Preload Recruitable Stroke Work Relationship Research Articles

Acute functional consequences of left ventriculotomy

Background. Left ventriculotomies are sometimes used during intracardiac congenital defect repair. Acute changes in left ventricular function after longitudinal or apical ventriculotomy were assessed using dynamic pressure-dimensional data. Methods. Ultrasonic dimension transducers along the major, minor, and septal free wall axes and micromanometers were placed in 24 piglets. Pressure-volume data were collected during caval occlusions at baseline and 60 minutes after warm cardiopulmonary bypass alone or with longitudinal ventriculotomy or apical left ventriculotomy. Hemodynamics, contractility, and contraction geometry were analyzed. Results. Cardipulmonary bypass caused decreased compliance in all groups, with equally decreased preload and cardiac output. Heart rate increased, but ventriculotomy led to a significantly greater increase. Longitudinal ventriculotomy produced a greater loss of stroke volume and ejection fraction than apical ventriculotomy. Contractility assessed by the preload recruitable stroke work relationship showed no difference between groups; however, all groups showed a slight increase in unit myocardial power at 60 minutes. Axis fractional shortening revealed that the septal freewall is responsible for 50% of stroke volume and that this axis is significantly impaired after longitudinal ventriculotomy. Conclusion. Apical left ventriculotomy impairs the less important major axis only and is predicted to be better tolerated.

Afterload Sensitivity of Nonlinear End-Systolic Pressure–Volume Relation vs Preload Recruitable Stroke Work in Conscious Dogs

The observationsin vivoof a non-linear, afterloadsensitive end-systolic pressure–volume relation (ESPVR) and a linear, load-insensitive preload recruitable stroke work (PRSW) relation may be reconciled by considering the PRSW as a product of both the ventricular ESPVR and the arterial elastance (Ea). We obtained pressure–volume data from eight conscious dogs. The ESPVR was nonlinear, and its trajectory was afterload-dependent. The PRSW was linear and load-independent. Arterial elastance changed with both acute reductions in preload and steady-state changes in afterload. The PRSW relation thus describes both myocardial function and ventricular–arterial interaction and is a useful index of cardiovascular performance in patients.

Effects of dynamic cardiomyoplasty on left ventricular systolic and diastolic performance in an acute canine model.

Although dynamic cardiomyoplasty (DCMP) is currently being evaluated as an alternative to end-stage congestive heart failure, the overall results of DCMP are variable and inconclusive. We evaluated the effect of classic DCMP on systolic and diastolic cardiac function in normal heart using reliable indicators which minimize the influences of load conditions. Six experimental dogs were evaluated with the acute nonpreconditioning model. The slope of the linear preload recruitable stroke work relationship (Mw) showed a significant increase with latissimus dorsi muscle (LDM) stimulation (postwrap non-stimulation 59.1+/-6.3, postwrap stimulation 98.6+/-9.7 erg cm(-3) x 10(3); P < 0.01), and the x-intercept (V0) was unchanged; these were utilized as the indicators of left ventricular systolic function. The constant of pressure decay (tau) increased after LDM wrap (prewrap 45.8+/-6.0, postwrap nonstimulation 69.3+/-10.3, postwrap stimulation 72.3+/-13.9 ms; P < 0.05), and the peak filling rate was unchanged after LDM wrap, which were utilized as the indicators of diastolic function. We concluded that classic dynamic cardiomyoplasty is effective in assisting systolic cardiac function, but may to some degree have a detrimental effect on the diastolic cardiac function.

Effect of Inhaled Nitric Oxide on Normal Human Left Ventricular Function

Objectives. This study determined the effects of inhaled nitric oxide (NO) on load-independent indexes of normal human left ventricular (LV) function.Background. Inhaled NO is a potent and selective pulmonary vasodilator. However, when it is used in patients with congestive heart failure, the decrease in pulmonary vascular resistance (PVR) is often associated with an increase in pulmonary capillary wedge pressure. NO has been shown to have a negative inotropic action, but it is not known whether it affects LV chamber function when delivered by inhalation.Methods. Eleven subjects (51 to 69 years old) with normal LV function (mean ejection fraction 72% [range 60% to 80%]) were studied. Four patients had concomitant coronary artery disease. Pressure-volume loop recordings were used to determine end-systolic and end-diastolic pressure-volume and preload recruitable stroke work relations. NO was delivered at 20 ppm for 10 min. In an additional group of patients with normal LV function, PVR (n = 5) and NO metabolites (n = 9) were measured.Results. There was no effect of inhaled NO on steady state LV pressures, volumes, contractility, contraction duration, active relaxation (time constant of relaxation, peak negative first derivative of left ventricular pressure), diastolic compliance or PVR. NO metabolites (methemoglobin and nitrate) were present in the LV cavity at the same concentration as right atrial venous blood, suggesting inactivation of free NO before arrival in the LV chamber. This study had a power of 0.995 to detect a 5% change in contractility (slope of preload recruitable stroke work relation) for alpha = 0.05, based on the multiple linear regression model used.Conclusions. These results indicate that 20 ppm of inhaled NO does not have significant effects on normal LV function. This lack of effect may be due in part to rapid inactivation of free NO in transit to the heart.(J Am Coll Cardiol 1997;30:49–56)

