Mechanical restitution curves reflect post-ischemic stunning in pigs

OBJECTIVES: The time constant of mechanical restitution (T(MRC)), proposed to reflect changes in calcium release and uptake, has been shown to increase in left ventricular (LV) failure. In this study, we tested the hypothesis that T(MRC) also can identify post-ischemic, reversible LV dysfunction (stunning). DESIGN: Stunning was induced by a series of left main coronary artery occlusions in eight anesthetized open chest pigs. Left ventricular pressure-volume relations were assessed using a pressure-volume catheter during right atrial pacing. Mechanical restitution curves (MRCs) were constructed using two different measures of contractile response: maximal first derivative of pressure (CR(dP/dtmax)) and stroke work (CR(SW)). RESULTS: Mean arterial pressure, stroke volume and dP/dtmax were decreased 30 min after stunning. Slopes of end-systolic pressure volume relation and preload recruitable stroke work, however, showed no significant changes after stunning. For MRCs based on CR(dP/dtmax), T(MRC) increased in all eight animals. Using CR(SW), T(MRC) increased in seven out of eight pigs. CONCLUSIONS: Ischemia-reperfusion induce changes in MRCs based on CR(dP/dtmax), and CR(SW). The MRC concept may have potential as a clinical left ventricular performance index.     

Desflurane, Sevoflurane, and Isoflurane Impair Canine Left Ventricular-Arterial Coupling and Mechanical Efficiency

Background: The effects of desflurane, sevoflurane, and isoflurane on left ventricular-arterial coupling and mechanical efficiency were examined and compared in acutely instrumented dogs.

Methods: Twenty-four open-chest, barbiturate-anesthetized dogs were instrumented for measurement of aortic and left ventricular (LV) pressure (micromanometer-tipped catheter), dP/dtmax, and LV volume (conductance catheter). Myocardial contractility was assessed with the end-systolic pressure-volume relation (Ees) and preload recruitable stroke work (Msw) generated from a series of LV pressure-volume diagrams. Left ventricular-arterial coupling and mechanical efficiency were determined by the ratio of Ees to effective arterial elastance (Ea; the ratio of end-systolic arterial pressure to stroke volume) and the ratio of stroke work (SW) to pressure-volume area (PVA), respectively.

Results: Desflurane, sevoflurane, and isoflurane reduced heart rate, mean arterial pressure, and left ventricular systolic pressure. All three anesthetics caused similar decreases in myocardial contractility and left ventricular afterload, as indicated by reductions in Ees, Msw, and dP/dtmax and Ea, respectively. Despite causing simultaneous declines in Ees and Ea, desflurane decreased Ees /Ea (1.02+/-0.16 during control to 0.62+/-0.14 at 1.2 minimum alveolar concentration) and SW/PVA (0.51+/-0.04 during control to 0.43+/-0.05 at 1.2 minimum alveolar concentration). Similar results were observed with sevoflurane and isoflurane.     

Left ventricular reshaping: effects on the pressure-volume relationship

OBJECTIVE: We tested whether the CardioClasp device (CardioClasp, Inc, Cincinnati, Ohio), a non-blood contact device, would improve left ventricular contractility by acutely reshaping the left ventricle and reducing left ventricular wall stress. METHODS: In dogs (n = 6) 4 weeks of ventricular pacing (210-240 ppm) induced severe heart failure. Left ventricular function was evaluated before and after placement of the CardioClasp device, which uses 2 indenting bars to reshape the left ventricle. Hemodynamics, echocardiography, and Sonometrics crystals dimension (Sonometrics Corporation, London, Ontario, Canada) were measured at steady state and during inferior vena caval occlusion. RESULTS: The CardioClasp device decreased the left ventricular end-diastolic anterior-posterior dimension by 22.8% +/- 1.9%, decreased left ventricular wall stress from 97.3 +/- 22.8 to 67.2 +/- 7.7 g/cm(2) (P =.003), and increased the fractional area of contraction from 21.3% +/- 10.5% to 31.3% +/- 18.1% (P =.002). The clasp did not alter left ventricular end-diastolic pressure, left ventricular pressure, left ventricular dP/dt, or cardiac output. With the CardioClasp device, the slope of the end-systolic pressure-volume relationship was increased from 1.87 +/- 0.47 to 3.22 +/- 1.55 mm Hg/mL (P =.02), the slope of preload recruitable stroke work versus end-diastolic volume was increased from 28.4 +/- 11.0 to 44.1 +/- 23.5 mm Hg (P =.02), and the slope of maximum dP/dt versus end-diastolic volume was increased from 10.6 +/- 4.6 to 18.6 +/- 7.4 mm Hg x s(-1) x mL(-1) (P =.01). The CardioClasp device increased the slope of the end-systolic pressure-volume relationship by 68.0% +/- 21.7%, the slope of preload recruitable stroke work versus end-diastolic volume by 50.7% +/- 18.1%, and the slope of maximum dP/dt versus end-diastolic volume by 85.7% +/- 28.9%. CONCLUSIONS: The CardioClasp device decreased left ventricular wall stress and increased the fractional area of contraction by reshaping the left ventricle. The CardioClasp device was able to maintain cardiac output and arterial pressure. The clasp increased global left ventricular contractility by increasing the slope of the end-systolic pressure-volume relationship, the slope of preload recruitable stroke work versus end-diastolic volume, and the slope of maximum dP/dt versus end-diastolic volume. In patients with heart failure, the CardioClasp device might be effective for clinical application.     

