Canine Left Ventricle Research Articles

Diameters of subendocardial arterioles and venules during prolonged diastole in canine left ventricles.

Using a needle-probe videomicroscope with a charge-coupled device (CCD) camera, we measured the diameter of subendocardial arterioles and venules during prolonged diastole beyond the time point at which coronary blood flow reached zero. In seven open-chest heart-blocked dogs, a sheathed needle probe with a doughnut-shaped balloon was introduced from the left atrial appendage and advanced into the left ventricle through the mitral valve. The tip of the probe was placed gently on the endocardial surface. Diameters of arterioles (n = 16) and venules (n = 16) at the beginning of long diastole ranged from 40 to 126 microns and from 32 to 192 microns, respectively. After cardiac arrest, the arteriolar diameter gradually declined with aortic pressure. Arteriolar diameters at zero flow decreased by 28 +/- 9% (mean +/- SD) compared with the initial diameter (P < .01). However, none of the subendocardial arterioles collapsed at zero flow or at 12 seconds after the beginning of prolonged diastole (8 to 9 seconds after zero flow) in an additional experiment (n = 5). In contrast to arteriolar diameter, venular diameter increased during prolonged diastole. Venular diameter at zero flow increased by 14 +/- 12% compared with the initial diameter (P < .01). We conclude that during prolonged diastole, when coronary arterial inflow ceases, subendocardial arteriolar diameter decreases without any visible collapse, whereas venular diameter increases.

Ejecting activation differs in energetics from ordinary positive inotropism in the canine left ventricle.

Ventricular ejection is known to have dual effects on the end-systolic pressure: the ejecting deactivation by a relatively large ejection against a low afterload versus the ejecting activation by a relatively small ejection against a high afterload. We studied how the increase in contractility index (Emax) by the ejecting activation would affect myocardial oxygen consumption (VO2). To this end, left ventricular steady-state ejecting contractions were produced with various stroke volumes from a fixed end-diastolic volume in an excised cross-circulated canine heart. The effect of the ejection-activated Emax on VO2 was assessed by the relation between VO2 and pressure-volume area (PVA). PVA is the total mechanical energy generated by ventricular contraction. In contrast to the elevation of the linear VO2-PVA relation in a parallel manner with an enhanced Emax by ordinary positive inotropic agents such as catecholamines and calcium, the ejection-activated Emax did not elevate the VO2-PVA relation. This result indicates that the ejecting activation enhances Emax in an energetically different manner from ordinary positive inotropism in the canine left ventricle.

Rotational deformation of the canine left ventricle measured by magnetic resonance tagging: effects of catecholamines, ischaemia, and pacing.

The aim was to investigate the generation of rotation of the left ventricular apex with respect to the base by magnetic resonance tagging, a non-invasive method of labelling the myocardium, in a canine model. 18 dogs were imaged at baseline and during: (1) inotropic stimulation with dobutamine; (2) chronotropic stimulation with atrial pacing; (3) anterior wall ischaemia; (4) posterior wall ischaemia; and (5) varying left ventricular activation site; six dogs underwent each intervention. Apical rotation of the apex (torsion) was quantified. The epicardium and the endocardium were considered separately, as were the anterior and posterior walls. Mean torsion of the epicardium [anterior 3.1(SEM 1.2) degrees, posterior 9.9(1.0) degrees] was less than that of the endocardium [anterior 8.1(2.6) degrees, posterior 14.9(2.0) degrees, p < 0.05 for both]. Anterior torsion was less than posterior torsion for both the epicardium, p < 0.05, and the endocardium, p < 0.05. Dobutamine increased torsion of both the epicardium [anterior 13.3(2.2) degrees, posterior 12.6(1.7) degrees, p < 0.05 for both] and the endocardium [anterior 24.6(2.3) degrees, posterior 16.5(2.1) degrees, p < 0.05 for both]. Atrial pacing at 160% baseline rate increased torsion of both the anterior wall [epicardium 6.6(1.0) degrees, endocardium 11.3(1.2) degrees, p < 0.05] and the posterior wall [epicardium 13.0(1.3) degrees, endocardium 19.4(1.9) degrees, p < 0.05]. Anterior wall ischaemia reduced torsion of the anterior wall only [epicardium -2.0(1.0) degrees, endocardium 6.7(2.3) degrees, both p < 0.05]. Posterior wall ischaemia reduced torsion of the posterior wall of the epicardium only [7.1(1.2) degrees, p < 0.05] but also reduced torsion of the anterior wall [epicardium 0.7(1.0) degrees, endocardium 2.4(1.6) degrees, p < 0.05 for both]. Altering the pattern of left ventricular activation by atrioventricular pacing reduced torsion of the posterior wall of the epicardium [6.6(1.2) degrees, p < 0.05] and of the anterior [3.6(1.9) degrees, p < 0.05] and posterior [7.1(1.6) degrees, p < 0.05] walls of the endocardium. Rotational deformation of the left ventricle is dependent on the pattern of left ventricular activation and the contractile state. That a decrease in the contractile state in one area (by ischaemia) can cause a decrease in rotation in another suggests that this rotation depends on the complex fiber arrangement of the whole ventricle.