Effects of Free Latissimus Dorsi Dynamic Cardiomyoplasty on Left Ventricular Function

In their experimental approach to dynamic cardiomyoplasty (DCMP), the authors hypothesized that a wrapping method using the proximal part of a free latissimus dorsi muscle (LDM) graft might augment ventricular contractility more than the classic Carpentier's wrapping method. The authors divided 12 mongrel dogs into a pedicled LDM graft group (Group 1, n = 6) and a free LDM graft group (Group 2, n = 6) to evaluate the properties of the different wrapping methods. To evaluate the effect of DCMP on left ventricular systolic and diastolic function, the authors used precise indicators that minimize the influences of load conditions. The slope of the linear preload recruitable stroke work relationship (Mw) and an X-intercept (Vo) were utilized as the indicator of left ventricular systolic function. The constants of pressure decay (tau) and peak filling rate (PFR) were measured to determine diastolic function. All experimental animals were evaluated with the acute, non preconditioning model. Mw was significantly increased with LDM stimulation in both groups (postwrap non stimulation 59.1 +/- 6.3; postwrap stimulation 98.6 +/- 9.7 erg.cm-3. 10(3); p < 0.01 in Group 1, postwrap non stimulation 66 +/- 6.7; postwrap stimulation 155 +/- 15.7 erg.cm-3.10(3), p < 0.001 in Group 2). Stimulated free LDM grafts significantly increased the Mw in comparison to pedicled grafts (p = 0.011). Vo was unchanged in both groups and there was no significant difference between the two groups. Tau increased after LDM wrap in both groups (p < 0.05), but there was no difference between the two groups (tau; prewrap 45.8 +/- 6.0; postwrap non stimulation 69.3 +/- 10.3; postwrap stimulation 72.3 +/- 13.9 msec in Group 1, prewrap 50.0 +/- 6.0; post wrap non stimulation 61.8 +/- 5.0; post wrap stimulation in 64.3 +/- 4.7 msec in Group 2). Peak filling rate was unchanged after LDM wrap in both groups. Free LDM grafts significantly increased left ventricular systolic function compared to the pedicled LDM. Although myocardial relaxation was impaired after LDM wrap in both groups, there was no difference between the two groups. The authors' results emphasize the explicit benefit of utilization of a free LDM graft in respect to left ventricular systolic function; the free LDM grafts have no gross detrimental effect on diastolic function when compared with a pedicle graft in the acute model.

Right ventricular dysfunction persists following brief right ventricular pressure overload.

Acute pulmonary hypertension may cause right ventricular (RV) contractile failure. While it has been assumed that restoration of normal loading conditions after acute pulmonary hypertension is sufficient for complete recovery of RV function, this has not been rigorously examined. The purpose of this study was to test the hypothesis that acute RV pressure overload produces RV contractile dysfunction that persists following restoration of control loading conditions. We subjected 18 autonomically-blocked, chloralose-anesthetized, open-chest pigs to 1 h of pulmonary artery constriction to increase RV systolic pressure from 35 +/- 1 to 55 +/- 1 mmHg, followed by 2 h of measurements after pulmonary artery constriction release. We determined regional RV free wall function from pressure-segment length loops and preload recruitable stroke work relations, and global RV function from stroke work vs. end-diastolic pressure relations. As expected, RV free wall systolic shortening diminished during pulmonary artery constriction, but the endo/epi blood flow ratio, lactate uptake, and coronary venous pH were not significantly changed. Following release of pulmonary artery constriction, RV systolic and diastolic pressure returned to control values. Nonetheless, contractile dysfunction persisted, with depressed RV free wall systolic shortening (70 +/- 22% of control), RV regional external work (59 +/- 11% of control at control end-diastolic length), and global RV stroke work (56 +/- 14% of control at control end-diastolic pressure). Depressed regional work was due to a parallel, rightward shift of the preload recruitable stroke work relation. Five pigs identically instrumented but not subjected to pulmonary artery constriction showed no significant over 3 h. Acute pulmonary hypertension causes RV contractile dysfunction that persists at least 2 h after restoration of control loading conditions. Contractile dysfunction is not attributable to RV ischemia during pressure overload.

Levosimendan enhances left ventricular systolic and diastolic function in conscious dogs with pacing-induced cardiomyopathy.

