Variable Unstressed Volume Keeps Normal Distributions of Canine Left Ventricular Contractility and Total Mechanical Energy under Atrial Fibrillation

We have reported that the contractility index (E(max)) and the total mechanical energy (PVA) of arrhythmic beats of the left ventricle (LV) distribute normally in canine hearts under electrically induced atrial fibrillation (AF). Here, E(max) is the ventricular elastance as the slope of the end-systolic (ES) pressure-volume (P-V) relation (ESPVR), and PVA is the systolic P-V area as the sum of the external mechanical work within the P-V loop and the elastic potential energy under the ESPVR. To obtain E(max) and PVA, we had to assume the systolic unstressed volume (V(o)) as the V-axis intercept of the ESPVR to be constant despite the varying E(max), since there was no method to obtain V(o) directly in each arrhythmic beat. However, we know that in regular stable beats V(o) decreases by approximately 7 ml/100 g LV with approximately 100 times the increases in E(max) from ~0.2 mmHg/(ml/100 g LV) of almost arresting weak beats to approximately 20 mmHg/(ml/100 g LV) of strong beats with a highly enhanced contractility. In the present study, we investigated whether E(max) and PVA under AF could still distribute normally, despite such E(max)-dependent V(o) changes. The present analyses showed that the E(max) changes were only approximately 3 times at most from the weakest to the strongest arrhythmic beat under AF. These changes were not large enough to affect V(o) enough to distort the frequency distributions of E(max) and PVA from normality. We conclude that one could practically ignore the slight E(max) and PVA changes with the Emax-dependent V(o) changes under AF.     

Predictability of O2 consumption from contractility and mechanical energy of absolute arrhythmic beats in canine heart

Left ventricular (LV) O2 consumption (V(O2)) per minute is measurable for both regular and arrhythmic beats. LV V(O2) per beat can then be obtained as V(O2) per minute minute divided by heart rate per minute minute for regular beats, but not for arrhythmic beats. We have established that V(O2) of a regular stable beat is predictable by V(O2) = a PVA + b E(max) + c, where PVA is the systolic pressure-volume area as a measure of the total mechanical energy of an individual contraction and E(max) is the end-systolic maximum elastance as an index of ventricular contractility of the contraction. Furthermore, a is the O2 cost of PVA, b is the O2 cost of E(max), and c is the basal metabolic V(O2) per beat. We considered it theoretically reasonable to expect that the same formula could also predict LV V(O2) of individual arrhythmic beats from their respective PVA and E(max) with the same a, b, and c. We therefore applied this formula to the PVA - Emax data of individual arrhythmic beats under electrically induced atrial fibrillation (AF) in six canine in situ hearts. We found that the predicted V(O2) of individual arrhythmic beats highly correlated linearly with either their V(O2) (r = 0.96 +/- 0.01) or E(max) (0.97 +/- 0.03) while both also highly correlated linearly with each other (0.88 +/- 0.04). This suggests that the above formula may be used to predict LV Vo2 of absolute arrhythmic beats from their Emax and PVA under AF.     

Cardiac changes to signalled shock avoidance in dogs

Alterations in heart rate (HR), left ventricular pressure (LVP), and maximum left ventricular dp/dt (LVdp/dt max) during a signalled avoidance task were studied in eight chronically prepared dogs. Four of these animals comprised a non-shock control group. In experimental animals, HR increased during the first two days of the avoidance task but did not change significantly during the last two days, while LVP remained at the supranormal post-training levels and LVdp/dt max increased over the course of the experiment. Control animals showed no change in HR or LVP, but LVdp/dt max decreased over the four experimental days. Changes in LVdp/dt max in experimentals reflect a consistent increase in cardiac sympathetic activation. However, HR changes indicate an initial increase and a subsequent decrease in sympathetic activity. It was therefore postulated that either differential activation of sympathetic cardiac fibers occurred such that during non-stress periods and subsequent exposure to stress, sympathetic influences predominate which are reflected only in LVdp/dt max changes, or sympathetic and parasympathetic fibers differentially control cardiac function during stress and non-stress conditions.     