Energetics of the negative and positive inotropism of pentobarbitone sodium in the canine left ventricle

Pentobarbitone (sodium) is an anaesthetic widely used in animal experiments. It is known to be a cardiovascular depressant and a coronary dilator, but its effects on myocardial energetics in relation to its negative and positive (due to Gregg's phenomenon) inotropism have not been studied. The aim of this study was therefore to determine whether and how pentobarbitone affects cardiac mechanoenergetics compared with other negative inotropic agents for which data are already available. The effects of graded doses of intracoronary pentobarbitone on mechanoenergetics were studied in the excised cross circulated left ventricles of 12 dogs. The framework of the Emax (a contractility index)--VO2 (myocardial oxygen consumption)--PVA (systolic pressure-volume area, a measure of total mechanical energy) relationships was fully utilised. Pentobarbitone increased Emax at low doses in five of the 12 hearts. In two of these five hearts, a marked coronary dilatation was found. Pentobarbitone decreased Emax dose dependently at high doses in all the hearts and lowered the VO2 intercept but not the slope (oxygen cost of PVA) of the VO2-PVA relation. There was no difference in oxygen cost of Emax between pentobarbitone and CaCl2, although they have opposite inotropism. These findings suggest that pentobarbitone depresses myocardial mechanoenergetics via suppression of total calcium handling in the excitation-contraction-relaxation coupling. Pentobarbitone at low doses partly acts as a positive inotropic agent, but at high doses it acts as a negative inotropic agent like beta blockers and calcium antagonists on cardiac mechanoenergetics in canine blood perfused hearts.

Left Ventricular Model Taking Account of Residual Stress.

At the present time, there is no adequate method for experimental measurement of wall stresses in the intact ventricle. Thus, many mechanical models to predict such stresses have been proposed, in which the residual stress was ignored so that the circumferential stress at the endocardium of the left ventricle was extremely large compared with that at the epicardium. The work expressed, such as oxygen consumption, is supposed to be almost uniform through the wall thickness, or to be somewhat larger at the endocardium than at the epicardium. The models may be improved by taking account of residual stress. To take residual stress into account in mechanical models, one must measure residual strains in the no-load state of the left ventricle. The residual strains were calculated by using sliced canine left ventricles obtained during isovolumic contraction. The residual strains determined from the experiment were applied to the model proposed in the present paper and the distributions of the wall stresses were obtained. As a result, the stress concentration at the endocardium of the left ventricle was found to be largely reduced.

Three Dimensional Strain Throughout the Canine Left Ventricle During Local Graded Ischema

Moore, Christopher B.S.E.; Veigh, Elliot Mc Ph.D.; Zerhouni, Elias M.D. Author Information

Effects of pentobarbital on inotropic state of isolated canine left ventricle.