We examined the left ventricular (LV) mechanical actions of levosimendan (LSM) before and after the development of pacing-induced cardiomyopathy in conscious dogs chronically instrumented for measurement of aortic and LV pressure, +dP/dt, subendocardial segment length, and cardiac output (CO). The slope (Mw) of the regional preload recruitable stroke work relation was used to assess myocardial contractility. Diastolic function was evaluated with a time constant of isovolumic relaxation (tau), the maximal rate of segment-lengthening velocity (dL/dt), and a regional chamber-stiffness constant (Kp). On different experimental days, dogs were assigned to receive LSM (12- or 24-microgram/kg loading dose and 0.2 or 0.4 microgram/kg/min infusion) before rapid ventricular pacing was initiated. Dogs were then paced at 240 beats/min for 22 +/- 2 days, and the low and high doses of LSM were repeated on separate days. LSM increased Mw and +dP/dt in dogs before the initiation of pacing, consistent with enhanced myocardial contractility. LSM also improved indices of LV diastolic function (decreases in tau and Kp and increases in dL/dt) in dogs before pacing. Rapid ventricular pacing over a 3-week period increased LV end-diastolic pressure and produced systolic (decreases in Mw and +dP/dt) and diastolic (increases in tau and Kp and decreases in dL/dt) dysfunction. LSM significantly (p < 0.05) increased Mw (54 +/- 3 to 98 +/- 6 mm Hg) +dP/dt and dL/dt (57 +/- 13 to 72 +/- 13 mm/s) and decreased tau (66 +/- 4 to 52 +/- 3 ms) and Kp (1.14 +/- 0.14 to 0.71 +/- 0.03 mm-1) in the presence of LV dysfunction. In contrast to the findings in normal dogs, however, LSM did not alter heart rate and calculated indices of myocardial oxygen consumption in dogs after pacing. The findings indicate that LSM produces favorable alterations in hemodynamics and positive inotropic and lusitropic effects in conscious dogs with left ventricular dysfunction.

Mechanisms of right ventricular dysfunction after pulmonary resection

Significant right ventricular (RV) dysfunction as measured by increased end-diastolic volume and reduced ejection fraction has been documented in the postoperative period after pulmonary resection. We hypothesized that changes in RV contractile state or afterload may contribute to this RV pump dysfunction. In part one of the study, RV preload was altered on postoperative day 2 (n = 6) by rapid infusion of Hespan to a total of 250, 500, and 1,000 mL. The relationship between RV stroke work and end-diastolic volume was plotted using linear regression. This preload recruitable stroke work relation had been previously validated as a load-insensitive index of RV contractility. The slopes of the preoperative relation (n = 35) and postoperative relation were compared. In part two of the study, RV afterload was reduced by continuous infusion of prostaglandin E1 (n = 6) through postoperative day 2 and RV pump function was assessed. Comparison of the slopes of the preload recruitable stroke work relation plotted preoperatively and on postoperative day 2 revealed no significant difference, indicating no change in RV contractile state. Infusion of prostaglandin E1 in the postoperative period (n = 6) significantly reduced pulmonary vascular resistance (3.67 +/- 0.19 versus baseline 5.72 +/- 0.19 dyne . s . cm-5/ m2; p < 0.05). However, RV ejection fraction remained significantly reduced (0.34 +/- 0.01 versus baseline 0.42 +/- 0.01; p < 0.05) and end-diastolic volume significantly increased (105 +/- 5 versus baseline 93 +/- 2 mL/m2; p < 0.05). Heart rate was increased compared with baseline throughout the postoperative period. The present study suggests that RV dysfunction after pulmonary resection is not caused by primary alterations in contractility or immediate changes in afterload. Better control of heart rate with minimal effect on inotropy may enhance RV pump function.

Bypass conduit vessel wall biology substantially influences downstream myocardial contractile response to injury from ischemia and reperfusion

Coronary vascular intraluminal release of endogenous endothelium-derived substances, such as prostacyclin, may affect downstream cardiac myocyte contractile function. With a “chronic” canine model of endothelialized and deendothelialized internal thoracic artery coronary grafts, we tested the hypothesis that higher basal release of endothelium-derived prostacyclin in internal thoracic artery bypass conduit effluent accelerates functional recovery of postischemic stunned myocardium in the intact circulation. Eleven dogs underwent left internal thoracic artery–left circumflex artery bypass, and the proximal circumflex artery was then ligated. Internal thoracic artery conduit endothelium was denuded by balloon catheter in five dogs before grafting and left intact in six dogs. After 7 days, awake dogs were studied to measure myocardial segment length in the circumflex region with ultrasonic dimension transducers, left ventricular pressure with micromanometers, and circumflex artery flow with an ultrasonic flow probe. Regional contractile function was quantified by the area beneath the linear preload recruitable stroke work relationship at baseline and at intervals after a 15-minute circumflex graft occlusion followed by 3 hours of reperfusion. Heart rate, left ventricular peak pressure, left ventricular end-diastolic pressure, left ventricular peak first derivative of pressure (dP/dt), and circumflex flow were similar (all p not significant) in endothelialized and nonendothelialized dogs during ischemia and reperfusion. Ischemia reduced the preload recruitable stroke work relationship to 44% ± 35% of control values ( p < 0.01) in endothelialized dogs and to 47% ± 18% of control values in nonendothelialized dogs ( p < 0.01) at 15 minutes of reperfusion, indicating a similar ( p not significant) initial degree of injury. During 3 hours of reperfusion, the preload recruitable stroke work relationship returned to 51% ± 17% of control values in endothelialized dogs but to only 35% ± 20% of control values in nonendothelialized dogs ( p < 0.02). Basal intraluminal release of endogenous prostanoids in excised internal thoracic artery conduits was subsequently quantified by ex vivo bioassay of vasoactive properties of conduit effluent on normal coronary artery smooth muscle. Endothelialized conduits induced greater smooth muscle relaxation than did nonendothelialized conduits (67% vs 23%), and this increased relaxation by endothelialized conduits was eliminated by indomethacin, a blocker of prostanoid synthesis. These data indicate that coronary bypass conduit endothelium–derived substances, such as prostacyclin, significantly influence downstream myocardial contractile response to ischemia and reperfusion, independent of alterations in coronary flow in the intact circulation. (J T HORAC C ARDIOVASC S URG 1996;111:62-73)