High mechanical efficiency of left ventricular arrhythmic contractions during atrial fibrillation

We analyzed the frequency distribution of the left ventricular (LV) mechanical efficiency of individual arrhythmic beats during electrically induced atrial fibrillation (AF) in normal canine hearts. This efficiency is the fraction of the external mechanical work (EW) in the total mechanical energy measured by the systolic pressure-volume area (PVA). The mean, median, and mode of this efficiency (EW/PVA) were as high as 78%, 80%, and 81%, respectively, on average in six hearts. These high efficiencies were comparable to that of the regular beats in these hearts. The frequency distribution of the EW/PVA during AF tended to skew to the higher side in all the hearts. Since the EW/PVA is directly related to both the ventriculo-arterial (or afterload) coupling ratio (E(a)/E(max); E(a) = effective arterial elastance, E(max) = end-systolic ventricular elastance) and the ejection fraction on a per-beat basis, we also analyzed their frequency distributions. We found them to skew enough to account for the rightward skewed frequency distribution of the EW/PVA during AF with the unexpectedly high mean EW/PVA. These results indicate that the LV arrhythmia during AF per se does not directly suppress the mean level of LV mechanical efficiency in normal canine hearts.     

The effect of left dorsal and ventral ansa subclavian transection on cardiac changes during behavioral stress in dogs

Alterations in heart rate (HR), left ventricular systolic pressure (LVP), and maximum rate of left ventricular pressure development (LVdp/dt max) during a 13 day Sidman shock avoidance task were studied in 3 groups of four chronically prepared dogs. In one group of animals the left dorsal and ventral ansa subclavian nerves were transected between the stellate and the caudal cervical ganglia. The second group of dogs was a neurologically intact, experimental stress group, and the third group was a neurologically intact, nonstress control. The intact stress group demonstrated phasic increases in HR and LVdp/dt max during the avoidance period of each day as well as tonic increases in HR, LVP, and LVdp/dt max during the 13 days of the experiment. The nerve transection animals showed no evidence of consistent phasic increases in any of the parameters during the avoidance period. Tonic levels of LVP and LVdp/dt max in the transection group were not significantly different from controls, but tonic levels of HR remained elevated. These results suggest that the integrity of the left ansa subclavian nerves is necessary for stress induced change in LVP, LVdp/dt max, and phasic increases in HR during the avoidance period of each day. However, right cardiac sympathetic, vagal and/or afferent influences are apparently responsible for stress induced tonic changes in HR.     

Effective arterial elastance of irregular beats during atrial fibrillation in canine left ventricle

Effective arterial elastance (E(a)) was originally defined as the end-systolic pressure (ESP)/stroke volume (SV) ratio of the left ventricle (LV). E(a) combined with LV contractility (E(max)), E(a)/E(max), proved to be powerful in analyzing the ventriculo-arterial coupling of normal and failing hearts in regular beats. However, E(a) sensitively changes with LV E(max), preload, and afterload widely changing among irregular beats. This has discouraged the use of E(a) during arrhythmia. However, we hypothesized that E(a) could serve as the effective afterload (not always arterial) elastance against ventricular ejection under arrhythmia. We tested this hypothesis by analyzing beat-to-beat changes in E(a) of irregular beats during electrically induced atrial fibrillation (AF) in normal canine in situ hearts. We newly found that during AF in each heart: 1) E(a) changed widely among irregular beats and became markedly high in weak beats with small SVs; 2) E(a) and E(a)/E(max) distributed non-normally with large skewness but 1/E(a) distributed more normally; 3) 1/E(a) correlated closely with end-diastolic volume, E(max) and preceding beat intervals; and 4) the reciprocal of mean 1/E(a) closely correlated with mean ESP/mean SV. These results support our hypothesis that E(a) can serve as the effective afterload elastance against ventricular ejection on a per-beat basis during AF. E(a)/E(max) can also quantify the ventriculo-afterload (not arterial) coupling on a per-beat basis. This study, however, warns that mean E(a) and mean E(a)/E(max) of irregular beats cannot necessarily represent their averages during AF.     