Although pentobarbital has been found to depress myocardial function, the magnitude of its direct effects on ventricular contraction at anesthetic concentrations has not been well quantified. The direct effects of pentobarbital on left ventricular function were measured by employing an isolated canine heart preparation with a blood oxygenator. Seven hearts were perfused with blood, dextran, and perfluorochemical artificial blood. Ventricular function was evaluated using the slope of the end-systolic pressure-volume relationship (Ees) and the maximal rate of pressure development (dP/dtmax) in ventricles contracting isovolumically in control, after a low dose (13 micrograms/ml), and after a high dose (48 micrograms/ml) of pentobarbital. These concentrations represent one-half and two times the typical value (25 micrograms/ml) found to produce anesthesia in canines (assessed by tail clamp or blink reflex). The low dose of pentobarbital did not produce clear-cut depression in contractile function. The high dose of pentobarbital produced significant reductions of Ees, and dP/dtmax: Ees decreased 29%, from a control of 4.30 +/- 0.84 to 3.05 +/- 0.49 mmHg/ml and dP/dtmax decreased 24%, from a control of 909 +/- 148 to 695 +/- 173 mmHg/s. Thus, the threshold for the direct depressant effect of pentobarbital on ventricular function falls within the range of half to double the typically-reported anesthetic concentrations.

Two-dimensional Echocardiographic Automated Border Detection Accurately Reflects Changes in Left Ventricular Volume

The objective of this study was to determine the relationship of on-line measurements of left ventricular cavity area generated by echocardiographic automated border detection to true volume measured by an intraventricular balloon in an isovolumically contracting isolated canine heart preparation. Seven excised dog hearts had placement of an intraventricular balloon and were perfused in an ex vivo apparatus. Left ventricular area data from the midventricular short-axis plane and pressure data were recorded on a computer through a customized hardware and software interface with the ultrasound system. Left ventricular volumes were varied from 5 ml to maximal values (30 to 40 ml) at 1-milliliter increments. Three increasing and decreasing volume ramps were analyzed on each of seven hearts for a total of 1260 simultaneous measurements. Linear regression analysis correlated mean automated border detection area with absolute volume from each preparation. A predominantly linear relationship was observed with an average correlation of r = 0.97 (y = 0.16x-0.69, SEE = 0.31 cm2, p < 0.01). Left ventricular area measures for six of seven dogs varied little during isovolumic contraction (< 0.4 cm2) but did show a systematic cardiac cycle-related variability in one dog (28% change in area, maximum to minimum, over all volumes). In conclusion, the relationship between cross-sectional area and left ventricular volume was predominantly linear and varied little during isovolumic contractions in the normal canine left ventricle. Echocardiographic automated border detection appears to be a promising method to reflect changes in left ventricular volume.

Prevention of acute regional ischemia with endocardial laser channels

Laser myocardial revascularization has been shown to reduce mortality and infarct size after left anterior descending coronary artery (I AD) ligation in dogs. It has not been shown to improve myocardial contractility in acute ischemia. In this study a holmium-yttrium-aluminum garnet laser (wavelength, 2.14 μm) was used to create nontransmural myocardial channels from the endocardial surface in the ischemic regions of the canine left ventricle. Twelve mongrel dogs (6 controls, 6 laser myocardial revascularizations) underwent 90 minutes of LAD ligation followed by 0 hours of reperfusion. The ischemic region was determined by methylene blue injection during brief LAD occlusion. Laser myocardial revascularization averaged three channels per square centimeter in the ischemic region created using 12 J/channel (600 mJ/pulse, 10 Hz) before LAD ligation. Contractility was assessed from regional preload recruitable stroke work (RPRSW), using pairs of segment length ultrasonic transducers in the ischemic and the nonischemic regions. Two-dimensional echocardiography corroborated with segmental length findings. In control dogs, the ischemic region was dyskinetic during LAD ligation and reperfusion. Dyskinesis of the ischemic region during systole produced negative values for regional stroke work, and RPRSW was considered zero. In 4 of 6 laser-revascularized dogs, RPRSW remained positive in the ischemic region. Two dogs had intermittent dyskinesis. The difference between laser-revascularized and control dogs in ischemic region RPRSW was significant ( p < 0.01 by Fischer's exact test). We conclude that laser myocardial revascularization from the endocardial surface preserves regional myocardial function during acute ischemia. Because holmium-yttrium-aluminum garnet laser energy can be transmitted through a flexible fiber, laser myocardial revascularization could become a percutaneous treatment for prevention of acute ischemia.

