Biomedical subjects

D A Kass

Publications and source records attributed to D A Kass.

At least 91 records · Page 5Linked to original sources

PubMed1995

systolic flow augmentation in hearts ejecting into a model of stiff aging vasculature. Influence on myocardial perfusion-demand balance.

Age-related arterial stiffening and widening of the pulse pressure elevates ventricular systolic wall stress while it lowers diastolic coronary perfusion pressure. These changes are thought to adversely alter the balance between myocardial work load and blood supply. To test this hypothesis, the native compliant thoracic aorta was surgically bypassed by a stiff tube in reflex-blocked anesthetized dogs. Ventricular outflow was directed into either native aorta or the bypass; the latter resulting in an increase in arterial pulse pressure from 37.8 to 107.5 mm Hg (P < .001), with minimal change in mean pressure and flow. Cardiac work load was assessed by pressure-volume area (PVA), which combines external and internal left ventricular work and is linearly related to myocardial oxygen consumption (MVO2), and by MVO2 itself. Regional phasic and mean coronary flow were measured in the left anterior descending coronary artery, and global flow was assessed by radiolabeled microspheres. Myocardial supply-demand balance was assessed by comparing flow at matched PVA or MVO2, flow-PVA relations, and endocardial-to-epicardial flow ratios. When blood flow was directed into the stiff bypass tube, peak systolic pressure, wall stress, and PVA all rose nearly 50%, yet diastolic perfusion pressure fell by 20 mm Hg (all P < .01). Rather than being compromised, however, mean coronary flow rose by 34%, maintaining the same endocardial-to-epicardial flow ratio (approximately 1.1). Flow augmentation persisted when data were compared at matched work load (PVA or MVO2), and mean arterial pressure, as well as over a range of work loads (P < .001 from ANCOVA of flow-PVA relations). The increased flow resulted from enhanced systolic perfusion, which nearly equaled diastolic flow when ejection passed into the stiff bypass. These data counter the notion that cardiac coupling with a stiff arterial system (as with aging) necessarily compromises myocardial flow versus metabolic demand. However, the data highlight a greater role of systolic flow under such conditions and also raise the novel suggestion that enhanced pulsatility of the arterial pressure waveform may itself augment coronary perfusion.

Aging↗

PubMed1995

Role of atrial contraction in diastolic pressure elevation induced by rapid pacing of hypertrophied canine ventricle.

The mechanism of diastolic pressure elevation induced by acute rapid pacing in pressure-load hypertrophied left ventricles (LVs) remains incompletely understood. It has been ascribed to abnormalities of coronary flow, metabolism, and calcium cycling. However, rapid pacing also alters the timing of atrial and ventricular stimulation relative to the diastolic filling period, and this could also influence diastolic pressures. To test the role of such mechanical factors, LV pressure-volume hemodynamics were measured in closed-chested anesthetized dogs during and after abrupt cessation of rapid atrial pacing. Twenty-one dogs were studied: 6 dogs with LV hypertrophy (LVH) induced by perinephritic hypertension, 5 sham-operated normotensive dogs, and 10 acute normotensive control dogs. In LVH dogs, but not in sham-operated or control dogs, end-diastolic pressure rose progressively with increasing heart rate from 5.6 +/- 3.1 mm Hg at baseline to 22.6 +/- 8.1 mm Hg at 220 beats per minute. In all hearts, rapid pacing shifted the timing of left atrial contraction so that it occurred near the onset of LV filling rather than at end diastole. However, in LVH hearts, early LV diastolic pressure and peak atrial pressure were also markedly elevated. Most striking, immediately after terminating the pacing, diastolic pressure declined to near baseline. This rapid pressure decline occurred just when atrial systole would have ensued and before ventricular activation would have followed had pacing continued. Thus, diastolic pressure elevation resolved before a change in ventricular pacing rate. The role of atrial contraction was further explored by simultaneous atrioventricular pacing. This shifted the time of atrial systole so that it occurred during LV isovolumic contraction, while maintaining the identical LV pacing rate. This change eliminated the diastolic pressure elevation found previously. Further analysis revealed that the pressure increase during rapid pacing was not due simply to partial LV filling imposed on a relaxing ventricle or to hypertension or an intact pericardium. These data indicate that mechanical effects of atrioventricular interaction play an important role in tachycardia-induced diastolic dysfunction in this model of LVH and can be more causative than ischemia or metabolic factors in this setting.

