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Biomedical subjects

D Burkhoff

Publications and source records attributed to D Burkhoff.

At least 109 records · Page 6Linked to original sources
PubMed1991

Nonlinearity and load sensitivity of end-systolic pressure-volume relation of canine left ventricle in vivo.

The effects of mechanical changes in loading conditions on the left ventricular end-systolic pressure-volume relation (ESPVR) were studied in nine open-chest dogs, including three dogs studied before and after beta-adrenergic blockade. Left ventricular pressure was measured with a micromanometer, and left ventricular volume was measured with a conductance catheter. ESPVRs were obtained by increasing left atrial inflow over wide volume ranges (as much as threefold) under three different conditions: control or high or low aortic impedance. High impedance was obtained by occlusion of the descending aorta, and low impedance was obtained by a shunt between the subclavian artery and the left atrium. In the unblocked animals in 21 of 28 runs, a second-order polynomial equation gave a better fit for the ESPVR than a linear relation. To quantify the effects of the changes in aortic impedance on the ESPVR, we calculated from the quadratic equation its volume intercept (V18) and its local slope (E18) at an end-systolic pressure (Pes) of 18 kPa. In the unblocked animals, a statistically significant difference was found in V18 between low impedance (21.50 +/- 6.27 ml) and high impedance (14.10 +/- 8.98 ml; p less than 0.005) and between control (19.14 +/- 9.58 ml) and high impedance (p less than 0.05). In most dogs, E18 was increased at high and decreased at low impedance, but not significantly. In the additional experiments with beta-blockade, the nonlinearity diminished somewhat, but the load dependency of the ESPVR remained present after beta-blockade because the same leftward shift of the ESPVR with high aortic impedance was found. Two other relations, namely, of dP/dtmax and of stroke work versus end-diastolic volume, were also investigated, which on the whole showed the same behavior as the ESPVR. These results indicate that the ESPVR and dP/dtmax-Ved and stroke work-end-diastolic volume relations, when studied over a wide volume range, are nonlinear and that changes in loading conditions influence indexes of contractility derived from these relations, especially the volume intercepts, in such a way that an increase in aortic impedance may be interpreted as an increase in contractility. Blocking the beta-adrenergic receptors did not influence the load dependency of the ESPVR but, in some cases, tended to decrease the nonlinearity in concordance with the relation between contractility and nonlinearity in isolated hearts.

Adrenergic beta-Antagonists↗
PubMed1990

Force interval relationship (FIR) related to the global function of the left ventricle: a computer study.

A model which relates the left ventricular (LV) geometry, structure and sarcomere properties to its global function, recently proposed by the authors, is extended to account for contractility changes which are a function of the heart rate, prematurity of the beat and calcium transients within the cell. To characterise LV function and relate it to fibre function under varying rhythm conditions, a model of muscle force restitution, based on calcium kinetics, was used to calculate the maximum fibre stress at the optimum sarcomere length sigma o as the parameter which depends on the heart rate, the test pulse interval TPI, the action potential duration APD and the restitution time constant. The global LV force interval relationship FIR was then calculated, and by comparing the calculated FIR to the experimental measurement (in dogs) at the ventricular level, the constants of the restitution of force at the fibre level were derived. Based on these constants, the LV function under ejecting conditions at various rhythm disturbances was calculated and related to the local, distributed parameters. This approach provides a tool to describe ventricular function as well as transmural distribution of stress and sarcomere length at a wide variety of loading and rhythm conditions based on given 'muscle level' parameters.

Biomechanical Phenomena↗
PubMed1990

Hemodynamic dependence of myocardial oxygen consumption indexes.

We tested the afterload and contractile state dependency of three indexes of myocardial oxygen consumption (MVO2): total energy requirement (Et), pressure work index (PWI), and pressure-volume area (PVA). MVO2 was measured in seven isolated canine hearts at four or five different end-diastolic volumes at each of three settings of afterload resistance and with the hearts contracting isovolumically. In several hearts, contractility was also varied by dobutamine infusion. Measured MVO2 (MMVO2) was compared with values predicted (PMVO2) by each index. There was always a high degree of correlation between MMVO2 and PMVO2 for each of the indexes. However, there was a large degree of variability in the coefficients of the MMVO2-PMVO2 relation from one heart to another. We also observed a statistically significant influence of both afterload and contractile state on the predictive power of each of the indexes. Thus each index that we tested had shortcomings in being able to predict MVO2 accurately over a wide range of hemodynamic conditions.

