Left Ventricular Diastolic Pressure-volume Relationship Research Articles

Physiologic Phenotype of Cardiogenic Shock Due to End-Stage Heart Failure and Acute Myocardial Infarction: Effect of ECLS

<h3>Purpose</h3> This study (i) models and compares the pathophysiology of cardiogenic shock (CS) due to end stage heart failure (ESHF) and acute myocardial infarction (AMI) using patient data and (ii) compares the effects extracorporeal life support (ECLS) in these 2 patient groups. <h3>Methods</h3> Data from consecutive patients with CS due to ESHF and AMI were used as the basis for simulating the hemodynamics with the computational model by Burkhoff et al. ESHF is defined as diagnosis of an ischemic or non-ischemic cardiomyopathy prior to CS. The effects of right atrial (RA) to femoral artery ECLS at 3.5L/min were simulated. <h3>Results</h3> Patient with ESHF had lower ejection fraction, more mitral regurgitation and higher right atrial pressure [TABLE]. Compared to AMI, CS due to ESHF is associated with (i) lower left (LV) and right ventricular (RV) diastolic pressure-volume relation (lower ‘stiffness') [FIGURE]; (ii) lower LV and RV end-systolic elastance (Ees) and (iii) larger pressure-volume loop area (PVA) corresponding to high myocardial oxygen consumption (MVO2), (iv) lower RV efficiency (ratio of stroke work to MVO2). ECLS increased systemic blood pressure and pulmonary artery wedge pressure (PAWP) in both groups, but patients with AMI had higher relative increase in PAWP due to the steeper diastolic pressure-volume relation compared to ESHF. <h3>Conclusion</h3> The hemodynamic phenotype in CS due to ESHF differs from AMI with higher LV and RV capacitance (lower 'stiffness'), lower LV and RV Ees (contractility) and lower RV efficiency in the former. ECLS increased systemic and pulmonary artery wedge pressure, which is more marked in AMI.

Impact of Castration on Changes in Left Ventricular Diastolic Pressure–Volume Relations Induced by Chronic Adrenergic Stimulation in Rats

A reduced testosterone concentration characterizes heart failure and independently predicts outcomes. Although testosterone replacement therapy may have non cardiac-related therapeutic benefits in heart failure, whether reduced testosterone concentrations protect against adverse left ventricular remodeling (LV dilatation) is uncertain. We therefore evaluated whether surgical castration modifies LV dilatation after 6 months of daily injections of the β-adrenergic receptor (AR) agonist, isoproterenol (ISO) (0.015 mg·kg(-1)·d(-1)), to rats. The extent of LV dilatation and LV systolic chamber dysfunction were determined using both echocardiography and isolated perfused heart procedures. The extent of LV dilatation was determined from LV diastolic pressure-volume (P-V) relationships. As compared with the saline vehicle-treated group, after 6 months of β-AR activation in sham-castrated rats, a marked right shift in the LV diastolic P-V relationship was noted with an increased LV volume intercept at 0 mm Hg diastolic pressure (LV V(0) in milliliters) (ISO = 0.38 ± 0.02, saline vehicle = 0.30 ± 0.02, P < 0.05). However, chronic β-AR activation did not alter LV systolic chamber function either in vivo (LV endocardial fractional shortening, echocardiography) or ex vivo (LV end systolic elastance). Although castration decreased body weight, castration failed to modify the impact of ISO on the LV diastolic P-V relationships or the LV volume intercept at 0 mm Hg diastolic pressure (LV V(0) in milliliters) (castration ISO = 0.35 ± 0.02, castration saline vehicle = 0.27 ± 0.03, P < 0.05). In conclusion, castration does not influence the extent of LV dilatation induced by chronic adrenergic activation in an animal model, where adverse LV remodeling precedes LV systolic chamber dysfunction.