Animals↗

PubMed1994

Ventricular systolic assessment in patients with dilated cardiomyopathy by preload-adjusted maximal power. Validation and noninvasive application.

BACKGROUND: Noninvasive cardiac-specific analysis of contractile function in patients with dilated heart failure remains problematic. This study tests whether maximal power divided by the square of end-diastolic volume (PWRmx/EDV2, or preload-adjusted PWRmx) can provide such assessment. METHODS AND RESULTS: To validate the load insensitivity of the PWRmx index and determine its response to contractile change, 24 subjects with chronic dilated cardiomyopathy underwent invasive pressure-volume catheterization study using the conductance catheter technique. Preload was transiently reduced by 30% using balloon occlusion of the inferior vena cava, and afterload impedance was lowered by 50%, induced by a bolus injection of nitroglycerin. Contractile state was varied by intravenous dobutamine, verapamil, or esmolol. PWRmx was calculated from the simultaneous product of ventricular pressure and rate of volume change (dV/dt), the latter derived from the volume catheter signal. PWRmx varied directly with preload but was minimally influenced by afterload. However, PWRmx/EDV2 was not significantly altered by either loading change. PWRmx/EDV2 did vary with contractility, correlating closely with changes in the end-systolic pressure-volume relation (r = .91, P < .001). To test the noninvasive application of this index, 12 additional patients were studied, with PWRmx/EDV2 derived from nuclear ventriculography combined with a novel method to measure central arterial pressures. Subjects received intravenous nitroprusside or dobutamine in random order. Ejection fraction increased similarly with both agents (+42.9 +/- 8.9% for dobutamine and +29.4 +/- 5.3% for nitroprusside, both P < .01). In contrast, PWRmx/EDV2 did not significantly change with nitroprusside but increased by 126 +/- 16.1% with dobutamine (P < .01). CONCLUSIONS: Preload-adjusted PWRmx is a steady-state index of ventricular systolic function that is sensitive to inotropic state and minimally influenced by physiological changes in afterload impedance or volume load. It appears useful for noninvasive cardiac-specific analysis of acute drug effects.

Cardiac Catheterization↗

PubMed1994

Endomyocardial gene expression during development of pacing tachycardia-induced heart failure in the dog.

Selective and specific changes in gene expression characterize the end-stage failing heart. However, the pattern and relation of these changes to evolving systolic and diastolic dysfunction during development of heart failure remains undefined. In the present study, we assessed steady-state levels of mRNAs encoding a group of cardiac proteins during the early development of left ventricular dysfunction in dogs with pacing-induced cardiomyopathy. Corresponding hemodynamic assessments were made in the conscious state in the same animals and at the same time points at baseline, after 1 week of ventricular pacing, and at the onset of clinical heart failure. Systolic dysfunction dominated after 1 week of pacing, whereas diastolic dysfunction was far more pronounced with the onset of heart failure. Atrial natriuretic factor mRNA was undetectable in 7 of 12 hearts at baseline but was expressed in all hearts at 1 week (P < .01 by chi 2 test), and it increased markedly with progression to failure (P = .05). Creatine kinase-B mRNA also rose markedly with heart failure (P < .01). Levels of mRNA encoding beta-myosin heavy chain, mitochondrial creatine kinase, phospholamban, and sarcoplasmic reticulum Ca(2+)-ATPase did not significantly change from baseline, despite development of heart failure. Additional analysis to determine if these mRNA changes were related to the severity of diastolic or systolic dysfunction revealed that phospholamban mRNA decreased in hearts with larger net increases in end-diastolic pressure (+19.2 +/- 1.9 mm Hg) compared with those hearts in which it did not change (+4.0 +/- 4.9, P < .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1993

Diastolic compliance of hypertrophied ventricle is not acutely altered by pharmacologic agents influencing active processes.

