External Cardiac Work Research Articles

Mechanisms of left ventricular systolic dysfunction in light chain amyloidosis: a multiparametric cardiac MRI study.

Cardiac systolic dysfunction is a poor prognostic marker in light-chain (AL) cardiomyopathy, a primary interstitial disorder; however, its pathogenesis is poorly understood. This study aims to analyze the effects of extracellular volume (ECV) expansion, a surrogate marker of amyloid burden on myocardial blood flow (MBF), myocardial work efficiency (MWE), and left ventricular (LV) systolic dysfunction in AL amyloidosis. Subjects with biopsy-proven AL amyloidosis were prospectively enrolled (April 2016-June 2021; Clinicaltrials.gov ID NCT02641145) and underwent cardiac magnetic resonance imaging (MRI) to quantify rest MBF by perfusion imaging, LV ejection fraction (LVEF) by cine MRI, and ECV by pre- and post-contrast T1 mapping. The MWE was estimated as external cardiac work from the stroke volume and mean arterial pressure normalized to the LV myocardial mass. Rest MBF in 92 subjects (62 ± 8 years, 52 men) with AL amyloidosis averaged 0.87 ± 0.21 ml/min/g and correlated with MWE (r = 0.42; p < 0.001). Rest MBF was similarly low in subjects with sustained hematologic remission after successful AL amyloidosis therapy (n = 21), as in those with recently diagnosed AL amyloidosis. Both MBF and MWE decreased by ECV tertile (p < 0.01 for linear trends). The association of ECV with MWE comprised a direct effect (84% of the total effect; p < 0.001) on MWE from adverse interstitial remodeling assessed by ECV and an indirect effect (16% of the total effect; p < 0.001) mediated by MBF. There was a significant base-to-apex gradient of rest MBF in subjects with higher amyloid burden. In AL amyloidosis, both MBF and MWE decrease as cardiac amyloid burden and ECV expansion increase. Both structural and vascular changes from ECV expansion and myocardial amyloid burden appear to contribute to lower MWE.

Myocardial External Efficiency in Asymptomatic Severe Primary Mitral Regurgitation Using 11C-Acetate PET.

Subjects with asymptomatic moderate-to-severe or severe primary mitral regurgitation are closely observed for signs of progression or symptoms requiring surgical intervention. The role of myocardial metabolic function in progression of mitral regurgitation is poorly understood. We used 11C-acetate PET to noninvasively measure myocardial mechanical external efficiency (MEE), which is the energetic ratio of external cardiac work and left ventricular (LV) oxygen consumption. Methods: Forty-seven patients in surveillance with mitral regurgitation and no or minimal symptoms prospectively underwent PET, echocardiography, and cardiac MRI on the same day. PET was used to simultaneously measure cardiac output, LV mass, and oxygen consumption to establish MEE. PET findings were compared between patients and healthy volunteers (n = 9). MEE and standard imaging indicators of regurgitation severity, LV volumes, and function were studied as predictors of time to surgical intervention. Patients were followed a median of 3.0 y (interquartile range, 2.0-3.8 y), and the endpoint was reached in 22 subjects (47%). Results: MEE in patients reaching the endpoint (23.8% ± 5.0%) was lower than in censored patients (28.5% ± 4.5%, P = 0.002) or healthy volunteers (30.1% ± 4.9%, P = 0.001). MEE with a cutoff lower than 25.7% was significantly associated with the outcome (hazard ratio, 7.5; 95% CI, 2.7-20.6; P < 0.0001) and retained independent significance when compared with standard imaging parameters. Conclusion: MEE independently predicted time to progression requiring valve surgery in patients with asymptomatic moderate-to-severe or severe primary mitral regurgitation. The study suggests that inefficient myocardial oxidative metabolism precedes clinically observed progression in mitral regurgitation.

