearity.

Multiple linear regression, in which several predictor variables are related to a response variable, is a powerful statistical tool for gaining quantitative insight into complex in vivo physiological systems. For these insights to be correct, all predictor variables must be uncorrelated. However, in many physiological experiments the predictor variables cannot be precisely controlled and thus change in parallel (i.e., they are highly correlated). There is a redundancy of information about the response, a situation called multicollinearity, that leads to numerical problems in estimating the parameters in regression equations; the parameters are often of incorrect magnitude or sign or have large standard errors. Although multicollinearity can be avoided with good experimental design, not all interesting physiological questions can be studied without encountering multicollinearity. In these cases various ad hoc procedures have been proposed to mitigate multicollinearity. Although many of these procedures are controversial, they can be helpful in applying multiple linear regression to some physiological problems.

Animals↗

The accuracy of inferring left ventricular volume from dimension depends on the frequency of information needed to answer a given question.

Left ventricular volume is an important variable in cardiovascular physiology. Because volume cannot be transduced directly, by necessity people measure one or more cardiac dimensions, then implicitly or explicitly estimate volume. Despite its common use, this practice has never been adequately justified. Previous validations of the use of left ventricular dimensions to infer volume have ignored the complexity of the relation between dimensions and volume, particularly over a broad range of hemodynamic states, and have not considered the frequency content of the volume signal needed to answer a given physiological question. We show that, strictly speaking, the assumptions underlying this practice are false. The resulting errors are of little practical consequence under many circumstances, whereas they can be quite important under other circumstances. We consider the frequency content of the volume signal to organize our examples and findings. In this general framework, we find that, for most assessments of volume change from dimension change at or below a frequency of about the heart rate (e.g., beat-to-beat end-diastolic volume), there is no limitation, provided all relevant dimensions are measured. However, for information at frequencies above the heart rate (i.e., rapid changes in volume or dimension), it is probably not possible to draw accurate conclusions about left ventricular volume from dimension data.

Animals↗

Mechanical determinants of transient changes in stroke volume.

To better define beat-to-beat regulation of stroke volume (SV), the several-beat transient response of the left ventricle (LV) to sudden changes in hydraulic loading impedance was studied. Data were collected from eight canine isolated heart-lung preparations with controlled LV loading impedance. At a selected diastolic interval, a sudden increase in hydraulic loading resistance was induced. The resulting transient response in SV, end-diastolic pressure (EDP), and end-systolic pressure (ESP) was analyzed by comparing the relative predictive capability of six competing models, each incorporating different degrees of complexity in the relationship between SV and EDP and ESP. The basic model assumed linear LV pressure-volume relationships at both end diastole and end systole. Incorporation of nonlinear, end-state interaction or coronary perfusion pressure effects into the basic model did not improve predictive performance. Models incorporating SV and ESP of the preceding beat as well as ejecting beat ESP and EDP were consistently superior to all other models. The ranking of the relative influence of the determinants of SV was 1) ejecting beat ESP, 2) preceding beat ESP, 3) ejecting beat EDP, and 4) preceding beat SV.

Animals↗

Arterial baroreflex control of heart rate in the horse, pig, and calf.

The heart rate (HR) response to stepwise changes in mean arterial pressure (MAP) produced by methoxamine and sodium nitroprusside was studied in conscious horses, pigs, and calves. The respective steady-state arterial baroreflex sensitivities (delta HR/delta MAP expressed as beats min-1 . mm of Hg-1) were -1.20, -1.21, and -0.39 for decreasing MAP and -0.08, -0.91, and -0.56 for increasing MAP. After parasympathetic nervous system (PNS) blockade with atropine, the reflex sensitivity to decreasing MAP in horses and the pigs decreased to -0.62 and -0.65, respectively (P less than 0.05), whereas the sensitivity in calves was not significantly different from the calves' base-line sensitivity (P greater than 0.05). In pigs, the sensitivity to increasing MAP decreased to -0.43 after PNS blockade (P less than 0.05). Horses and calves had a response to small increases in MAP similar to that observed in the absence of PNS blockade. There was no additional change in HR with larger increases in MAP in these 2 species. These responses indicate that varying degrees of mixed PNS and sympathetic nervous system activity changes mediate the baroreflex change in HR seen for increasing and decreasing MAP in pigs and for decreasing MAP in horses. Predominantly PNS activity is responsible for the response to increasing MAP in the horses and calves, whereas predominantly sympathetic nervous system activity is responsible for the response to decreasing MAP in calves. Comparisons were made between the observations in these 3 species and other mammalian species.

Animals↗