Left and right ventricular diastolic function during acute pericardial tamponade

The aim of the study was to determine the effect of acute pericardial tamponade on left (LV) and right ventricular (RV) intracavitary and transmural pressure-volume (P-V) relations and to assess the effect of changing blood volume during tamponade on LV and RV volumes. The experiments were done in 11 acutely instrumented anaesthetized dogs in which LV and RV volumes were determined by computed tomography (CT) (n = 5) and LV and RV diameters by sonomicrometry (n = 6). Pressures were measured in the pericardium (balloon transducer), in the aorta and in the ventricles. Incremental pericardial infusion (up to 180 ml) caused a progressive left and upward shift of the LV and the RV intracavitary P-V relationship. This shift was entirely due to increased pericardial pressure (PP). The induction of tamponade caused no change in the LV and RV transmural P-V relationship. During tamponade with ventricular filling pressures above 10-15 mmHg, blood volume expansion caused only minimal increase in LV and RV volumes. In conclusion, pericardial tamponade shifted the LV and the RV intracavitary diastolic P-V relation by increasing PP. However, there was no change in the transmural P-V relationship, indicating unchanged myocardial compliance. Volume loading caused only minimal increase in LV and RV volumes during tamponade.     

Left ventricular external constraint: Relationship between pericardial,pleural and esophageal pressures during positive end-expiratory pressure and volume loading in dogs

Left ventricular (LV) diastolic filling is limited by the constraining effects exerted by the pericardium (PE) and the lung/chest wall. The aim of the present study was to assess the validity of various estimates of external cardiac constraint, compared to pericardial surface pressure (P_pe) measured lateral to the LV myocardium. In nine anesthetized dogs we measured P_pe, pleural surface pressure (P_pl) (lateral to the pericardium) and esophageal pressure (P_es) under conditions of volume loading and positive end-expiratory pressure (PEEP). We measured P_pe and P_pl with flat, liquidcontaining silastic rubber balloons and P_es with an air-containing cylindrical balloon. After instrumentation, the chest was resealed and continuous suction (−5 mm Hg, 1 mm Hg=0.133 kPa) was maintained. Volume loading with incremental intravenous infusions of saline was used to increase LV end-diastolic pressure to 20–25 mm Hg. PEEP of 0, 10 and 20 mm Hg were applied at baseline and after each increment of volume loading. At low volume, increases in PEEP caused simultaneous increases in LV end-diastolic pressure (P<0.01) and in P_pe (P<0.0001) but a reduction in transmural LV pressure (P<0.0005). P_pl and P_es both increased with PEEP (P<0.001 and P<0.01, respectively). However, P_pe always exceeded P_pl, while P_es remained at only approximately 1/3 P_pl throughout. Volume loading caused a significant increase in P_pe (P<0.0001) and a smaller, but significant increase in P_pl (P<0.05). P_es remained unchanged during volume loading. Thus external cardiac constraint increased markedly during volume loading and PEEP as evidenced by a marked elevation of P_pe. Both P_pl and P_es markedly underestimated this increase. Therefore, calculation of transmural LV pressure by subtracting pleural or esophageal pressure from intracavitary pressure can lead to overestimation of LV preload. The decrease in cardiac output during PEEP occurs secondary to decreased preload, i.e. decreased transmural pressure and end-diastolic dimension. Analysis of performance using cardiac function curves does not suggest a change in contractility with PEEP.     

Reduced cardiac stiffness following exercise is associated with preserved myocardial collagen characteristics in the rat