Systemic and coronary hemodynamic actions and left ventricular functional effects of levosimendan in conscious dogs.

We examined the effects of levosimendan, a new myofilament Ca2+ sensitizer with phosphodiesterase (PDE)-inhibiting properties, on systemic and coronary hemodynamics and left ventricular (LV) systolic and diastolic function in conscious dogs with intact and blocked autonomic nervous system (ANS) reflexes. Twenty experiments were conducted in 10 dogs chronically instrumented for measurement of aortic and LV pressure, the peak rate of increase and decrease in LV pressure (+dP/dtmax and -dP/dtmin), subendocardial segment length, diastolic coronary blood flow (CBF) velocity, and cardiac output (CO). The slope (Mw) of the regional preload recruitable stroke work relation was used to assess myocardial contractility. Diastolic function was evaluated by -dP/dtmin, a time constant of isovolumic relaxation (tau), maximum segment lengthening velocity during rapid ventricular filling (dL/dtmax), and a regional chamber stiffness constant (Kp). Dogs were randomly assigned to receive levosimendan (0.5, 1.0, 2.0, and 4.0 micrograms.kg-1.min-1) with or without ANS blockade. On separate experimental days, systemic and coronary hemodynamics and LV pressure-segment length diagrams and waveforms were recorded after 10-min equilibration at each dose in the conscious ANS-intact or ANS-blocked state. Levosimendan increased heart rate (HR), CO, mean and diastolic CBF velocity, and pressure-work index (PWI, an estimate of myocardial oxygen consumption) and decreased LV end-diastolic pressure (EDP), systemic vascular resistance (SVR), end-systolic and end-diastolic segment length, and mean and diastolic coronary vascular resistance (CVR) in dogs with intact ANS function. Levosimendan-induced increases in HR and PWI and decreases in SVR were attenuated by ANS blockade. Levosimendan caused equivalent dose-dependent increases in Mw in ANS-intact and ANS-blocked dogs, consistent with a positive inotropic effect independent of ANS activity. Levosimendan decreased tau (e.g., 35 +/- 1 ms during control to 29 +/- 1 ms at the high dose) and increased the magnitude of LV -dP/dtmin in dogs with intact but not blocked ANS reflexes, suggesting that relaxation was enhanced by favorable changes in systemic hemodynamics or ANS activation and direct effects of this drug on lusitropic state. Levosimendan also increased dL/dtmax to a greater degree in ANS-intact dogs, indicating that improvement of rapid ventricular filling was also partially dependent on ANS tone. No changes in Kp were observed in either experimental group. The results indicate that levosimendan decreases preload and afterload and has positive inotropic and lusitropic properties. The actions of levosimendan on diastolic function are largely mediated by the ANS.

Accelerated recovery of postischemic stunned myocardium after induced expression of myocardial heat-shock protein (HSP70)

