Glucose-insulin-potassium preserves systolic and diastolic function in ischemia and reperfusion in pigs

Clinical and experimental studies have suggested benefit of treatment with intravenous glucose-insulin-potassium (GIK) in acute myocardial infarction. However, patients hospitalized with acute coronary syndromes often experience recurrent myocardial ischemia without infarction that may cause progressive left ventricular (LV) dysfunction. This study tested the hypothesis that anticipatory treatment with GIK attenuates both systolic and diastolic LV dysfunction resulting from ischemia and reperfusion without infarction in vivo. Open-chest, anesthetized pigs underwent 90 min of moderate regional ischemia (mean subendocardial blood flow 0.3 ml x g(-1) x min(-1)) and 90 min reperfusion. Eight pigs were treated with GIK (300 g/l glucose, 50 U/l insulin, and 80 meq/l KCl; infused at 2 ml x kg(-1) x h(-1)) beginning 30 min before ischemia and continuing through reperfusion. Eight untreated pigs comprised the control group. Regional LV wall area was measured with orthogonal pairs of sonomicrometry crystals. GIK significantly increased myocardial glucose uptake and lactate release during ischemia. After reperfusion, indexes of regional systolic function (external work and fractional systolic wall area reduction), regional diastolic function (maximum rate of diastolic wall area expansion), and global LV function (LV positive and negative maximum rate of change in pressure with respect to time) recovered to a significantly greater extent in GIK-treated pigs than in control pigs (all P < 0.05). The findings suggest that the clinical utility of GIK may extend beyond treatment of acute myocardial infarction to anticipatory metabolic protection of myocardium in patients at risk for recurrent episodes of ischemia.     

Myocardial transfection with naked DNA plasmid encoding hepatocyte growth factor prevents the progression of heart failure in dogs

This study examined the effects of localized intramyocardial injections of hepatocyte growth factor (HGF) naked DNA plasmid on the progression of left ventricular (LV) dysfunction and remodeling in dogs with moderate heart failure (HF). Twenty-one dogs with intracoronary microembolization-induced HF [LV ejection fraction (EF) = 35-40%] were randomized into three treatment groups, namely, high-dose HGF plasmid (4.0 mg, n = 7), low-dose HGF plasmid (0.4 mg, n = 7), and sham-operated controls treated with normal saline (n = 7). A total of 10-15 injections of HGF plasmid or saline were made directly into the anterior wall of LV. LV EF and end-systolic volume (ESV) were measured before randomization (pretreatment) and at the end of 3 mo of follow-up (posttreatment). Treatment effect (Δ) was calculated as the change from pre- to posttreatment. Protein expression of sarcoplasmic reticulum (SR) Ca(2+)-cycling proteins was determined in LV tissue obtained from the sites of HGF injection and remote areas. Low-dose HGF attenuated the decline in EF (ΔEF: -3 ± 1 vs. -8 ± 1%, P < 0.05) and the increase in ESV (ΔESV: 6 ± 2 vs. 10 ± 1 ml, P < 0.05) seen in control sham-operated dogs, whereas high-dose HGF significantly increased EF (ΔEF: 4 ± 1 vs. -8 ± 1%, P < 0.05) and prevented the increase in ΔESV (ESV: -1 ± 1 vs. 10 ± 1 ml, P < 0.05) compared with control dogs. Treatment with high- and low-dose HGF improved the expression of the SR Ca(2+)-cycling proteins compared with controls. In conclusion, regional intramyocardial injections of HGF naked DNA plasmid improve regional and global LV function and prevent progressive LV remodeling.     

Impact of surgical ventricular restoration on ventricular shape, wall stress, and function in heart failure patients