Telomere length and adrenergic-induced left ventricular dilatation and systolic chamber dysfunction in rats

The mechanisms responsible for telomere shortening in heart failure are uncertain. We evaluated whether left ventricular (LV) dilatation and systolic chamber dysfunction produced by chronic β-adrenergic receptor (β-AR) activation is associated with leukocyte or cardiac telomere shortening. Following 6 months of daily injections of the β-AR agonist, isoproterenol (0.02 mg/kg/day) or the saline vehicle to rats, the extent of LV dilatation and LV systolic chamber dysfunction were determined using echocardiography and isolated perfused heart procedures, and relative telomere length of leukocyte (LTL) and cardiac (CTL) deoxyribonucleic acid were determined using a quantitative real-time polymerase chain reaction assay. β-AR activation resulted in LV dilatation as indexed by increased LV diastolic diameters (9.2 ± 0.6 vs. 8.4 ± 0.9 mm, P = 0.01) and increased diastolic volume intercepts at zero pressure of the LV diastolic pressure-volume relationship (isolated, perfused heart preparation) (0.40 ± 0.06 vs. 0.37 ± 0.08 ml, P = 0.03). Moreover, β-AR activation resulted in LV systolic chamber dysfunction as indexed by reductions in LV endocardial fractional shortening (0.40 ± 0.05 vs. 0.45 ± 0.06, P = 0.01) and the slope of the LV systolic pressure-volume relation (609 ± 176 vs. 901 ± 230, P = 0.01). Although LTL decreased with age in rats receiving either the β-AR agonist or the saline vehicle (P < 0.05), neither CTL (-0.10 ± 0.14 vs. -0.15 ± 0.12, P = 0.3) nor LTL (-0.11 ± 0.19 vs. -0.15 ± 0.18, P = 0.5) were modified by β-AR activation. In conclusion, chronic β-AR activation sufficient to produce LV dilatation and systolic chamber dysfunction is not associated with alterations in leukocyte or cardiac telomere length. Telomere shortening in chronic heart failure is unlikely to be attributed to chronic β-AR activation.

Right and Left Ventricular Diastolic Pressure–Volume Relations: A Comprehensive Review

Ventricular compliance alterations can affect cardiac performance and adaptations. Moreover, diastolic mechanics are important in assessing both diastolic and systolic function, since any filling impairment can compromise systolic function. A sigmoidal passive filling pressure-volume relationship, developed using chronically instrumented, awake-animal disease models, is clinically adaptable to evaluating diastolic dynamics using subject-specific micromanometric and volumetric data from the entire filling period of any heartbeat(s). This innovative relationship is the global, integrated expression of chamber geometry, wall thickness, and passive myocardial wall properties. Chamber and myocardial compliance curves of both ventricles can be computed by the sigmoidal methodology over the entire filling period and plotted over appropriate filling pressure ranges. Important characteristics of the compliance curves can be examined and compared between the right and the left ventricle and for different physiological and pathological conditions. The sigmoidal paradigm is more accurate and, therefore, a better alternative to the conventional exponential pressure-volume approximation.

Optimal hematocrit: a Procrustean bed for maximum oxygen transport rate?

physiological systems are characterized by multiple interdependent components that collectively subserve various processes and functions. In seeking better understanding of the performance of such complex systems, we must identify and evaluate alternative ways and operating schemes, comparing their

Dietary-Induced Obesity Hastens the Progression From Concentric Cardiac Hypertrophy to Pump Dysfunction in Spontaneously Hypertensive Rats