On-line estimation of stroke volume by means of echocardiographic automated border detection in the canine left ventricle

Echocardiographic automated border detection (ABD) is a new on-line technique that can determine the interface between blood and myocardial tissue and calculate left ventricular (LV) cavity area in real time. The objective of this study was to determine whether ABD measurements of the LV cavity area could be used to estimate LV stroke volume at basal conditions and during large changes in LV stroke volume induced by inferior vena caval occlusions in an open-chest canine model. Seven dogs had LV stroke volume measured by electromagnetic flow from the ascending aorta with epicardial recordings of ABD echocardiographic area at the midventricular short-axis level. Simultaneous beats of stroke volume were recorded along with ABD echo area during baseline apnea and during IVC occlusions. Neither ABD echo stroke area nor stroke volume varied significantly during apnea baseline. Changes in stroke area were closely correlated with changes in stroke volume for 540 matched beats from 24 IVC occlusions: R = 0.93, standard error of the estimate = 5%, y = 0.92 x + 0.4 ( p < 0.001). Echocardiographic ABD appears to be a promising new on-line method of determining rapid alterations in LV stroke volume; it also has potential applications to multiple investigational and clinical settings.

Relation between regional electrical activation time and subepicardial fiber strain in the canine left ventricle

To determine the relation between regional electrical activation time and fiber strain, epicardial electrical activation and deformation were measured in six open-chest dogs at the left ventricular anterior free wall after 15 min of right atrial, left ventricular free wall, left ventricular apex, or right ventricular outflow tract pacing, when end-diastolic pressure was normal or elevated (volume-loading). Regional electrical activation was measured using a 192-electrode brush. Regional subepicardial fiber strain (ef) was measured simultaneously in 16 regions, using optical markers which were attached to the epicardial surface and recorded on video. When relating regional ef during the ejection phase to regional activation time, the best correlation was found when a hemodynamic time reference rather than an electrophysiological one is used. Using the moment of the maximum rate of change of left ventricular pressure as the time reference for electrical activation, regional electrical activation time (t(ea)) and the degree of ef during the ejection phase could be fitted by a linear regression equation ef = a t(ea) + b, in which a = -3.46 +/- 0.73 s-1 an b = -0.28 +/- 0.05. For electrical activation times ranging from -40 to -80 ms, fiber strain was estimated with an accuracy of +/- 0.026 (+/- SE) with this relation. During right atrial pacing, t(ea) and ef were on the average -48 ms and -0.10 respectively. On further investigation, the relation between ef and t(ea) appeared to be influenced by end-diastolic pressure. For normal (1.1 kPa) and elevated end-diastolic pressure (1.8 kPa), the slope of the linear regression line was -3.96 and -2.86 s-1, respectively. Three conclusions may be drawn. Firstly, the time interval between the moment of regional electrical activation and the moment of the maximum rate of change of left ventricular pressure is an index of regional fiber strain. Secondly, it can be concluded from the above equations that electrical asynchrony of more than 30 ms causes non-uniformities in the degree of ef of the order of mean ef during pacing from the right atrium. Finally, differences in fiber strain during asynchronous electrical activation are less pronounced at larger filling pressures.

Relationship between local myocardial adenylyl cyclase activity and local coronary blood flow in the dog heart.