Cardiac power output accurately reflects external cardiac work over a wide range of inotropic states in pigs

BackgroundCardiac power output (CPO), derived from the product of cardiac output and mean aortic pressure, is an important yet underexploited parameter for hemodynamic monitoring of critically ill patients in the intensive-care unit (ICU). The conductance catheter-derived pressure-volume loop area reflects left ventricular stroke work (LV SW). Dividing LV SW by time, a measure of LV SW min− 1 is obtained sharing the same unit as CPO (W). We aimed to validate CPO as a marker of LV SW min− 1 under various inotropic states.MethodsWe retrospectively analysed data obtained from experimental studies of the hemodynamic impact of mild hypothermia and hyperthermia on acute heart failure. Fifty-nine anaesthetized and mechanically ventilated closed-chest Landrace pigs (68 ± 1 kg) were instrumented with Swan-Ganz and LV pressure-volume catheters. Data were obtained at body temperatures of 33.0 °C, 38.0 °C and 40.5 °C; before and after: resuscitation, myocardial infarction, endotoxemia, sevoflurane-induced myocardial depression and beta-adrenergic stimulation. We plotted LVSW min− 1 against CPO by linear regression analysis, as well as against the following classical indices of LV function and work: LV ejection fraction (LV EF), rate-pressure product (RPP), triple product (TP), LV maximum pressure (LVPmax) and maximal rate of rise of LVP (LV dP/dtmax).ResultsCPO showed the best correlation with LV SW min− 1 (r2 = 0.89; p < 0.05) while LV EF did not correlate at all (r2 = 0.01; p = 0.259). Further parameters correlated moderately with LV SW min− 1 (LVPmaxr2 = 0.47, RPP r2 = 0.67; and TP r2 = 0.54). LV dP/dtmax correlated worst with LV SW min− 1 (r2 = 0.28).ConclusionCPO reflects external cardiac work over a wide range of inotropic states. These data further support the use of CPO to monitor inotropic interventions in the ICU.

Speckle-Tracking Echocardiographic Strain Analysis Reliably Estimates Degree of Acute LV Unloading During Mechanical LV Support by Impella.

Non-invasive means of evaluating appropriate cardiac unloading remain to be established. We hypothesized that myocardial deformation assessed by echocardiographic speckle-tracking strain analysis can reliably estimate the degree of left ventricular (LV) unloading under mechanical circulatory support. A total of 24 Yorkshire pigs underwent Impella-mediated acute LV unloading 1-2weeks after myocardial infarction (MI). Echocardiographic and invasive pressure-volume measurements were used to evaluate the degree of LV unloading. Pressure-volume analysis before and after LV unloading exhibited a significant decrease in stroke work (3399 ± 1440 to 1244 ± 659mmHgml, p < 0.001), suggesting reduced external cardiac work. Both longitudinal strain (- 14.6 ± 4.1% to - 10.6 ± 2.3%, p < 0.001) and circumferential strain (- 18.7 ± 6.1% to - 9.3 ± 3.5%, p < 0.001) decreased after LV unloading, and there were linear relationships between stroke work and echocardiographic longitudinal (r = - 0.61, p < 0.001) as well as circumferential strains (r = - 0.75, p < 0.001). Echocardiographic LV strain analysis offers a non-invasive assessment of LV unloading in subacute MI.

Does Late Gadolinium Enhancement Still have Value? Right Ventricular Internal Mechanical Work, Ea/Emax and Late Gadolinium Enhancement as Prognostic Markers in Patients with Advanced Pulmonary Hypertension via Cardiac MRI