In vitro studies suggest that interventions targeted at myocardial gene regulation of endogenous cytoprotective elements, such as heat-shock protein, may attenuate myocardial ischemic injury. We tested the hypothesis that heat shock-induced expression of myocardial heat-shock protein before ischemia accelerates functional recovery of postischemic stunned myocardium in the intact circulation. Sixteen dogs underwent partial femoral arteriovenous bypass and core temperature was raised to 42° C for 15 minutes in eight dogs (heat-shocked) and maintained at 37° C in eight dogs (nonheat-shocked). After 24 hours dogs were studied to measure myocardial segment length in the circumflex artery region with ultrasonic dimension transducers, left ventricular pressure with a micromanometer, and circumflex coronary flow with an ultrasonic probe. Regional contractile function was quantified by the area beneath the linear preload recruitable stroke work relationship at baseline and at intervals during reperfusion after a 15-minute circumflex artery occlusion followed by 3 hours of reperfusion. Baseline and peak reperfusion hyperemic circumflex flows were 37 ± 9 ml/min and 154 ± 33 ml/min, respectively, in heat-shocked dogs ( p < 0.001) and 46 ± 24 ml/min and 171 ± 57 ml/min, respectively, in nonheat-shocked dogs ( p < 0.001), with no differences between groups ( p = not significant) at any time during reperfusion. Heart rate and left ventricular peak pressure, end-diastolic pressure, and first derivative of left ventricular pressure were similar (all p = not significant) in heat-shocked and nonheat-shocked dogs during ischemia and reperfusion. Before ischemia, preload recruitable stroke work relationship did not differ ( p = not significant) in heat-shocked and nonheat-shocked dogs. Ischemia reduced preload recruitable stroke work relationship to 32% ± 8% control ( p < 0.001) in heat-shocked dogs and to 19% ± 15% control in nonheat-shocked dogs ( p < 0.001) at 15 minutes of reperfusion, indicating a similar ( p = not significant) initial degree of injury. During 3 hours of reperfusion, preload recruitable stroke work relationship returned to 80% ± 38% control in heat-shocked dogs but to only 33% ± 13% control in nonheat-shocked dogs ( p < 0.0001). Myocardial expression of heat-shock protein, quantified by optical densitometry of Western blots using an antibody specific for HSP70, was greater in heat-shocked than in nonheat-shocked dogs (108 ± 27 versus 71 ± 14 densitometry units, p < 0.005). Exact causal mechanisms remain to be defined, but these data indicate (1) hyperthermic bypass triggers induction of myocardial heat-shock protein and (2) elevated myocardial heat-shock protein is associated with accelerated recovery of stunned myocardium. Promotion of endogenous molecular cytoprotective systems represents a novel and potentially useful strategy for myocardial protection. (J T HORAC C ARDIOVASC S URG 1995;109:753-64)

Cardiodynamic conditions for the linearity of preload recruitable stroke work.

Studies reported in the literature show that the stroke work (SW) versus end-diastolic volume (Ved) relationship, namely, the preload recruitable stroke work relation (PRSW), is experimentally linear in closed-chest dog hearts and its slope reflects left ventricular contractility. We considered the theoretical cardiodynamic conditions necessary for the linearity of the SW-Ved relation by utilizing ventricular end-systolic elastance, Emax (ventricular contractility), and effective arterial elastance, Ea (arterial afterload). We simulated the SW-Ved relation, using four theoretical models of the left ventricle, as follows: Ea is constant and the end-systolic pressure-volume relation (ESPVR) is linear (model 1), or nonlinear (model 2), and Ea is variable and ESPVR is linear (model 3), or nonlinear (model 4). The results show that the SW-Ved relation can be linear in both linear and nonlinear ESPVR models (models 3 and 4) only when Ea is variable. In these models, end-systolic pressure (Pes) and Ea should gradually fall, maintaining the stroke volume (SV) relatively constant with decreases in Ved until the low end of the physiological Ved range. Then, Ea should rise sharply so that Pes does not fall below the critical level. These results suggest that the autoregulation mechanisms of an intact animal operate to adapt the arterial afterload against acute changes in LV preload, maintaining cardiac output and coronary artery pressure. Such mechanisms may thus produce a linear SW-Ved relation over a wide range of conditions.

Blood cardioplegia in the senescent heart

As an increasingly aged population undergoes cardiac surgery, myocardial protective strategies must address the fundamental differences between adult and senescent myocardium. In a test of the hypothesis that senescent myocardium is less tolerant of cardioplegic arrest, adult (0.5 to 1.0 years) and senescent (6 to 9 years) sheep underwent 55 minutes of hypothermic blood cardioplegic arrest. A 5-minute dose of terminal warm blood cardioplegic solution was administered followed by 30 minutes of vented reperfusion. Left ventricular volume was monitored by means of sonomicrometric crystals in three orthogonal planes. Myocardial function was assessed with the preload recruitable stroke work relationship. Diastolic function was assessed with two techniques: the “stiffness” coefficient ( β ), derived from the exponential end-diastolic pressure-volume relationship, and the time constant of isovolumic left ventricular pressure decay (tau). Data were acquired before arrest and after the reperfusion period. Contractility in the adult hearts was well preserved (preload recruitable stroke work: 63.7 ± 6.1 versus 56.8 ± 4.1 mJ/beat per milliliter per 100 gm, prearrest versus postarrest, p = not significant). In contrast, senescent heart contractility was poorly preserved (56.8 ± 4.1 versus 35.4 ± 4.2 mJ/beat per milliliter per 100 gm, p < 0.025). Early diastolic relaxation (tau) was prolonged in the adult hearts (42.5 ± 3.3 versus 48.8 ± 3.5 msec prearrest versus postarrest, p < 0.05), whereas the senescent hearts were essentially unchanged (49.3 ± 3.1 versus 52.3 ± 4.5 msec, p = 0.35). Myocardial stiffness ( β ) was unchanged in both groups. When compared with adult hearts, contractility in senescent hearts is poorly preserved after cold blood cardioplegic arrest. Active diastolic relaxation, however, is more prolonged in adult hearts. Passive diastolic properties are unchanged in both groups. Because there are specific age-related differences in tolerance to cardioplegic arrest, extrapolation of myocardial protective strategies from studies in adult hearts to elderly patients may not be appropriate. (J T HORAC C ARDIOVASC S URG 1995; 109: 269-74)