Surgical ventricular restoration (SVR) was designed to treat patients with aneurysms or large akinetic walls and dilated ventricles. Yet, crucial aspects essential to the efficacy of this procedure like optimal shape and size of the left ventricle (LV) are still debatable. The objective of this study is to quantify the efficacy of SVR based on LV regional shape in terms of curvedness, wall stress, and ventricular systolic function. A total of 40 patients underwent magnetic resonance imaging (MRI) before and after SVR. Both short-axis and long-axis MRI were used to reconstruct end-diastolic and end-systolic three-dimensional LV geometry. The regional shape in terms of surface curvedness, wall thickness, and wall stress indexes were determined for the entire LV. The infarct, border, and remote zones were defined in terms of end-diastolic wall thickness. The LV global systolic function in terms of global ejection fraction, the ratio between stroke work (SW) and end-diastolic volume (SW/EDV), the maximal rate of change of pressure-normalized stress (dσ*/dt(max)), and the regional function in terms of surface area change were examined. The LV end-diastolic and end-systolic volumes were significantly reduced, and global systolic function was improved in ejection fraction, SW/EDV, and dσ*/dt(max). In addition, the end-diastolic and end-systolic stresses in all zones were reduced. Although there was a slight increase in regional curvedness and surface area change in each zone, the change was not significant. Also, while SVR reduced LV wall stress with increased global LV systolic function, regional LV shape and function did not significantly improve.     

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.     

Passive diastolic modelling of human ventricles: Effects of base movement and geometrical heterogeneity

Left-ventricular (LV) remodelling, associated with diastolic heart failure, is driven by an increase in myocardial stress. Therefore, normalisation of LV wall stress is the cornerstone of many therapeutic treatments. However, information regarding such regional stress–strain for human LV is still limited. Thus, the objectives of our study were to determine local diastolic stress–strain field in healthy LVs, and consequently, to identify the regional variations amongst them due to geometric heterogeneity. Effects of LV base movement on diastolic model predictions, which were ignored in the literature, were further explored. Personalised finite-element modelling of five normal human bi-ventricles was carried out using subject-specific myocardium properties. Model prediction was validated individually through comparison with end-diastolic volume and a new shape-volume based measurement of LV cavity, extracted from magnetic resonance imaging. Results indicated that incorporation of LV base movement improved the model predictions (shape-volume relevancy of LV cavity), and therefore, it should be considered in future studies. The LV endocardium always experienced higher fibre stress compared to the epicardium for all five subjects. The LV wall near base experienced higher stress compared to equatorial and apical locations. The lateral LV wall underwent greater stress distribution (fibre and sheet stress) compared to other three regions. In addition, normal ranges of different stress–strain components in different regions of LV wall were reported for five healthy ventricles. This information could be used as targets for future computational studies to optimise diastolic heart failure treatments or design new therapeutic interventions/devices.     

Cardiac diastolic dysfunction in conscious dogs with heart failure induced by chronic coronary microembolization

Left ventricular (LV) diastolic dysfunction is a fundamental impairment in congestive heart failure (CHF). This study examined LV diastolic function in the canine model of CHF induced by chronic coronary embolization (CCE). Dogs were implanted with coronary catheters (both left anterior descending and circumflex arteries) for CCE and instrumented for measurement of LV pressure and dimension. Heart failure was elicited by daily intracoronary injections of microspheres (1.2 million, 90- to 120-microm diameter) for 24 +/- 4 days, resulting in significant depression of cardiac systolic function. After CCE, LV maximum negative change of pressure with time (dP/dt(min)) decreased by 25 +/- 2% (P < 0.05) and LV isovolumic relaxation constant and duration increased by 19 +/- 5% and 25 +/- 6%, respectively (both P < 0.05), indicating an impairment of LV active relaxation, which was cardiac preload independent. LV passive viscoelastic properties were evaluated from the LV end-diastolic pressure (EDP)-volume (EDV) relationship (EDP = be(alpha*EDV)) during brief inferior vena caval occlusion and acute volume loading, while the chamber stiffness coefficient (alpha) increased by 62 +/- 10% (P < 0.05) and the stiffness constant (k) increased by 66 +/- 13% after CCE. The regional myocardial diastolic stiffness in LV anterior and posterior walls was increased by 70 +/- 25% and 63 +/- 24% (both P < 0.05), respectively, after CCE, associated with marked fibrosis, increase in collagen I and III, and enhancement of plasminogen activator inhibitor-1 (PAI-1) protein expression. Thus along with depressed LV systolic function there is significant impairment of LV diastolic relaxation and increase in chamber stiffness, with development of myocardial fibrosis and activation of PAI-1, in the canine model of CHF induced by CCE.     