Investigate the impact of Right Ventricular (RV) Internal Work (IW), ratio of arterial to ventricular end-systolic elastance (Ea/Emax), and RV Insertion Point (IP) Late Gadolinium Enhancement (LGE) on outcome in Pulmonary Hypertension (PH) patients. LGE is well known to be present within the RVIPs and Inter Ventricular Septum (IVS) in PH patients, but its prognostic role remains complex and potentially overestimated via 2D qualitative relative to the 3D quantitative measures now available. However, Ea/Emax, a measure of ventricular-arterial coupling and IW, when added to external cardiac work i.e. the P-V loop area as correlates to the heart's energy demands, might fundamentally improve measures of prognosis as they interrogate physiology beyond just the RV. Cardiac Magnetic Resonance Imaging (CMR) of 124 PH patients (age = 60±13, 85F) referred to a large tertiary PH center, was retrospectively examined for RV volumetric and functional indices and RVIP LGE%. Right Heart Catheterizations (RHC) performed within 1±2 months of the CMR were reviewed. Ea/Emax was derived as RV End-Systolic Volume (ESV/RVSV). IW was estimated as RVESV ×(RV end-systolic pressure-RV diastolic pressure). Patients were followed from date of CMR for up to 5 years for MACE (death, hospitalized RV failure, initiation of parenteral prostacyclin, sustained ventricular arrhythmia or referral for lung transplantation). MACE was high; 48/124 (39%) patients had MACE by 1.6±1.3 years. Neither RVIP nor IVS LGE using visual assessment or even 3D quantization predicted MACE. The strongest predictor of MACE was RVIW (OR=1.00013, p<0.002), vs. mPAP, RV mass, RV EF and IP LGE. Surprisingly, neither a single time-point RVIP nor whole IVS LGE% can predict outcome in the largest cohort of PH patients studied to date when compared with conventional or contemporary metrics of disease progression. CMR-LGE appears to lose its' prognostic value in PH patients in stark contradistinction to all other left and right-sided human myocardial pathologies.

On-X Heart Valve Prosthesis: Numerical Simulation of Hemodynamic Performance in Accelerating Systole.

Numerical simulation of the bileaflet mechanical heart valves (BMHVs) has been of interest for many researchers due to its capability of predicting hemodynamic performance. A lot of studies have tried to simulate this three-dimensional complex flow in order to analyze the effect of different valve designs on the blood flow pattern. However, simplified models and prescribed motion for the leaflets were utilized. In this paper, transient complex blood flow in the location of ascending aorta has been investigated in arealistic model by fully coupled simulation. Geometry model for the aorta and the replaced valve is constructed based on the medical images and extracted point clouds. A 23-mm On-X Medical BMHV as the new generation design has been selected for the flow field analysis. The two-way coupling simulation is conducted throughout the accelerating phase in order to obtain valve dynamics in the opening process. The complex flow field in the hinge recess is captured precisely for all leaflet positions and recirculating zones and elevated shear stress areas have been observed. Results indicate that On-X valve yields relatively less transvalvular pressure gradient which would lower cardiac external work. Furthermore, converging inlet leads to a more uniform flow and consequently less turbulent eddies. However, the leaflets cannot open fully due to middle diffuser-shaped orifice. In addition,asymmetric butterfly-shaped hinge design and converging orifice leads to better hemodynamic performance. Withthe help of two-way fluid solid interaction simulation, leaflet angle follows the experimental trends more precisely rather than the prescribed motion in previous 3D simulations.

Abstract 12411: Prognostic Value of Cardiovascular Magnetic Resonance-Derived Indices of Right Ventriculo-Arterial Coupling and Internal Mechanical Work in Pulmonary Hypertension

Objectives: External cardiac work performed is represented by the area within the ejection loop (P-V) and correlates poorly with the heart’s total energy demands until the internal work component is added. Further, the ratio of the arterial elastance (E a ) to the ventricular end-systolic elastance (E max ) is a measure of ventriculo-arterial coupling. We investigated the impact of both indices of right ventricular (RV) performance on outcome in patients with pulmonary hypertension (PH). Methods: Cardiac magnetic resonance (CMR) studies of a retrospective consecutive cohort of 115 PH pts (61±14 yrs) were examined for RV volumetrics, functional indices and the presence of RV late gadolinium enhancement (LGE) from 2008-2014. Right heart cath (RHC) parameters were included in the analysis (performed within 1±1.5 mo of CMR) as was 3D RV mass and RVEF. The E a /E max ratio was derived in part as RV end-systolic volume (ESV)/RV stroke volume. Internal mechanical work was estimated as RVESV*(RV-ES pressure- RV-ED pressure). Patients were followed up to 5 yrs. Results: During follow-up, 42/115 (37%) pts had a MACE. On a multivariable logistic regression analysis, the strongest predictor of MACE was the internal RV mechanical work followed in order by E a /E max versus mean pulmonary artery pressure, RV mass, RV EF, and RV LGE. The strongest predictors of time to MACE were the RV internal mechanical work (χ 2 =10.8) and E a /E max ratio (χ 2 =9.2). Kaplan-Meier analysis of time to MACE for quartiles of RV internal mechanical work and E a /E max are shown in Figure 1A &amp; B. Conclusions: Higher RV internal mechanical work and E a /E max are both markers for worsening prognosis in PH patients; E a /E max having the added advantage of being an entirely non-invasive CMR derivation and statistically equivalent. Both metrics were superior to standard clinical metrics including RV LGE, RVEF, PA pressure and RV mass and for the first time address integrated cardio-pulmonary physiology as early markers for MACE.