We determined whether the increment in cardiac end-diastolic compliance (a reduced diastolic stiffness constant) following endurance training is related to alterations in myocardial collagen characteristics. Sixteen weeks of habitual exercise (Ex) in rats, which produced left ventricular (LV) hypertrophy (LVH) [LV weight in g: Ex=1.01 (0.04), sedentary control?=?0.89 (0.04); P<0.05], resulted in a reduced LV end-diastolic (LVED) chamber stiffness [slope of the linearised LVED pressure versus LVED internal diameter relation in kPa?·?mm^?1: Ex=0.67 (0.03), control=0.80 (0.03); P<0.05]. The increased LVED chamber distensibility was associated with an attenuated myocardial stiffness [slope of the linearised LVED stress versus strain relation in g?·?cm^?2; Ex=15 (3), control=25?(2); P<0.05]. Although LV total collagen content (mg) was increased in the exercised rats [Ex=5.0?(0.3), control=4.1 (0.2); P<0.05], this was a reflection of the presence of LVH, as the myocardial collagen concentration (μg?·?mg^?1 LV wet weight) was unaltered [Ex=4.9 (0.2), control=4.6 (0.2)]. Furthermore, habitual exercise did not influence the percentage of myocardial collagen extracted following cyanogen bromide digestion (an index of collagen cross-linking), [i.e. Ex=38 (3), control=38 (3)], nor the proportion of myocardial collagen phenotypes I and III [I/III; Ex=3.04 (0.20), control=2.85 (0.22)]. In conclusion, exercise-induced increments in end-diastolic myocardial distensibility are unlikely to be a consequence of alterations in the properties of myocardial collagen.     

Left ventricular diastolic relaxation and pressure-diameter relations during ischaemic left ventricular failure in the dog

The significance of severe ischaemic left ventricular (LV) failure on the LV isovolumic relaxation process and diastolic chamber stiffness has been investigated in nine open-chest pentobarbital-anaesthetized dogs. LV failure was induced by bolus injections of 50 micron microspheres into left coronary vascular bed until LV minor axis diameter had increased about 25% and end-diastolic pressure about 20 mmHg. Such ischaemic LV failure did not shift the relation between diastolic LV pressure and minor axis diameter compared with pressure-diameter curves obtained before induction of failure. Neither inotropic nor chronotropic stimulation evoked such shifts. Assuming exponential pressure decline, LV relaxation was significantly slower during failure, but proceeded in all experimental conditions at rates which indicated complete relaxation in late diastole. Analysis of the pressure decline during LV relaxation demonstrated that this process proceeded faster than assumed by an exponential function both before and during LV failure.     

Mueller maneuver and LV function in coronary artery disease

Decreasing pleural pressure impedes the ejection of blood from the left ventricle (LV), may lead to decreased LV compliance because of interdependence effects and leads to increased transmural LV systolic and diastolic pressure. Previous work from this laboratory has shown that patients with coronary artery disease (CAD) often develop akinetic segments of the LV wall during the Mueller maneuver. In the presence of increased LV transmural pressure regional akinesis could be caused either by the development of regional ischemia or by mechanical inhibition of motion of an area of nonfunctional myocardium as would be caused by previous myocardial infarction (MI). The present study was designed to distinguish between these two mechanisms by determining if the presence of CAD alone is sufficient to lead to regional akinesis or if prior MI is necessary. We used first pass radionuclide ventriculography (RVG) in the 30° LAD supine position to measure LV ejection fraction (EF), end-diastolic (EDV) and end-systolic (ESV) volumes, heart rate and to assess regional wall motion during the Mueller maneuver. This was done in four groups of subjects: (1) 13 normal subjects, (2) 25 patients with CAD but no prior MI, (3) 13 patients with prior nontransmural MI and (4) 36 patients with prior transmural MI. All subjects had angina pectoris and underwent contrast coronary arteriography. Most also underwent routine contrast left ventriculography as well. There were no significant differences among the three patient groups as regards medications, extent and severity of CAD, and response to routine exercise tolerance testing. EF decreased significantly in the three patient groups (4%–9%, p<0.01) but not in the normals during the Mueller maneuver. Heart rate increased (5–10 bpm, p<0.05) in the normals and in patient groups 2 and 4. EDV decrease in all four subject groups (8%–10%, p<0.01), while ESV remained unchanged. Akinesis of the LV wall developed during the Mueller maneuver only in one group-2 patient, but did so in 17/36 patients with prior transmural MI (group 4, p<0.001). One-half of the akinetic LV wall segments seen during the Mueller maneuver on RVG were not seen on routine contrast ventriculography. We tested the effects of posture (supine versus upright) on the response to the Mueller maneuver in six normal subjects and found no changes in the response of EDV and ESV to the Mueller maneuver. We conclude that (1) the appearance of LV wall akinesis during the Mueller maneuver signifies the presence of prior transmural MI, and not just CAD; (2) the Mueller maneuver can enhance the sensitivity of the RVG for detecting nonfunctional myocardium; (3) regional akinesis develops even when LV volume decreases, suggesting it is due to changes in LV transmural pressure; (4) there are changes in LV function which can lead to a decrease in global EF during the Mueller maneuver; (5) the effects of the Mueller maneuver on LV volume are complex, variable and are subject to multifactorial influences.     