We explored whether dietary-induced obesity hastens the transition from concentric left ventricular (LV) hypertrophy to pump dysfunction in spontaneously hypertensive rats (SHRs) and the mechanisms thereof. After feeding rats a diet for 4 to 5 months, obesity was induced in SHRs and Wistar-Kyoto (WKY) control rats. Obesity was not associated with abnormal blood glucose control (glycosylated hemoglobin) or with increases in systolic blood pressure. However, in SHRs, but not in WKY rats, obesity was associated with a reduced LV chamber systolic function, as determined by echocardiography, and in isolated perfused heart studies. A marked increase in LV end diastolic diameter and a right shift in the LV diastolic pressure-volume relation were noted in obese SHRs but not in obese WKY rats. Moreover, LV intrinsic myocardial systolic function, as determined from the slope of the linearized LV systolic stress-strain relationship (LV myocardial end systolic elastance), was markedly reduced in obese as compared with lean SHRs, whereas LV myocardial end systolic elastance was maintained in obese WKY rats. Obesity increased LV weight, cardiomyocyte width, cardiomyocyte apoptosis (TUNEL), the activity of myocardial matrix metalloproteinases (zymography), and serum leptin concentrations in SHRs but not in WKY rats. In conclusion, SHRs are susceptible to the adverse effects of dietary-induced obesity on the heart, an effect that hastens the progression from concentric LV hypertrophy to pump dysfunction independent of blood pressure changes or alterations in glycosylated hemoglobin. This effect may be mediated through a proclivity of SHRs to developing both obesity-induced effects on cardiomyocyte apoptosis and activation of myocardial collagenases through leptin resistance and obesity-induced hypertrophy.

Implantation of a Three-Dimensional Fibroblast Matrix Improves Left Ventricular Function and Blood Flow after Acute Myocardial Infarction

This study was designed to determine if a viable biodegradable three-dimensional fibroblast construct (3DFC) patch implanted on the left ventricle after myocardial infarction (MI) improves left ventricular (LV) function and blood flow. We ligated the left coronary artery of adult male Sprague-Dawley rats and implanted the 3DFC at the time of the infarct. Three weeks after MI, the 3DFC improved LV systolic function by increasing (p < 0.05) ejection fraction (37 +/- 3% to 62 +/- 5%), increasing regional systolic displacement of the infarcted wall (0.04 +/- 0.02 to 0.11 +/- 0.03 cm), and shifting the passive LV diastolic pressure volume relationship toward the pressure axis. The 3FDC improved LV remodeling by decreasing (p < 0.05) LV end-systolic and end-diastolic diameters with no change in LV systolic pressure. The 3DFC did not change LV end-diastolic pressure (LV EDP; 25 +/- 2 vs. 23 +/- 2 mmHg) but the addition of captopril (2mg/L drinking water) lowered (p < 0.05) LV EDP to 12.9 +/- 2.5 mmHg and shifted the pressure-volume relationship toward the pressure axis and decreased (p < 0.05) the LV operating end-diastolic volume from 0.49 +/- 0.02 to 0.34 +/- 0.03 ml. The 3DFC increased myocardial blood flow to the infarcted anterior wall after MI over threefold (p < 0.05). This biodegradable 3DFC patch improves LV function and myocardial blood flow 3 weeks after MI. This is a potentially new approach to cell-based therapy for heart failure after MI.

Rebuttal from Drs. Warburton and Gledhill

Rebuttal from Drs. Warburton and Gledhill

Preservation of diastolic function in monocrotaline-induced right ventricular hypertrophy in rats

During ischemic heart diseases and when heart failure progresses depletion of myocardial energy stores occurs. D-Ribose (R) has been shown to improve cardiac function and energy status after ischemia. Folic acid (FA) is an essential cofactor in the formation of adenine nucleotides. Therefore, we assessed whether chronic R-FA administration during the development of hypertrophy resulted in an improved cardiac function and energy status. In Wistar rats (n = 40) compensatory right ventricular (RV) hypertrophy was induced by monocrotaline (30 mg/kg; MCT), whereas saline served as control. Both groups received a daily oral dose of either 150 mg.kg(-1).day(-1) dextrose (placebo) or R-FA (150 and 40 mg.kg(-1).day(-1), respectively). In Langendorff-perfused hearts, RV and left ventricular (LV) pressure development and collagen content as well as total RV adenine nucleotides (TAN), creatine content, and RV and LV collagen content were determined. In the control group R-FA had no effect. In the MCT-placebo group, TAN and creatine content were reduced, RV and LV diastolic pressure-volume relations were steeper, RV systolic pressures were elevated, RV and LV collagen content was increased, and RV-LV diastolic interaction was altered compared with controls. In the MCT-R-FA group, TAN, RV and LV diastolic stiffness, RV and LV collagen content, and RV-LV diastolic interaction were normalized to the values in the control group while creatine content remained depressed and RV systolic function remained elevated. In conclusion, the depression of energy status in compensated hypertrophic myocardium observed was partly prevented by chronic R-FA administration and accompanied by a preservation of diastolic function and collagen deposition.

