Changes In Contractile State Research Articles

Beat-by-beat volume calibration refines pressure-volume derived indices of left ventricular function in the rat

Objective: Cardiac pressure-volume studies have advanced much of our understanding of mammalian cardiovascular physiology. Using admittance or conductance technology, the advantage of this technology over other methods to assess cardiovascular function is the ability to derive beat-by-beat pressure-volume loops and generate estimations of myocardial work (stroke work), as well as load-independent systolic (i.e., contractility) and diastolic (i.e., compliance) function from a caval occlusion. While these catheters are capable of extremely accurate recordings of cardiac pressure, volume measurement relies on a series of calibration steps that are oft-performed in isolation or at discrete timepoints. We propose a novel method that enables the refinement of ventricular volume measurement by enabling a beat-by-beat calibration of stroke volume (SV) at baseline and, most importantly, during caval occlusion where both the shape and characteristics of the ventricle are dynamically changing. Hypothesis: We hypothesised that beat-by-beat calibration of SV has a significant effect on PV-catheter derived indices of left ventricle (LV) function. Methodology: Data were collected from 10 rodents that were intubated, ventilated, and urethane anesthetized. We placed an admittance pressure-volume catheter (1.6F Scisense, Transonic Systems, Inc.) into the LV via an apical approach following thoracotomy, a perivascular flow probe (Transonic Systems, Inc.) was placed around the ascending aorta, a blood pressure catheter in the iliac artery, femoral venous lines for fluid/drug infusions, and an arterial line for blood gas analysis. We then assessed baseline and load-independent systolic function using the admittance catheter with and without beat-by-beat volume corrections obtained by integration of the perivascular flow data. Results: Firstly, we confirmed that the standard metrics of load-independent systolic function were increased in response to dobutamine (β1 agonist) and reduced in response to esmolol (β1 blocker). We then found that beat-by-beat volume correction from the perivascular flow probe increased baseline measures of SV and stroke work (SW). Comparing indices of load-independent systolic function calculated from corrected vs. uncorrected values of SV and SW, we found that beat-by-beat volume correction resulted in no significant change in d P/dt max - V ed (P=0.339) but a significant increase in PRSW (from 116±18 to 129±20 mmHg, P=0.020). Conclusions: Standard approaches to PV studies are able to accurately discern changes in contractile state. However, beat-by-beat calibration of the volume signal improves the absolute determination of volume indices and therefore influences derived measures of contractility. This research was funded by an NSERC Alliance grant to CRW and Mitacs Accelerate Postdoctoral Fellowship to OHW. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sodium Nitroglycerin and Hypercapnic Stimuli Reduce Cerebral Vascular Bed Compliance in Humans

Human cerebral arteries dilate to various stimuli and this change in contractile state is often quantified as a steady-state change in vascular resistance. In oscillatory blood flow, compliance of the vascular bed also contributes to the regulation of cerebral perfusion. However, very little is known about the impact of cerebral dilation on cerebral vascular bed compliance. Therefore, the present study examined the impact of cerebral vasodilatory stimuli on cerebrovascular compliance in humans. Fifteen young, healthy adults (27 ± 5 years, 7 females) participated in the present study. Participants completed a sodium nitroglycerin (SNG) protocol involving a 2-minute baseline period, administration of one 0.4 mg sublingual spray of SNG, followed by 10 minutes of data collection. Following the completion of the SNG protocol, participants rested for at least 5 minutes after which the hypercapnia protocol was completed. Following a 2-minute baseline period, participants breathed a low percentage (5-6%) carbon dioxide (CO2)gas mixture for 4 minutes followed by a 3-minute recovery period breathing room air. Throughout the experimental protocols, blood pressure (BP) waveforms (finger photoplethysmography; Finapres Medical Systems) and middle cerebral artery blood velocity (BV) waveforms (transcranial Doppler ultrasound; Multigon Industries) were collected in the supine position. Five individual BP and corresponding BV waveforms were extracted during each protocol's baseline period, at each minute of SNG and CO2, and during the last minute of the CO2 recovery period. The waveforms were input into a modified Windkessel model and an index of cerebrovascular compliance (Ci) was calculated. During the SNG protocol, Ci was 5.0e-4 ± 2.3e-4 cm·s-1·mmHg-1 at baseline and decreased significantly by minute 7 of SNG administration (P = 0.01, d = 1.07). Overall, Ci decreased by 29% to its nadir, 3.6e-4 ± 1.2e-4 cm·s-1·mmHg-1, at minute 10 of the protocol (P = 0.01, d = 0.98). During the hypercapniaprotocol, Ci was 4.4e-4 ± 2.0e-4 cm·s-1·mmHg-1 at baseline and decreased significantly by minute 1 of breathing CO2 (P = 0.003, d = 1.04). Overall, Ci was reduced by 30% to its lowest value of 3.1e-4 ± 1.4e-4 cm·s-1·mmHg-1 by minute 4 of hypercapnia (P < 0.001, d = 1.56). However, following 3 minutes of recovery, Ci increased to 4.2e-4 ± 1.5e-4 cm·s-1·mmHg-1, which was not different from baseline values (P = 0.86). BP remained unchanged during the SNG protocol (BSL: 87 ± 8 mmHg, Min 10: 89 ± 8 mmHg; P = 0.99), while it increased by 5 mmHg during the hypercapnia protocol (BSL: 86 ± 10 mmHg, Min 4: 91 ± 10 mmHg; P < 0.001, d = 1.44). However, no significant relationship was observed between the change in BP and the change in Ci with hypercapnia (r = -0.09, P = 0.75). Both vasodilatory stimuli reduced Ci by approximately 30% from supine baseline values. The attenuation of Ci likely relates to the predominance of collagen fibers in supporting wall tension during vessel distension.