The effect of decreased intrathoracic pressure on ventricular function

SUMMARY  Large decreases in inspiratory intrathoracic pressure (ITP) occur during obstructive apnoeas. The cardiac effects of apnoea-associated decreased ITP come from the interaction of increased preload (venous return) on the right ventricle (RV) and increased afterload on the left ventricle (LV), and are modulated by the autonomic effects of shifts in blood volume and hypoxaemia. During obstructed breathing, venous return increases by as much as three-fold during inspiration even though mean flow may change little. This leads to a substantial inspiratory increase in RV end-diastolic and stroke volume. Because of ventricular interdependence, there is a decrease in LV diastolic compliance and corresponding decrease LV preload.
Sustained decreases in ITP (Müller manoeuvre) inhibit LV ejection, and hence increase LV afterload. However, breathing against an obstructed airway (repetitive short Müller manoeuvre) is not necessarily modelled by the sustained manoeuvre. Animal studies indicate that with airway obstruction, for the first beat or two of inspiration the primary effect on the LV is a reduction in stroke volume related to a decrease in preload, and afterload, if anything, decreases. In fact, afterload only increases during early expiration when stroke volume increases. When obstructive and central apnoeas are paired for duration and blood-gas alterations, there are increases in pulmonary blood volume with central apnoeas and in RV volume with obstructive apnoeas, consistent with the postulation that the primary effect of obstructive apnoeas is on venous return.
In conclusion, the putative role of decreased ITP in increasing LV afterload under conditions appropriate to OSA is not well supported by experimental studies. However, effects with very large swings in ITP as might be seen under the most extreme forms of OSA, and differences in timing of the swings between diastole and systole have yet to be investigated.     

Dissociation of pressure-rate product from myocardial oxygen consumption in dog

Although the pressure-rate product (double product; DP) is generally recognized as a good index of myocardial oxygen consumption (VO2), catecholamines are reported to change the VO2-DP relationship. However, the separate influences of chronotropism and inotropism on the VO2-DP relation have not been studied. Therefore, we examined these influences in anesthetized open-chest dogs by cardiac pacing and dobutamine infusion. We observed two different VO2-DP lines under the separate chronotropic and inotropic changes. We interpreted such VO2-DP relations by the concept of the pressure-volume area (PVA). PVA is a measure of total mechanical energy for ventricular contraction and is a specific area in the ventricular pressure-volume (P-V) diagram circumscribed by the end-systolic and end-diastolic P-V relation curves and the systolic segment of the P-V trajectory. The empirical VO2-PVA relation that had been obtained in our previous studies reasonably simulated the dissociation of DP from VO2 under separate changes in chronotropism and inotropism.     

Effect of reduced total blood volume on left ventricular volumes and kinetics in type 2 diabetes

Aim: Although impaired left ventricular (LV) diastolic function is commonly observed in patients with type 2 diabetes, it remains unclear whether the impairment is caused by altered LV relaxation or changes in LV preload. The purpose of this study was to examine the influence of LV function and LV loading conditions on stroke volume in men with type 2 diabetes. Methods: Cardiac magnetic resonance imaging scans were performed in eight men with type 2 diabetes and 11 non-diabetic men matched for age, weight and physical activity level. Total blood volume was determined with the Evans blue dye dilution technique. Results: End-diastolic volume (EDV), the ratio of peak early to late mitral inflow velocity (E/A) and stroke volume were lower in men with type 2 diabetes than in non-diabetic individuals. Peak filling rate and peak ejection rate were not different between diabetic and non-diabetic individuals; however, men with type 2 diabetes had proportionally longer systolic duration than non-diabetic individuals. Heart rate was higher and total blood volume was lower in men with type 2 diabetes. The lower total blood volume was correlated with a lower EDV in men with type 2 diabetes. Conclusions: Men with type 2 diabetes have an altered cardiac cycle and lower end-diastolic and stroke volume. A lower total blood volume and higher heart rate in men with type 2 diabetes suggest that changes in LV preload, independent of changes in LV relaxation or contractility, influence LV diastolic filling and stroke volume in this population.     