Left Stellate Ganglion Block Impairs Left Ventricular Function

Stellate ganglion block (SGB) is an established procedure for the diagnosis and treatment of chronic pain. SGB results in an acute sympathetic denervation of a part of the left ventricular (LV) wall innervated by the blocked ganglion, which may impair regional contractility. The resulting imbalance of myocardial contractility in different LV regions may affect LV function adversely by increasing LV asynchrony. Seven anesthetized open chest dogs were instrumented for measurement of aortic and LV pressure (tip manometers), cardiac output (CO, thermodilution), and regional LV wall thickness (WT, sonomicrometry) in the anteroapical (predominantly innervated by the right stellate ganglion) and posterobasal wall (left stellate ganglion). The contractility of both regions was assessed using the relationship between preload recruitable stroke work and end-diastolic WT relationship (MW). The timing of regional myocardial wall motion was evaluated by means of the phase of the first harmonic of the Fourier transform of the WT signals, LV asynchrony by the phase difference (PD) between both regions, and LV diastolic function by the time constant of isovolumic relaxation (tau). Measurements were performed before and after left SGB (LSGB). Mean arterial pressure was 105 +/- 25 (mean +/- SD) before and 97 +/- 10 mm Hg after LSGB (not significant). CO remained unchanged (3.09 +/- 1.03 vs 2.93 +/- 1.07 L/min). LSGB significantly reduced contractility in the posterobasal myocardium (MW -162 +/- 26 vs -80 +/- 7 mm Hg; P < 0.01), accompanied by a delay of regional wall motion within the cardiac cycle (phase 202 +/- 18 vs 223 +/- 17 degrees; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerobic blood cardioplegia for revascularization of acute infarct: Effects of delivery temperature

The effects of different cardioplegia temperatures on myocardial protection with continuous aerobic blood cardioplegia were studied in a canine model of acute regional injury after left anterior descending coronary artery occlusion and subsequent revascularization. Twenty-five animals underwent 90 minutes of occlusion followed by revascularization during 60 minutes of electromechanical arrest with continuous retrograde blood cardioplegia delivered at one of three temperatures: 18 °C (n = 8), 28 °C (n = 8), and 37 °C (n = 9). Left ventricular protection was assessed in a right heart bypass model in terms of the left ventricular pressure -volume relationships, myocardial oxygen consumption regional myocardial blood flow, adenosine triphosphate concentration, and water content. The preload recruitable stroke work relationship at 90 minutes after reperfusion was better in the 18 °C and 28 °C groups than that in the 37 °C group (18 °C, 85 ± 14 erg × 10 3/mL; 28 °C, 77 ± 17 erg × 10 3/mL; 37 °C, 58 ± 13 erg × 10 3/mL; p < 0.05). The maximum elastance and stress-strain relationships showed there were no significant differences between the groups at 90 minutes. The myocardial oxygen consumption was greatest in the 37 °C group during the first hour after reperfusion (18 °C, 5.4 ± 1.4 mL O 2 · min −1 100 g −1; 28 °C 4.7 ± 1.1 mL 0 2 · min −1 · 100 g −1; 37 °C, 6.3 ± 1.6 mL O 2 · min −1 100 g −1; p < 0.05). The regional myocardial blood flow, adenosine triphosphate concentration, and myocardial water content were similar in the three groups. After 18 °C cardioplegic arrest, there was a trend toward a need for an increased number of countershocks to reestablish organized cardiac activity (18 °C, 1.8 ± 1.2; 28 °C, 0.6 ± 0.5; 37 °C, 0.8 ± 1.2; p = 0.07). Continuous hypothermic aerobic retrograde blood cardioplegia brings about an improvement in ventricular functional protection compared with normothermic delivery and promotes efficient postarrest oxygen utilization.