Functional Requirements of a Mathematical Model of Muscle Contraction.

Muscle modeling has a long history. Models typically belong to the class of lumped models built around Hill's contractile element, or to crossbridge models at the ultrastructure level. Lumped models built on the contractile element are not sufficiently dynamic, since the muscle's contractile properties are set a priori by the force-velocity relation. We have shown that the force-velocity relation is not a unique descriptor of muscle's contractile state [1]. Alternatively, description of muscle as a time and length dependent force generator may be used to model muscle dynamics. This paper defines the functional requirements of a mathematical model of muscle contraction and evaluates how closely a lumped model based on ultrastructural dynamics resembles muscle. This single model was found able to describe isometric and isotonic contractions, the force-length relation, the force-velocity relation, and changes in contractile state and contraction rate. This approach may help link macro contractile properties, such as the force-velocity relation, to micro dynamics of crossbridge bonds. It may also be useful as a component of larger physiological models and simulations.

Matrix Revisited

Metabolic signaling mechanisms are increasingly recognized to mediate the cellular response to alterations in workload demand, as a consequence of physiological and pathophysiological challenges. Thus, an understanding of the metabolic mechanisms coordinating activity in the cytosol with the energy-providing pathways in the mitochondrial matrix becomes critical for deepening our insights into the pathogenic changes that occur in the stressed cardiomyocyte. Processes that exchange both metabolic intermediates and cations between the cytosol and mitochondria enable transduction of dynamic changes in contractile state to the mitochondrial compartment of the cell. Disruption of such metabolic transduction pathways has severe consequences for the energetic support of contractile function in the heart and is implicated in the pathogenesis of heart failure. Deficiencies in metabolic reserve and impaired metabolic transduction in the cardiomyocyte can result from inherent deficiencies in metabolic phenotype or maladaptive changes in metabolic enzyme expression and regulation in the response to pathogenic stress. This review examines both current and emerging concepts of the functional linkage between the cytosol and the mitochondrial matrix with a specific focus on metabolic reserve and energetic efficiency. These principles of exchange and transport mechanisms across the mitochondrial membrane are reviewed for the failing heart from the perspectives of chronic pressure overload and diabetes mellitus.