Load independence of temperature-dependent Ca2+ recirculation fraction in canine heart

Intramyocardial Ca(2+) recirculation fraction (RF) critically determines the economy of excitation-contraction coupling. RF is obtainable from the exponential decay of the postextrasystolic potentiation of left ventricular (LV) contractility. We have shown that RF remains unchanged despite increasing LV volume (LVV) at normothermia, but decreases with increasing temperature at a constant LVV. However, it remains unknown whether the temperature-dependent RF was not due to the simultaneously changed peak LV pressure (LVP) at a constant LVV. We hypothesized that this temperature-dependent RF would be independent of the simultaneous change in LVP. We used nine excised, cross-circulated canine hearts and allowed their LVs to contract isovolumically. During stable regular beats at 500 msec intervals, we inserted an extrasystolic beat at 360 msec interval followed by the postextrasystolic beats (PESs) at 500 msec intervals. We equalized the temperature-dependent peak LVPs of the regular beats at 36 degrees C and 38 degrees C to the peak LVP level of the stable regular beat at 33 degrees C by adjusting LVV. We fitted the same equation: nEmax = a.exp[-(i - 1)/tau(e)] + b.exp[-(i - 1)/tau(s)]cos[pi(i - 1)] + 1, used before to the normalized Emax (maximum elastance) values of PESi (i = 1-6) relative to the regular beat Emax. RF given by exp(-1/tau(e)) decreased by 19% to 38 degrees C from 33 degrees C. The temperature coefficient (Q(10)) of 1/RF was significantly greater than 1.3. The present results indicated a similar temperature dependence of RF and its Q(10) to those we observed previously without equalizing peak LVP. Thus, the temperature-dependent RF is independent of ventricular loading conditions.     

The effect of an increase in aortic pressure upon the inotropic state of eat and dog left ventricles

1. The effect of increased aortic pressure on the inotropic state of the left ventricle was studied in isolated cat hearts, perfused with bovine red cells in Tyrode solution, ejecting into a hydraulic model with the same input impedance as that of the cat aorta.2. Inotropic state was assessed at a controlled left ventricular end-diastolic pressure by interpolating single isovolumic beats by means of an occluder in the aortic cannula.3. When such isovolumic beats during periods of raised aortic pressure were compared with those during control periods, the difference in peak isovolumic pressure ranged from -0.3 to +0.5 kPa indicating differences in inotropic state which were small and inconsistent in direction.4. The maximum rate of rise of left ventricular pressure (dP/dt(max).) of ejecting beats was little affected by a rise of aortic pressure and the direction of changes was inconsistent.5. The effect of increased aortic pressure was studied in intact dogs after cardiac denervation; left ventricular end-diastolic pressure was uncontrolled and therefore rose to a higher steady level.6. No consistent change of dP/dt(max). was found during the period of increased aortic pressure.7. All flow and pressure variables remained steady during the period of increased aortic pressure after the higher level of left ventricular end-diastolic pressure had been established.8. These results demonstrate that neither the positive inotropic effect nor the negative inotropic effect of increased load dominates in these preparations. This may be the result of a balance between the two effects, or they may be of unimportant magnitude under physiological conditions.     

Postextrasystolic contractility normally decays in alternans in canine in situ heart

We have reported that the postextrasystolic (PES) potentiation of left ventricular (LV) contractility usually decays in alternans at heart rates above 80-100 beats/min in the canine excised, cross-circulated heart. We examined whether the PES contractility would also decay in alternans even in the canine in situ heart presumably more physiological than the excised heart. In anesthetized, ventilated, and open-chest mongrel dogs, we measured LV pressure and volume with a micromanometer and a conductance catheter cannulated into the LV and obtained LV end-systolic maximum elastance (E(max)) as the reasonably load-independent contractility index. We inserted an extrasystole followed by a compensatory pause into steady-state regular beats at heart rates above 90 beats/min and analyzed the PES decay pattern of E(max). We found that E(max) potentiated in the first PES beat decayed in alternans within 5-6 PES beats. This indicates that PES contractility also decays in alternans in the normal canine in situ heart.     