1. This study tested the hypothesis that heterogeneity of myocardial adenylyl cyclase activity exists and contributes to the heterogeneity of blood flow in canine myocardium, in which flow varies in different areas at any one moment or in a single area at different times. 2. Tissue adenylyl cyclase activity was measured simultaneously with coronary blood flow in the left ventricle of eight anaesthetized open-chest dogs. Coronary flow was measured using radioactive microspheres under control conditions and after sympathetic stimulation. The ventricle was cut into 15 subepicardial and 15 subendocardial sections in which both flow and adenylyl cyclase (basal and forskolin-stimulated) activity were assayed. 3. Control coronary flow was 73.1 +/- 19.9 ml min-1 100 g-1 and ansa subclavia nerve stimulation increased flow to 93.2 +/- 26.1. Baseline adenylyl cyclase activity averaged 51.9 +/- 38.8 pmol min-1 mg protein-1, while forskolin-stimulated activity was 588.2 +/- 393.6. Method variability was approximately 10% of the mean, much less than the biological variability of 70%. 4. Regression analysis of control flow vs baseline adenylyl cyclase activity produced the equation: flow = 0.25 (Adenylyl Cyclase)+60.6, (r = 0.47, P < 0.0001). The equation for stimulated flow vs stimulated adenylyl cyclase was: flow = 0.03 (Adenylyl Cyclase)+73.1, (r = 0.51, P < 0.0001). 5. Thus, significant heterogeneity of tissue adenylyl cyclase activity existed in the heart. There was also a direct linear relationship between adenylyl cyclase activity and coronary flow heterogeneity in canine left ventricle.

Adrenoceptor recovery after heart failure in the dog

The role of myocardial beta receptors in pacing induced congestive heart failure is uncertain. The aims of the study were therefore (1) to examine total beta adrenoceptor density in canine left ventricle during pacing induced heart failure; and (2) to evaluate whether there is a relationship between beta adrenoceptor numbers and circulating noradrenaline during progression of heart failure. Heart failure was examined at different stages: early (after 1 week of pacing at 250 beats.min-1); peak (after 4 weeks of pacing); and after recovery (4 weeks after pacing was discontinued). Myocardial beta adrenoceptor density was assessed by radioligand binding with iodocyanopindolol. Plasma noradrenaline was determined by high performance liquid chromatography with electrochemical detection. Compared to control, left ventricular beta adrenoceptor density was: (1) not significantly different in early heart failure, at 2540(SEM 460) v 3160(260) fmol.g-1 wet weight in control; (2) decreased 63% at peak heart failure [1180(100) fmol.g-1, p < 0.01]; and (3) restored to control density after recovery from heart failure [3430(540) fmol.g-1]. The beta adrenoceptor dissociation constant was unaltered throughout. There was an inverse correlation between myocardial beta adrenoceptor density and plasma noradrenaline (r = -0.785, p < 0.01). The progressive decline in beta adrenoceptor density as heart failure develops and the capacity of beta adrenoceptors to return to control levels after recovery from the experimental heart failure state suggests that there is a reversible abnormality in beta adrenoceptors during heart failure.

Effects of coronary blood flow on myocardial grey level amplitude in two dimensional echocardiography: an experimental study

The aims were: (1) to evaluate whether differences in absolute and cyclic echocardiographic image amplitude exist in different layers (subendocardium and subepicardium) and regions (septal, anterior, lateral, inferior wall) of the canine left ventricle; (2) to assess the dependence of these variables upon local variations of coronary blood flow. In six anaesthetised open chest dogs the circumflex coronary artery was cannulated and perfused by a roller pump with blood from their own femoral artery. Maximum coronary vasodilatation was obtained by continuous adenosine infusion. The absolute values and the transmural distribution of coronary blood flow were measured by radionuclide labelled microspheres. Echo images were obtained in short axis view by a commercially available electronic sector scanner with a 5.0 MHz transducer directly placed on the epicardial surface of the right ventricle, and digitised off-line into a matrix of 256 x 256 pixels with 25% grey level per pixel. The average grey level was calculated for each region of interest. In 32 different conditions, circumflex flow ranged from 0.80 to 12.89 ml.min-1.g-1 and the endocardial/epicardial ratio of flow from 0.53 to 1.73. In the circumflex region (subjected to flow changes) segmental amplitude varied from 76(SD 20) (end diastole) to 56(18) (end systole), p < 0.001. In all regions, a consistent cyclic variation was found, ranging from 9(14) to 28(16)%. For all levels of flow, subendocardial and subepicardial regions showed similar values of both absolute amplitude and cyclic variation. No significant relationship was found between transmural distribution of blood flow and either segmental amplitude (r = 0.26) or cyclic variation (r = 0.04). (1) a consistent cyclic grey level variation is present in all regions of the canine left ventricle, but subendocardial and subepicardial layers show similar values of both absolute amplitude and cyclic variation; (2) in the absence of severe underperfusion and echocardiographically detectable dyssynergy, absolute amplitude and cyclic variation are totally unrelated to changes in coronary blood flow.