Right Ventricular Strain in Pulmonary Hypertension

Since 2009, there have been ≥170 articles published in the cardiopulmonary literature on right ventricular (RV) echocardiographic strain imaging, including several in Circulation: Cardiovascular Imaging . Of particular interest has been the effort to use RV echocardiographic strain imaging to assess RV systolic function in pulmonary hypertension and the relationship of RV strain to disease severity and outcomes. In this issue of Circulation: Cardiovascular Imaging , Fine et al,1 from the Mayo Clinic echo group, report on retrospectively evaluated data on the relationship of RV strain to outcomes in the largest such study to date, encompassing 575 patients with known or suspected pulmonary hypertension without elevated pulmonary venous pressure during a median follow-up period of 16.5 months.1 The data show a strong association between reductions in mean longitudinal strain and all-cause mortality, and cardiopulmonary mortality and cardiopulmonary events. An exhaustive biostatistical analysis shows the relationship to be quantitative, stronger than that of other echo indices including tricuspid annular plane systolic excursion, independent of clinical covariates and resulting in a significant improvement in predictive value when combined with relevant clinical variables, as reflected in a significant increase in the integrated discrimination improvement index and the c-statistic for the primary end point. Thus, the results promise to improve clinical risk assessment significantly for such patients and may improve clinical decision making. Article see p 711 The apparent benefit is, in large part, a reflection of the relatively weak performance of older 2-dimensional (2D) echocardiographic indices of RV performance including fractional area change and tricuspid annular plane systolic excursion in this setting. RV imaging has been a minefield for echocardiography in adults since its inception. The complexity of ventricular shape, the thinness of the RV free wall, and the limitations in adults of transthoracic and subcostal windows in permitting full visualization …

Sevoflurane does not alter norepinephrine-induced intracellular Ca2+ changes in the diabetic rat aorta

The effect of volatile anesthetics on the mechanism(s) of vascular contraction in diabetes mellitus (DM) has not been fully understood. The current study was designed to determine the effects of sevoflurane on the norepinephrine (NE)-induced changes in contractile state and intracellular Ca²(+) concentrations ([Ca²(+)](i)) in the spontaneously developing type 2 DM rat. The effects of sevoflurane on NE (10⁻⁶M)-induced vasoconstriction and increase in [Ca²(+)](i) in the aortas from Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 DM model, and from age-matched control Long-Evans Tokushima Otsuka (LETO) rats were investigated using an isometric force transducer and fluorometer with fura-2 as an indicator of [Ca²(+)](i). Norepinephrine-induced increases in tension and [Ca²(+)](i) in OLETF rats were 54.8%, 95% confidence interval (CI) 36.9-72.6% and 58.8%, 95% CI 51.5-66.1%, respectively, and in LETO rats they were 46.4%, 95% CI 39.0-53.7% and 53.8%, 95% CI 46.9-60.7%, respectively, when expressed as the percentage relative to that induced by KCl 30 mM. In LETO rats, sevoflurane at a concentration of 3.4% inhibited the vascular contraction (9.4%, 95% CI 6.3-12.6%; P < 0.001) and the increase in [Ca²(+)](i) (33.3%, 95% CI 27.4-39.2%; P = 0.002). In OLETF rats, however, sevoflurane failed to affect either the NE-induced contraction (43.6%, 95% CI 28.3-58.9%; P = 0.68) or the elevation in [Ca²(+)](i) (60.5%, 95% CI 56.3-64.8%; P = 0.93). Sevoflurane at clinically relevant concentrations inhibited the NE-induced increase in [Ca²(+)](i) in the aortic smooth muscle from normal rats but not in that from type 2 DM rats. Thus, a Ca²(+)- signalling pathway resistant to sevoflurane appears to exist in the type 2 DM rat aorta.

The effect of erythropoietin on exercise capacity, left ventricular remodeling, pressure-volume relationships, and quality of life in older patients with anemia and heart failure with preserved ejection fraction.

A prospective, open-label, 3-month study was conducted to evaluate the feasibility and short-term clinical effect of subcutaneous erythropoietin injections in patients with anemia and heart failure with preserved ejection fraction (ejection fraction, 55%+/-2%). Using a dose-adjusted algorithm to effect a rate of rise in hemoglobin not to exceed 0.4 g/dL /wk, hemoglobin (10.8+/-0.3 to 12.2+/-0.3 g/dL) and red blood cell volume (1187+/-55 to 1333+/-38 mL) increased with an average weekly dose of 3926 units. Functional measures increased from baseline (6-minute walk test [289+/-24 to 331+/-22 m], exercise time [432+/-62 to 571+/-51 s], and peak oxygen consumption [8.2+/-0.7 to 9.4+/-0.9 mL/kg/min], all P<.05). End-diastolic volume declined significantly (8% volumetric decrease, 108+/-3 to 100+/-3 mL, P =.03), but there were no significant changes in left ventricular mass or estimated left ventricular end-diastolic pressure. Pressure-volume analysis demonstrated a reduction in ventricular capacitance at an end-diastolic pressure of 30 mm Hg without significant changes in contractile state.