Variability of ventricular excitation interval does not reflect fluctuation in atrial excitation interval during exercise in humans: AV nodal function as stabilizer

We have recently reported that the atrioventricular (AV) nodal mechanism functions to cancel fluctuation in the atrial excitation interval during a stair-stepping exercise. However, it remained unknown at which level of heart rate (HR) this mechanism started to operate and whether fluctuation in the interval might influence AV conduction over the following beats. To solve these questions, the variability of PP, RR, and PR intervals and their interrelationships were analyzed throughout ergometer exercise in eight subjects. The variability of the RR interval decreased to 0.7% of the control at 160 beats/min during exercise, much more than the PP interval variability, which decreased to 10%, despite the same shortened average interval. In contrast, the PR interval variability tended to increase by 87% during exercise, but the mean PR interval decreased. A strong inverse relationship between PP and the subsequent change in PR [deltaPR] intervals became evident during exercise, implying that the deltaPR interval canceled fluctuation in the PP interval. However, there was little correlation between the RR and deltaPR intervals and between the PP interval and the next PR intervals in the forthcoming beat. When the slope of the PP-deltaPR relationship, considered as sensitivity of the AV nodal function opposing an alteration in the PP interval, was plotted against the PP interval, the AV nodal function curve was approximated to a sigmoidal curve having a threshold of PP interval near 650 ms and a maximum plateau level of the slope near 1.0. We conclude that when HR exceeds 90-100 beats/min during dynamic exercise, the AV nodal mechanism will function to cancel fluctuation in the PP interval within one beat and keep the RR interval constant.     

Increased cardiac contractility in rats exposed to 5 bar

The left ventricular pressure, arterial blood pressure and heart rate were studied in three series of pentobarbital-anaesthetized rats exposed to 5-bar normoxic (PO2 = 0.2 bar) environments: nitrogen-oxygen (15 and 60 min) and helium-oxygen (15 min). The maximal left ventricular pressure (LVP max) and the maximal velocities of LVP rise (+ dP/dt max) and fall (- dP/dt) were significantly (P less than 0.01) increased immediately after reaching normoxic 5 bar (He, 13-28%; N2, 13-23%) and during the exposure at 5 bar (He, 22-44%; N2, 13-18%). The pulse pressure increased significantly (He, 50-62%; N2, 30-34%; P less than 0.01) during the hyperbaric exposure. No changes in heart rate or end-diastolic and mean arterial pressure were detected. The present findings indicate an enhanced cardiac contractility (+ dP/dt max) at 5 bar, with the greatest increase found when He was used as inert gas. The increased contractility was of significant duration (at least 60 min), and was not completely reversed until 5-10 min after decompression.     

Effects of epoprostenol and sildenafil on right ventricular function in hypoxic volunteers: a tissue Doppler imaging study

Sildenafil and epoprostenol are effective therapies in pulmonary arterial hypertension (PAH). Both drugs increase cardiac output, which has been in part attributed to improved right ventricular (RV) contractility. We therefore used tissue Doppler imaging (TDI) to test whether sildenafil and epoprostenol might differently affect RV function in normal subjects before and after induction of acute hypoxic pulmonary hypertension. Ten healthy volunteers underwent this randomized, double-blind, placebo-controlled cross-over study. Echocardiographic measurements were obtained 60 min after the intake of a placebo or 50 mg sildenafil or under 8 ng/kg/min iv epoprostenol, in normoxia or after 60 min of hypoxic breathing (FIO₂ of 0.12). Right ventricular systolic function was assessed by systolic strain (ε), strain rate (SR), isovolumic contraction acceleration (IVA) and tricuspid annulus plane systolic excursion (TAPSE), and diastolic function by tricuspid annulus E/A ratio and isovolumic relaxation time related to RR interval (IRT/RR). Pulmonary artery pressure was calculated from the acceleration time of pulmonary flow and cardiac output from the left ventricular outflow tract flow-velocity. Hypoxia increased pulmonary vascular resistance (PVR) by 78%, did not affect indices of RV systolic function, decreased E/A and increased IRT/RR. Epoprostenol more than sildenafil increased cardiac output, apical ε and TAPSE, the latter in proportion to decreased PVR. In addition, apical SR was increased only by epoprostenol. None of the drugs affected IVA, basal SR, E/A and IRT/RR. These results are not suggestive of intrinsic positive inotropic effects of either sildenafil or epoprostenol at maximal doses tolerated by normal subjects.     