Effect of isosorbide dinitrate infusion on the canine left ventricular force-length relationship.

Recently, the slope (Ec) of the left ventricular (LV) end-systolic force-diameter (Fes-Des) relationship has been proposed as a new index for assessing myocardial contractility. Using this relationship, the effects of ISDN on LV myocardial contractility were evaluated in 10 healthy adult mongrel dogs. After the intravenous infusion of propranolol and atropine to produce autonomic blockade, the inferior vena cava was gradually occluded for 20 sec to decrease preload while the dogs were kept apneic. The LV diameter was measured by ultrasonic crystals and LV pressure was measured by a micromanometer. After the control measurements, the dogs received intravenous ISDN (1, 5, 10, or 50 micrograms/kg/min), and inferior vena caval occlusion was repeated. Ec and the extrapolated diameter intercept (D0) of the LV Fes-Des relationship were determined for each dog from the end-systolic data. The differences in heart rate between the control state and ISDN infusion at any dose were not statistically significant. The Ec and D0 values also showed no significant changes with ISDN infusion (Ec: 80 +/- 19, 83 +/- 20, 84 +/- 17, 82 +/- 24, and 87 +/- 24 g/cm for 0, 1, 5, 10, and 50 micrograms/kg/min, respectively. D0: 1.38 +/- 0.42, 1.38 +/- 0.40, 1.38 +/- 0.38, 1.34 +/- 0.40, and 1.36 +/- 0.40 cm for 0, 1, 5, 10, and 50 micrograms/kg/min, respectively). These findings suggested that intravenous ISDN did not affect myocardial contractility in the normal in situ canine left ventricle.

Single and dual excitation of the conductance-volume catheter analysed in a spheroidal mathematical model of the canine left ventricle.

The conductance method employs a multi-electrode catheter to generate an electrical field and measure intracavitary segmental conductances. Left ventricular (LV) volumes are calculated using an algorithm which assumes the electrical field to be homogeneous. This assumption may be violated leading to a non-linear relation between conductance-derived and true volumes. In addition, this relation may vary between segments. A new method is introduced which uses a more homogeneous field. Volume estimates using the conventional single excitation and the new dual excitation method were compared in a mathematical model of a canine LV, which was varied over a large volume range. With single excitation the slope factors, relating conductance-derived and true volumes, varied from 0.50 to 0.76 between segments and was 0.65 for total LV volume. Using dual excitation the segmental slope variability was reduced (range: 0.74-0.77) and the slope factor for total volume increased to 0.76. The linearity of the relation between conductance-derived and true volume was improved with dual excitation and extended over a larger range.

Mechanoenergetic effects of pimobendan in canine left ventricles. Comparison with dobutamine.