79 Examination of potential sources of smooth muscle for use as a transplantable, innervated sphincter.

Aim: To examine the electrical and mechanical properties of different smooth muscle tissues for their suitability to assist the malfunctioning urethral sphincter in the treatment of stress urinary incontinence.Methods: Changes in contractile state and membrane potential, in response to nerve stimulation, were measured from guinea‐pig mesenteric veins, detrusor smooth muscle and rat dartos.Results: Intracellular recordings made from mesenteric veins (diameter 100–250 ??m) displayed stable resting membrane potentials (RMPs) of –65.2 ± 2.7 mV (10 cells, five animals). Stimulation with long trains at low frequencies (80s, 0.5–2 Hz), evoked slow sustained membrane depolarizations and constrictions which reached a peak within 50s. Stimulation at 2Hz evoked a membrane depolarization of 16.3 ± 4mV and a 17 ± 7% reduction in vessel diameter. Upon cessation of stimulation, the membrane potential and blood vessel diameter rapidly returned to baseline levels. Detrusor smooth muscle cells had RMPs of –40 ± 4 mV (n = 3). Stimulation at frequencies of 1 to 5 Hz evoked muscle action potentials and contractions. Contractions evoked by long trains of nerve stimulation were not sustained for the duration of stimulus. For example, a stimulus train of 80 s at 1 Hz, evoked a contraction of 20 ± 9 mN which reduced to 3 ± 1 mN (n = 3). Hyoscine reduced the secondary phase of the contraction from 3 ± 0.4 mN to 0.7 ± 0.4 mN (P &lt; 0.01, n = 3). Rat dartos smooth muscle had a RMP of –64 ± 1 mV (n = 38). Long trains of low frequency nerve stimulation (1 Hz for 80s), evoked a slow membrane depolarization of 15 ± 4 mV and sustained contraction of 12 ± 2 mN. Increasing the frequency of stimulation caused a graded increase in the amplitude of both the membrane depolarization and contraction. Following the cessation of stimulus, the membrane potential and force generated by the smooth muscle immediately returned to baseline. All responses were blocked by the α‐adrenoceptor antagonists phentolamine (1 μM) and prazosin (0.1 μM).Conclusion: Smooth muscles of the mesenteric vein and dartos display contractile properties which make them suitable for use as transplantable sphincters. In addition, dartos smooth muscle possesses similar pharmacological properties to the proximal urethral sphincter.

Assessment of Left Ventricular Contractile State by Preload-Adjusted Maximal Power Using Echocardiographic Automated Border Detection

Objectives. We sought to assess the ability of preload-adjusted maximal power measured by echocardiographic automated border detection (ABD) to quantify left ventricular (LV) contractility by determining the effects of alterations in preload, afterload and contractile state.Background. Preload-adjusted maximal power can reflect LV contractile state relatively independent of changes in loading conditions.Methods. Eight anesthetized dogs had placement of aortic electromagnetic flow probes, LV and arterial pressure catheters and inferior vena caval (IVC) occluders; four had placement of thoracic aortic balloon occluders. Echocardiographic ABD measures of cross-sectional area were used as a surrogate for LV volume, and flow was estimated as the first derivative of area with respect to time. Power was calculated as the product of flow and pressure.Results. Preload independence during vena caval occlusions was achieved by preload adjustment (÷[end-diastolic area]3/2). Afterload independence was demonstrated by preload-adjusted maximal power being unaffected by acute increases in LV systolic pressure induced by aortic occlusion. ABD preload-adjusted maximal power reflected changes in contractile state: increasing with dobutamine infusion from 36 ± 14 to 70 ± 15 mW/cm4(p < 0.05 vs. control) and decreasing with propranolol infusion from 35 ± 13 to 17 ± 7 mW/cm4(p < 0.05 vs. control). These changes were significantly correlated with calculations of preload-adjusted maximal power using aortic flow (r = 0.90, SEE 10.5 mW/cm4) and load-independent measures of end-systolic elastance from pressure–area loops (r = 0.90, SEE 10.6 mW/cm4). Calculations of normalized preload-adjusted maximal power using arterial pressure were also closely correlated with similar calculations using LV pressure (r = 0.99, SEE 3%).Conclusions. Preload-adjusted maximal power using echocardiographic ABD can predict LV contractile state relatively independent of loading conditions and has potential for clinical application.