Positive Inotropic and Lusitropic Effects of Triiodothyronine in Conscious Dogs with Pacing-induced Cardiomyopathy

Background: The effects of triiodothyronine (T3) on systemic hemodynamics, myocardial contractility (preload recruitable stroke work slope; Mw), and left ventricular (LV) isovolumic relaxation (time constant; tau) were examined before and after the development of pacing-induced cardiomyopathy in conscious dogs.

Methods: Dogs (n = 8) were chronically instrumented for measurement of aortic and LV pressure, dP/dtmax, subendocardial segment length, and cardiac output. Dogs received escalating doses (0.2, 2.0, and 20.0 mg/kg, intravenous) of T3 over 5 min at 1-h intervals, and peak hemodynamic effects were recorded 10 min after each dose and 24 h after the final dose. Dogs were then continuously paced at 220-240 beats/min for 21 + /- 2 days. Pacing was temporarily discontinued after the development of severe LV dysfunction, and administration of T3 was repeated.

Results: T3 produced immediate and sustained (24 h) increases (P < 0.05) in Mw and dP/dtmax in dogs before the initiation of pacing, consistent with a positive inotropic effect. No changes in tau occurred. Rapid ventricular pacing over 3 weeks increased baseline heart rate (sinus rhythm) and LV end-diastolic pressure, decreased mean arterial and LV systolic pressures, and caused LV systolic (decreases in Mw and dP/dtmax) and diastolic (increases in tau) dysfunction. T3 caused immediate and sustained increases in Mw (63 +/- 7 during control to 82 +/- 7 mmHg after the 2 mg/kg dose) and decreases in tau (65 +/- 8 during control to 57 +/- 6 ms after the 20 mg/kg dose), indicating that this hormone enhanced myocardial contractility and shortened LV relaxation, respectively, in the presence of chronic LV dysfunction. In contrast to the findings in dogs with normal LV function, T3 did not affect heart rate and calculated indices of myocardial oxygen consumption and reduced LV end-diastolic pressure (27 +/- 3 during control to 20 +/- 2 mmHg after the 2 mg/kg dose) in cardiomyopathic dogs.     

Evaluation of left ventricular function in anesthetized patients using femoral artery dP/dt(max)

OBJECTIVE: The purpose of this study was to compare dP/dt(max) estimated from a femoral artery pressure tracing to left ventricular (LV) dP/dt(max) during various alterations in myocardial loading and contractile function. PARTICIPANTS: Seventy patients scheduled for elective coronary artery bypass surgery. METHODS: All patients were instrumented with a high-fidelity LV catheter, a pulmonary artery catheter, and a femoral arterial catheter. In 40 patients, hemodynamic measurements were performed before and after passive leg raising and before and after calcium administration (5 mg/kg); and in 30 other patients, hemodynamic measurements were performed before and after dobutamine infusion (5 microg/kg/min over 10 minutes). RESULTS: LV and femoral dP/dt(max) were significantly correlated (r = 0.82, p < 0.001), but femoral dP/dt(max) systematically underestimated LV dP/dt(max) (bias = -361 +/- 96 mmHg/s). Passive leg raising induced significant increases in central venous pressure and LV end-diastolic pressure, but femoral dP/dt(max), stroke volume, and LV dP/dt(max) remained unaltered. Calcium administration induced significant and marked increases in LV dP/dt(max) (23% +/- 9%) and femoral dP/dt(max) (37% +/- 14%) associated with a significant increase in stroke volume (9% +/- 2%). Dobutamine infusion also induced significant and marked increases in LV dP/dt(max) (25% +/- 8%) and femoral dP/dt(max) (35% +/- 12%) associated with a significant increase in stroke volume (14% +/- 3%). Overall, a very close linear relationship (r = 0.93) and a good agreement (bias = -5 +/- 17 mmHg/s) were found between changes in LV dP/dt(max) and changes in femoral dP/dt(max). A very close relationship was also observed between changes in LV dP/dt(max) and changes in femoral dP/dt(max) during each intervention (leg raising, calcium administration, and dobutamine infusion). CONCLUSION: Femoral dP/dt(max) underestimated LV dP/dt(max), but changes in femoral dP/dt(max) accurately reflected changes in LV dP/dt(max) during various interventions.     