Animals↗
PubMed1990

Oxygen consumption is less in rat hearts arrested by low calcium than by high potassium at fixed flow.

The purpose of the present study was to determine whether myocardial oxygen consumption (MVO2) differs when the heart is arrested by hyperkalemic arresting solution (ASK) or by hypocalcemic arresting solution (ASCa) when coronary flow is maintained constant. MVO2 was measured in 12 isolated, Langendorff-perfused rat hearts alternately perfused with ASK (20 mM K+ and 1.5 mM Ca2+) and ASCa (5 mM K+ and 0.08 mM Ca2+). Six of the hearts were perfused with ASK for 10 min, ASCa for 5 min, ASK for a second 5 min, and finally ASCa for 5 min; ASCa and ASK were opposite in this sequence for the other six hearts. Measurements of MVO2 during ASK and ASCa arrest, taken at the end of each perfusion period, were analyzed to distinguish the independent influences of time and perfusate composition on MVO2 in the arrested hearts (analysis of covariance). Consistent with previous findings, MVO2 decreased with time after the onset of cardiac arrest with both solutions. The average per minute fall was 0.0003 ml O2.min-1.g-1 (P less than 0.01). However, at any given time after arrest, MVO2 averaged 0.004 ml.min-1.g-1 less during ASCa arrest than during ASK arrest (P less than 0.01), which amounted to a 15% reduction in MVO2. To test whether the increased MVO2 during hyperkalemic arrest was dependent on calcium in the perfusion medium, a third series of six hearts was studied in which MVO2 values measured during ASCa and ASK arrest were compared with those measured during arrest by hyperkalemic-hypocalcemic solution (ASK,Ca: 20 mM K+, 0.08 mM Ca2+).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Mechanically induced action potential changes and arrhythmia in isolated and in situ canine hearts.

Stretch of excised myocardial tissue causes electrophysiological and potentially arrhythmogenic changes in transmembrane action potentials but corresponding data of the intact mammalian heart are lacking. The effects of increases in ventricular volume and pressure on epicardial monophasic action potentials were therefore investigated in isolated, cross circulated and in situ canine hearts. In seven isolated hearts, increases in ventricular volume and pressure resulted in (1) a linearly related decrease in action potential amplitude (r = 0.988; slope = 0.41% amplitude.ml-1; volume intercept = 17.6 ml), mainly due to a decrease in maximum diastolic potential; (2) a decrease in action potential plateau duration (at 20% repolarisation) by 19 (SD 8)%; and (3) appearance of early afterdepolarizations, reaching up to 18% of total action potential amplitude. Afterdepolarizations occurred only when ventricular outflow was obstructed at end diastole but not at end systole. In eight in situ hearts, increase in left intraventricular pressure produced by transient occlusions of the ascending aorta was also accompanied by decrease in maximum diastolic potential and action potential plateau duration, and by appearance of early afterdepolarizations. In both isolated and in situ intact ventricles, the loading induced electrophysiological changes were associated with occurrence of ectopic ventricular beats. These data show that mechanical overload produces significant electrophysiological changes in the intact canine ventricle which may lead to arrhythmia.

Action Potentials↗
PubMed1989

Influence of mean pressure on aortic impedance and reflections in the systemic arterial system.