Editorial: Left ventricular dysfunction after open repair of simple confenital heart defects in infants and children

Editorial: Left ventricular dysfunction after open repair of simple confenital heart defects in infants and children

DOES DIGOXIN (DIG) ACTIVATE SODIUM-CALCIUM (NA-CA) EXCHANGE IN INTACT IMMATURE MAMMALIAN MYOCARDIUM? † 190

Although Na-Ca exchange has been clearly demonstrated in isolated immature cardiomyocytes, the degree to which DIG can stimulate Na-Ca exchange has not been studied in the intact, beating immature mammalian heart. We studied 37 paced, isovolumically contracting, constant pressure-perfused 3-week old New Zealand white rabbit modified Langendorff heart preparations at 37° C: 1) DIG dose-response curves under varying perfusate [Ca]; 2) response to DIGvs. low potassium (1 mM KCl) perfusate (which stimulates Na-Ca exchange) in 1.3 mM perfusate [Ca]; 3) resPonse to DIG vs. low K, in 0.2 uM nifedipine and 1.3 mM [Ca]. Results are expressed as% of baseline (mean± SE). DIG exerted inotropic and lusitropic effects only at 1 uM, but the degree increased with decreasing [Ca] in dose-dependent fashion. Low K consistently enhanced contractility and relaxation. During nifedipine Ca channel blockade, contractility and relaxation decreased markedly, recovered somewhat with 1 uM DIG, and were enhanced further with low K, with greater recovery of contractility than relaxation. As changes in contractile state are most directly related to Ca fluxes, our results show that Na-Ca exchange can be stimulated in the intact heart to enhance Ca entry and efflux markedly, corresponding to improved inotropy and lusitropy. DIG can stimulate Na-Ca exchange only to a limited degree, except under conditions of low [Ca]; under physiologic conditions of 1.0 mM [Ca], DIG has no significant inotropic actions. Interpretation of prior results with DIG should take into account the[Ca] used in the preparation. TableTable Table

Modified left ventricular mechanical restitution plots during atrial fibrillation in humans: The effect of interval dependent changes in contractile state

Modified left ventricular mechanical restitution plots during atrial fibrillation in humans: The effect of interval dependent changes in contractile state

Changes in electrocardiographic morphology reflect instantaneous changes in left ventricular volume and output in cardiac surgery patients

We examined the relation between changes in R-to-T wave amplitude ratios (R:T) and left ventricular (LV) performance as cardiac output was rapidly varied by inferior vena caval occlusion in 6 subjects prior to cardiopulmonary bypass. To assess the influence of contractility, paired studies before and after bypass were performed in 4 subjects. Stroke volume and cardiac output were assessed by aortic flow probe, and transesophageal echocardiographic LV area measures using the automated border-detection method were used to give LV stroke area, stroke force, maximal LV area, fractional area change, end-systolic elastance, and preload recruitable stroke force. Data were collected on computer and analyzed by linear regression. Significant changes in R:T and measured LV variables during the inferior vena caval occlusion were stroke volume (r = 0.81), LV stroke area (r = 0.77), LV stroke force (r = 0.81), maximal LV area (r = 0.78), and cardiac output (r = 0.80). However, R:T varied inconsistently in relation to fractional area change. After cardiopulmonary bypass, the linear relation between R:T with LV stroke force, LV stroke volume, and maximal LV area persisted, but at a lesser slope. Although absolute pre-inferior vena caval occlusion R:T did not correlate with end-systolic elastance or preload recruitable stroke force, the change in the slope of these linear relations correlated well with the change in end-systolic elastance after surgery (r = 0.92). Instantaneous changes in electrocardiographic morphology reflect changes in LV preload-dependent variables, whereas long-term changes in electrocardiographic morphology may also reflect changes in contractile state.

Regional myocardial function curve of the ventricle.