Induction of angiogenesis and inhibition of apoptosis by hepatocyte growth factor effectively treats postischemic heart failure

BACKGROUND: Heart failure following myocardial infarction (MI) is a significant cause of morbidity and mortality and remains a difficult therapeutic challenge. Hepatocyte growth factor (HGF) is a potent angiogenic and anti-apoptotic protein whose receptor is upregulated following MI. This study was designed to investigate the ability of HGF to prevent heart failure in a rat model of experimental MI. METHODS: The rats underwent direct intramyocardial injection with replication-deficient adenovirus encoding HGF (n = 7) or null virus as control (n = 7) 3 weeks following ligation of the left anterior descending coronary artery. Analysis of the following was performed 3 weeks after injection: cardiac function by pressure-volume conductance catheter measurements; LV wall thickness; angiogenesis by Von Willebrand's factor staining; and apoptosis by the TUNEL assay. The expression levels of HGF and the anti-apoptotic factor Bcl-2 were analyzed by Western blot. RESULTS: Adeno-HGF-treated animals had greater preservation of maximum LV pressure (HGF 77 +/- 3 vs. control 64 +/- 5 mmHg, p < 0.05), maximum dP/dt (3024 +/- 266 vs. 1907 +/- 360 mmHg/sec, p < 0.05), maximum dV/dt (133 +/- 20 vs. 84 +/- 6 muL/sec, p < 0.05), and LV border zone wall thickness (1.98 +/- 0.06 vs. 1.53 +/- 0.07 mm, p < 0.005). Angiogenesis was enhanced (151 +/- 10.0 vs. 90 +/- 4.5 endothelial cells/hpf, p < 0.005) and apoptosis was reduced (3.9 +/- 0.3 vs. 8.2 +/- 0.5%, p < 0.005). Increased expression of HGF and Bcl-2 protein was observed in the Adeno-HGF-treated group. CONCLUSIONS: Overexpression of HGF 3 weeks post-MI resulted in enhanced angiogenesis, reduced apoptosis, greater preservation of ventricular geometry, and preservation of cardiac contractile function. This technique may be useful to treat or prevent postinfarction heart failure.     

Preserved myocardial energetics in acute ischemic left ventricular failure -- studies in an experimental pig model.

OBJECTIVE: We hypothesised that acute ischemic left ventricular failure is characterised by depressed systolic and diastolic function combined with inefficiency in oxygen to mechanical work energy transfer. METHODS: Eight anaesthetised pigs (32+/-3 kg) were employed in an in vivo open chest model. Intraventricular combined pressure and conductance catheters were used to generate continuous left ventricular pressure-volume relations. Myocardial oxygen consumption (MVO(2)) was determined from coronary flow and coronary arteriovenous oxygen difference. After baseline measurements, ischemia was induced by repeated left coronary injections of 50 microm polystyrene microspheres until stroke volume was reduced by 30%. Haemodynamic and biochemical measurements were repeated 30, 90 and 150 min after microembolisation. RESULTS: Coronary embolisation induced a significant reduction in stroke work (2749+/-504-1473+/-449 mmHg ml, P<0.05) at 30 min compared to baseline. Post-embolic contractility was reduced measured by the slope of the preload recruitable stroke work index (66.2+/-12.8-50.0+/-5.8 mmHg, P<0.05) and the slope of the curvilinearly fitted end-systolic pressure-volume relation in V(0) (7.1+/-2.2-4.9+/-2.2 mmHg/ml, P<0.05). The dP/dt(min) decreased (2076+/-291-1468+/-266 mmHg/s, P<0.05), but there was no significant change in diastolic stiffness or Tau. Following the 30 min measurements, there were only small changes in most indices. We found no change in myocardial oxygen consumption for basal metabolic processes or excitation-contraction coupling (unloaded MVO(2)), and there were no changes in conversion of oxygen to total mechanical work (MVO(2)-PVA slope). However, decreased mechanical efficiency (SW/MVO(2)) paralleled an increased ratio of arterial elastance to ventricular elastance. CONCLUSIONS: Coronary microembolisation in pigs induce a stable ischemic left ventricular failure characterised by reduced contractility and minimally impaired diastolic function. In this acute ischemic left ventricular failure, the main contributor to all over cardiovascular inefficiency is increased ratio of arterial- to ventricular elastance, a setting that impairs mechanical efficiency. However, efficiency of oxygen to total mechanical work transfer in the myocardium is unaltered. The mechanism behind this finding is elusive and warrants further investigation.     