The present investigation sought to determine the extent to which primary changes in mean arterial pressure (MAP) might influence the calculated aortic impedance. In seven open-chest, anesthetized, autonomically blocked dogs, we measured aortic impedance using white-noise analysis at various levels of MAP achieved by adjusting the height of a left atrial reservoir rather than by pharmacological intervention. Impedance spectra so obtained were parameterized according to best-fit wind-kessel models (Ra, Rc, Ca) and three parameters to characterize wave reflections: the frequency at which the phase of the impedance approached or crossed through 0 degree (phi 0), the frequency of the first minimum of the impedance modulus (fmin), and the amplitude of the first oscillation of the impedance modulus (a 1). The dependency of each of these parameters on MAP was investigated. In addition, we calculated the reflection coefficient spectrum (RCS). Results show that windkessel parameters were not significantly influenced by MAP and that the reflection parameters and the RCS depended on increased levels of MAP in a manner consistent with an increase in pulsewave velocity.

Animals↗
PubMed1988

In vitro studies of isolated supported human hearts.

We developed methods to revive human hearts, obtained at the time of cardiac transplantation, and study them in the physiology laboratory. The hearts were arrested with cardioplegic solution at the time of explanation and transported to the laboratory at 4 degrees C. The hearts were perfused with a human blood based solution whose flow rate, temperature, and ionic concentration were controlled. Six hearts with various endstage cardiomyopathies were revived in this manner. Once perfusion was started, the hearts maintained a steady contractile state for approximately 30 min during which time data could be collected. Within this time period we could measure end-systolic and end-diastolic pressure-volume relations, the time courses of contraction and relaxation, and the influence of heart rate and premature stimulation on contractile state. The results suggest that evidence of specific cellular abnormalities in human heart disease might be obtained from measurements of global ventricular performance. Furthermore, the type of abnormality identified, namely sarcoplasmic reticulum dysfunction, in several forms of cardiomyopathy was in concordance with results obtained in muscle bath studies of similarly diseased human and animal myocardium.

Cardiomyopathy, Dilated↗
PubMed1988

Interrelation between end-systolic pressure-volume and pressure-wall thickness relations.

We predicted the shape of the end-systolic pressure-thickness relationship (ESPTR) by modeling the left ventricle as thick-walled sphere. To test the validity of the predicted relationships, we then measured the ESPTR over wide volume ranges in seven isolated blood-perfused canine hearts. Both simulation and experiments demonstrated that the ESPTR is curvilinear. However, within a physiological left ventricular systolic pressure range (80-150 mmHg), the ESPTR was described reasonably well by a straight line. Within that pressure range, changes in left ventricular contractile state, assessed by slope changes of the end-systolic pressure-volume relationship, were associated with almost parallel shifts in the ESPTR. In contrast, in a low pressure range (less than 80 mmHg), contractility changes were associated with slope changes of the ESPTR. We conclude that, in general, there are limitations in the application of ESPTR for assessing left ventricular contractility, but if the limitations are recognized and accounted for, then the ESPTR may be useful for assessing contractility changes in vivo.

Animals↗
PubMed1988

Assessment of Windkessel as a model of aortic input impedance.

To facilitate the analysis of aortic-ventricular coupling, simplified models of aortic input properties have been developed, such as the three-element Windkessel. Even though the impedance spectrum of the Windkessel reproduces the gross features of the real aortic input impedance, it fails to reproduce many of its details. In the present study we assessed the physiological significance of the differences between real and Windkessel impedance. We measured aortic input impedance spectra from five anesthetized open-chest dogs under a wide range of conditions. For each experimentally determined spectrum we estimated the corresponding values of the best-fit Windkessel parameters. By computer simulation we imposed both the real and best-fit Windkessel impedances on a model left ventricle and assessed the differences in seven different coupling variables. The analysis indicated that the Windkessel model provides a reasonable representation of afterload for purposes of predicting stroke volume, stroke work, oxygen consumption, and systolic and diastolic aortic pressures. However, the Windkessel model significantly underestimates peak aortic flow, slightly underestimates mean arterial pressure, and, of course, does not provide realistic aortic pressure and flow waveforms.

Animals↗
PubMed1988

Effect of nisoldipine on coronary resistance, contractility and oxygen consumption of the isolated blood-perfused canine left ventricle.