To understand the pathophysiology of diseased hearts, we devised a new regional myocardial function curve and investigated its properties. Regional work per unit volume of the myocardium (RWM) was calculated by integrating mean wall stress (sigma) with respect to the natural logarithm of the reciprocal of wall thickness [ln(1/H)] over a cardiac cycle. Regarding the end-diastolic ln(1/H) as the preload for the region of concern on the assumption that the myocardium is incompressible, we defined the relation between RWM and end-diastolic ln(1/H) as the regional myocardial function curve. In ten mongrel dogs, we measured left ventricular pressure, left ventricular internal diameter, and wall thickness with a catheter-tip micromanometer and ultrasonic dimension gauges during volume loading to obtain the regional myocardial function curve. We examined the sensitivity of the regional myocardial function curve to changes in contractile state (isoproterenol, propranolol) and changes in afterload (pressure loading by a balloon-occlusion catheter). The linear fit to the data points of the regional myocardial function curve under each condition always achieved a very good correlation coefficient (greater than 0.62). Isoproterenol increased the slope of the regional myocardial function curve from 9.7 +/- 0.9 (SEM) mJ/cm3 to 14.4 +/- 1.0 mJ/cm3 (P < 0.01), with no significant changes in the x-intercept, while propranolol decreased it to 5.6 +/- 1.2 mJ/cm3 (P < 0.01) with no significant changes in the x-intercept.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute effects of balloon valvuloplasty and pacing on left ventricular performance in children with moderate pulmonary valve stenosis, analysed by systolic and diastolic pressure-volume relationships.

Right ventricular overload of volume and/or pressure type may affect left ventricular systolic and diastolic function. This has been shown in animal studies and has been suggested in non-invasive studies in man. Altered geometry of the left ventricle, myocardial hypertrophy and changes in contractile state may be responsible for the change in function. Balloon valvuloplasty is an effective treatment for isolated valvular pulmonary stenosis in children, and results in an immediate decrease of right ventricular systolic pressure. Whether this results in immediate changes in left ventricular performance is unknown. Eight children (age 5.2 to 13.9 years) with moderate pulmonary valve stenosis underwent pulmonary balloon valvuloplasty under general anaesthesia. Left ventricular function measurements before and after valvuloplasty were performed using a combined micromanometer-conductance catheter to obtain end-systolic (ESPVR) and end-diastolic (EDPVR) pressure-volume relationships employing inferior vena cava occlusion both at normal and pacing-induced increased heart rates. Pulmonary valvuloplasty resulted in a decrease in peak systolic right ventricular pressure from 62.8 +/- 13.5 to 34.4 +/- 7.3 mmHg (P < 0.001), without significant changes in left ventricular systolic and end-diastolic pressure, or in cardiac index. The ESPVR was fitted to a linear function to obtain the slope (Ees) and the volume intercept at 75 mmHg (V75). The EDPVR was fitted to an exponential function. At baseline, Ees was 1.68 +/- 0.99 mmHg.ml-1 and V75 was 33.6 +/- 21.8 ml. Neither valvuloplasty nor pacing, which increased mean heart rate from 81 to 112 beats.min-1 (P < 0.001), resulted in significant changes of the parameters Ees or V75.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of myocardial alpha 1-adrenergic receptor stimulation and blockade on contractility in humans.

Although alpha-adrenergic receptors are present in both normal and failing human left ventricular myocardium and mediate a positive inotropic effect in several other species, it is not known whether stimulation of myocardial alpha-adrenergic receptors exerts a positive inotropic effect or contributes to basal contractile state in vivo in humans. We studied 15 patients with angiographically normal coronary arteries (seven with normal left ventricular function and eight with left ventricular failure). To avoid the confounding effects of changes in ventricular loading conditions and systemic reflex mechanisms, the alpha-adrenergic receptor-selective antagonist phentolamine and agonist phenylephrine were infused directly into the left main coronary artery, and the change in contractile state was assessed by measuring left ventricular peak (+)dP/dt. Phentolamine alone had no effect on left ventricular contractility. Phenylephrine exerted a concentration-related positive inotropic effect in patients with normal as well as those with failing ventricles. The alpha-adrenergic effect of phenylephrine, defined as the component blocked by phentolamine, was significantly less in patients with ventricular failure (108 +/- 28 mm Hg/sec) than in normal subjects (248 +/- 54 mm Hg/sec; p less than 0.03). Myocardial alpha-adrenergic receptors do not contribute to the maintenance of basal left ventricular contractile state in humans. However, stimulation of myocardial alpha-adrenergic receptors exerts a positive inotropic effect, the magnitude of which may be attenuated in patients with heart failure.