Administration of a tumor necrosis factor inhibitor at the time of myocardial infarction attenuates subsequent ventricular remodeling.

BACKGROUND: Tumor necrosis factor (TNF) causes myocardial extracellular matrix remodeling and fibrosis in myocardial infarction and chronic heart failure models. Pre-clinical and clinical trials of TNF inhibition in chronic heart failure have shown conflicting results. This study examined the effects of the administration of a TNF inhibitor immediately after myocardial infarction on the development of heart failure. METHODS: Lewis rats underwent coronary artery ligation and then received either intravenous etanercept (n = 14), a soluble dimerized TNF receptor that inhibits TNF, or saline as control (n = 13). Leukocyte infiltration into the infarct borderzone was evaluated 4 days post-ligation in 7 animals (etanercept = 4, control = 3). After 6 weeks, the following parameters were evaluated in the remaining animals: cardiac function with a pressure-volume conductance catheter, left ventricular (LV) geometry, and borderzone collagenase activity. RESULTS: Etanercept rats had significantly less borderzone leukocyte infiltration 4 days post-infarction than controls (10.7 +/- 0.5 vs 18.0, +/-2.0 cells/high power field; p < 0.05). At 6 weeks, TNF inhibition resulted in significantly reduced borderzone collagenase activity (110 +/- 30 vs 470 +/- 140 activity units; p < 0.05) and increased LV wall thickness (2.1 +/- 0.1 vs 1.8 +/- 0.1 mm, p < 0.05). Etanercept rats had better systolic function as measured by maximum LV pressure (84 +/- 3 mm Hg vs 68 +/- 5 mm Hg, p < 0.05) and the maximum change in left ventricular pressure over time (maximum dP/dt) (3,110 +/- 230 vs 2,260 +/- 190 mm Hg/sec, p < 0.05), and better diastolic function as measured by minimum dP/dt (-3,060 +/- 240 vs -1,860 +/- 230 mm Hg/sec; p < 0.05) and the relaxation time constant (14.6 +/- 0.6 vs 17.9 +/- 1.2 msec; p < 0.05). CONCLUSIONS: TNF inhibition after infarction reduced leukocyte infiltration and extracellular matrix turnover and preserved cardiac function.     

Evaluation of echocardiography indices of systolic function: a comparative study using pressure-volume loops in patients undergoing coronary artery bypass surgery

Transoesophageal echocardiography measures of systolic left ventricular function obtained during coronary artery bypass surgery are heavily influenced by alterations in loading conditions. No validation of these measurements against load independent indices obtained by pressure-volume loop analysis has been undertaken in humans. Ten patients undergoing coronary artery bypass surgery underwent simultaneous transoesophageal echocardiography and pressure-volume loop analysis of cardiac function at different loading conditions (reduced preload, increased afterload and atrial pacing). Fractional area change, afterload corrected fractional area change, and lateral basal wall peak systolic myocardial velocity, along with dP/dt, were compared to the preload recruitable stroke work relationship. There were no significant differences between the echocardiography measures when compared to the preload recruitable stroke work relationship; however, dP/dt varied significantly across loading conditions (p<0.001). Transoesophageal echocardiography adequately assesses systolic function across loading conditions commonly seen during coronary artery bypass surgery.     