Nisoldipine reportedly has little direct myocardial effect. However, because of interactions between the heart and vascular load, the effects on myocardial contractility and left ventricular oxygen consumption (LVO2) have not been established. The authors performed experiments on six isolated, blood-perfused canine left ventricles that were isovolumically contracting and paced at constant rate. Coronary arterial pressure (CAP) and coronary blood flow were measured for evaluation of coronary vascular resistance, and coronary arteriovenous oxygen difference was measured for determination of LVO2. Intracoronary injection of 1 and 10 micrograms of nisoldipine decreased coronary vascular resistance by 16.9 and 36.8% (CAP approximately 40 mm Hg), respectively, and by 21.5 and 47.7% (CAP approximately 80 mm Hg). At both doses, nisoldipine caused no decrease in peak systolic pressure as long as CAP was kept constant at 80 mm Hg. However, when CAP was decreased to 40 mm Hg, peak systolic pressure was significantly decreased even without nisoldipine. This impaired contractile state was associated with a decreased coronary blood flow and a slight decrease in LVO2, whereas 10 micrograms of nisoldipine at CAP approximately 80 mm Hg increased LVO2 significantly. Using the end-systolic pressure-volume relationship as an index of contractility, the authors found nisoldipine not to change the contractile state at CAP approximately 80 mm Hg. They conclude that nisoldipine decreases coronary vascular resistance over a wide range of CAP. It neither depresses the contractile state nor decreases LVO2 in the canine left ventricle. Nisoldipine might effectively counteract anginal attacks by dilating the coronary vessels without depressing myocardial contractility as found in this study on normal ventricle.

Animals↗
PubMed1987

Influence of ventricular contractility on non-work-related myocardial oxygen consumption.

The relationship between myocardial oxygen consumption (MVO2) and the total pressure-volume area (PVA), which represents the total mechanical work performed during a cardiac cycle, has been shown to be linear and independent of loading conditions: MVO2 = aPVA + b. When inotropic state is enhanced, the MVO2-PVA relation shifts upward (increase in b), and when inotropic state is depressed the relation shifts downward (decrease in b). However, the quantitative relationship between contractility and b (the non-work-related myocardial oxygen consumption) determined over a wide range of contractilities is not known. In seven isolated blood perfused canine hearts, left ventricular (LV) contractility was increased by dobutamine and decreased with nifedipine or reduction of coronary blood flow. At each level of contractility, the end-systolic pressure-volume relationship (ESPVR) and the MVO2-PVA relation were determined. For each heart, the resulting values of b (ml O2/beat) were plotted as a function of Emax (mmHg/ml), an index of contractility defined as the slope of the ESPVR. There was a linear relation between Emax and b over a wide range of contractilities; on average, b (ml O2/beat) = 0.0036 Emax (mmHg/ml) + 0.0101 [r = 0.929-0.978 (95% confidence interval)], when Emax was varied over an average range of 2.8-9.6 mmHg/ml. These results suggest a common underlying determinant of contractility and non-work-related oxygen consumption.

Animals↗
PubMed1987

Contractility-dependent curvilinearity of end-systolic pressure-volume relations.

The shape of the end-systolic tension-length relationship (ESTLR) changes when contractile state is changed, whereas the end-systolic pressure-volume relationship (ESPVR) remains linear despite changes in contractility. To investigate this disparity, the ESPVR was determined with contractility altered extensively by dobutamine, BAY K 8644, nifedipine, lowering coronary blood flow, and the introduction of extrasystolic and postextrasystolic stimulations. The ESPVRs were fitted by nonlinear regression analysis to the parabolic equation Pes = aVes2 + bVes + c, where Pes is end-systolic pressure, Ves is end-systolic volume, and a, b, and c are parameters. There was a negative, statistically significant correlation between a, which serves as a shape index of the ESPVR, and E'max, the slope of the ESPVR in a low volume range. When E'max was large a was negative, indicating increasing concavity of the ESPVR to the volume axis at high contractility. When E'max was small a was positive, indicating convexity of the ESPVRs to the volume axis at low contractility. Within the average range of E'max between 3.4 and 7.8 mmHg/ml, however, the parabolic fit to the data was not statistically better than a linear fit over the range of volumes testable in the isolated heart. We conclude that the shape of the ESPVR measured in the isolated canine heart changes with contractile state. In accordance with previous interpretations of shape changes in the muscle ESTLR, these results are consistent with the existence of length-dependent activation of cardiac muscle in the intact heart.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1987

Quantitative comparison of canine right and left ventricular isovolumic pressure waves.