OBJECTIVE: To test, by studying the acute effects of drugs that influence active processes, the hypothesis that in humans with marked ventricular hypertrophy, reduced chamber compliance is primarily caused by passive structural changes. DESIGN: An uncontrolled (before-after) study. SETTING: University Medical Center. PATIENTS: Fourteen patients with ventricular hypertrophy (19 +/- 4.5-mm diastolic-wall thickness) and normal resting systolic function were studied while they had invasive cardiac catheterization. INTERVENTION: Intravenous beta-blocker (esmolol) or calcium channel blocker (verapamil) or both. MEASUREMENTS: Left ventricular function was determined by pressure-volume relations. Volume was measured using conductance catheter, providing a continuous voltage signal proportional to chamber volume. Pressure was measured by micromanometer. Cardiac-specific assessment of change in chamber contractility and diastolic compliance due to each drug was determined. RESULTS: Both drugs lowered contractility by approximately 30% (P < 0.01). Esmolol slowed relaxation and reduced early peak filling rate, whereas verapamil delayed the time to peak filling (all P < 0.05). In contrast to the effects of both drugs on active contraction and early diastole, late-diastolic compliance was unaltered, and end-diastolic pressure-volume relations were almost identical. CONCLUSION: Neither beta-receptor nor calcium channel blockade acutely alters left ventricular compliance despite substantial active effects manifest in systole and early diastole. This supports the notion that chamber compliance is principally determined by passive structural elements in the heart rather than by active processes.

Adrenergic beta-Antagonists↗

PubMed1993

Ventricular-arterial interaction: cardiac effects of mean versus pulsatile arterial load.

The influence of the two principal components of vascular loading, mean resistance and pulsatile load, on the contractile and energetic performance of the left ventricle are discussed. The data suggest that while large changes in mean resistance leading to varying ejection fraction can influence both cardiac systolic mechanics and energetic efficiency, substantial changes in pulsatile loading do not. They provide an explanation for why pulsatile loading does not necessarily result in a coronary supply/demand imbalance. By not significantly altering chamber systolic performance of elastance (i.e. stiffness), the pulsatile load results in parallel increases in coronary systolic pressure and flow, allowing adequate perfusion despite the reduced mean diastolic perfusion pressure. Future studies are required to better determine how cardiac disease alters the interplay between vascular load and cardiac performance.

Coronary Vessels↗

PubMed1993

Pressure-volume analysis of changes in cardiac function in chronic cardiomyoplasty.

Reports of clinical improvement in human studies of dynamic cardiomyoplasty lack support by consistent objective hemodynamic evidence. Animal studies have also yielded conflicting results, likely due to nonuniform models, particularly the use of unconditioned wraps, and to limitations in commonly used study modalities caused by exaggerated heart motion during wrap stimulation. Our purpose was to assess the primary functional properties of the heart wrapped by conditioned muscle using pressure-volume relation analysis based on conductance catheter volume data. Compared with the unstimulated state, 1:1 stimulation caused an increase in contractility and decreases in end-diastolic volume and stroke work. Assisted beats during 1:2 stimulation showed an increase in contractility and a decrease in end-diastolic volume. Unassisted beats (1:2) showed decreases in end-diastolic volume and stroke work. There was no augmentation of cardiac output or ejection fraction with stimulation (1:1 or 1:2). We conclude that in the nonfailing heart, increased contractility does not augment cardiac output, ejection fraction, and stroke work because of a simultaneous decrease in end-diastolic volume. These changes in contractility and end-diastolic volume may prove therapeutic for dilated cardiomyopathy.

Animals↗

PubMed1993

Transient time course of cocaine-induced cardiac depression versus sustained peripheral vasoconstriction.