Functional recovery of the native heart after cardiomyoplasty in sheep with heart failure: passive and dynamic effects of volume loading

BACKGROUND: Dynamic cardiomyoplasty (d-CMP) encourages reverse remodeling and improved contractility and stroke work (SW) efficiency of the failing native heart. This contrasts with passive cardiomyoplasty (p-CMP), which provides "passive girdling." To further evaluate pump recovery we assessed native left ventricular performance (without assist) 6 months after dynamic and passive CMP in sheep with heart failure with acute volume loading. METHODS: Heart failure (left ventricular ejection fraction 26%+/-8%) induced by coronary microembolization was followed by CMP in 11 sheep. After 8 weeks of muscle "training," paced cardiac assist was undertaken in the d-CMP group (n = 6). Five sheep with heart failure served as controls. Six months later the pressure-volume relationship was derived before and after volume loading by colloid solution. Latissimus dorsi muscle pacing was previously ceased in the d-CMP group. RESULTS: Volume loading increased left ventricular end-diastolic volume and pressure in all groups. After volume loading in d-CMP, the SW and pressure-volume area were increased, and SW efficiency remained unchanged. In p-CMP neither variable changed, whereas in control heart failure SW efficiency decreased due to a rise in pressure-volume area with stable SW. CONCLUSIONS: Based on response to volume loading, the failing native heart after 6 months of d-CMP showed functional recovery from "active girdling," whereas p-CMP prevented functional deterioration through passive girdling. The failing control heart progressively deteriorated.     

A Comparison of Left Ventricular Performance Indices Measured by Transesophageal Echocardiography with Automated Border Detection

Background: Automated border detection (ABD) allows semiautomated measurement of left ventricular (LV) areas. They can be combined with left ventricular pressure signals to generate pressure-area loops and pressure-dimension indices of contractility. This study compared conventional indices of ventricular performance (fractional area change [FAC] and circumferential fiber shortening [Vcfc]) with pressure-dimension indices of contractility. A secondary aim was to compare the effects of volatile anesthetics on the indices.

Methods: Using transesophageal echocardiography with automated border detection, FAC and Vcfc were obtained in 23 patients after cardiopulmonary bypass. Left ventricular pressures were obtained with a left ventricular catheter. Preload reduction by inferior vena caval occlusion was used to obtain end-systolic elastance (Ees), preload recruitable stroke force (PRSF), and dP/dtmax [middle dot] EDA-1 (EDA = end-diastolic area). In 11 patients, the measurements were repeated at 1 end-tidal minimum alveolar concentration of halothane or isoflurane. The results are expressed as mean +/- SD.

Results: After cardiopulmonary bypass, FAC was 31.1 +/- 7.9%, Vcfc was 0.6 +/- 0.2 circ [middle dot] s-1, Ees was 25.8 +/- 11.6 mmHg [middle dot] cm-2, PRSF was 60.8 +/- 26.6 mmHg, and dP/dtmax [middle dot] -EDA-1 was 245 +/- 123.4 mmHg [middle dot] s-1 [middle dot] cm-2. At 1 minimum alveolar concentration of a volatile anesthetic agent, FAC, Vcfc, and dP/dtmax [middle dot] EDA-1 remained unchanged. Significant decreases in Ees (19%) and PRSF (28%) were observed.     

Effect of passive cardiac containment on ventricular synchrony and cardiac function in awake dogs.

OBJECTIVE: Passive restraint of the left ventricle (LV) has been shown to have beneficial effects on acute hemodynamics and reverse remodeling in both animal and human models. The goals of this study were to test whether a left ventricular support device (LVSD) improves LV synchrony and/or affects cardiac performance. METHODS: Ten dogs were chronically instrumented to measure hemodynamics and LV volume (sonomicrometry). Congestive heart failure (CHF) was induced by repeated intracoronary microembolization via a chronically implanted coronary catheter. The LVSD was implanted after establishment of CHF in five animals, and five animals were observed as controls. All animals were then observed for 8 weeks. A mathematical model to measure LV synchrony was used to evaluate LV motion over time. RESULTS: Mean arterial pressure and LV pressures was significantly increased after LVSD therapy, and LV pressure-volume relationships were shifted leftwards, although no change was seen in ejection fraction, end-systolic elastance, or LV dP/dt versus control. There was no significant change in diastolic function in LVSD animals compared with control animals. End-diastolic volumes were reduced by 15% after 8 weeks with LVSD treatment, versus an increase of 8% in control animals (p<0.05). Synchrony was significantly improved with LVSD therapy compared with control (9% vs 76% of baseline) in 1 of 11 ventricular dimension axes (Anterior-Apex). CONCLUSIONS: LVSD therapy provided only minimal improvement in ventricular synchrony and partially improved hemodynamics. Further study into mechanisms of benefit are warranted.     