Ghrelin抑制大鼠心肌梗死后心室重构

目的:探讨Ghrelin对大鼠心肌梗死后心室重构的影响及其机制。方法:结扎SD大鼠前降支造成急性心肌梗死(AMI)模型,并设假手术组。结扎24h后,存活大鼠给予Ghrelin(100μg/kg)或生理盐水皮下注射,每天两次。4周后,超声心动图和血流动力学方法检测心功能,实时定量PCR检测梗死心肌白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)mRNA表达,Western-blot检测核转录因子-κB(NF-κB)活性。结果:与假手术组相比,AMI模型组左室收缩内径(LVESD)、左室舒张内径(LVEDD)、左室舒张末压力(LVEDP)都明显增加(P<0.01);而左室收缩压(LVSP)、压力变化值最大值(dp/dtmax)、左室短轴缩短率(FS)都显著降低(P<0.01)。与AMI模型组相比,Ghrelin治疗组LVEDP、LVEDD以及LVESD明显变小(P<0.01),而dp/dtmax及FS显著增加(P<0.01)。梗死后心肌IL-1β、TNF-αmRNA表达增强,Ghrelin治疗后IL-1β、TNF-αmRNA表达明显降低(P<0.01)。AMI模型组心肌核蛋白P65表达明显增加,而胞浆蛋白I-κBα含量显著减少(P<0.01),Ghrelin治疗明显降低梗死心肌核蛋白P65表达(P<0.01),同时增加胞浆蛋白I-κBα含量(P<0.01)。结论:Ghrelin能够抑制心肌梗死后心室重构,改善心功能,可能与其抑制炎症介质表达及NF-κB活性有关。     

Direct measurement of left ventricular interstitial adenosine

Characterization of adenosine's role as a regulator of coronary blood flow requires accurate measurement of endogenous adenosine concentration in the left ventricular (LV) interstitial compartment. Existing techniques for determining adenosine in this compartment are indirect, requiring the acceptance of major assumptions before conclusions can be drawn. We describe a new technique utilizing a LV epicardial diffusion well that allows us to make rapid, direct measurement of LV interstitial adenosine concentration, avoiding many problems inherent in existing techniques. Our results show adenosine concentrations of 555 pmol/ml in resting anesthetized dogs, indicating a resting adenosine level well within the vasoactive range. Further experiments using intramyocardial bolus injections of methylene blue dye and [8-14C]adenosine indicate that the epicardial well receives adenosine from a transmural distribution of LV interstitium and not from epicardial sources only. The transmural interstitial adenosine is transported via small lymphatics to the epicardial surface of the heart where diffusion occurs into the epicardial well. We also examined diffusion characteristics of the parietal pericardial membrane and found that the rate constant of adenosine diffusion for this and the visceral pericardium are of the same order of magnitude, indicating that the extensively used standard pericardial superperfusate method probably underestimates cardiac interstitial adenosine concentration by 50% or more. The influence of the parietal pericardium adequately explains why our resting adenosine concentrations using the epicardial well are higher than those recently reported using the standard pericardial superperfusate method.     