Influence of Volatile Anesthetics on Myocardial Contractility In Vivo

The direct effects of desflurane on myocardial contractility in vivo have not been characterized. Therefore, the purpose of this investigation was to systematically examine the effects of desflurane on myocardial contractile function and compare these actions to equianesthetic concentrations of isoflurane in chronically instrumented dogs. Contractility was evaluated using an established index of inotropic state, the preload recruitable stroke work (PRSW) versus end-diastolic segment length (EDL) relationship. Since autonomic nervous system tone may influence the hemodynamic effects of the volatile anesthetics in vivo, experiments were performed in the presence of pharmacologic blockade of the autonomic nervous system. Two groups of experiments were performed with seven dogs instrumented for measurement of aortic and left ventricular pressure, the maximum rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, coronary blood flow velocity, and cardiac output. After autonomic nervous system blockade, ventricular pressure-segment length loops were generated using preload reduction via partial inferior vena caval occlusion. The PRSW versus EDL relation was calculated from the pressure-length loops. Dogs were then anesthetized with 1.0 or 1.5 MAC desflurane or isoflurane in a random fashion, and measurements were repeated after 30 min of equilibration at each anesthetic concentration. The PRSW versus EDL slope reflected similar changes in contractile state when desflurane or isoflurane was administered (53 +/- 4 during control to 26 +/- 4 erg.cm-2 x 10(-3).mm-1 at 1.5 MAC desflurane, and 57 +/- 5 during control to 31 +/- 3 erg.cm-2 x 10(-2).mm-1 at 1.5 MAC isoflurane). In conclusion, desflurane and isoflurane produced equivalent direct decreases in myocardial contractility.

Myocardial stiffness derived from end-systolic wall stress and logarithm of reciprocal of wall thickness. Contractility index independent of ventricular size.

The slope of the end-systolic pressure-volume relation (ESPVR) is useful in assessing acute changes in contractile state. However, a limitation of ESPVR is that its slope decreases progressively as ventricular size increases without this change necessarily indicating a change in contractile state. In this respect, an index of contractile function that is independent of ventricular size would have an obvious advantage. The exponential constant (k) of the end-systolic relation between wall stress (sigma) and the natural logarithm of the reciprocal of wall thickness [ln(1/H)], sigma = Cekln(1/H), corresponds to the stiffness constant of the myocardium (kSM), a contractile index that should be independent of ventricular size and geometry. To examine the size independence of kSM, we studied left ventricular kSM during beta-blockade (to stabilize inotropic state) in 25 normal dogs with greatly differing ventricular sizes whose end-diastolic volumes ranged from 14 to 82 ml. The kSM was nearly constant (3.6 +/- 0.4) over this wide range of end-diastolic volumes and thus was independent of end-diastolic volume. Conversely, ESPVR, also obtained during beta-blockade, was closely and negatively correlated to end-diastolic volume (r = 0.92). To test the ability of kSM to measure changes in contractile state, we altered contractile state pharmacologically. The kSM increased from 3.7 +/- 0.5 to 4.8 +/- 0.8 (p less than 0.01) with infusion of dobutamine (after reversal of beta-blockade) and decreased to 3.1 +/- 0.3 (p less than 0.05) with inhalation of isoflurane, a negative inotrope, during beta-blockade (p less than 0.05). We conclude that kSM is independent of ventricular size and is sensitive to changes in inotropic state. As such, it should be useful as an index of contractile function.

