Olsen Co

Linearity of the Frank-Starling relationship in the intact heart: the concept of preload recruitable stroke work.

The Frank-Starling relationship generally has been examined with filling pressure as the index of preload, resulting in a curvilinear function that plateaus at higher filling pressures. To investigate this relationship further in the intact heart, 32 dogs were chronically instrumented with left ventricular and pleural micromanometers and with regional (10 dogs) or global (22 dogs) ultrasonic dimension transducers. Seven days after implantation, left ventricular pressure and regional or global dimensions were recorded in the conscious state. After autonomic blockade, preload was varied by vena caval occlusion. Myocardial function was assessed by calculating regional or global stroke work, and preload was measured as end-diastolic segment length or chamber volume. The relationship between stroke work and either end-diastolic segment length or chamber volume (termed the preload recruitable stroke work relationship) was highly linear in every study (mean r = .97) and could be quantified by a slope (MW) and x-intercept (LW). Previous nonlinear relationships between stroke work and filling pressure seemed to reflect the exponential diastolic pressure-volume curve. Over the physiologic range of systolic arterial pressures produced by infusion of nitroprusside or phenylephrine, no significant change was observed in MW or LW in the normal dog. Calcium infusion increased both regional and global MW by 71 +/- 19% and 65 +/- 9%, respectively (p less than .02), with no significant change in LW. To normalize for ventricular geometry and heart rate, stroke work was computed from circumferential stress-strain data and converted to myocardial power output, which was then plotted against end-diastolic circumferential strain. This relationship also was highly linear, and the slope, Mmp (mW/cm3 of myocardium), is proposed as a potential measure of intrinsic myocardial performance independent of loading, geometry, and heart rate.

The end-systolic pressure-volume relationship in conscious dogs.

The end-systolic pressure-volume relationship (ESPVR) has been shown to be an afterload-insensitive descriptor of ventricular inotropic state in the isolated heart. The purpose of this study was to examine the effects of changes in afterload, heart rate, intravascular volume, autonomic tone, and inotropic state on the ESPVR in conscious dogs. In 30 dogs, left ventricular and pleural pressures were measured with micromanometers, and left ventricular volume was assessed with global ultrasonic crystals. The ESPVR was obtained during vena caval occlusions in each dog during pharmacologic afterload interventions at control and after autonomic blockade. Analysis of variance techniques were used to compare the slopes (Emax) and intercepts (Vd) of ESPVR regression lines in a given study. All estimates of the ESPVR in conscious dogs involved large extrapolations to obtain estimates of Vd. Repeat determinations of Emax at control in the unblocked state were significantly different in six of eight dogs (p less than .05). After autonomic blockade, these differences were significant in only one of eight dogs. Changes in heart rate and volume loading had minimal effects on the ESPVR. In the absence of autonomic blockade, increases in inotropic state with either calcium or dobutamine tended to cause parallel shifts in the ESPVR. After autonomic blockade, Emax increased with augmentation of inotropic state, while Vd was unchanged. ESPVRs obtained at different afterloads showed statistically significant differences in Emax and in Vd in 12 of 14 dogs. However, no statistically significant relationship of Emax to afterload was observed. Thus, the ESPVR is probably valid in conscious dogs, but measurement with an intact cardiovascular system is hampered by statistically significant variability in Emax and Vd with changes in afterload. Baseline variability is magnified by the autonomic nervous system, probably mediated through sympathetic reflexes.

Diminished stroke volume during inspiration: a reverse thoracic pump.

In 12 conscious dogs, a three-dimensional array of pulse-transit ultrasonic transducers was used to measure left ventricular anterior-posterior minor, septal-free wall minor, and basal-apical major diameters. Matched micromanometers measured left ventricular, right ventricular, and intrapleural pressures. Electromagnetic ascending aortic blood flow and right ventricular transverse diameter were measured in five of the dogs. A major cause of the inspiratory decline in stroke volume in this preparation appeared to be reflex tachycardia and autonomic changes associated with inspiration. However, when heart rate was controlled by atrial pacing or pharmacologic autonomic attenuation (propranolol and atropine), stroke volume still decreased around 10%, with an inspiratory decrease in pleural pressure of 10 mm Hg. Based on the measurements of ventricular dimension, venous return to the right ventricle appeared to be augmented significantly during inspiration and the transient increase in right ventricular volume was associated with leftward interventricular septal shifting and altered diastolic left ventricular geometry. However, left ventricular end-diastolic volume was changed minimally, implying that alterations in preload were not important. Moreover, transmural left ventricular ejection pressure, calculated as intracavitary minus pleural pressure, was not significantly changed, and it seemed that neither pressure nor geometric components of afterload were altered significantly by inspiration. The inspiratory fall in left ventricular stroke volume correlated best with the decline in intracavitary left ventricular ejection pressure referenced to atmospheric pressure. It is hypothesized that during ejection, left ventricular pressure referenced to atmospheric pressure is the hydraulic force effecting stroke volume and that the decline in this effective left ventricular ejection pressure is responsible for the inspiratory fall in stroke volume through a reverse thoracic pump mechanism.