Recovery mismatch between myocardial blood flow and cardiac workload after physical exercise: a positron emission tomography study.

We studied the interrelation between oxygen consumption and myocardial blood flow (MBF) during recovery. MBF is directly dependent on oxygen consumption. The latter is linearly related to the heart rate-blood pressure product (RPP, bpm × mmHg), an index reflecting external cardiac work. In the immediate post-exercise period, cardiac output decreases considerably. This is expected to be paralleled by a rapid fall in oxygen demand, rendering ischaemia unlikely. Thus, the phenomenon of ST-segment depression during recovery remains unexplained. (15)O-labelled water and positron emission tomography were used to measure MBF in 14 young healthy volunteers (mean age 27 ± 3 years) during the following study conditions: (i) at rest, (ii) during a steady submaximal supine bicycle exercise stress within the scanner, and (iii) during recovery immediately after cessation of exercise. During recovery, RPP decreased by 43% (18 768 ± 1337 vs. 11 652 ± 3224, P < 0.001). In contrast, the associated decrease in MBF (2.52 ± 0.52 vs. 1.93 ± 0.50 mL/min/g, P < 0.001) and perfusion reserve (2.68 ± 0.51 vs. 2.03 ± 0.42, P < 0.001) was significantly less pronounced (-24%, P < 0.01), indicating a relative delay in MBF recovery compared with cardiac work load. The mismatch between a rapid decrease in cardiac workload but preserved hyperaemic response early after cessation of physical exercise suggests an uncoupling of cardiac work and MBF during recovery.

Cardiac resynchronization therapy and AV optimization increase myocardial oxygen consumption, but increase cardiac function more than proportionally

BackgroundThe mechanoenergetic effects of atrioventricular delay optimization during biventricular pacing (“cardiac resynchronization therapy”, CRT) are unknown. MethodsEleven patients with heart failure and left bundle branch block (LBBB) underwent invasive measurements of left ventricular (LV) developed pressure, aortic flow velocity-time-integral (VTI) and myocardial oxygen consumption (MVO2) at 4 pacing states: biventricular pacing (with VV 0ms) at AVD 40ms (AV-40), AVD 120ms (AV-120, a common nominal AV delay), at their pre-identified individualised haemodynamic optimum (AV-Opt); and intrinsic conduction (LBBB). ResultsAV-120, relative to LBBB, increased LV developed pressure by a mean of 11(SEM 2)%, p=0.001, and aortic VTI by 11(SEM 3)%, p=0.002, but also increased MVO2 by 11(SEM 5)%, p=0.04.AV-Opt further increased LV developed pressure by a mean of 2(SEM 1)%, p=0.035 and aortic VTI by 4(SEM 1)%, p=0.017. MVO2 trended further up by 7(SEM 5)%, p=0.22.Mechanoenergetics at AV-40 were no different from LBBB.The 4 states lay on a straight line for Δexternal work (ΔLV developed pressure×Δaortic VTI) against ΔMVO2, with slope 1.80, significantly >1 (p=0.02). ConclusionsBiventricular pacing and atrioventricular delay optimization increased external cardiac work done but also myocardial oxygen consumption. Nevertheless, the increase in cardiac work was ~80% greater than the increase in oxygen consumption, signifying an improvement in cardiac mechanoenergetics. Finally, the incremental effect of optimization on external work was approximately one-third beyond that of nominal AV pacing, along the same favourable efficiency trajectory, suggesting that AV delay dominates the biventricular pacing effect — which may therefore not be mainly “resynchronization”.