Comparison of End-Systolic Pressure—Length Relations and Preload Recruitable Stroke Work as Indices of Myocardial Contractility in the Conscious and Anesthetized, Chronically Instrumented Dog

Development of an index of myocardial contractility that is both load independent and easily quantified in vivo has been a difficult task. Recently, three measures of contractile state have been advocated that appear to fulfill these requirements: the end-systolic pressure-length relationship (ESPLR), the ESPLR area, and regional preload recruitable stroke work (PRSW). Because the effects of halothane and isoflurane on these indices of contractility have yet to be studied, the purpose of this investigation was to compare the effects of these volatile anesthetics on contractile function as evaluated via these techniques in chronically instrumented dogs. Because autonomic nervous system tone substantially influences systemic hemodynamics in vivo, experiments were performed in the presence of pharmacologic blockade of the autonomic nervous system. Four groups comprised the 36 experiments that were performed with nine dogs. Following inhalational induction, the dogs were maintained on 1.5 MAC and 2 MAC of halothane or isoflurane. Pressure-length loops were generated after 1 h of equilibration using preload reduction via partial inferior vena caval occlusion or afterload augmentation by a phenylephrine infusion. The PRSW and ESPLR were then calculated, respectively. Slope and length intercept variables obtained from the ESPLR failed to significantly change from control with increasing levels of anesthetic depth despite substantial decreases in other indices of contractility. However, combination of slope and length intercept parameters into the ESPLR area model proved to be a sensitive and easily calculable measure of depressed myocardial function. Similarly, regional PRSW slope precisely reflected changes in contractile state when halothane (62 +/- 10 for control to 30 +/- 6 erg.cm-2.10(-3).mm-1 at 2 MAC) or isoflurane (83 +/- 14 for control to 55 +/- 8 erg.cm-2.10(-3).mm-1 at 2 MAC) were administered. The PRSW slope also demonstrated a significant difference in depressed contractility when equianesthetic concentrations of halothane and isoflurane were compared (63 +/- 7% of control with halothane versus 86 +/- 4% of control with isoflurane at 1.5 MAC; 50 +/- 5% of control with halothane versus 70 +/- 6% of control with isoflurane at 2 MAC). The ESPLR area also accurately demonstrated the differential depression in contractile function suggested by recent in vitro studies when equianesthetic doses of halothane and isoflurane were compared in vivo. Therefore, while ESPLR slope and length intercept variables fail as indices of myocardial contractility, ESPLR area and regional PRSW slope were shown to be useful indicators of contractile state in the conscious and anesthetized dog.

Simultaneous conductance catheter and dimension assessment of left ventricle volume in the intact animal.

We compared left ventricle (LV) volume (V) simultaneously measured using the conductance catheter (VM) with volume calculated from three LV dimensions (VD) determined ultrasonically from endocardial crystals. Seven adult mongrel dogs (20-30 kg) were anesthetized and instrumented to measure micromanometer LV pressure and V. Three pairs of crystals were placed orthogonally in subendocardial positions and a conductance catheter was placed in the LV retrograde across the aortic valve. Under steady-state conditions, over the range of a single cardiac cycle, the relation between VM and VD was well described by a straight line. There was an excellent correlation of conductance and dimension volumes with r equal to 0.97 +/- 0.04 and SEE 0.8 +/- 0.5 ml. The gain (1/alpha) and parallel conductance volume (alpha VC) were constant. At lower volumes obtained during bicaval occlusion, however, the relation between VM and VD was curvilinear. 1/alpha and alpha VC both decreased as LVV fell. Thus, determination of absolute volume using the conductance catheter depended on the conditions under which the data were obtained. Under steady-state conditions, alpha VC calculated by both the saline method (mean +/- SD, 50 +/- 15 ml) and by regression of VM and VD, (45 +/- 21 ml) were similar. Consequently, absolute LV end-diastolic volumes and end-systolic volumes by the conductance and dimension methods were similar (53 +/- 14 ml and 38 +/- 14 ml vs. 56 +/- 17 ml and 44 +/- 16 ml, respectively, p = NS). When volume decreased during bicaval occlusion, there was a progressively greater decrease in VM as compared with VD. The absolute slope (EES) of the end-systolic pressure-volume relation (ESPVR) was consistently higher by the dimension method, group average, 16.3 +/- 7.6, than by the catheter, 8.5 +/- 5.9, p less than 0.05. The direction and magnitude of the change in EES at different inotropic states (autonomic blockade; dobutamine), however, was similarly measured by both the conductance catheter and dimension method. We conclude that the gain and offset of the conductance catheter are relatively constant at steady state but vary when volume is reduced by caval occlusion. Thus, the conductance catheter accurately measures absolute volumes at steady state but can underestimate the slope and position of the ESPVR when it is determined by caval occlusion. The conductance catheter does, however, accurately measure the directions and magnitude of change in contractile state.