Cardiac dilatation and pump dysfunction without intrinsic myocardial systolic failure following chronic β-adrenoreceptor activation

There is no direct evidence to indicate that pump dysfunction in a dilated chamber reflects the impact of chamber dilatation rather than the degree of intrinsic systolic failure resulting from myocardial damage. In the present study, we explored the relative roles of intrinsic myocardial systolic dysfunction and chamber dilatation as mediators of left ventricular (LV) pump dysfunction. Administration of isoproterenol, a beta-adrenoreceptor agonist, for 3 mo to rats (0.1 mg.kg(-1).day(-1)) resulted in LV pump dysfunction as evidenced by a reduced LV endocardial fractional shortening (echocardiography) and a decrease in the slope of the LV systolic pressure-volume relation (isolated heart preparations). Although chronic beta-adrenoreceptor activation induced cardiomyocyte damage (deoxynucleotidyl transferase-mediated dUTP nick-end labeling) as well as beta(1)- and beta(2)-adrenoreceptor inotropic downregulation (attenuated contractile responses to dobutamine and salbutamol), these changes failed to translate into alterations in intrinsic myocardial contractility. Indeed, LV midwall fractional shortening (echocardiography) and the slope of the LV systolic stress-strain relation (isolated heart preparations) were unchanged. A normal intrinsic myocardial systolic function, despite the presence of cardiomyocyte damage and beta-adrenoreceptor inotropic downregulation, was ascribed to marked increases in myocardial norepinephrine release, to upregulation of alpha-adrenoreceptor-mediated contractile effects as determined by phenylephrine responsiveness, and to compensatory LV hypertrophy. LV pump failure was attributed to LV dilatation, as evidenced by increased LV internal dimensions (echocardiography), and a right shift and increased volume intercept of the LV diastolic pressure-volume relation. In conclusion, chronic sympathetic stimulation, despite reducing beta-adrenoreceptor-mediated inotropic responses and promoting myocyte apoptosis, may nevertheless induce pump dysfunction primarily through LV dilatation, rather than intrinsic myocardial systolic failure.

Aldosterone Receptor Blockade Prevents the Transition to Cardiac Pump Dysfunction Induced by β-Adrenoreceptor Activation

The transition from compensated to decompensated left ventricular hypertrophy (LVH) in hypertension involves excessive beta-adrenoreceptor (beta-AR) stimulation. To explore whether aldosterone receptor activation contributes toward beta-AR-induced left ventricular (LV) decompensation in hypertensive LVH, the effect of spironolactone (SPIRO; 80 mg x kg(-1) x day(-1)) on LV cavity dimensions, function, and chamber remodeling mechanisms was evaluated in spontaneously hypertensive rats (SHR) receiving a low dose of the beta-AR agonist isoproterenol (ISO) at 0.02 to 0.04 mg x kg(-1) . day for 4.5 months. ISO administered to SHR resulted in an increased 24-hour urinary aldosterone excretion and LV cavity dimensions, a right shift in LV diastolic pressure-volume relations, a decreased LV relative wall thickness, and increased total, noncross-linked, type I and type III myocardial collagen concentrations without further enhancing increased myocardial norepinephrine (NE) release. ISO reduced pump function without modifying intrinsic myocardial systolic function or inducing further myocyte necrosis or apoptosis. ISO only increased LV cavity volumes after prolonged periods of administration. SPIRO abolished ISO-induced chamber dilatation, wall thinning, and pump dysfunction and reduced total, noncross-linked, type I and type III myocardial collagen concentrations but failed to modify blood pressure, volume preloads, intrinsic myocardial systolic function, myocardial NE release, or the degree of necrosis or apoptosis. In conclusion, these results suggest that aldosterone receptor blockade, through load-independent effects, may be useful in preventing the transition from compensated LVH to dilatation and pump dysfunction mediated by chronic beta-AR activation.