Placental growth factor provides a novel local angiogenic therapy for ischemic cardiomyopathy

BACKGROUND: Heart failure occurs predominantly due to coronary artery disease and may be amenable to novel revascularization therapies. This study evaluated the effects of placental growth factor (PlGF), a potent angiogenic agent, in a rat model of ischemic cardiomyopathy. METHODS: Wistar rats underwent high proximal ligation of the left anterior descending coronary artery and direct injection of PlGF (n = 10) or saline as a control (n = 10) into the myocardium bordering the ischemic area. After 2 weeks, the following parameters were evaluated: ventricular function with an aortic flow probe and a pressure/volume conductance catheter, left ventricular (LV) geometry by histology, and angiogenesis by immunofluorescence. RESULTS: PlGF animals had increased angiogenesis compared to controls (22.8 +/- 3.5 vs. 12.4 +/- 3.2 endothelial cells/high-powered field, p < 0.03). PlGF animals had less ventricular cavity dilation (LV diameter 8.4 +/- 0.2 vs. 9.2 +/- 0.2 mm, p < 0.03) and increased border zone wall thickness (1.85 +/- 0.1 vs. 1.38 +/- 0.2 mm, p < 0.03). PlGF animals had improved cardiac function as measured by maximum LV pressure (95.7 +/- 4 vs. 73.7 +/- 2 mmHg, p = 0.001), maximum dP/dt (4206 +/- 362 vs. 2978 +/- 236 mmHg/sec, p = 0.007), and ejection fraction (25.7 +/- 2 vs. 18.6 +/- 1%, p = 0.02). CONCLUSIONS: Intramyocardial delivery of PlGF following a large myocardial infarction enhanced border zone angiogenesis, attenuated adverse ventricular remodeling, and preserved cardiac function. This therapy may be useful as an adjunct or alternative to standard revascularization techniques in patients with ischemic heart failure.     

Perioperative assessment of left ventricular function by pressure-volume loops using the conductance catheter method

Interpretation of perioperative measurements of cardiac function during cardiac surgery is complicated by changes in loading conditions induced by anesthesia, cardiopulmonary bypass (CPB), and the surgical procedure itself. Quantification of left ventricular (LV) function by pressure-volume relations as obtained by the conductance catheter would be advantageous because load-independent indices can be determined. Accordingly, we evaluated methodological aspects of the conductance-catheter technique and documented LV function before and after CPB in eight patients undergoing coronary artery bypass grafting. LV pressure-volume loops by transesophageal echocardiography-guided transaortic application of the conductance catheter were obtained at steady-state and during preload reduction by temporary occlusion of the inferior cava. All patients remained hemodynamically stable, and no complications occurred. Complete data were acquired within 15 min before and after CPB. Cardiac output (5.2 +/- 1.3 L/min to 6.0 +/- 1.4 L/min) and LV ejection fraction (46% +/- 17% to 48% +/- 19%) did not change, but end-diastolic pressure increased significantly after CPB (8 +/- 2 mm Hg to 16 +/- 7 mm Hg; P < 0.05). Load-independent systolic indices remained constant (end-systolic elastance: 1.31 +/- 1.20 mm Hg/mL to 1.13 +/- 0.59 mm Hg/mL). Diastolic function changed significantly after CPB, as the relaxation time constant decreased from 64 +/- 6 ms to 52 +/- 5 ms (P < 0.05) and the chamber stiffness constant increased from 0.016 +/- 0.014/mL to 0.038 +/- 0.016/mL (P < 0.05). We conclude that the conductance catheter method provides detailed data on perioperative myocardial function and may be useful for evaluating the effects of new surgical and anesthetic procedures. IMPLICATIONS: Pressure-volume loops provide on-line quantification of intrinsic systolic and diastolic myocardial function in a load-independent fashion. This study shows the feasibility of perioperative pressure-volume analysis by use of the conductance-catheter method. This method provides detailed data about the immediate effects of surgery and may be used to evaluate complex cardiac procedures.     

Cardiomyoplasty reduces myocardial oxygen consumption: implications for direct mechanical compression