Cardiac function during mild hypothermia in pigs: increased inotropy at the expense of diastolic dysfunction

Aim: The induction of mild hypothermia (MH; 33 °C) has become the guideline therapy to attenuate hypoxic brain injury after out-of-hospital cardiopulmonary resuscitation. While MH exerts a positive inotropic effect in vitro, MH reduces cardiac output in vivo and is thus discussed critically when severe cardiac dysfunction is present in patients. We thus assessed the effect of MH on the function of the normal heart in an in vivo model closely mimicking the clinical setting. Methods: Ten anaesthetized, female human-sized pigs were acutely catheterized for measurement of pressure–volume loops (conductance catheter), cardiac output (Swan-Ganz catheter) and for vena cava inferior occlusion. Controlled MH (from 37 to 33 °C) was induced by a vena cava inferior cooling catheter. Results: With MH, heart rate (HR) and whole body oxygen consumption decreased, while lactate levels remained normal. Cardiac output, left ventricular (LV) volumes, peak systolic and end-diastolic pressure and dP/dt_max did not change significantly. Changes in dP/dt_min and the time constant of isovolumetric relaxation demonstrated impaired active relaxation. In addition, MH prolonged the systolic and shortened the diastolic time interval. Pressure–volume analysis revealed increased end-systolic and end-diastolic stiffness, indicating positive inotropy and reduced end-diastolic distensibility. Positive inotropy was preserved during pacing, while LV end-diastolic pressure increased and diastolic filling was substantially impaired due to delayed LV relaxation. Conclusion: MH negatively affects diastolic function, which, however, is compensated for by decreased spontaneous HR. Positive inotropy and a decrease in whole body oxygen consumption warrant further studies addressing the potential benefit of MH on the acutely failing heart.     

Modification of regional myocardial performance caused by blood withdrawal and infusion in acute ischaemic canine heart

The effect of changes in preload on regional myocardial motion in acute ischaemia was examined by miniature ultrasonic gauges after left anterior descending coronary artery occlusion in eight open chest dogs with the pericardium preserved. Left ventricular end-diastolic pressure was varied by blood withdrawal and infusion. When preload changed, isovolumetric shortening in the non-ischaemic region was inversely related to that in the ischaemic region. When preload decreased, stroke volume decreased and was accompanied by a decrease in end-diastolic length and ejection shortening in the non-ischaemic region together with an increase in isovolumetric bulging in the ischaemic region. When preload increased, these variables changed in opposite directions. These results indicate that in acute ischaemia: (1) changes in isovolumetric shortening in the non-ischaemic and ischaemic regions were related with each other when the level of volume expansion varied, and suggest that; (2) stroke volume is affected by end-diastolic length, ejection shortening in the non-ischaemic region and isovolumetric bulging in the ischemic region.     

The effects of asymmetric ventricular filling on left–right ventricular interaction in the normal rat heart

Heart failure is characterised by ventricular dysfunction and with the potential for changes to ventricular volumes constraining the mechanical performance of the heart. The contribution of this interaction from geometric changes rather than fibrosis or metabolic changes is unclear. Using the constant pressure Langendorff-perfused rat heart, the volume interaction between left ventricle (LV) and right ventricle (RV) was investigated. RV diastolic stiffness (P?<?0.001) and developed pressure (P?<?0.001) were significantly lower than LV. When the RV was fixed at the end-diastolic volume (EDV) or EDV?+?50?%, both LV systolic and diastolic performance were unaffected with increasing LV balloon volume. However, at fixed LV volume, RV systolic performance was significantly decreased when LV volume increased to EDV?+?50?% when RV volume was increased incrementally between 50 and 300?μl (P?<?0.001). Systolic interaction in RV was noted as declining RV peak systolic load with increasing LV systolic pressure (P?<?0.05) and diastolic interaction was noted for RV when LV volume was increased from EDV to EDV?+?50?% (P?<?0.05). RV diastolic wall stress was increased with increasing LV balloon volume (P?<?0.05), but LV wall stress was unaltered at fixed RV balloon volume. Taken together, increasing LV volume above EDV decreased systolic performance and triggered ventricular constraint in the RV but the RV itself had no effect on the performance of the LV. These results are consistent with overload of the LV impairing pulmonary perfusion by direct ventricular interaction with potential alteration to ventilation–perfusion characteristics within the lung.     