The effects of left heart assist on right ventricular muscle mechanics and ventricular coupling in the injured heart

So that we could better characterize the effects of left heart assist on right ventricular myocardial muscle mechanics and ventricular mechanical coupling in the injured heart, nine dogs underwent 30 minutes of global cardiac ischemia supported by cardiopulmonary bypass followed by randomly varied levels of left heart assist at 0, 1.0, and 2.0 L/min (0, 37 +/- 4, and 74 +/- 7 ml/kg per minute). A centrifugal pump with left ventricle-to-aorta bypass was used with the intent to cause left ventricular volume unloading but without complete left ventricular pressure unloading. Right ventricular regional free wall and septal-free wall dimensions were measured by a sonomicrometer and right ventricular pressure by a micromanometer. Pressure and dimension data were acquired over a range of preloads produced by transient vena caval occlusion and at steady state at an initial control point and after ischemia at each level of left heart assist. Right ventricular regional early diastolic function was assessed by percent segmental relaxation during the first third of diastole, end-diastolic compliance by the end-diastolic pressure-dimension relationship, systolic contractile performance by the slope (Mw) and dimension axis intercept (Lw) of the linear preload recruitable stroke work relationship, and right ventricular isovolumic relaxation by the pressure decay time constant. Ischemia reduced Mw of both the free wall (38.3 +/- 16.1 to 16.4 +/- 4.2 erg.cm-3 x 10(3), p < 0.01) and septal free wall (30.2 +/- 12.7 to 13.4 +/- 4.9 erg.cm-3 x 10(3), p < 0.01) and shifted Lw rightward (1.3 +/- 0.3 to 1.4 +/- 0.3 mm, p < 0.01, and 2.8 +/- 0.8 to 3.0 +/- 0.9 mm, p < 0.01), which confirmed myocardial ischemic injury. There were no effects of left heart assist on free wall or septal-free wall systolic contractile performance assessed by Mw and Lw or on early diastolic relaxation assessed by percent segmental relaxation during the first third of diastole in either right ventricular region (all p = not significant). There were also no observed characteristic alterations of free wall or septal-free wall end-diastolic pressure-dimension relationships with left heart assist. The pressure decay time constant decreased with increasing levels of left heart assist (51 +/- 14, 49 +/- 16, and 43 +/- 11 msec, p < 0.05), which indicated an improvement in right ventricular isovolumic relaxation attributable to left heart assist. These data demonstrate that mechanical ventricular interactive effects during left heart assist are beneficial, but limited to isovolumic relaxation in the injured heart.(ABSTRACT TRUNCATED AT 400 WORDS)

In vivo measurements of skeletal muscle in a linear configuration powering a hydraulically actuated VAD.

Linear contracting skeletal muscle can provide more power and physiologic efficiency for cardiac assistance than muscle wrapping configurations. In this study, the insertion of the porcine latissimus dorsi muscle was removed from the humerus and reattached to a muscle powered ventricular assist device (MVAD), consisting of a mechanical to hydraulic piston energy convertor coupled to a Thoratec VAD. Effects of muscle preload stretch and thoracodorsal nerve stimulation parameters on in vivo unconditioned muscle work and MVAD stroke volume were studied. Stroke work increased linearly with muscle preload, and the slope of this relationship (Mprsw) provided an index of muscle "contractility," similar to the preload-recruitable stroke work relationship for the heart. With 5 V, 220 microseconds stimulation pulses over a 200 msec contraction period at 60 bpm, the Mprsw increased with stimulation frequencies from 0.055 J/cm at 30 Hz to 0.149 J/cm at 60 Hz, and to 0.212 J/cm at 90 Hz. Stroke work up to 1 J was achieved during muscle shortening of 2.5 cm with forces up to 6 kgf and energy convertor pressure of 112 psi (approximately 760 kPa). This produced an ejected MVAD stroke volume of 40 ml into a systolic pressure of 92 mmHg on a mock loop, at a filling pressure of 10 mmHg. The MVAD is designed as an alternative to cardiac transplantation, to provide completely implantable circulatory support free from batteries and other power conditioning hardware required with electromechanical systems.

Ischemia-dependent efficacy of phosphodiesterase inhibition

To evaluate the inotropic efficacy of phosphodiesterase inhibition in hearts with and without ischemic injury, 27 sheep were evaluated sonomicrometrically during incremental volume loading on right heart bypass. Contractility was assessed with the preload recruitable stroke work relationship. Active relaxation rate was estimated using the time constant of isovolumic pressure decay (tau). For nonischemic assessment, groups 1 and 2 (n = 6 each) underwent 45 minutes of vented perfusion after which milrinone was administered to group 1; group 2 served as nonischemic controls. There was no detectable increase in preload recruitable stroke work or decrement in tau after milrinone administration. Groups 3 and 4 underwent 15 minutes of 37 °C ischemia (aortic cross-clamping) followed by 30 minutes of vented reperfusion. Milrinone was then administered to group 3 (n = 7); group 4 (n = 8) served as ischemically injured controls. Inotropic and lusitropic effects were present (group 3 preload recruitable stroke work: 35.4 ± 5.8 mJ · beat −1 · 100 g −1 · mL −1 before milrinone to 49.5 ± 4.4 mJ · beat −1 · 100 g −1 · mL −1 after milrinone [ p < 0.05]; group 3 tau: 51.8 ± 5.5 ms before milrinone to 32.2 ± 2.5 ms after milrinone [ p < 0.02]). Although milrinone restored contractility and increased the rate of active relaxation in the postischemic hearts, there was no detectable inotropic effect in nonischemic hearts. In this model, milrinone augments contractility and relaxation in postischemic myocardium but offers little inotropic benefit in non-ischemically injured hearts.