Diastolic left ventricular function Experimental study of the early filling period using the Voigt model

The left ventricular (LV) diastolic function is usually described by the diastolic part of the LV pressure-volume relationship (PVR). The mathematical analysis of the PVR provides parameters of diastolic LV as well as myocardial function. Up to now, all approaches assume the myocardium as a passive elastic medium. This implies that each increase in LV volume is associated with a corresponding increase in LV pressure. Obviously this does not agree with actual PVR's during the LV early filling phase, where a decrease of pressure (due to relaxation) can be observed. Therefore, we analysed the LV diastolic PVR using the Voigt model to provide a better understanding of the concomitant processes of relaxation and filling especially during the early diastole. LV volumes and pressures were measured in an experimental study (6 pigs) using biplane cineangiography (100 frames/s) and simultaneous pressure measurements (catheter tip manometer). LV volumes were determined from all cine frames of total cardiac cycles. Instantaneous (beat to beat) changes in duration (Deltat(f)) of the LV filling period were achieved by atrial stimulation and by releasing post-extrasystolic beats. A total of 26 PVR's with different Deltat(f) were evaluated. According to the Voigt model the compliance (product of the resting volume V(0) and the elastic coefficients) of the total muscle fibre (V(0).K(tot)) and of the serial elastic element (V(0).K(se)) were calculated (average: V(0).K(tot) = 3.43 ml/ mmHg; V(0).K(se) = 5.07 ml/mmHg; n = 26). The interindividual differences between the compliances were in some individuals significant (V(0).K(tot): p < 5% in 6 of 15 Wilcoxon tests ; V(0).K(se): p < 5% in 3 of 15 Wilcoxon tests) but the intraindividual range of these parameters (due to different Deltat(f)) were in some cases as pronounced as the interindividual differences. As in 22 of 26 measurements V(0).K(tot) is less than V(0).K(se) it must be concluded that the early diastolic PVR cannot be described by passive elasticity and the laws of elastomechanics only. These inconsistencies can be explained by the early diastolic LV suction (untwisting) as well as by recent findings regarding the titin filament. Both mechanisms augment LV diastolic filling even in unfavourable working conditions (shortened filling) such as exercise.

Quantification of left ventricular diastolic pressure-volume relations during routine cardiac catheterization by two-dimensional digital echo quantification and left ventricular micromanometer

Background: Currently there is no simple clinical method for quantifying the left ventricular (LV) diastolic pressure-volume relation. Echocardiographic-automated endocardial border detection, however, may be combined with LV micromanometer to construct LV pressure-volume loops. We investigated the feasibility of on-line display and sampling of LV pressure-volume loops by such an approach. For this purpose we used a new echocardiographic digital echo quantification (DEQ) method in combination with LV pressures on-line and in real-time. Methods: Eighteen patients were screened by conventional echocardiography and DEQ. Ten of the patients with high quality images were included in the study. Left ventricular pressures and volumes were recorded simultaneously and were displayed on-line as pressure-volume loops. Changes in LV volume were induced by intravenous saline. Left ventricular chamber compliance was estimated as change in volume divided by change in pressure from minimum diastolic pressure to end-diastolic pressure (average LV chamber compliance). Results: Left ventricular pressure-volume loops were displayed on-line during the examination. When compared with the Simpson's method, DEQ underestimated end-diastolic volume (EDV) by 35% and overestimated end-systolic volume (ESV) by 14%. Beat-to-beat variability for ESV and EDV were 7.4% ± 0.8% and 7.2% ± 0.7 %, respectively. Volume loading increased LV end-diastolic pressure (LVEDP) from 14.0 ± 1.6 to 24.7 ± 2.0 mm Hg (P <.05) and EDV from 79 ± 10 to 85 ± 11 mL (NS), and decreased LV chamber compliance from 4.0 ± 0.7 to 2.0 ± 0.3 mL/mm Hg (P <.05). Conclusion: The current study demonstrates that LV pressure-volume loops can be displayed and evaluated in real-time during routine cardiac catheterization. This may represent a clinically useful method for identifying patients with reduced chamber compliance. The underestimation of the volumes by DEQ compared with the Simpson's method suggests that further refinements should be performed to improve the endocardial border detection algorithm. (J Am Soc Echocardiogr 2002;15:225-32.)