New approaches in small animal echocardiography: imaging the sounds of silence

Systolic and diastolic dysfunction of the left ventricle (LV) is a hallmark of most cardiac diseases. In vivo assessment of heart function in animal models, particularly mice, is essential to refining our understanding of cardiovascular disease processes. Ultrasound echocardiography has emerged as a powerful, noninvasive tool to serially monitor cardiac performance and map the progression of heart dysfunction in murine injury models. This review covers current applications of small animal echocardiography, as well as emerging technologies that improve evaluation of LV function. In particular, we describe speckle-tracking imaging-based regional LV analysis, a recent advancement in murine echocardiography with proven clinical utility. This sensitive measure enables an early detection of subtle myocardial defects before global dysfunction in genetically engineered and rodent surgical injury models. Novel visualization technologies that allow in-depth phenotypic assessment of small animal models, including perfusion imaging and fetal echocardiography, are also discussed. As imaging capabilities continue to improve, murine echocardiography will remain a critical component of the investigator's armamentarium in translating animal data to enhanced clinical treatment of cardiovascular diseases.     

Dynamic effects of positive-pressure ventilation on canine left ventricular pressure-volume relations.

Positive-pressure ventilation (PPV) may affect left ventricular (LV) performance by altering both LV diastolic compliance and pericardial pressure (Ppc). We measured the effect of PPV on LV intraluminal pressure, Ppc, LV volume, and LV cross-sectional area in 17 acute anesthetized dogs. To account for changes in lung volume independent of changes in Ppc and differences in contractility, measures were made during both open- and closed-chest conditions, during closed chest with and without chest wall binding, and after propranolol-induced acute ventricular failure (AVF). Apneic end-systolic pressure-volume relations (ESPVR) were generated by inferior vena caval occlusions. With the open chest, PPV had no effects. With the chest closed, PPV inspiration decreased LV end-diastolic volume (EDV) along its diastolic compliance curve and decreased end-systolic volume (ESV) such that the end-systolic pressure-volume domain was shifted to a point left of the LV ESPVR, even when referenced to Ppc. The decrease in EDV was greater in control than in AVF conditions, whereas the shift of the ESV to the left of the ESPVR was greater with AVF than in control conditions. We conclude that the hemodynamic effects of PPV inspiration are due primarily to changes in intrathoracic pressure and that the inspiration-induced decreases of LV EDV reflect direct effects of intrathoracic pressure on LV filling. The decreases in LV ESV exceed the amount explained solely by a reduction in LV ejection pressure.     

Closed-chest cell injections into mouse myocardium guided by high-resolution echocardiography

The mouse is an important model for the development of therapeutic stem cell/bone marrow cell implantation to treat ischemic myocardium. However, its small heart size hampers accurate implantation into the left ventricular (LV) wall. Precise injections have required surgical visualization of the heart, which is subject to complications and is impractical for delayed or repeated injections. Furthermore, the thickness of the myocardium is comparable to the length of a needle bevel, so surgical exposure does not prevent inadvertent injection into the LV cavity. We describe the use of high-resolution echocardiography to guide nonsurgical injections accurately into the mouse myocardial wall. We optimized this system by using a mixture of ultrasound contrast and fluorescent microspheres injected into the myocardium, which enabled us to interpret the ultrasound image of the needle during injection. Quantitative dye injection studies demonstrated that guided closed-chest injections and open-chest injections deliver comparable amounts of injectate to the myocardium. We successfully used this system in a mouse myocardial infarction model to target the injection of labeled cells to a region adjacent to the infarct. Intentional injection of tracer into the LV cavity resulted in a small accumulation in the myocardium, suggesting that non-guided cell injections into mouse hearts may appear to be successful even if the majority of the injectate is lost in the chamber. The use of this system will allow more precise cellular implantation into the mouse myocardium by accurately guiding injections to desired locations, confirming successful implantation of cells, in a clinically relevant time frame.     