Myocardial Na+/H+ exchanger-1 (NHE1) content is decreased by exercise training

The effect of exercise training on myocardial Na(+)/H(+) exchanger-1 (NHE1) protein expression was examined. Adult female Sprague-Dawley rats were randomly divided into sedentary (S; n = 8) and exercised (E; n = 9) groups. Twenty-four hours after the last exercise bout, hearts were weighed and connected to an isolated perfused working heart apparatus for evaluation of cardiac functional performance. Heart weight and heart weight/body weight from E rats was significantly increased by 7.1 and 7.2 % (P < 0.05), respectively, compared with S hearts. The E hearts displayed 15 % greater cardiac output and 35 % external cardiac work compared with the S group at both low and high workloads (P < 0.05 for both parameters). Left ventricular tissue from the same hearts was homogenized and NHE1 and Na(+)/Ca(2+) exchanger (NCX) content determined by Western blotting. E hearts had a 38 % (P < 0.001) reduction in NHE1 content related to S hearts, and there was no difference in NCX content between groups. Cytochrome c oxidase activity in plantaris increased by 100 % (P < 0.05) and was assessed as a marker of mitochondria content and to verify training status. Our data indicate that exercise training at an intensity that results in cardiac hypertrophy and improved performance is accompanied by decreased NHE1 content in heart.

Modeling to Link Regional Myocardial Work, Metabolism and Blood Flows

Given the mono-functional, highly coordinated processes of cardiac excitation and contraction, the observations that regional myocardial blood flows, rMBF, are broadly heterogeneous has provoked much attention, but a clear explanation has not emerged. In isolated and in vivo heart studies the total coronary flow is found to be proportional to the rate-pressure product (systolic mean blood pressure times heart rate), a measure of external cardiac work. The same relationship might be expected on a local basis: more work requires more flow. The validity of this expectation has never been demonstrated experimentally. In this article we review the concepts linking cellular excitation and contractile work to cellular energetics and ATP demand, substrate utilization, oxygen demand, vasoregulation, and local blood flow. Mathematical models of these processes are now rather well developed. We propose that the construction of an integrated model encompassing the biophysics, biochemistry and physiology of cardiomyocyte contraction, then combined with a detailed three-dimensional structuring of the fiber bundle and sheet arrangements of the heart as a whole will frame an hypothesis that can be quantitatively evaluated to settle the prime issue: Does local work drive local flow in a predictable fashion that explains the heterogeneity? While in one sense one can feel content that work drives flow is irrefutable, the are no cardiac contractile models that demonstrate the required heterogeneity in local strain-stress-work; quite the contrary, cardiac contraction models have tended toward trying to show that work should be uniform. The object of this review is to argue that uniformity of work does not occur, and is impossible in any case, and that further experimentation and analysis are necessary to test the hypothesis.

88 Evaluation of the impact of AV delay variation on the acute mechanoenergetic efficiency of cardiac resynchronisation therapy and assessment of performance of non-invasive vs invasive haemodynamic optimisation

BackgroundThe impact of varying AV delay on the acute mechanoenergetic efficiency of cardiac resynchronisation therapy (CRT) is not known; nor is known if non-invasive haemodynamic optimisation by blood pressure agrees...