BACKGROUND: This study investigates the possibility of reducing myocardial oxygen consumption by dynamic cardiomyoplasty in chronic heart failure. The sheep model used is relevant for cardiac assist using direct mechanical cardiac compression. METHODS: In 7 sheep, heart failure was induced by staged intracoronary microembolization followed by dynamic cardiomyoplasty. Six months later, the effect of latissimus dorsi muscle stimulation in the 2:1 mode (on, cardiomyoplasty; off, control) was studied. Left ventricular pressure-volume loops were obtained by conductance, micromanometer, and inferior vena cava occlusion catheter. Myocardial oxygen consumption was derived from left main coronary artery blood flow and oxygen content of arterial and coronary sinus blood. RESULTS: Cardiomyoplasty had no significant effect on left ventricular hemodynamic variables such as end-systolic pressure. However, cardiomyoplasty increased stroke volume and ejection fraction significantly by 11% +/- 12% and 11% +/- 10%, respectively. Although pressure-volume area and external work did not increase with cardiomyoplasty, myocardial oxygen consumption decreased by 21% +/- 11%. Therefore, cardiomyoplasty increased myocardial efficiency (external work/myocardial oxygen consumption) by 16% +/- 13%. CONCLUSIONS: Despite limited hemodynamic improvement from dynamic cardiac compression by cardiomyoplasty in sheep with chronic heart failure, myocardial oxygen consumption was significantly reduced. These findings provide a rationale for reverse remodeling of the failing heart using direct mechanical compression.     

Effects of halothane, sevoflurane and desflurane on the force-frequency relation in the dog heart in vivo

PURPOSE: Frequency potentiation is the increase in force of contraction induced by an increased heart rate (HR). This positive staircase phenomenon has been attributed to changes in Ca2+ entry and loading of intracellular Ca2+ stores. Volatile anesthetics interfere with Ca2+ homeostasis of cardiomyocytes. We hypothesized that frequency potentiation is altered by volatile anesthetics and investigated the influence of halothane (H), sevoflurane (S) and desflurane (D) on the positive staircase phenomenon in dogs in vivo. METHODS: Dogs were chronically instrumented for measurement of left ventricular (LV) pressure and cardiac output. Heart rate was increased by atrial pacing from 120 to 220 beats x min(-1) and the LV maximal rate of pressure increase (dP/dt(max)) was determined as an index of myocardial performance. Measurements were performed in conscious dogs and during anesthesia with 1.0 minimal alveolar concentrations of each of the three inhaled anesthetics. RESULTS: Increasing HR from 120 to 220 beats x min(-1) increased dP/dt(max) from 3394 +/- 786 (mean +/- SD) to 3798 +/- 810 mmHg sec(-1) in conscious dogs. All anesthetics reduced dP/dt(max) during baseline (at 120 beats x min(-1): H, 1745 +/- 340 mmHg x sec(-1); S, 1882 +/- 418; D, 1928 +/- 454, all P < 0.05 vs awake) but did not influence the frequency potentiation of dP/dt(max) (at 220 beats x min(-1): H, 1981 +/- 587 mmHg x sec(-1); S, 2187 +/- 787; D, 2307 +/- 691). The slope of the regression line correlating dP/dt(max) and HR was not different between awake and anesthetized dogs. Increasing HR did not influence cardiac output in awake or anesthetized dogs. CONCLUSION: These results indicate that volatile anesthetics do not alter the force-frequency relation in dogs in vivo.     

Reshaping the remodelled left ventricle: a new concept.

OBJECTIVE: Based on the law of Laplace, transventricular tension members were designed to diminish wall stress by changing the left ventricle (LV) globular shape to a bilobular one, thus reducing the ventricular wall radius of curvature. This concept was tested in a model of congestive heart failure. METHODS: Seven calves were used for the study (74.3+/-4.2 kg). Treatment efficacy was assessed with sonomicrometric wall motion analysis coupled with intraventricular pressure measurement. Preload increase was applied stepwise with tension members in released and tightened position. RESULTS: Tightening of the tension members improved systolic function for CVP>10 mmHg (dP/dt: 828+/-122 vs. 895+/-112 mmHg/s, P=0.019, for baseline and 20% stress level reduction respectively; wall thickening: 11.6+/-1.5 vs. 13.3+/-1.7%, P<0.001) and diastolic function (LV end-diastolic pressure: 15.9+/-4.8 vs. 13.6+/-2.7 mmHg, P<0.001, for CVP>10 mmHg; peak rate of wall thinning: -12.2+/-2.2 vs. -14+/-2.3 cm(2)/s, P<0.001 and logistic time constant of isovolumic relaxation: 48.4 +/-10.9 vs. 39.8+/-9.6ms, P<0.001, for CVP>5 mmHg). CONCLUSIONS: This less aggressive LV reduction method significantly improves contractility and relaxation parameters in this model of congestive heart failure.     

Alterations in Canine Left Ventricular-arterial Coupling and Mechanical Efficiency Produced by Propofol

Background: Propofol reduces blood pressure by decreasing left ventricular (LV) afterload and myocardial contractility. This investigation tested the hypothesis that propofol preserves LV-arterial coupling and mechanical efficiency because of these simultaneous hemodynamic actions.