OBJECTIVES: The goal of this study was to define in vivo the magnitude and temporal course of cocaine-induced cardiac depression separate from peripheral vascular loading changes. BACKGROUND: Cocaine administration immediately alters arterial pressure, ventricular filling, contractility and heart rate. These combined changes have complicated previous analyses of the cardiac effects of cocaine, because routine measures of function are influenced by all these factors. METHODS: Pressure-volume loops and relations were measured by conductance catheter technique in 10 intact chest anesthetized dogs before and up to 30 min after administration of cocaine (3 mg/kg intravenously). Heart rate was kept constant by atrial pacing, and data were obtained before and after ganglionic blockade. RESULTS: Cocaine decreased ejection fraction, cardiac output and maximal rate of rise of left ventricular pressure (dP/dtmax) and increased arterial vascular resistance (all p < 0.05). The maximal change occurred by 2 min and was fully sustained for the next 30 min. In contrast, contractile indexes based on pressure-volume analysis (e.g., end-systolic pressure-volume relation) decreased only briefly at 2 min (by -19%) and returned to control value after 5 to 10 min. Reflex blockade with hexamethonium eliminated cocaine-induced vasoconstriction, but the magnitude and brevity of cardiac depression were unaltered. Ejection fraction, dP/dtmax and cardiac output now also decreased transiently, suggesting that the sustained changes observed before blockade in these variables were load related. Analogous load effects also explained changes in peak filling rate. CONCLUSIONS: Cocaine induces brief direct cardiac depression that is temporally dissociated from more sustained peripheral vasoconstriction. This dissociation is not measured by traditional left ventricular function analysis because of simultaneous load change. The transience of cardiac depression suggests that it probably does not play a major role in late adverse sequelae of cocaine administration.

Analysis of Variance↗

PubMed1993

Ventricular stroke work and efficiency both remain nearly optimal despite altered vascular loading.

Recent clinical and animal studies have suggested that ventricular-vascular coupling normally operates at either optimal ventricular efficiency (EFF = stroke work/myocardial oxygen consumption) or stroke work (SW) and that efficiency in particular is compromised by cardiac dysfunction. These distinctions between coupling states at maximal work vs. efficiency are largely based on theoretical models. To date, there are few direct experimental data defining optimal conditions for each parameter, respectively, in the same heart or tests of whether changes from these conditions must produce significant declines in both parameters. Therefore, 10 isolated blood-perfused canine hearts were studied at varying contractilities, with the heart ejecting into a simulated three-element Windkessel model of arterial impedance. For a given inotropic state [indexed by the slope of the end-systolic pressure-volume relationship (Ees)], myocardial oxygen consumption and SW were measured over a broad range of afterload resistances. The latter was indexed by the effective arterial elastance (Ea) and ventricular-vascular interaction expressed by the ratio of Ea to Ees (Ea/Ees). On average, maximal SW occurred at Ea/Ees = 0.80 +/- 0.16, whereas EFF was maximal at Ea/Ees = 0.70 +/- 0.15 (P < 0.01). However, these differences were small, and both SW and EFF were > or = 90% of their respective optima over a broad overlapping range of Ea-to-Ees ratios (0.3-1.3, corresponds with ejection fractions ranging from approximately 40 to 80%). These data show that both SW and efficiency are nearly maximal under many conditions of ventricular-vascular interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Diminished contractile response to increased heart rate in intact human left ventricular hypertrophy. Systolic versus diastolic determinants.

BACKGROUND: Experimental studies indicate that in addition to diastolic dysfunction, hypertrophied myocardium can display depressed contractile responses, particularly at rapid heart rates, compounding reserve limitations. This study tests whether such abnormalities exist in intact human subjects at physiological paced rates and, if so, whether they are linked to simultaneous rate-dependent deterioration in diastolic function. METHODS AND RESULTS: Ten subjects with left ventricular hypertrophy (LVH) and 8 normal control subjects were studied. Most LVH patients presented with dyspnea and/or pulmonary edema and had concentric hypertrophy. Since rapid pacing simultaneously alters cardiac filling volumes and pressures, pressure-volume relation analysis was used to better define changes in contractile response. Patients were instrumented with a conductance catheter and micromanometer for pressure-volume data recording and a balloon occluder at the right atrial-inferior vena caval junction to vary filling and thus generate function relations. Data were obtained at baseline and at three atrial pacing rates (100, 120, 150 min-1). In addition, single-beat force-interval data were used to indirectly examine calcium cycling kinetics. LVH subjects demonstrated baseline diastolic abnormalities, including prolonged relaxation, elevated end-diastolic pressure, and reduced chamber compliance. However, systolic function was similar to that in control subjects. With rapid pacing, normal subjects displayed a positive contractile response, whereas this was markedly diminished in LVH subjects. With abrupt termination of pacing and return to slower sinus rhythm, LVH subjects displayed greater initial potentiation followed by a more rapid decline than control subjects, suggesting abnormalities of calcium handling. Despite contractile abnormalities, diastolic function did not further deteriorate with rapid pacing and thus did not appear to be tightly linked to the systolic changes. CONCLUSIONS: Pacing stress in intact human LVH can result in systolic impairment superimposed on preexisting but not worsened diastolic dysfunction. Abnormal calcium handling probably contributes prominently to this response.