Preload maintenance and the left ventricular response to prolonged exercise in men

This study examined whether left ventricular function was reduced during 3 h of semi-recumbent ergometer cycling at 70% of maximal oxygen uptake while preload to the heart was maintained via saline infusion. Indices of left ventricular systolic function (end-systolic blood pressure-volume relationship, SBP/ESV) and diastolic filling (ratio of early to late peak filling velocities into the left ventricle, E:A) were calculated during recovery and compared with baseline resting data. During exercise in seven healthy, trained male subjects, an arterial catheter allowed continuous assessment of arterial pressure, stroke volume (SV), cardiac output ( ) and an index of contractility (dP/dt(max)). A venous catheter assessed that central venous pressure (CVP) was maintained throughout rest, exercise and 10 min into recovery. Both systolic blood pressure and heart rate (HR) increased with the onset of exercise (from 132 +/- 5 to 185 +/- 19 mmHg and from 66 +/- 9 to 135 +/- 23 beats min(-1); increases from rest to the end of the first 5 min of exercise in SBP and HR, respectively) but systolic blood pressure did not change from 30 to 180 min of exercise ( approximately 150 mmHg), while heart rate only increased by 8 +/- 9 beats min(-1) (means +/- s.d.; P > 0.05). The attenuated increase in HR compared with other studies suggests that the maintained CVP ( approximately 5 mmHg) helped to prevent cardiovascular drift in this protocol. Stroke volume, and dP/dt(max) were all increased with the onset of exercise (from 85 +/- 8 to 120 +/- 18 ml, from 5.4 +/- 1.3 to 16.5 +/- 3.3 l min(-1) and from 14.4 +/- 4 to 28 +/- 8 mmHg s(-1); values from rest to the end of the first 5 min of exercise for SV, and dP/dt(max), respectively) and were maintained during exercise. There was no difference in the SBP/ESV ratio from pre- to postexercise. Conversely, E:A was reduced from 2.0 +/- 0.4 to 1.6 +/- 0.5 postexercise (P < 0.05), returning to normal values at 24 h postexercise. This change in diastolic filling could not be fully explained (r(2) = 0.39) by an increased heart rate and, with CVP unchanged, it is likely to represent some depression of intrinsic relaxation properties of left ventricular myocytes. Three hours of semi-supine cycling resulted in no evidence of a depression in left ventricular systolic function, while left ventricular diastolic function declined postexercise.     

8-OH-DPAT prevents cardiac arrhythmias and attenuates tachycardia during social stress in rats

The aim of this study was to apply a behavioural stress paradigm for studying the neural mechanisms underlying stress-induced arrhythmias, and to test whether such arrhythmias could be suppressed by systemic administration of 8-OH-DPAT, a 5-HT1A agonist possessing central sympatholytic properties. The study was conducted on adult male rats instrumented for telemetric recordings of ECG, body temperature and locomotor activity. In the first experiment, rats were subjected to social defeat after either 8-OH-DPAT (100 µg/kg s.c.) or vehicle injection. In the second experiment, prior to vehicle/8-OH-DPAT administration, animals were pre-treated with zatebradine, a blocker of the pacemaker current. 8-OH-DPAT caused prolongation of basal RR interval, increase in locomotion and hypothermia. Subjecting vehicle-treated animals to social defeat caused shortening in RR interval, increase in locomotor activity and hyperthermia, and provoked the occurrence of premature ventricular and supraventricular beats; all these effects were substantially attenuated by 8-OH-DPAT. Zatebradine caused prolongation of RR interval. In zatebradine/vehicle-treated rats, the incidence of ventricular and supraventricular premature beats during defeat increased 2.5-fold and 3.5-fold, respectively. 8-OH-DPAT administered after zatebradine significantly reduced these stress-induced arrhythmias. We conclude that: i) pharmacologically induced prolongation of RR interval may contribute to an increased susceptibility to stress-induced cardiac arrhythmias, possibly due to the prolongation of the ventricular diastolic period with restored excitability; and ii) systemic administration of 8-OH-DPAT abolishes these arrhythmic events, likely by suppressing stress-induced cardiac sympathetic outflow.     