Prediction of the External Work of the Native Heart From the Dynamic H‐Q Curves of the Rotary Blood Pumps During Left Heart Bypass

The ventricular performance is dependent on the drainage effect of rotary blood pumps (RBPs) and the performance of RBPs is affected by the ventricular pulsation. In this study, the interaction between the ventricle and RBPs was examined using the pressure-volume (P-V) diagram of the ventricle and dynamic head pressure-bypass flow (H-Q) curves (H, head pressure: arterial pressure minus ventricular pressure vs. Q, bypass flow) of the RBPs. We first investigated the relationships in a mock loop with a passive fill ventricle, followed by validation in ex vivo animal experiments. An apical drainage cannula with a micro-pressure sensor was especially fabricated to obtain ventricular pressure, while three pairs of ultrasonic crystals placed on the heart wall were used to derive ventricular volume. The mock loop-configured ventricular apical-descending aorta bypass revealed that the external work of the ventricle expressed by the area inside the P-V diagrams (EW(Heart) ) correlated strongly with the area inside dynamic H-Q curves (EW(VAD)), with the coefficients of correlation being R² = 0.869 ∼ 0.961. The results in the mock loop were verified in the ex vivo studies using three Shiba goats (10-25 kg in body weight), showing the correlation coefficients of R² = 0.802 ∼ 0.817. The linear regression analysis indicated that the increase in the bypass flow reduced pulsatility in the ventricle expressed in EW(Heart) as well as in EW(VAD) . Experimental results, both mock loop and animal studies, showed that the interaction between cardiac external work and H-Q performance of RBPs can be expressed by the relationships "EW(Heart) versus EW(VAD) ." The pulsatile nature of the native heart can be expressed in the area underneath the H-Q curves of RBPs EW(VAD) during left heart bypass indicating the status of the level of assistance by RBPs and the native heart function.

Myocardial Na+/H+ Exchanger (NHE) Content is Decreased by Exercise Training

The sarcolemmal NHE extrudes an intracellular proton in exchange for an extracellular sodium. Skeletal muscle NHE content increases in response to relatively intense exercise training and thereby helps these cells tolerate the stress of an exercise-induced acid load. Measurements of mRNA content suggest that exercise training also elevates NHE in the heart. However, mRNA expression does not always correspond to expression of its protein. An increase in NHE in the heart can be considered to be maladaptive as it can cause damage in response to certain stresses, including ischemia-reperfusion (I-R). During I-R, increased NHE activity results in high intracellular Na+ accumulation, which leads to an increase in intracellular Ca2+ via the Na+/Ca2+ exchanger. The Ca2+ overload then causes contractile dysfunction and cell death. PURPOSE: To determine whether myocardial NHE protein expression is altered by exercise training. METHODS: Adult female Sprague-Dawley rats were divided into sedentary (S, N=8) and exercised (E, N=8) groups. E participated in a 5-week exercise program consisting of running on a treadmill 5 days/week up a 6° incline. Duration and intensity of exercise were gradually increased until the animals were running for 1 hr at 30 meters/min. The exercise room was maintained at 8°C. Twenty-four hrs after the last exercise bout, hearts were weighed and connected to an isolated perfused working heart apparatus for evaluation of cardiac functional performance. Ventricular tissue was homogenized, heart protein measured by Biuret method, and NHE determined by Western blotting. Cytochrome oxidase (Cytox) activity in plantaris was determined as a marker of mitochondria content and to verify training status. Data were analyzed using a two-tailed t-test with P<0.05 as the limit for statistical significance. RESULTS: E increased Cytox 92% in plantaris (P<0.05). E also increased (P<0.05) heart weight by 7.1%, heart weight/body weight by 7.2%, cardiac output (CO) by 21.1%, external cardiac work (CO x systolic pressure) by 35.8%. NHE content was 38% lower in E than in S (P<0.05). CONCLUSION: Exercise training at an intensity that results in cardiac hypertrophy and improved performance is accompanied by decreased NHE content in heart. This decrease in NHE could contribute to exercise-induced cardioprotection.

Dual Chamber Coupled Pacing Increases External Cardiac Work but Not Efficiency in Dogs with Ischemic Heart Failure

Dual Chamber Coupled Pacing Increases External Cardiac Work but Not Efficiency in Dogs with Ischemic Heart Failure

Interaction of exercise and simvastatin on myocardial ischemia‐reperfusion (I‐R) injury: Role of nitric oxide.