Methods: Experiments were conducted in open-chest dogs (n = 8) instrumented for measurement of aortic and LV pressure, dP/dtmax, and LV volume. Myocardial contractility was assessed with the slope (E sub es) of the LV end systolic pressure-volume relationship. Effective arterial elastance (Ea; the ratio of end systolic arterial pressure to stroke volume), stroke work (SW), and pressure-volume area (PVA) were determined from the LV pressure-volume relationships. Dogs were studied 30 min after instrumentation and after 15-min intravenous infusions of propofol at 5, 10, 20, and 40 mg [center dot] kg sup -1 [center dot] h sup -1.

Results: Propofol caused dose-dependent decreases in Ees (4.7 +/- 0.9 during control to 2.7 +/- 0.5 mmHg/ml during the high dosage) and dP/dtmax, indicating a direct negative inotropic effect. Ea increased at the 10 mg [center dot] kg sup -1 [center dot] h sup -1 dose of propofol but decreased at higher dosages. Propofol decreased the ratio of Ees to Ea (0.88 +/- 0.13 during control to 0.56 +/- 0.10 during the high dosage), consistent with impairment of LV-arterial coupling. Propofol also reduced the ratio SW to PVA (0.54 +/- 0.03 during control to 0.45 +/- 0.03 during the 20 mg [center dot] kg sup -1 [center dot] h sup -1), suggesting a decline in LV mechanical efficiency. SW and PVA recovered toward baseline values at the 40 mg [center dot] kg sup -1 [center dot] h sup -1 dose.     

Effect of phosphodiesterase III inhibitor on contractility, afterload, and vascular capacitance during right heart bypass preparation

OBJECTIVES: Phosphodiesterase III inhibitors, which have both positive inotropic and vasodilatory effects, occasionally cause hypotension due to afterload reduction and possibly due to preload reduction caused by the increase in vascular capacitance. METHODS: Six open-chest adult mongrel dogs were used to compare the effects on left ventricular contractility, afterload, and vascular capacitance of the phosphodiesterase III inhibitor, olprinone, with those of dobutamine using a right-heart-bypass model. Contractility and afterload were evaluated by the left ventricular pressure-volume relations with the use of a conductance catheter to derive the end-systolic elastance (Ees) and the effective arterial elastance (Ea). Vascular capacitance change was evaluated by reservoir volume change under a constant bypass flow (80 ml/kg per minute). RESULTS: Ees increased significantly both with dobutamine (7.6 +/- 2.8 to 14.3 +/- 4.8 mmHg/ml, p < 0.05) and with olprinone (7.6 +/- 2.9 to 11.5 +/- 4.2 mmHg/ml, p < 0.05). Ea did not change with dobutamine (14.4 +/- 3.5 to 14.5 +/- 3.6 mmHg/ml, p = 0.9), whereas it decreased with olprinone (14.0 +/- 4.1 to 11.4 +/- 3.8 mmHg/ml, p = 0.093). Reservoir volume increased after the infusion of dobutamine (-94.0 +/- 39.8 ml), and decreased after the infusion of olprinone (-114.0 +/- 62.3 ml). The difference was statistically significant (p = 0.007). The reservoir volume change indicated that vascular capacitance decreased with dobutamine, and increased with olprinone. CONCLUSIONS: Pre- and afterload reduction of olprinone combined with the positive inotropic effect are useful in treating congestive heart failure and managing low cardiac output syndrome after cardiac surgery.     

Systolic and diastolic pressure-volume relationships during cardiac surgery

Seven patients undergoing elective coronary artery bypass surgery were studied to assess left ventricular (LV) performance by pressure-volume loops. LV pressure was measured by micromanometry and instantaneous LV volume by a conductance catheter. Continuous pressure-volume relationships were determined during preload reduction before and after cardiopulmonary bypass (CPB). End-systolic elastance (Ees), as the slope of the end-systolic pressure-volume relationship (ESPVR), and diastolic elastance (Ed) were calculated from these interventions. Changes in position of the Ees were assessed at V75, the value of LV end-systolic volume at 75 mm Hg of LV pressure. From pre-CPB to post-CPB, Ees increased in three patients with a decrease of V75 in two patients, and Ees decreased in four patients with a concomitant increase in V75. Ed increased significantly (P less than 0.01) following CPB, demonstrating a decrease of ventricular distensibility. It is concluded that continuous measurement of LV pressure-volume relationships using the conductance catheter is feasible and may be a useful tool to estimate LV performance during cardiac surgery.