Contribution of myocardium hydraulic skeleton to left ventricular wall interaction and synergy in dogs

The most premature motion change after coronary occlusion is early diastolic thinning of the ischemic left ventricular (LV) wall, with concomitant thickening of the normoperfused wall. We aimed 1). to demonstrate that these early changes are the result of the absence of fluid within the ischemic myocardium (hydraulic skeleton) rather than to cell anoxia and 2). to quantitate the contribution of the lack of hydraulic skeleton to left ventricular asynergy of contraction in seven anesthetized dogs submitted to acute, short-lasting circumflex artery (Cx) occlusion (ischemia) and to perfusion of the Cx with an oxygen-free solution (anoxia). We analyzed the time course of regional work index (WI, area of the LV pressure-wall thickness loop) and regional efficiency (defined as the ratio of WI to the maximum possible work). Interwall asynergy was defined as the difference between the regional efficiency of the anterior and posterior walls. After 9-10 s, posterior wall efficiency decreased 37 +/- 6% with anoxia and 72 +/- 3% with ischemia (P < 0.025), and interwall asynergy was 0 +/- 6% with anoxia and 32 +/- 5% with ischemia (P < 0.05). The contribution of absent hydraulic skeleton to interwall asynergy (calculated as the difference between %asynergy in anoxia and %asynergy in ischemia) was 30 +/- 8% (P < 0.05). In conclusion, the earliest wall motion change observed after acute coronary occlusion, namely ischemic wall thinning concomitant with normoperfused wall thickening during isovolumic relaxation, is the result of the absence of intracoronary fluid. The lack of hydraulic skeleton within the myocardium contributes approximately 30% to interwall asynergy.     

Mechanism of sudden cardiac death in pigs with viable chronically dysfunctional myocardium and ischemic cardiomyopathy

Pigs with viable chronically dysfunctional myocardium and ischemic cardiomyopathy are at high risk of sudden cardiac death (SCD). We sought to identify the arrhythmic mechanism of SCD, the relation to changes in left ventricular (LV) function, and inducibility of malignant arrhythmias before SCD. Juvenile pigs (n = 72) were instrumented with chronic stenoses on proximal left anterior descending and circumflex arteries. Survival was only 29% 3 mo after instrumentation, and all deaths were sudden and without prodromal symptoms of heart failure. Triphenyltetrazolium chloride staining demonstrated necrosis in only nine animals averaging 2.3 +/- 0.9% of the LV, with no difference between SCD animals and survivors. Implantable loop recorders (n = 13) documented both ventricular fibrillation (n = 6) and bradyasystole (n = 2) as the arrhythmic mechanism of death. Although regional and global function were depressed [anteroseptal wall thickening 1.8 +/- 0.2 vs. 4.2 +/- 0.2 mm in Sham animals (P < 0.001); fractional shortening 21 +/- 2 vs. 31 +/- 1% in Sham animals (P < 0.01)], there were no differences between SCD animals and survivors. LV mass increased in animals with ischemic cardiomyopathy and was greater in animals with SCD (4.0 +/- 0.2 vs. 3.1 +/- 0.1 g/kg in survivors; P < 0.001). Serial programmed ventricular stimulation failed to induce any sustained arrhythmias. We conclude that pigs with viable dysfunctional myocardium and globally reduced LV function have a high rate of SCD with a spectrum of arrhythmias similar to patients with ischemic cardiomyopathy. The risk is independent of necrosis but appears to increase with LV hypertrophy. Like patients with ischemic cardiomyopathy, programmed stimulation is insensitive to predict SCD when viable dysfunctional myocardium is the pathological substrate.     

Dehydration reduces left ventricular filling at rest and during exercise independent of twist mechanics

The purpose of this study was to determine whether the reduction in stroke volume (SV), previously shown to occur with dehydration and increases in internal body temperatures during prolonged exercise, is caused by a reduction in left ventricular (LV) function, as indicated by LV volumes, strain, and twist ("LV mechanics"). Eight healthy men [age: 20 ± 2, maximal oxygen uptake (VO?max): 58 ± 7 ml·kg?1·min?1] completed two, 1-h bouts of cycling in the heat (35°C, 50% peak power) without fluid replacement, resulting in 2% and 3.5% dehydration, respectively. Conventional and two-dimensional speckle-tracking echocardiography was used to determine LV volumes, strain, and twist at rest and during one-legged knee-extensor exercise at baseline, both levels of dehydration, and following rehydration. Progressive dehydration caused a significant reduction in end-diastolic volume (EDV) and SV at rest and during one-legged knee-extensor exercise (rest: Δ-33 ± 14 and Δ-21 ± 14 ml, respectively; exercise: Δ-30 ± 10 and Δ-22 ± 9 ml, respectively, during 3.5% dehydration). In contrast to the marked decline in EDV and SV, systolic and diastolic LV mechanics were either maintained or even enhanced with dehydration at rest and during knee-extensor exercise. We conclude that dehydration-induced reductions in SV at rest and during exercise are the result of reduced LV filling, as reflected by the decline in EDV. The concomitant maintenance of LV mechanics suggests that the decrease in LV filling, and consequently ejection, is likely caused by the reduction in blood volume and/or diminished filling time rather than impaired LV function.     