Calcium↗

PubMed1993

Validation of a method for noninvasive measurement of central arterial pressure.

The goal of this study was to validate a newly improved noninvasive method for calibrated measurement of the ascending portion of the central arterial pressure wave in humans. Noninvasive pressure waveforms were generated by measuring the time delay between the R wave of the electrocardiogram and onset of brachial artery flow (by Doppler) during computer-controlled upper arm cuff deflation. This delay shortens with falling cuff pressure (becoming near constant at and below diastolic pressure), so that a plot of pressure versus time delay yields the ascending portion of the arterial waveform. These waveforms were compared with simultaneous invasive ascending aortic pressures in 57 adult patients (31 by fluid manometer [group A] and 26 by catheter-tipped micromanometer [group B]) during routine cardiac catheterization. Patient age ranged from 26 to 77 years. Eighty percent of group A patients and 40% of group B had coronary artery disease. Noninvasive systolic and diastolic pressures were very similar to invasive values in both groups (Pni = 0.98 x Pi, r = 0.99, p < 0.0001). Instantaneous pressure differences between waveforms were also similar in both groups, averaging between 4.5 and 5.5 mm Hg. Micromanometer and noninvasive pressure data were also obtained before and after intravenous nitroglycerin (n = 5) and isometric handgrip (n = 8) and demonstrated good agreement. A potential application of these pressures is for estimating maximal ventricular power to assess systolic function. This was tested using invasive pressure-volume data from four patients under a variety of conditions (exercise, pacing, etc.).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Ventriculo-arterial coupling: concepts, assumptions, and applications.

Recent investigations have yielded new insights into the interaction of the left ventricle with the arterial system. These studies have employed a variety of coupling frameworks to quantify this interaction, and each makes several simplifying assumptions. In this article, we review these frameworks, their major findings, assumptions, and clinical applications, and examine future directions for this research.

Animals↗

PubMed1992

Clinical evaluation of left heart function by conductance catheter technique.

Methods to obtain pressure-volume loops in humans and their application to clinical diagnosis and treatment of cardiac disease are discussed. The method employs a conductance catheter, micromanometer, and inferior vena caval balloon occluder to reversibly and rapidly vary venous return. Multiple cardiac cycles measured during this manoeuvre are used to derive a variety of systolic and diastolic function indices, as well as estimates of vascular loading, and cardiac energetics. Strengths and weaknesses of the method as well as pressure-volume indexes themselves are briefly discussed. Lastly, three clinical examples are presented which serve to demonstrate how pressure-volume analysis can provide useful clinical information regarding diagnosis and/or treatment in subjects with heart failure symptoms.

Atrial Fibrillation↗

PubMed1992

Mechanism of global functional recovery despite sustained postischemic regional stunning.

BACKGROUND: The mechanisms whereby reperfusion of a 20-minute coronary occlusion result in global functional recovery despite persistent regional dysfunction were studied in 11 open-chest reflex-blocked dogs. METHODS AND RESULTS: Pressure-volume and pressure-thickness relations were simultaneously determined before, during, and after reperfusion of left anterior descending artery (LAD) occlusion. Wall thickness was determined by sonomicrometry in both ischemic and remote regions. Chamber systolic function was assessed by end-systolic pressure-volume relations (ESPVR) obtained by conductance catheter and defined by a slope (Ees) and volume shift at a common end-systolic pressure (delta Ves). LAD occlusion produced regional systolic thinning (-7 +/- 6%) and global left ventricular dysfunction (ESPVR shifted rightward (delta Ves = +8.6 +/- 5.1 ml, p less than 0.001) with no Ees change). After nearly 1 hour of reperfusion, LAD region thickening remained markedly reduced at 4 +/- 7% (versus 23 +/- 8%, control), yet chamber systolic function fully recovered (ESPVR shifted back leftward delta Ves = -8.9 +/- 6.5 ml). Ischemia induced a leftward shift and systolic thinning of LAD region pressure-thickness relations. Reperfusion returned end-systolic pressure-thickness relations halfway to their control position and diastolic relations fully to control position. This was primarily due to increased passive stiffening in about half the hearts and a partial return of active function in the remaining ones. The net effect was to eliminate systolic thinning over a physiological loading range, thus normalizing chamber systolic performance. Reflex activation, remote hyperfunction, or altered chamber loading did not account for the postreperfusion disparity between global and regional function. CONCLUSIONS: These data suggest a mechanism to account for greater functional benefits of reperfusion beyond that anticipated from regional wall motion analysis.