Mode of frequency distribution of external work efficiency of arrhythmic beats during atrial fibrillation remains normal in canine heart

The external work (EW) efficiency of individual arrhythmic beats of the left ventricle (LV) cannot directly be obtained since LV O₂ consumption (VO₂) of each beat cannot directly be measured under beat-to-beat varying contractile and loading conditions. We, however, have recently reported that VO₂ of each arrhythmic beat can reasonably be estimated by VO₂ = aPVA + bE_max + c even under varying PVA and E_max. Here, PVA is the LV pressure–volume (P–V) area as a measure of the LV total mechanical energy, E_max is the LV end-systolic elastance as an index of the LV contractility, a is a constant O₂ cost of PVA, b is a constant O₂ cost of E_max, and c is the basal metabolic VO₂ of the beat, all on a per-beat basis. Using the above formula in this study, we calculated VO₂ of the individual arrhythmic beats from their measured PVA and E_max during electrically induced atrial fibrillation (AF) in normal canine hearts. We then calculated their LV EW efficiency by dividing their measured EW with the estimated VO₂. We found that the thus calculated EW efficiency of the arrhythmic beats had a rightward skewed distribution with a mode of 15% and a maximum of 18% around a mean of 13% on average in six hearts. This mode remained comparable to the efficiency (15%) at regular tachycardia though 22% lower than mean arrhythmic tachycardia.     

Cardiac changes during behavioral stress in dogs.

Alterations in heart rate (HR), left ventricular systolic pressure (LVP), and maximum rate of left ventricular pressure development (LV dP/dtmax) during a Sidman avoidance task were studied in eight chronically prepared dogs. Four of these animals comprised a nonstressed control group. In the experimental group, in addition to phasic increases in HR, LVP, and LV dP/dtmax during the avoidance period of each day, tonic increases in these measures were also observed over the 13 days of the experiment. Left ventricular systolic pressure was found to be least sensitive to the stress procedure inasmuch as the phasic changes were no longer present after the 10th day and tonic levels were within base-line values by the 13th day. When alterations in cardiac activity were observed in the nonstressed animals, there were decreases in function. It was concluded that controlled behavioral stress produces increased cardiac performance without increased bodily activity. It was also hypothesized that preavoidance increases in heart rate in experimental animals were the result of vagal influences on the heart, whereas avoidance increases in HR, LV dP/dtmax, and LVP were functions of increased beta-sympathetic activity on the heart and adaptive peripheral vascular changes.     

An arrhythmia classification system based on the RR-interval signal

OBJECTIVE: This paper proposes a knowledge-based method for arrhythmic beat classification and arrhythmic episode detection and classification using only the RR-interval signal extracted from ECG recordings. METHODOLOGY: A three RR-interval sliding window is used in arrhythmic beat classification algorithm. Classification is performed for four categories of beats: normal, premature ventricular contractions, ventricular flutter/fibrillation and 2 degrees heart block. The beat classification is used as input of a knowledge-based deterministic automaton to achieve arrhythmic episode detection and classification. Six rhythm types are classified: ventricular bigeminy, ventricular trigeminy, ventricular couplet, ventricular tachycardia, ventricular flutter/fibrillation and 2 degrees heart block. RESULTS: The method is evaluated by using the MIT-BIH arrhythmia database. The achieved scores indicate high performance: 98% accuracy for arrhythmic beat classification and 94% accuracy for arrhythmic episode detection and classification. CONCLUSION: The proposed method is advantageous because it uses only the RR-interval signal for arrhythmia beat and episode classification and the results compare well with more complex methods.     