Estimation of preload recruitable stroke work relationship by a single-beat technique in humans

The slope of the preload recruitable stroke work relationship (M(w)) is a highly linear, load-insensitive contractile index. To investigate whether M(w) can be determined from a single steady-state beat, 45 patients were studied during cardiac catheterization. Single-beat M(w) (SBM(w)) was calculated directly from the baseline stroke work and baseline left ventricular (LV) end-diastolic volume (EDV(B)), and the volume-axis intercept (V(w)) was estimated as k x EDV(B) + (k - 1) x LV(wall), where k is the ratio of the epicardial shell volumes corresponding to V(w) and EDV(B) and LV(wall) is the wall volume. The mean of individual k values was 0.72 +/- 0.04, which correlated with LV mass significantly (r = 0.60, P < 0.001). SBM(w) calculated from a constant k of 0.7 predicted M(w) well (r = 0.88, P < 0.0001), and the prediction improved slightly when k was estimated from individual LV mass (r = 0.93, P < 0.0001). Subgroup analyses revealed that the single-beat technique also worked in patients with small or large LV mass or volume or with regional wall motion abnormalities. The absolute change in SBM(w) after dobutamine infusion also correlated with that in M(w). In conclusion, M(w) can be estimated from a steady-state beat without alteration of preload.     

Ischemic cardiomyopathy in pigs with two-vessel occlusion and viable, chronically dysfunctional myocardium

A chronic left anterior descending coronary artery (LAD) stenosis leads to the development of hibernating myocardium with severe regional hypokinesis but normal global ventricular function after 3 mo. We hypothesized that two-vessel occlusion would accelerate the progression to hibernating myocardium and lead to global left ventricular (LV) dysfunction and heart failure. Pigs were instrumented with a fixed 1.5-mm constrictor on the proximal LAD and circumflex arteries. After 2 mo, there were no overt signs of right-heart failure and triphenyl tetrazolium chloride infarction was trivial (1.4 +/- 0.1% of the LV). Compared with shams, regional function [myocardial systolic excursion (DeltaWT); 2.1 +/- 0.3 vs. 4.6 +/- 0.4 mm, P < 0.05] and resting perfusion (0.90 +/- 0.13 vs. 1.32 +/- 0.09 ml small middle dot min(-1) small middle dot g(-1), P < 0.05) were reduced, consistent with hibernating myocardium. Pulmonary systolic (45.9 +/- 3.3 vs. 36.5 +/- 2.2 mmHg, P < 0.05) and wedge pressures (19.1 +/- 1.6 vs. 11.2 +/- 0.9 mmHg, P < 0.05) were increased with global ventricular dysfunction (ejection fraction 43 +/- 2 vs. 50 +/- 2%, P < 0.05). Early LV remodeling was present with increased cavity size and mass. Reductions in sarcoplasmic reticulum Ca(2+)-ATPase and phospholamban were confined to the dysfunctional LAD region with no change in calsequestrin. Thus combined stenoses of the LAD and circumflex arteries accelerate the development of hibernating myocardium and result in compensated heart failure.     