Animals↗

PubMed1992

Reduced left ventricular compliance in human mitral stenosis. Role of reversible internal constraint.

BACKGROUND: The mechanisms of depressed left ventricular (LV) pump performance in human mitral stenosis (MS) remain poorly understood, because reduced filling alone affects many hemodynamic measurements. Therefore, pressure-volume relations were examined in nine subjects with MS and compared with eight age-matched normal controls. METHODS AND RESULTS: Data were obtained by conductance catheter/micromanometer technique with transient inferior vena cava occlusion used to alter load and generate pressure-volume relations. In a subset of patients (n = 5), data were obtained both acutely and at 3 months (n = 4) after balloon valvuloplasty. MS patients had reduced cardiac output (3.3 +/- 0.9 versus 5.6 +/- 1.7 l/min) and end-diastolic volume (68.0 +/- 6.9 versus 115 +/- 31 ml) versus controls (p less than 0.001), with a mean transvalvular gradient of 14 +/- 6 mm Hg and estimated valve area of 0.6 +/- 0.2 cm2. Systolic function as assessed by the end-systolic pressure-volume relation was virtually the same in MS and control subjects. In contrast, end-diastolic pressure-volume relations in MS were consistently shifted leftward and had an increased slope (lower compliance) at matched pressure ranges (6.5 +/- 3.0 versus 2.2 +/- 0.53 ml/mm Hg at a mean diastolic pressure of 8 mm Hg, p less than 0.001). This change was not a result of reduced LV filling or probably of increased right heart loading. Valvuloplasty acutely returned chamber compliance to near normal, a change that was sustained at 3-month follow-up. Systolic function was little altered at this time. CONCLUSIONS: These data indicate an impairment of diastolic function in human MS that can be acutely reversed by balloon valvuloplasty. Lowered LV compliance probably results from a functional restriction caused by ventricular attachment to a thickened and immobile valve apparatus.

Cardiac Catheterization↗

PubMed1992

Effective arterial elastance as index of arterial vascular load in humans.

BACKGROUND: This study tested whether the simple ratio of ventricular end-systolic pressure to stroke volume, known as the effective arterial elastance (Ea), provides a valid measure of arterial load in humans with normal and aged hypertensive vasculatures. METHODS AND RESULTS: Ventricular pressure-volume and invasive aortic pressure and flow were simultaneously determined in 10 subjects (four young normotensive and six older hypertensive). Measurements were obtained at rest, during mechanically reduced preload, and after pharmacological interventions. Two measures of arterial load were compared: One was derived from aortic input impedance and arterial compliance data using an algebraic expression based on a three-element Windkessel model of the arterial system [Ea(Z)], and the other was more simply measured as the ratio of ventricular end-systolic pressure to stroke volume [Ea(PV)]. Although derived from completely different data sources and despite the simplifying assumptions of Ea(PV), both Ea(Z) and Ea(PV) were virtually identical over a broad range of altered conditions: Ea(PV) = 0.97.Ea(Z) + 0.17; n = 33, r2 = 0.98, SEE = 0.09, p less than 0.0001. Whereas Ea(PV) also correlated with mean arterial resistance, it exceeded resistance by as much as 25% in older hypertensive subjects (because of reduced compliance and wave reflections), which better indexed the arterial load effects on the ventricle. Simple methods to estimate Ea (PV) from routine arterial pressures were tested and validated. CONCLUSIONS: Ea(PV) provides a convenient, useful method to assess arterial load and its impact on the human ventricle. These results highlight effects of increased pulsatile load caused by aging or hypertension on the pressure-volume loop and indicate that this load and its effects on cardiac performance are often underestimated by mean arterial resistance but are better accounted for by Ea.