Impaired distensibility of the left ventricle after stiffening of the right ventricle.

Acute and chronic alterations of right ventricular (RV) wall properties can change left ventricular (LV) performance. We investigated whether and how stiffening of the RV free wall alters LV diastolic distensibility. We used cross-circulated isolated hearts, in which the LV and RV were independently controllable. Stiffness of the RV free wall was altered by intramuscular injections of glutaraldehyde into the RV free wall after right coronary artery ligation. We measured circumferential and longitudinal regional lengths in the septum and LV free wall. During data acquisition, RV volume was held constant. After the RV free wall was stiffened by glutaraldehyde, the LV diastolic pressure-volume relation shifted upward and became steeper. Importantly, stiffening of the RV free wall increased the diastolic regional area in the septum and LV free wall under constant LV volume. The augmented regional dimensions may result in enhanced regional tension under constant LV volume and may be related to the observed increase in LV diastolic intracavitary pressure. The impaired LV diastolic distensibility by stiffening of the RV free wall may be at least partly explained by myocardial stretch, probably due to LV deformation.

The role of nitric oxide in the failing heart.

Nitric oxide (NO) has effects on contractility, energetics and gene expression of failing myocardium. Initial studies on isolated cardiomyocytes showed NO to reduce systolic shortening but intracoronary infusions of NO-donors or of NO synthase (NOS) inhibitors failed to elicit changes in baseline LV contractility indices such as LVdP/dt(max). Intracoronary infusions of NO-donors or of substance P, which releases NO from the coronary endothelium, however demonstrated NO to induce a downward displacement of the left ventricular (LV) diastolic pressure-volume relation, consistent with increased LV diastolic distensibility. In end-stage failing myocardium, the increased oxygen consumption is related to reduced NO production and in isolated cardiomyocytes, NO blunts the norepinephrine-induced expression of the fetal gene programme thereby preserving myocardial calcium homeostasis.In dilated cardiomyopathy, changed endomyocardial NOS gene expression has been reported. Because of lower endomyocardial NOS gene expression in patients with higher functional class and lower LV stroke work, increased endomyocardial NOS gene expression seems to be beneficial rather than detrimental for the failing heart. A beneficial effect of increased NOS gene expression could result from NO's ability to increase LV diastolic distensibility, to augment LV preload reserve, to reduce myocardial oxygen consumption and to prevent downregulation of calcium ATPase. Upregulated endomyocardial NOS gene expression has also been reported in athlete's heart and could therefore play a role in physiological LV remodeling. Reduced endomyocardial NO content because of decreased NO or increased superoxide production could lower LV diastolic distensibility and contribute to diastolic heart failure. In many conditions such as aging, hypertension, diabetes or posttransplantation, the increased incidence of diastolic heart failure is indeed paralleled by reduced endothelium-dependent vasodilation.

Effects of MCI-154, a calcium sensitizer, on left ventricular systolic and diastolic function in pacing-induced heart failure in the dog.