A model of the mechanics of the left ventricle

The relation between cardiac muscle mechanics and left ventricular (LV) pump function is simulated by a mathematical model. In the following article special attention is paid to the relation between LV pressure and LV volume on the one hand and the transmural distribution of sarcomere length and fiber stress on the other. The LV is simulated by a thick-walled cylinder composed of 8 concentric shells. The myocardial material is assumed to be anisotropic. The orientation and sequential activation of the muscle fibers across the LV wall are considered per shell. Twisting of the base with respect to the apex around the axis of the LV is simulated by rotation of the upper cross-sectional surface of the cylinder with respect to the lower one aroud the axis of the cylinder. The model reveals that twisting of the LV is an important means to equalize transmural differences in sarcomere shortening and end-systolic fiber stress. When torsion is allowed, transmural differences in sarcomere shortening and end-systolic fiber stress are less than 18% and 16%, respectively. When torsion is prevented as in most of the models of LV-mechanics described in literature, these transmural differences increase up to 32% and 42%, respectively. Supported by the Foundation for Medical Research FUNGO, which is subsidized by the Netherlands organization for the Advancement of Pure Research.     

Reversibility and Pathohistological Basis of Left Ventricular Remodeling in Hibernating Myocardium

The phenomenon of left ventricular (LV) remodeling with dilatation, wall thinning, and increased muscle mass has previously been reported in pigs with 7-day myocardial hibernation. This study investigated cellular and extracellular basis and reversibility of the structural LV remodeling with hibernating myocardium. Five groups of pigs were included: Group A: 7-day myocardial hibernation with a fixed coronary stenosis; Group B: 7-day hibernation with subsequent 3-week reperfusion by release of the stenosis; Group C: control group with sham operation; Group D: 24-hour myocardial hibernation to define structural mechanism of initial wall thinning in the hibernating region without confounding factors of cell loss or hypertrophy, Group E: 4-week myocardial hibernation to exclude the possibility of spontaneous regression of LV remodeling with hibernation. LAD flow decreased by 38 ± 12% (p < 0.01) with a significant decrease in systolic wall thickening at 7 days of hibernation with severe coronary stenosis (Group A). End-diastolic wall thickness decreased by 19% (p < 0.01) accompanied by a decrease in myocyte number across the wall (44%) and in myocyte density (24%), a significant increase in myocyte width (17%), a mild increase in interstitial tissues in hibernating region, and significant increases in LV diastolic volume and in LV mass at 7 days. After reperfusion (Group B), LV volume decreased, LV ejection fraction improved, and myocyte hypertrophy regressed with a decreased LV mass index without a significant change in interstitial tissue. LV remodeling progressed with further increases in LV volume, mass, and interstitial fibrosis in 4-week hibernation. In pigs undergoing 24 hours of myocardial hibernation (Group D), end-diastolic LV wall thickness decreased significantly in the hibernating region with a proportional decrease in the transmural myocyte number but without changes in myocyte width, myocyte density, or interstitial tissues. Therefore, progressive gross LV remodeling associated with hibernating myocardium is accompanied by increasing myocyte hypertrophy and interstitial fibrosis. In hibernating myocardial region, wall thinning is proportional to a decreased myocyte number across the LV wall, indicating slippage of myocytes as a preponderant mechanism for the wall thinning. Myocyte hypertrophy develops within 7 days in hibernating myocardium, causing an increase in LV mass. These changes are partially reversible after reperfusion.     

Role of intraoperative transesophageal echocardiography in coronary artery bypass grafting

Transesophapeal echocardiography (TEE) can be used as a diagnostic tool during cardiac surgery to direct the surgical procedure and diagnose unanticipated problems. TEE bas also been one of the most important means of monitoring myocardial ischemia during coronary artery bypas grafting procedures. The cardiac anesthesiologist can apply intraoperative TEE in evaluating coronary artery anatomy and aorta atherosclerosis,assessing diastolic left ventricular function and preload,measuring intracardiac pressure and cardiac output,detecting ischaemic mitral regurgitation,intracardiac air and pericardial effusion.     