The interaction of statins and exercise are not well known, yet they are often co-prescribed for cardiovascular health. Here we investigate the interaction of simvastatin (SIM) and exercise on myocardial tolerance to I-R. Female rats (22–25/gp) were sedentary control (S), fed 10 mg SIM/kg/day (SD), exercised on a treadmill (70% VO2max, 60 min/d, 5 d/wk) (R), or fed SIM + exercise (RD) for 4 wks. Isolated perfused working hearts were subjected to 30 min ischemia then reperfused. Some were perfused with 100 μM L-NAME to prevent nitric oxide involvement. I-R recovery of pre-ischemic cardiac external work was 17.6±6.6% in S. Recovery was higher (P<0.05) in SD (37.7±7.7%) and R (40.1±7.7%) and tended to be highest in RD (49.7±7.1%). Recovery was not improved further by supplementing RD with Coenzyme Q (CoQ) to replace CoQ lost by SIM treatment. Compared to S, LDH release during reperfusion was decreased in SD, R, and RD by similar amounts. LDH release was lowest of all in RD+CoQ. Although eNOS expression was similar among groups, L-NAME abrogated protection in SD, but did not attenuate protection in R or RD. Only SIM treatment increased prostaglandin production and only exercise increased HSP72 content. We conclude that NO is a critical mediator of statin-induced protection, but not exercise-induced protection. Also, combining the treatments may provide more protection than either alone. Supported by AHA-Texas Affiliate.

Evaluation of cardiac performance of the dog after induction of portal hypertension and gastric ischemia

AbstractObjective: To determine changes in hemodynamic and cardiac energetic parameters in dogs after induction of portal hypertension and gastric ischemia. These blood flow alterations are similar to changes seen in splanchnic blood flow in dogs with gastric dilatation volvulus syndrome (GDV).Design: Original experimental study.Setting: Veterinary teaching hospital.Animals: Seven purpose‐bred, intact male dogs.Interventions: Standard midline laparotomy and median sternotomy were performed under general anesthesia. Dogs were instrumented to obtain arterial blood pressure, aortic flow, cardiac chamber pressures, central venous pressure, portal flow, and portal pressure. Colored microsphere technology was used for the determination of myocardial blood flow. Measurements and samples were obtained at baseline, following induction of portal hypertension, and after induction of portal hypertension and gastric ischemia.Measurements and main results: Left ventricular myocardial blood flow was increased from 81.8±20.1 mL/100 g/min at baseline to 127.7±57.2 mL/100 g/min (P=0.02) after induction of portal hypertension and gastric ischemia. Myocardial oxygen consumption increased from 142.2±27.4 J/min/100 g at baseline to 219.1±33.4 J/min/100 g (P=0.003) after induction of portal hypertension and gastric ischemia, but cardiac external work remained unchanged (13.67±6.2 to 13.27±9.6 J/min; P=0.78; power=0.79). Cardiac efficiency decreased from 11.6±6.1% at baseline to 7.6±5.1% (P=0.017) after induction of portal hypertension and gastric ischemia.Conclusions: Transfer of energy within the myocardium was less efficient after induction of portal hypertension and ischemia of the stomach wall. On the basis of these results, alterations in cardiac function associated with GDV may result from deterioration of cardiac efficiency.

The effects of altering time delays of coupled pacing during acute atrial fibrillation