小鼠病毒性心肌炎的心肌结构及左室功能变化的初步研究

目的:探讨病毒性心肌炎时的心肌结构与收缩力变化的关系。方法:建立病毒性心肌炎的动物模型,观测病毒损伤阶段和免疫损伤阶段心肌的超微结构和心肌收缩力改变。结果:病毒性心肌炎早期的心肌细胞的线粒体超微结构发生了变化,心肌细胞收缩力下降,左室压(LVP)为(14.2±0.8)kPa,dp/dt为(273.1±10.0)kPa/s,正常对照LVP为(17.1±0.7)kPa,dp/dt为(359.8±9.3)kPa/s,P＜0.01;后期心肌组织严重损害,不仅有线粒体溶解破坏,而且肌原纤维变细、减少等,并且心肌收缩力指标明显下降,LVP为(11.8±0.2)kPa,dp/dt为(209.5±6.9)kPa/s,与早期相比差异有显著,P＜0.01。结论:病毒性心肌炎早期,即病毒损伤期,造成心脏功能下降的原因主要是病毒引起心肌细胞的超微结构改变,特别是对线粒体的损伤,使心肌细胞供能障碍,心肌收缩力减小;病毒性心肌炎后期,免疫反应造成心肌组织损害较病毒直接损害更严重,造成心肌收缩力明显减小。     

Heart-rate-proportional oxygen consumption for constant cardiac work in dog heart

We studied whether there is an optimal heart rate (HR) that would minimize myocardial oxygen consumption (MVO2) per min for a constant minute cardiac work. We measured minute MVO2 (ml O2/min) of the left ventricle paced at increasing rates (100-200 beats/min) in 10 right-heart-bypassed dogs. In each experiment, cardiac output was kept constant with a constant-flow bypass pump, and mean aortic pressure was also kept constant by inflation or deflation of an intra-aortic balloon. Minute cardiac work was thus kept constant. Minute MVO2 was obtained as the product of mean coronary arteriovenous O2 difference and mean coronary blood flow drained from the collapsed right ventricle. Both left ventricular Emax (contractility index defined as the slope of the left ventricular end-systolic pressure-volume relation) and PVA (pressure-volume area as a measure of total mechanical energy of contraction) were obtained by an abrupt aortic occlusion method. The obtained-minute MVO2-HR relationship showed a good linear positive correlation (r = 0.824-0.995) in every heart. We accounted for this relationship by the changes in PVA and Emax that we had proposed as primary determinants of MVO2. We conclude that minute MVO2 for a constant minute cardiac work increased monotonically with increases in HR from 100 to 200 beats/min, being minimum at the lowest HR, and that this relation was ascribable to the HR-proportional increase in the MVO2 component for the excitation-contraction coupling.     

The Effect of Heart Rate, Preload, and Afterload on the Viscoelastic Properties of the Swine Myocardium

Experiments were performed to test the hypothesis that viscoelastic properties of the swine myocardium are independent of heart rate (HR), preload (PL), and afterload (AL). Left ventricular pressure and aortic flow (AoF) waveforms were recorded in 13 swine. At different paced heart rates, an inferior vena caval occlusion (IVC) was used to reduce PL, then the IVC was released and simultaneously the aorta was clamped to increase AL. Equivalent left ventricular pressure waveform pairs consisting of an ejecting waveform (denoted as LVP) and isovolumic waveform (denoted as hydromotive pressure, HMP) were selected according to specified criteria resulting in 371 equivalent waveform pairs. From the selected waveform pairs and corresponding aortic flow waveforms, the viscoelastic properties (k and epsilon1) were estimated by HMP = LVP + epsilon1 V(EJ) + k x LVP x AoF. Here epsilon1 is the parallel elastance, k is the myocardial friction, and V(EJ) is the integral of AoF over ejection. Next, using k, epsilon1, LVP, and AoF waveforms, HMP was estimated using the equation above. To validate the model, the measured HMP and model-calculated HMP were compared for 371 matched waveform pairs (R2 = 0.97, SEE = 3.7 mmHg). The viscoelastic parameters (k and epsilon1) did not exhibit any clear or predictable dependence on HR, PL, and AL.