MCI-154 is a positive inotropic agent that increases the myofilament response to Ca2+. Whether MCI-154 has beneficial effects on left ventricular dysfunction in chronic heart failure is not known. We examined the effects of MCI-154 on left ventricular systolic and diastolic function in pacing-induced heart failure in dogs. We studied eight anesthetized dogs before and 2 to 4 weeks after rapid right ventricular pacing. Left cineventriculograms with simultaneous left ventricular pressures (tip manometer) were obtained before and during intravenous administration of MCI-154 (I.O. microgram.kg-1.min-1 for 15 minutes) in the control and heart-failure states. Left ventricular volume dynamics was derived from frame-by-frame (20-ms) analyses of left ventricular angiograms. In heart failure, left ventricular contractility as assessed by shifts of the end-systolic pressure-volume ratio, evaluated by inferior vena cava occlusion, was improved by MCI-154 (+ 1.94 mm Hg/mL, P < .05) to an extent similar to that in the control state (+2.47 mm Hg/mL, P < .05). MCI-154 also accelerated left ventricular relaxation, assessed by the time constant of isovolumic pressure decay (T1/2), in both states. The absolute decrease in T1/2 with MCI-154 in heart failure was significantly greater than in the control state (-8.2 versus -3.1 ms, P < .05). In heart failure, MCI-154 shifted the left ventricular diastolic pressure-volume relation clearly downward, suggesting increased diastolic distensibility. MCI-154 improved not only left ventricular systolic function but also diastolic relaxation and distensibility in a chronic heart failure model.

Gadolinium Attenuates the Upward Shift of the Left Ventricular Diastolic Pressure-Volume Relation During Pacing-Induced Ischemia in Dogs

The mechanism of the reversible upward shift of the left ventricular diastolic pressure-volume relation during demand ischemia is controversial. To assess the possibility that cation influx through stretch-activation channels may contribute to the upward shift, we asked whether gadolinium, a blocker of the stretch-activated channels, attenuates the upward shift of the diastolic pressure-volume relation during pacing-induced ischemia in 5 dogs. To produce pacing-induced ischemia, we constricted the left anterior descending and circumflex coronary arteries to reduce their flows by approximately 30% and paced the left atrium at 150 to 180 beats per minute for 3 minutes. We measured left ventricular pressure, volume, and two segment lengths with micromanometers, a conductance catheter, and ultrasonic crystals, respectively. We recorded these variables during baseline, coronary stenosis, and pacing-induced ischemia (immediately after rapid pacing). After injecting 20 mg/kg (76 mumol/kg) gadolinium, we repeated the measurements during coronary stenosis (gadolinium experiment) and pacing-induced ischemia (pacing-induced ischemia plus gadolinium experiment). For each measurement, we recorded the variables in steady state to obtain diastolic pressure-volume and pressure-segment length loops and then during a brief (within 25 seconds) inferior vena caval occlusion to obtain the left ventricular end-diastolic pressure-volume relation. We found that left ventricular diastolic pressure-volume and pressure-segment length loops in steady-state beats shifted upward from coronary stenosis to pacing-induced ischemia. After injection of gadolinium, the upward shift from gadolinium to pacing-induced ischemia plus gadolinium was smaller than the shift from coronary stenosis to pacing-induced ischemia. Similarly, the left ventricular end-diastolic pressure-volume relation obtained during vena caval occlusion shifted upward (by 2.2 +/- 0.6 [SE] mm Hg) from coronary stenosis to pacing-induced ischemia. After injection of gadolinium, the upward shift from gadolinium to pacing-induced ischemia plus gadolinium was smaller (by -2.1 +/- 0.4 mm Hg). These results indicate that gadolinium, a blocker of stretch-activated channels, attenuates the upward shift of the diastolic pressure-volume relation during pacing-induced ischemia, suggesting that the cation influx through stretch-activated channels may contribute to this upward shift.

The effect of left ventricular chamber compliance on early diastolic filling during coronary reperfusion.