Influence of the velocity of changes in end-diastolic volume on the starling mechanism of isolated left ventricles

1. In this study the relationships between active developed systolic pressure, end-diastolic pressure and different diastolic volumes are studied in Tyrode perfused isolated rabbit left ventricles. Contractions were isovolumic.
2. Rapid diastolic volume changes were imposed on top of different preset basic diastolic volumes. These volume changes are shown to produce systolic and diastolic pressure values that cannot be explained by assuming a single pressure-volume relation during systole and diastole. The changes in pressure are in the same direction but higher than is expected on the basis of the increase or decrease of the ventricular end-diastolic volume alone.
3. The variation of the diastolic pressure-volume relation cannot be explained by assuming variations of the heart's passive elasticity or viscous effects within its wall. During diastole the effect is completely reversible without concomitant systolic effects. No velocity dependent effect of the quick volume change could be observed if the time duration was varied between 10 and 65 ms. The results are in keeping with the hypothesis that active force generating mechanisms may be present during the diastolic pause.
4. The effects observed during systole suggest the possibility of length dependent activation of the myocardial cells. This results in different inotropic conditions of the heart at identical volumes, depending on how these volumes were installed. These volumes may be considered to affect intrinsic properties of the muscle cells on a beat to beat basis.

     

Diastolic myocardial stiffness in gradually developing left ventricular hypertrophy in dog

The effects of gradually developing left ventricular pressure overload on diastolic myocardial stiffness were studied in a chronic moderate hypertrophy model. A snug aortic band was placed beneath the left coronary artery in six puppies 4.5 wk of age, and hemodynamic studies were performed 33.5 wk later. In all six dogs, moderate pressure gradients (10-58 mmHg) developed across the constriction, and angiographic area of the aortic constriction was significantly smaller than for a control group, 4.9 +/- 0.5 vs. 8.4 +/- 0.8 mm2/kg, (mean +/- SE, P less than 0.05). Increases occurred in left ventricular (LV) wall thickness (1.08 +/- 0.07 vs. 0.83 +/- 0.04 cm, P less than 0.05), LV wall mass (5.2 +/- 0.3 vs. 4.1 +/- 0.2 g/kg, P less than 0.05), and wall thickness-to-radius ratio (0.67 +/- 0.04 vs. 0.50 +/- 0.03, P less than 0.01), whereas no differences were noted in LV end-diastolic pressure (11 +/- 1 vs. 9 +/- 1 mmHg), LV end-diastolic volume (LVEDV, 2.06 +/- 0.22 vs. 2.35 +/- 0.15 ml/kg) or ejection fraction (71 +/- 4 vs. 71 +/- 3%). The values of LV wall mass, LVEDV, and aortic constriction are normalized to body weight. Diastolic LV myocardial stiffness was examined in terms of the elastic stiffness-stress relations. There were small and insignificant differences in end-diastolic stress (17.3 +/- 1.5 vs. 20.4 +/- 3.8 g/cm2), myocardial stiffness constant (Km, 13.7 +/- 5.6 vs. 11.2 +/- 3.3), and end-diastolic elastic stiffness (221 +/- 67 vs. 221 +/- 79 g/cm2) between hypertrophied and control hearts. No significant differences in the elastic stiffness of hypertrophied and normal muscle were observed over the common stress range of 5-25 g/cm2. We conclude that moderate left ventricular hypertrophy in chronic, gradually developing pressure overload is an adaptation process associated with normal myocardial stiffness.     

Effect of positive end-expiratory pressure on ventricular function in dogs.

Artificial ventilation with positive end-expiratory pressure (PEEP) reduces venous return by raising intrathoracic pressure. To determine whether PEEP decreases cardiac output further by depressing myocardial function, we constructed Starling curves, using rapid dextran infusion in 7 anesthetized dogs ventilated with zero (ZEEP) and 20 cm PEEP. The changes in stroke volume and in left ventricular stroke work (LVSW) when PEEP was added or removed were significantly greater than could be attributed to the corresponding change in transmural left ventricular end-diastolic pressure (LVEDPTM) on these Starling curves. To the extent that PEEP did not alter left ventricular diastolic volume-pressure characteristics, these data indicated PEEP depressed ventricular function. Identical changes with PEEP in cardiac output (-30%), esophageal pressure (+10 cmH2O), and left ventricular function were observed after pulmonary edema was induced with oleic acid. These results confirm and extend recent suggestions that high levels of PEEP depress left ventricular function in dogs, accounting for about half of the reduction in cardiac output before and during acute pulmonary edema.