Coupled pacing (CP), which consists of delivering a premature electrical stimulation to the heart after the effective refractory period of ventricular activation, is a novel method for controlling ventricular rate during atrial fibrillation (AF). It also has been established that CP improves pump function by enhancing external cardiac work and myocardial efficiency. The purpose of the present study was to determine if two time delays for CP (short and long) would result in similar improvements in ventricular function. In a canine model, we applied CP at two time delays (CP-S and CP-L) during two stages: sinus rhythm (SR) and acute AF. The cardiac responses to CP during SR served as the nontachycardic and nondepressed control. During both rhythms, we shortened the coupling interval until we obtained maximal contractility, designated CP-S. Next, we increased the delay until we started to see a measurable secondary contraction (left ventricular pressure development of approximately 20 mmHg). These longer delays were designated CP-L. Our results showed that the ventricular rate of intrinsic activation (VRIA) remained decreased despite prolongation of the time delay of CP during both AF and SR. Also, both delays of CP increased left ventricular systolic pressure (LVSP) and dLVP/dt, which are indices of myocardial contractility. In contrast, CP increased external cardiac work only during AF. Prolonging this time delay did not markedly decrease the improvement in external cardiac work. Myocardial O(2) consumption (MVO(2)) did not significantly change as the result of CP during either SR or AF. Finally, myocardial efficiency improved during AF as the result of CP at both time delays. In conclusion, shorter time delays for CP increased contractile strength during both SR and AF. However, extending the time delay of CP had minimal effects on diminishing the improved ventricular pump function and energetics that resulted from CP during AF. Thus, the maximal enhancement of myocardial contractility via CP-S was not needed to maintain the improved ventricular function during acute AF when CP is applied.

Habitual low-intensity exercise does not protect against myocardial dysfunction after ischemia in rats

It is well established that participation in a chronic exercise program can reduce coronary heart disease (CHD) risk factors and improve myocardial tolerance to ischemia-reperfusion (I-R) injury. Low-intensity exercise programs are known to be effective in reducing CHD risk factors in humans and rats, but whether similar programs are of sufficient intensity to improve intrinsic tolerance to I-R injury has not been established. Thus, the purpose of this study is to determine whether low-intensity exercise provides self-protection to the heart against I-R injury. Male, Sprague-Dawley rats were exercised on a treadmill at an intensity of 55-60% VO2max, 40 min/day, 5 days/week for 16 weeks. Reperfusion injury following 20 min of global ischemia was evaluated using the isolated perfused working heart model. Left ventricular content of the cytoprotective protein heat shock protein 70 (HSP70) was determined by Western blotting. The exercise program elevated HSP70 2.7-fold, but did not provide enhanced protection following 20 min of ischemia. Final post-ischemic recovery of cardiac external work was 63+/-9% of pre-ischemic value in the sedentary group (n=9) and 51+/-11% in the exercising group (n=9) (P>0.05). Post-ischemic lactate dehydrogenase release was also similar between groups and the magnitude of release was low, consistent with stunning. Regular exercise at 55-60% VO2max is below the threshold intensity necessary to induce intrinsic cardioprotection against I-R injury. Furthermore, elevated myocardial HSP70 is not necessarily a marker of improved protection against dysfunction associated with stunning.

Coupled pacing improves cardiac efficiency during acute atrial fibrillation with or without cardiac dysfunction.

Coupled pacing (CP), a method for controlling ventricular rate during atrial fibrillation (AF), consists of a single electrical stimulation applied to the ventricles after each spontaneous activation. CP results in a mechanical contraction rate approximately one-half the rate during AF. Paired stimulation in which two electrical stimuli are delivered to the ventricles has also been proposed as a therapy for heart failure. Although paired stimulation enhances contractility, it greatly increases energy consumption. The primary hypothesis of the present study is that CP improves cardiac function during acute AF without a similar increase in energy consumption because of the reduced rate of ventricular contractions. In a canine model, CP was applied during four stages: sinus rhythm (SR), acute AF, cardiac dysfunction (CD), and AF in the presence of cardiac dysfunction. The rate of ventricular contraction decreased in all four stages as the result of CP. In addition, we determined the changes in external cardiac work, myocardial oxygen consumption, and myocardial efficiency in the each of four stages. CP partially reversed the effects of AF and CD on external cardiac work, whereas myocardial oxygen consumption increased only moderately. In all stages but SR, CP increased myocardial efficiency because of the marked increases in cardiac work compared with the moderate increases in total energy consumed. Thus this pacing therapy may be a viable therapy for patients with concurrent atrial fibrillation and heart failure.