Adult↗

PubMed1992

Alterations in left ventricular mechanics, energetics, and contractile reserve in experimental heart failure.

The contributions of changes in primary systolic and diastolic properties, limitations of contractile reserve, and alterations in energy efficiency to the left ventricular dysfunction seen with chronic pacing tachycardia were investigated. Seven dogs (heart failure group) were ventricularly paced at 250 beats per minute for 26.3 +/- 2.9 days and compared with a separate control group (n = 8). STudies were performed with isolated, metabolically supported hearts coupled to a computer-controlled loading system. Pressure-volume relations and myocardial oxygen consumption (MVO2) were measured to assess chamber systolic and diastolic properties and efficiency (relation between MVO2 and pressure-volume area [PVA]). Systolic function was reduced in failure hearts versus controls as assessed by the slope of the end-systolic pressure-volume relation (1.29 +/- 0.94 versus 2.71 +/- 0.98 mm Hg/ml, p less than 0.01) and lowered end-systolic stiffness at a matched stress (956.1 +/- 123.5 versus 1,401.7 +/- 431.7 g/cm2, p less than 0.05). Diastolic chamber and myocardial stiffness were unaltered in failure hearts, but the unstressed diastolic-arrested volume was significantly larger (33.3 +/- 3.9 versus 21.9 +/- 7.6 ml, p less than 0.01). Inotropic response to increased heart rate and exogenous beta-adrenergic stimulation (dobutamine HCl) was significantly impaired in failure compared with control hearts. Most interestingly, failure hearts had a lowered slope of the MVO2-PVA relation (2.1 +/- 1.1 versus 2.9 +/- 1.4 ml O2.mm Hg-1.ml-1.100 g left ventricle-1, p less than 0.001), indicating increased efficiency of chemomechanical energy conversion. The y intercept of the MVO2-PVA relation, which reflects oxygen costs of basal metabolism and excitation-contraction coupling, was unchanged in the two groups despite decreased contractility of the heart failure hearts. These results demonstrate reduced chamber and myocardial contractility, dilatation without alteration of passive myocardial properties, impaired contractile reserve, and novel alterations in cardiac efficiency in this model of heart failure.

Animals↗

PubMed1992

Effect of reduced aortic compliance on cardiac efficiency and contractile function of in situ canine left ventricle.

This study tests the hypothesis that arterial vascular stiffening adversely influences in situ left ventricular contractile function and energetic efficiency. Ten reflex-blocked anesthetized dogs underwent a bypass operation in which a Dacron graft was sewn to the ascending aorta and connected to the infrarenal abdominal aorta via a plastic conduit. Flow was directed through either native aorta or plastic conduit by placement of vascular clamps. Arterial properties were measured from aortic pressure-flow data, and ventricular function was assessed by pressure-volume (PV) relations. Coronary sinus blood was drained via an extracorporeal circuit for direct measurement of myocardial O2 consumption (MVO2). Data at multiple steady-state preload volumes were combined to derive chamber function and energetics relations. Energetic efficiency was assessed by the inverse slope of the MVO2-PV area relation. Directing flow through plastic versus native aorta resulted in a 60-80% reduction in compliance but little change in mean resistance. Arterial pulse pressure rose from 34 to 99 mm Hg (p less than 0.001). Contractile function assessed by the end-systolic PV relation, stroke work-end-diastolic volume relation, and dP/dtmax at matched end-diastolic volume did not significantly change. However, MVO2 increased by 32% (p less than 0.01) and was matched by a rise in PV area, such that the MVO2-PV area relation and efficiency was unaltered. The MVO2 required to sustain a given stroke volume, however, increased from 20% to 40%, depending on the baseline level (p less than 0.001). Thus, whereas the contractile function and efficiency of normal hearts are not altered by ejection into a stiff vascular system, the energetic cost to the heart for maintaining adequate flow is increased. This suggests a mechanism whereby human vascular stiffening may yield little functional decrement at rest but limit reserve capacity under conditions of increased demand.

Aging↗