Cardiac effects of endothelin receptor antagonism in endotoxemic pigs

Myocardial depression in sepsis is frequently encountered clinically and contributes to morbidity and mortality. Increased plasma levels of endothelin-1 (ET-1) have been described in septic shock, and previous reports have shown beneficial effects on cardiovascular performance and survival in septic models using ET receptor antagonists. The aim of the current study was to investigate specific cardiac effects of ET receptor antagonism in endotoxicosis. Sixteen domestic pigs were anesthetized and subjected to endotoxin for 5 h. Eight of these pigs were given tezosentan (dual ET receptor antagonist) after 3 h. Cardiac effects were evaluated using the left ventricular (LV) pressure-volume relationship. Endotoxin was not associated with any effects on parameters of LV contractile function [end-systolic elastance (Ees), preload recruitable stroke work (PRSW), power(max)/end-diastolic volume (PWR(max)/EDV) and dP/dt(max)/end-diastolic volume (dP/dt(max)/EDV)] but with impairments in isovolumic relaxation (time constant for pressure decay, tau) and mechanical efficiency. Tezosentan administration decreased Ees, PWR(max)/EDV, and dP/dt(max)/EDV, while improving tau and LV stiffness. Thus, dual ET receptor antagonism was associated with a decline in contractile function but, in contrast, improved diastolic function. Positive hemodynamic effects from ET receptor antagonism in acute endotoxemia may be due to changes in cardiac load and enhanced diastolic function rather than improved contractile function.     

Effect of acute high-intensity interval exercise on postexercise biventricular function in mild heart failure

We studied the acute effect of high-intensity interval exercise on biventricular function using cardiac magnetic resonance imaging in nine patients [age: 49 ± 16 yr; left ventricular (LV) ejection fraction (EF): 35.8 ± 7.2%] with nonischemic mild heart failure (HF). We hypothesized that a significant impairment in the immediate postexercise end-systolic volume (ESV) and end-diastolic volume (EDV) would contribute to a reduction in EF. We found that immediately following acute high-intensity interval exercise, LV ESV decreased by 6% and LV systolic annular velocity increased by 21% (both P < 0.05). Thirty minutes following exercise (+30 min), there was an absolute increase in LV EF of 2.4% (P < 0.05). Measures of preload, left atrial volume and LV EDV, were reduced immediately following exercise. Similar responses were observed for right ventricular volumes. Early filling velocity, filling rate, and diastolic annular velocity remained unchanged, while LV untwisting rate increased 24% immediately following exercise (P < 0.05) and remained 18% above baseline at +30 min (P < 0.05). The major novel findings of this investigation are 1) that acute high-intensity interval exercise decreases the immediate postexercise LV ESV and increases LV EF at +30 min in patients with mild HF, and this is associated with a reduction in LV afterload and maintenance of contractility, and 2) that despite a reduction in left atrial volume and LV EDV immediately postexercise, diastolic function is preserved and may be modulated by enhanced LV peak untwisting rate. Acute high-intensity interval exercise does not impair postexercise biventricular function in patients with nonischemic mild HF.     

Does fitness level modulate the cardiovascular hemodynamic response to exercise?

Subjects with greater aerobic fitness demonstrate better diastolic compliance at rest, but whether fitness modulates exercise cardiac compliance and cardiac filling pressures remains to be determined. On the basis of maximal oxygen consumption (VO2max), healthy male subjects were categorized into either low (LO: VO2max=43+/-6 ml.kg-1.min-1; n=3) or high (HI: VO2max=60+/-3 ml.kg-1.min-1; n=5) aerobic power. Subjects performed incremental cycle exercise to 90% Vo(2max). Right atrial (RAP) and pulmonary artery wedge (PAWP) pressures were measured, and left ventricular (LV) transmural filling pressure (TMFP=PAWP-RAP) was calculated. Cardiac output (CO) and stroke volume (SV) were determined by direct Fick, and LV end-diastolic volume (EDV) was estimated from echocardiographic fractional area change and Fick SV. There were no between-group differences for any measure at rest. At a submaximal workload of 150 W, PAWP and TMFP were higher (P<0.05) in LO compared with HI (12 vs. 8 mmHg, and 9 vs. 4 mmHg, respectively). At peak exercise, CO, SV, and EDV were lower in LO (P<0.05). RAP was not different at peak exercise, but PAWP (23 vs. 15 mmHg) and TMFP (12 vs. 6 mmHg) were higher in LO (P<0.05). Compared with less fit subjects, subjects with greater aerobic fitness demonstrated lower LV filling pressures during exercise, whereas SV and EDV were either similar (submaximal exercise) or higher (peak exercise), suggesting superior diastolic function and compliance.     