Pericardial influences on ventricular filling in the conscious dog. An analysis based on pericardial pressure.

Twenty-five dogs were chronically instrumented to investigate the effects of the normal pericardium on cardiac function. Pulse-transit ultrasonic transducers were implanted to measure multiple ventricular dimensions. The pericardium was incised transversely at the base of the heart and precisely reapproximated, so as to disturb its characteristics minimally. One week later, the dogs were studied in the conscious state, and left ventricular, right ventricular, pericardial, and pleural pressures were measured with matched micromanometers. Data were recorded before and after blood volume expansion. Absolute end-diastolic pericardial pressure varied directly with pleural pressure during the respiratory cycle. Tran pericardial pressure (pericardial-pleural pressure) varied little with respiration and was related directly to ventricular diameter during the cardiac cycle with peak transpericardial pressure uniformly occurring at end-diastole. With volume infusion, normalized end-diastolic minor axis diameter and left ventricular transmural pressure (left ventricular-pleural pressure) increased significantly from 0.14 ± 0.01 and 9.5 mm Hg ± 1.0 mm Hg, respectively, in the control state to 0.20 ± 0.01 and 19.3 mm Hg ± 1.2 mm Hg after volume loading. End-diastolic transpericardial pressure also increased significantly from 2.3 ± 0.5 mm Hg to 4.1 ± 0.3 mm Hg, and represented approximately 21% of transmural left ventricular pressure. When measurements were obtained sequentially after implantation, transpericardial pressure was initially high but decreased with time, presumably due to pericardial creep. After volume loading, right ventricular end-diastolic transmural pressure averaged 9.6 mm Hg, and pericardial pressure constituted 42% of right ventricular pressure. Thus, pericardial restraining effects may predominantly influence right ventricular filling and affect the left ventricle through series interaction. In the normal conscious dog, transpericardial pressure remains low over the entire physiological range, and the direct influence of the normal pericardium on diastolic filling of the left ventricle appears to be minimal.

The coronary pressure-flow determinants left ventricular compliance in dogs.

Displacement of the left ventricular diastolic pressure-dimension relationship (change in compliance) has been observed with alterations in coronary perfusion pressure. The relative contribution of coronary (myocardial) blood flow, as compared with the perfusion pressure at which flow occurs, was studied in 10 dogs during diastolic relaxation by potassium arrest during cardiopulmonary bypass. The normalized left ventricular pressure-dimension relationships, obtained during passive, gradual filling of the left ventricle (0–20 mm Hg) were shifted progressively to the left as coronary perfusion pressure was Increased. Myocardial blood flow was 0.06 ml/mg per min ± 0.02 ml/mg per min (mean ± SEM) at a coronary perfusion pressure of 40 mm Hg and increased to 0.38 ml/mg per min ± 0.11 ml/mg per min as the coronary perfusion pressure was raised to 120 mm Hg. Addition of adenosine significantly Increased myocardial blood flow by 109% at a coronary perfusion pressure of 80 and by 147% at a coronary perfusion pressure of 120 mm Hg, but caused no additional significant shifts in the pressure-dimension relationships, compared to the same coronary perfusion pressures without adenosine. Coronary perfusion pressure, and not coronary blood flow, is a more direct determinant of cardiac diastolic properties.

Mechanical correlates of the third heart sound

In seven chronically instrumented conscious dogs, micromanometers measured left ventricular pressure, and ultrasonic dimension transducers measured left ventricular minor-axis diameter; the latter recording was filtered to examine data between 20 and 100 Hz. Acceptable external heart sounds were recorded with a phonocardiographic microphone in four of the seven dogs. With each dog sedated, intubated and mechanically ventilated, data were obtained during hemodynamic alterations produced by volume loading, phenylephrine, calcium infusion and vena caval occlusion. Damped oscillations were noted consistently in the left ventricular diameter waveform toward the end of rapid ventricular filling. These wall vibrations, assessed by the filtered diameter, correlated well with the third heart sound (S3) on the phonocardiogram. The peak frequency of the wall vibrations increased with increased diastolic pressure (p = 0.004), probably reflecting an increase in myocardial wall stiffness. In contrast, the amplitude of the vibrations varied directly with left ventricular filling rate (p = 0.0001). Thus, S3 seemed to be related specifically to ventricular wall vibrations during rapid filling, and the spectra of the amplitude-frequency relation shifted toward the audible range with increases in diastolic pressure, wall stiffness or filling rate. Spectral analysis of S3 may be useful in assessing pathologic changes in myocardial wall properties.

Diastolic Myocardial Mechanics and the Regulation of Cardiac Performance

Over the past 15 years, the primary goal of our physiology laboratory has been to improve the understanding of basic myocardial function in both normal and diseased hearts. Very early in our studies, it became evident that existing descriptors of myocardial performance were deficient, and initial efforts were expended to develop basic models of ventricular geometry, diastolic properties, and systolic function. Later work has been directed toward applying these models to the study of pathophysiology in ischemic heart disease and chronic volume overload. Although this investigation is still in progress, enough information is currently available to provide insight into basic aspects of diastolic myocardial function, to propose several hypotheses on how the heart adapts to clinical heart disease, and to provide direction for future clinical investigation of myocardial mechanics in humans. This chapter will review these topics primarily through publications from our laboratory, each of which contains full references.