Revascularization for acute regional infarct: Superior protection with warm blood cardioplegia

Continuous retrograde warm blood cardioplegia was compared with two widely used hypothermic myocardial protection techniques in a canine model of acute regional myocardial ischemia with subsequent revascularization. Animals (n = 30) underwent 45 minutes of left anterior descending coronary artery occlusion then cardioplegic arrest (60 minutes), followed by separation from caidiopulmonary bypass and data collection. The cold oxygenated crystalloid cardioplegia group (CC; n = 8) and the cold blood cardioplegia group (CB; n = 10) had cardiopulmonary bypass at 28 °C, antegrade arrest, and intermittent retrograde delivery. The warm blood cardioplegia group (WB; n = 12) had normothermic cardiopulmonary bypass, antegrade arrest, and continuous retrograde delivery. Overall ventricular function (preload recruitable stroke work relationship; ergs × 10 3/mL) was significantly ( p < 0.001) better for WB (WB, 80 ± 11; CB, 67 ± 13; CC, 57 ± 12). Systolic function (maximum elastance relationship; mm Hg/mL) was also significantly ( p < 0. 001) better for WB (WB, 11.6 ± 3.6; CB, 8.6 ± 2.7; CC, 6.2 ± 1.3). Diastolic function (stress-strain relationship; dynes × 10 3/cm 2) revealed significantly ( p < 0.001) decreased compliance for CC (WB, 20 ± 6; CB, 19 ± 7; CC, 27 ± 11). Left anterior descending coronary artery regional adenosine triphosphate/adenosine diphosphate ratios were significantly ( p = 0.02) worse for CC (WB, 10.2 ± 2.3; CB, 9.4 ± 2.6; CC, 5.6 ± 1.5). Myocardial edema significantly ( p =0.03) increased over time only in the CC animals (WB, 0.4% ± 2.3%; CB, −0. 3% ± 3.6%; CC, 5.5% ± 2.3%). In this model of acute regional myocardial ischemia and revascularization, continuous retrograde warm aerobic blood cardioplegia provided superior myocardial protection compared with cold oxygenated crystalloid cardioplegia with intermediate results for cold blood cardioplegia.

Quantitation of volatile anesthetic-induced depression of myocardial contractility using a single beat index derived from maximal ventricular power

Development of an index of myocardial contractility that is load independent and that can be derived from a single cardiac cycle in vivo has important intraoperative ramifications. Recently, a new index of contractile state based on maximal ventricular power (the rate of ventricular work) has been proposed that appears to fulfill these requirements. This investigation compared the efficacy and sensitivity of this novel method of measurement of myocardial contractility to the slope (M w) of the preload recruitable stroke work (PRSW) relationship, an established measure of left ventricular function derived from left ventricular pressure-segment length loops in dogs before and during volatile anesthetic-induced cardiac depression. Sixteen experiments in two groups were performed using eight dogs chronically instrumented for measurement of aortic and left ventricular pressure, left ventricular dP/dt, subendocardial segment length, intrathoracic pressure, and thoracic aortic blood flow. The maximal ventricular power index (PWR max/EDL 2) was calculated as the product of peak aortic blood pressure and peak aortic blood flow divided by the square of end-diastolic segment length. M w was obtained from a series of left ventricular pressure-segment length loops generated by abrupt vena caval occlusion. Systemic hemodynamics and myocardial contractility using these two methods were re corded in the conscious state and after 30 minutes of equilibration at 1.25, 1.5, or 1.75 MAC isoflurane or halothane. PWR max/EDL 2 decreased in a dose-dependent fashion with isoflurane (6.2 ± 0.9 during the conscious control state to 1.9 ± 0.3 mmHg · L/min/mm 2 at 1.75 MAC) and halothane (6.8 ± 0.8 during the conscious control state to 1.8 ± 0.2 mmHg · L/min/mm 2 at 1.75 MAC), indicating direct negative inotropic effects. Similar declines in M w were observed with the administration of each agent. PWR max/EDL 2 was highly correlated with M w during administration of both volatile anesthetics. PWR max/EDL 2 suggested quantitative differences between the negative inotropic actions of isoflurane and halothane at 1.25 MAC, but no differences between these agents could be identified at higher concentrations, in contrast to the findings using M w. The results indicate that PWR max/EDL 2 quantitatively identifies depression of myocardial contractility produced by isoflurane and halothane and compares to a certain degree to M w, an established measure of volatile anesthetic-induced myocardial depression in chronically instrumented dogs.