We hypothesized that the effect of pimobendan (UD-CG 115 BS) to increase calcium sensitivity of contractile protein might result in less myocardial oxygen consumption (VO2) in comparison with dobutamine when they enhance ventricular contractility to the same extent. To examine this hypothesis, we compared the effects of pimobendan and dobutamine on left ventricular contractility and energetics using the frameworks of Emax (contractility index) and the relation between VO2 and PVA (systolic pressure-volume area, a measure of left ventricular total mechanical energy). We measured VO2, Emax, PVA, and force-time integral (FTI) in excised, cross-circulated, nonfailing dog hearts. The slope of the VO2-PVA relation reciprocally indicates the efficiency from PVA-dependent VO2 to the total mechanical energy (contractile efficiency). The VO2 intercept of the VO2-PVA relation, i.e., PVA-independent VO2, reflects energy utilization for excitation-contraction coupling. The ratio of FTI to PVA-dependent VO2 can be called contractile economy. Both drugs comparably enhanced Emax. Although the contractile economy was greater by 14 +/- 19% (p less than 0.05) for pimobendan than for dobutamine, the contractile efficiency was similar between the two drugs. Oxygen cost of contractility, defined as the slope of the relation between the PVA-independent VO2 and Emax, was the same between the two drugs. Other mechanoenergetic effects of both drugs were similar except for a greater coronary vasodilating effect of pimobendan. Pimobendan has almost the same mechanoenergetic effects as dobutamine but slightly greater contractile economy and coronary vasodilation. The calcium-sensitizing effect of pimobendan did not save the oxygen cost of contractility.

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.

Intracavitary ultrasound impairs left ventricular performance: presumed role of endocardial endothelium.

Irradiation of isolated cardiac muscle by high-power, high-frequency, continuous wave ultrasound selectively damages endocardial endothelium (EE). We evaluated this ultrasound effect in vivo on the performance of the intact ejecting canine left ventricle (LV). A cylindrical ultrasound probe (0.9 MHz, 25 W), mounted on a catheter, was inserted in the LV cavity through an apical stab wound and was activated for 60, 120, and 240 s, followed each time by a recovery period of 10-15 min. Ultrasound transiently and repeatedly abbreviated the time interval from end diastole to peak (-)dP/dt (from 241 +/- 30 to 229 +/- 32 ms after 240 s; P < 0.001), accelerated LV pressure fall, did not alter peak (+)-dP/dt or peak systolic pressure, increased diastolic and systolic segment lengths, and decreased fractional shortening. Microscopic analysis revealed dispersed granulocytes attached to the EE. EE cells were visibly damaged only in a limited area surrounding the probe. Accordingly, high-power, high-frequency, continuous wave ultrasound reversibly modulated LV performance, presumably by transient alteration of EE function.

Stretch-induced depolarizations as a trigger of arrhythmias in isolated canine left ventricles.

Transient diastolic stretch of the left ventricle predictably elicits arrhythmias. To investigate the mechanism of such stretch-induced arrhythmias, monophasic action potentials were recorded from six blood-perfused isolated canine left ventricles with an epicardial contact electrode. Stretch-induced arrhythmias were elicited using a computerized servo-pump system that increased left ventricular volume for 250 ms during early diastole. Depolarizations that coincided with the onset of stretch were observed that always preceded the stretch-induced arrhythmia. As stretch volume (delta V) increased from 10 to 30 ml, the amplitude of the stretch-induced depolarization increased progressively and the probability of eliciting an arrhythmia rose from 30 to 94%. To exclude motion artifact, additional recordings were made after the heart was depolarized by increasing the perfusate K+ concentration to 154 mM (K arrest). After K arrest, the stretch-induced depolarizations were reduced by 95% or more (P less than 0.05) at all stretch volumes. Thus the change in monophasic action potential signal during transient diastolic stretch reflects actual depolarization of the myocardium with negligible motion artifact. When the stretch-activated channel blocker, Gd3+ (10 microM), was administered, which produces potent inhibition of stretch-induced arrhythmias in our model, the stretch-induced depolarizations were substantially reduced in magnitude. Our results show that as diastolic stretch increases, stretch-induced depolarizations become larger and reach threshold potential more often; consequently, the probability of eliciting a stretch-induced arrhythmia increases. This mechanism of arrhythmogenesis may be particularly important in patients with regionally or globally dilated left ventricles.