An Energetic Analysis of Myocardial Performance

Cardiovascular dynamics is one of the oldest lines of medical research, having its origins in the work of William Harvey in the seventeenth century. Yet despite its long history, conceptual understanding of cardiac performance is advancing more rapidly than ever, and many different scientifc approaches are currently yielding exciting new insights. This chapter reviews 15 years of work from our laboratories at Duke University on the quantitative assessment of diastolic and systolic ventricular function. Our approach to the analysis of chamber geometry, ventricular interaction, and diastolic mechanical properties is described, leading to the observation of a fundamentally linear relationship between myocardial energy production (net external work) and end diastolic fiber length. This relationship is further validated and expanded to provide a useful estimate of myocardial inotropism that is applicable to pathophysiologic analysis of myocardial ischemia and hypertrophy. Finally, recent extensions of this technique to human studies have proven useful to the understanding of cardiopulmonary interactions and valvular heart disease. As knowledge of myocardial adaptive mechanisms improves, enhanced diagnostic and therapeutic capabilities could translate into significant advances in patient care.

A Physiologic Comparison of External Cardiac Massage Techniques

On the basis of recent investigation, controversy has arisen regarding which of several cardiopulmonary resuscitation methods optimizes hemodynamics. The present study was designed to compare five recently described chest compression techniques: high-impulse manual chest compression at 150/min, mechanical compression at 60/min with simultaneous ventilation, mechanical compression at 60/min with simultaneous ventilation and either systolic or diastolic abdominal compression, and pneumatic vest compression at 60/min. Eight dogs were chronically instrumented with electromagnetic flow probes in the ascending and descending aorta while matched micromanometers measured aortic, left ventricular, and pleural pressures. At study, each dog was anesthetized with morphine, intubated, and the heart was fibrillated by rapid ventricular pacing. The five cardiopulmonary resuscitation methods were performed randomly in each preparation within 7 to 10 minutes of arrest. In four dogs, brachiocephalic blood flow was computed as total cardiac output minus descending aortic blood flow, and in all dogs coronary perfusion pressure was calculated as mean diastolic aortic pressure minus mean diastolic left ventricular pressure. Average cardiac output for seven studies was 662 +/- 61 ml/min with high-impulse manual compression, 340 +/- 46 ml/min with mechanical compression and simultaneous ventilation, 336 +/- 45 ml/min with mechanical compression and simultaneous ventilation with systolic abdominal compression, 366 +/- 52 ml/min with mechanical compression and simultaneous ventilation with diastolic abdominal compression, and 196 +/- 29 ml/min with vest resuscitation (high-impulse manual compression significantly greater than other techniques by multivariate analysis, p less than 0.05). Brachiocephalic blood flow generally followed cardiac output and was statistically the greatest with high-impulse manual compression at 273 +/- 47 ml/min (p less than 0.05). Finally, high-impulse manual compression provided the highest coronary perfusion pressure of 31 +/- 4 mm Hg (p less than 0.05) compared to 23 +/- 2 mm Hg for mechanical compression and simultaneous ventilation, 23 +/- 2 mm Hg for mechanical compression and simultaneous ventilation with systolic abdominal compression, 23 +/- 3 mm Hg for mechanical compression and simultaneous ventilation with diastolic abdominal compression, and 11 +/- 2 mm Hg for vest resuscitation. These data demonstrate that high-impulse manual compression generated physiologically and statistically superior hemodynamics when compared with other methods in this model of cardiopulmonary resuscitation.

Beneficial Effects of Endotracheal Extubation on Ventricular Performance Implications for Early Extubation After Cardiac Operations

Early endotracheal extubation has been shown to be a safe postoperative management option in patients having cardiac operations. However, few objective data exist on the response of ventricular performance to early termination of controlled ventilation. Seven patients undergoing routine elective coronary artery bypass grafting or adult repair of atrial septal defect were studied after intraoperative placement of left ventricular micromanometers, left ventricular minor axis dimension crystals, and left atrial and intrapleural pressure catheters. Physiologic data were recorded intraoperatively, during controlled mandatory ventilation in the intensive care unit, and during spontaneous respiration immediately after extubation. Extubation to spontaneous breathing was associated with a significant decline in intrapleural pressure and significant increases in left ventricular end-diastolic diameter, ejection diameter shortening, stroke work, and cardiac output. The augmented left ventricular diastolic filling seemed to result from the fall in intrapleural pressure and perhaps from normalization of right ventricular afterload. The preload recruitable stroke work relationship showed that myocardial contractility remained constant after extubation, and ventricular function improved primarily because of increased preload associated with shifting of the capacitance blood volume toward the chest. Thus endotracheal extubation enhances cardiac performance after uncomplicated cardiac surgical procedures, and by this mechanism early extubation may be clinically beneficial as a routine adjunct to postoperative care.