This study was designed to assess the changes in left ventricular (LV) diastolic filling and to evaluate the dynamic determinants of LV diastolic filling during coronary reperfusion after acute myocardial ischemia. We examined LV diastolic pressure-volume relations (D-PVRs) using the conductance catheter technique with a high-fidelity micromanometer, and the transmitral flow using transesophageal pulsed Doppler echocardiography in 9 open-chest anesthetized dogs with the pericardium opened. We measured early diastolic peak flow velocity (E), late diastolic peak flow velocity (A), the ratio of peak E to peak A (E/A), operational chamber compliance at the minimum LV pressure [(dV/VdP) nadir], and the time constant of LV relaxation (TC). Acute regional myocardial ischemia was produced by occluding the proximal portion of the left anterior descending coronary artery. Data were acquired at baseline, 10 min after acute myocardial ischemia, and after 15 and 90 min of reperfusion under left atrial pacing at 100 beats/min. During myocardial ischemia, D-PVRs shifted upward and rightward on the same curvilinear relationship compared with that at baseline (LV end-diastolic pressure (LVEDP) from 7.3 to 10.5 mmHg, LVEDV from 25 to 31 ml, both p < 0.01), accompanied by a decrease in peak E and E/A (E from 41 to 25 cm/sec, E/A from 1.7 to 1.1, both p < 0.01) and a prolongation of TC (from 25.4 to 30.3 msec, p < 0.01). After coronary reperfusion, D-PVRs returned to baseline accompanied by an improvement in the peak E and E/A ratio. No significant changes in peak A were observed in any of the stages. There was no correlation between peak E and TC, however, a significant positive correlation was observed between peak E and (dV/VdP) nadir (r = 0.76, p < 0.01). In conclusion, this study demonstrated that, using pulsed Doppler echocardiography, the improvement of diastolic filling after coronary reperfusion was based mainly on changes in early diastolic filling, and that LV operational chamber compliance at early diastole, rather than a LV relaxation property, might play an important role in determining early diastolic filling during coronary reperfusion.

Effects of sublingually administered nifedipine on left ventricular isovolumic relaxation, diastolic filling, and distensibility in patients with chronic coronary artery disease

The acute effects of nifedipine (20 mg) on left ventricular diastolic function were investigated in 16 patients with chronic coronary artery disease by measuring left ventricular pressure with a manometer-tipped catheter and by measuring volume with cineangiography. Heart rates were maintained by right atrial pacing. Left ventricular peak systolic pressure (− 15%; p < 0.01 vs control) decreased significantly. With afterload reduction, left ventricular ejection fraction (− 11%; p < 0.01) increased. There was no significant change in left ventricular end-diastolic pressure. The diastolic peak filling rate of left ventricular volume significantly increased (+36%; p < 0.05), whereas the time from end-systole to the peak filling rate remained unchanged. Administration of nifedipine did not improve left ventricular relaxation as assessed by the isovolumic pressure decay. There was also no significant change in the left ventricular diastolic pressure-volume relationship. We conclude that nifedipine improves left ventricular systolic function with afterload reduction but has little or no effect on left ventricular diastolic properties in patients with chronic coronary artery disease.

Effect of AICD patch electrodes on the diastolic pressure-volume curve in pigs

Although the automatic implantable cardioverter defibrillator (AICD) is effective against malignant ventricular arrhythmias, the effects of AICD patches on left ventricular diastolic properties have not been defined. Accordingly, extrapericardial (group E, n = 5) or intrapericardial (group I, n = 6) AICD patches were implanted through a median sternotomy in 11 anesthetized pigs. Six weeks later, using a left thoracotomy, the hearts were arrested with hypothermic cardioplegia. A balloon catheter was inserted into the left ventricle through the aortic root, and pressure-volume curves were measured before and after sequential removal of patches and pericardium. A dense intrapericardial fibrotic reaction in group I was not present in group E. Normalized left ventricular filling volumes in group E were significantly larger at pressures of 5.1 to 10, 15.1 to 20, and 20.1 to 28 mm Hg compared with group I ( p < 0.05). We conclude that intrapericardial AICD patches adversely affect left ventricular diastolic pressure-volume relations and recommend that AICD patches be placed in the extrapericardial location clinically whenever possible.