The mechanical properties of the right and left ventricles (RV and LV) have previously been studied separately. However, because of differences in RV and LV architecture, geometry, and muscle mass, it is not obvious how the properties of the two chambers would relate to each other. This study compared the time courses of RV and LV isovolumic pressure waves (LVP, RVP, respectively) measured simultaneously in the same heart. We compared RVP and LVP in each of five isolated, supported canine hearts after pentobarbital anesthesia. RV and LV volumes were varied independently so that on various beats peak LVP exceeded, equaled, or was less than peak RVP. There was a delay of approximately 35 ms between the onset of LV and RV pressure waves with atrial pacing, but only 5 ms with ventricular pacing. LVP and RVP were measured and digitized at a sampling rate of 200 Hz. Pressure waves were offset and rescaled by their respective amplitudes so that for each beat the pressure wave had a minimum value of 0% at end diastole and a maximum value of 100% at end systole. RVP was then shifted in time so that its upstroke was synchronous with that of the LVP at the point of 50% of maximal developed pressure. The rescaled, time-shifted RVP was plotted as a function of the rescaled LVP for each point of the cardiac cycle, and the relation between the two was quantified by their root mean square difference (Drms). Drms averaged 2.3 +/- 1.5% (SD) for the first half of contraction, 1.5 +/- 0.4% for the second half of contraction, and 4.6 +/- 1.6% during relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

In vitro validation of a new cardiac catheter technique for recording monophasic action potentials.

Monophasic action potential (MAP) recording with non-suction, 'contact' electrode catheters has been shown possible and safe during clinical catheterization, but direct validation of this new technique is lacking. We therefore recorded these contact electrode MAPs simultaneously with transmembrane action potentials (TAPs) from closely adjacent sites in perfused and superfused rabbit septum preparations and performed a quantitative comparison between the two signals for duration and area at 30, 60 and 90% repolarization. To obtain a variety of action potential durations and configurations for the comparison, the rate and rhythm of stimulation and the extracellular calcium or potassium ion concentration were changed. With action potential duration at 90% repolarization made to vary from 150 to 513 ms, the mean absolute difference +/- SD between the simultaneous intra- and extracellular recordings was 5.4 +/- 11.3 ms and the linear correlation coefficient was r = 0.96 +/- 0.03. Similar agreement between the two types of recordings was found for measurements for area and at 60 and 30% repolarization levels. These data confirm that MAPs recorded with this clinically safe contact electrode technique can be used to measure accurately the repolarization time course of transmembrane action potentials.

Animals↗
PubMed1986

Influence of pacing site on canine left ventricular force-interval relationship.

We tested the hypothesis that while absolute extrasystolic (ES) and postextrasystolic (PES) dP/dtmax would be influenced by pacing site, if these values were normalized by the steady-state dP/dtmax obtained with the same pacing site, they would be independent of pacing site. We employed an isovolumetrically contracting isolated heart preparation with a balloon placed in the left ventricle. Pacing electrodes were placed on the atrium and four different epicardial ventricular sites. While pacing from each site separately, a steady mechanical state was established at a constant rate, and the interval between beats was then perturbed. The same pacing sequence was used while pacing from each of the five sites. On each ES and PES beat, dP/dtmax was expressed as a percentage of the steady-state dP/dtmax. The normalized responses measured with each ventricular pacing site (DPventr) were plotted as a function of the normalized responses obtained with atrial pacing (DPatr). On average, DPventr = 1.02 DPatr - 3.2% (n = 6, with r2 = 0.989), indicating that pacing site did not significantly influence the "normalized" force-interval relationship. Thus the basic information retrievable from measurements of the ventricular force-interval relationship is independent of the site from which the heart is paced.

Animals↗