Changes in regional myocardial volume during the cardiac cycle: implications for transmural blood flow and cardiac structure

Although previous studies report a reduction in myocardial volume during systole, myocardial volume changes during the cardiac cycle have not been quantitatively analyzed with high spatiotemporal resolution. We studied the time course of myocardial volume in the anterior mid-left ventricular (LV) wall of normal canine heart in vivo (n = 14) during atrial or LV pacing using transmurally implanted markers and biplane cineradiography (8 ms/frame). During atrial pacing, there was a significant transmural gradient in maximum volume decrease (4.1, 6.8, and 10.3% at subepi, midwall, and subendo layer, respectively, P = 0.002). The rate of myocardial volume increase during diastole was 4.7 +/- 5.8, 6.8 +/- 6.1, and 10.8 +/- 7.7 ml.min(-1).g(-1), respectively, which is substantially larger than the average myocardial blood flow in the literature measured by the microsphere method (0.7-1.3 ml.min(-1).g(-1)). In the early activated region during LV pacing, myocardial volume began to decrease before the LV pressure upstroke. We conclude that the volume change is greater than would be estimated from the known average transmural blood flow. This implies the existence of blood-filled spaces within the myocardium, which could communicate with the ventricular lumen. Our data in the early activated region also suggest that myocardial volume change is caused not by the intramyocardial tissue pressure but by direct impingement of the contracting myocytes on the microvasculature.     

Left ventricular mechanical limitations to stroke volume in healthy humans during incremental exercise

During incremental exercise, stroke volume (SV) plateaus at 40-50% of maximal exercise capacity. In healthy individuals, left ventricular (LV) twist and untwisting ("LV twist mechanics") contribute to the generation of SV at rest, but whether the plateau in SV during incremental exercise is related to a blunting in LV twist mechanics remains unknown. To test this hypothesis, nine healthy young males performed continuous and discontinuous incremental supine cycling exercise up to 90% peak power in a randomized order. During both exercise protocols, end-diastolic volume (EDV), end-systolic volume (ESV), and SV reached a plateau at submaximal exercise intensities while heart rate increased continuously. Similar to LV volumes, two-dimensional speckle tracking-derived LV twist and untwisting velocity increased gradually from rest (all P < 0.001) and then leveled off at submaximal intensities. During continuous exercise, LV twist mechanics were linearly related to ESV, SV, heart rate, and cardiac output (all P < 0.01) while the relationship with EDV was exponential. In diastole, the increase in apical untwisting was significantly larger than that of basal untwisting (P < 0.01), emphasizing the importance of dynamic apical function. In conclusion, during incremental exercise, the plateau in LV twist mechanics and their close relationship with SV and cardiac output indicate a mechanical limitation in maximizing LV output during high exercise intensities. However, LV twist mechanics do not appear to be the sole factor limiting LV output, since EDV reaches its maximum before the plateau in LV twist mechanics, suggesting additional limitations in diastolic filling to the heart.     

Left ventricular diastolic dysfunction in type 2 diabetes patients: a novel 2D strain analysis based on cardiac magnetic resonance imaging

Objective: This study was to develop a strain analysis method to evaluate the left ventricular (LV) functions in type 2 diabetic patients with an asymptomatic LV diastolic dysfunction. Methods: Two groups (10 asymptomatic type 2 diabetic subjects and 10 control ones) were considered. All of the subjects had normal ejection fraction values but impaired diastolic functions assessed by the transmitral blood flow velocity. For each subject, based on cardiac MRI, global indexes including LV volume, LV myocardial mass, cardiac index (CI), and transmitral peak velocity, were measured, and regional indexes (i.e., LV deformation, strain and strain rate) were calculated through an image-registration technology. Results: Most of the global indexes did not differentiate between the two groups, except for the CI, LV myocardial mass and transmitral peak velocity. While for the regional indexes, the global LV diastolic dysfunction of the diabetic indicated an increased strain (0.08?±?0.044 vs. ?0.031?±?0.077, p?=?0.001) and a reduced strain rate (1.834?±?0.909 vs. 3.791?±?2.394, p?=?0.033) compared to the controls, moreover, the local LV diastolic dysfunction reflected by the strain and strain rate varied, and the degree of dysfunction gradually decreased from the basal level to the apical level. Conclusions: The results showed that the strain and strain rates are effective to capture the subtle alterations of the LV functions, and the proposed method can be used to estimate the LV myocardial function based on cardiac MRI.