Direct Myocardial Depressant Research Articles

Septic Cardiomyopathy.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis-induced myocardial dysfunction represents reversible myocardial dysfunction which ultimately results in left ventricular dilatation or both, with consequent loss of contractility. Studies on septic cardiomyopathy report a wide range of prevalence ranging from 10% to 70%. Myocardial damage occurs as a result of weakened myocardial circulation, direct myocardial depression, and mitochondrial dysfunction. Mitochondrial dysfunction is the leading problem in the development of septic cardiomyopathy and includes oxidative phosphorylation, production of reactive oxygen radicals, reprogramming of energy metabolism, and mitophagy. Echocardiography provides several possibilities for the diagnosis of septic cardiomyopathy. Systolic and diastolic dysfunction of left ventricular is present in 50-60% of patients with sepsis. Right ventricular dysfunction is present in 50-55% of cases, while isolated right ventricular dysfunction is present in 47% of cases. Left ventricle (LV) diastolic dysfunction is very common in septic shock, and it represents an early biomarker, it has prognostic significance. Right ventricular dysfunction associated with sepsis patients with worse early prognosis. Global longitudinal stress and magnetic resonance imaging (MRI) of the heart are sufficiently sensitive methods, but at the same time MRI of the heart is difficult to access in intensive care units, especially when dealing with critically ill patients. Previous research has identified two biomarkers as a result of the integrated mitochondrial response to stress, and these are fibroblast growth factor-21 (FGF-21) and growth differentiation factor-15 (GDF-15). Both of the mentioned biomarkers can be easily quantified in serum or plasma, but they are difficult to be specific in patients with multiple comorbidities. Mitochondrial dysfunction is also associated with reduced levels of miRNA (microRNA), some research showed significance of miRNA in sepsis-induced myocardial dysfunction, but further research is needed to determine the clinical significance of these molecules in septic cardiomyopathy. Therapeutic options in the treatment of septic cardiomyopathy are not specific, and include the optimization of hemodynamic parameters and the use of antibiotic thera-pies with targeted action. Future research aims to find mechanisms of targeted action on the initial mechanisms of the development of septic cardiomyopathy.

The Effects of Propofol on Left Ventricular Global Longitudinal Strain.

To determine if hemodynamic changes secondary to propofol administration are a result of direct myocardial depression as measured by global longitudinal strain (GLS). The authors hypothesized that propofol would cause a significant worsening in GLS, indicating direct myocardial depression. Prospective, observational. Endoscopy suite at a single academic medical center. Patients undergoing outpatient, elective endoscopic procedures at an outpatient clinic of a single tertiary care academic medical center. None. Limited transthoracic echocardiograms were performed before and after patients received propofol for endoscopic procedures. Post-processing measurements included GLS, 2D (dimensional) ejection fraction (2D EF), and 3D EF. Using paired sample Student's t test, no statistically significant change in GLS, 2D EF, or 3D EF was found despite statistically significant hypotension. In fact, there was a trend toward more negative GLS (improved myocardial function) in patients after receiving propofol. We found propofol did not cause a reduction in systolic function as measured by GLS, a sensitive measure of myocardial contractility. Therefore, decreases in blood pressure after a propofol bolus in spontaneously breathing patients are likely due to decreased vascular tone and not impaired left ventricular systolic function. These results should be considered in the management of propofol-induced hypotension for spontaneously breathing patients.

Sepsis-induced cardiac dysfunction: a review of pathophysiology.

It is well known that cardiac dysfunction in sepsis is associated with significantly increased mortality. The pathophysiology of sepsis-induced cardiac dysfunction can be summarized as involving impaired myocardial circulation, direct myocardial depression, and mitochondrial dysfunction. Impaired blood flow to the myocardium is associated with microvascular dysfunction, impaired endothelium, and ventriculo-arterial uncoupling. The mechanisms behind direct myocardial depression consist of downregulation of β-adrenoceptors and several myocardial suppressants (such as cytokine and nitric oxide). Recent research has highlighted that mitochondrial dysfunction, which results in energy depletion, is a major factor in sepsis-induced cardiac dysfunction. Therefore, the authors summarize the pathophysiological process of cardiac dysfunction in sepsis based on the results of recent studies.

Assessment of dexmedetomidine effects on left ventricular function using pressure-volume loops in rats.

The role of dexmedetomidine on left ventricular function is ambiguous. We analyzed pressure-volume loops to investigate whether dexmedetomidine has a myocardial depressive effect. Thirty-two Sprague-Dawley rats were anesthetized and a pressure-volume loop catheter was advanced into the left ventricle. Rats were divided into four groups (n=8 each). The control group received a 10-min infusion of 0.1ml of normal saline, and the other three groups received 1.0 (Dex1.0 group) , 2.5 (Dex2.5 group), and 5.0μg/kg (Dex5.0 group) dexmedetomidine in a similar fashion to the control group. Steady-state hemodynamic parameters were recorded. The inferior vena cava was occluded intermittently to assess preload-independent indices. Compared with the control group, changes in the Dex1.0 group were insignificant. In the Dex2.5 group, only the systolic blood pressure was higher (vs control, P=0.03), and other parameters were insignificant. The Dex5.0 group exhibited a lower heart rate, higher systolic blood pressure, higher arterial elastance (vs control, all P<0.001), and unaltered cardiac output. The Dex5.0 group showed steeper slopes of end-systolic pressure increment and end-systolic pressure-volume relationship than the control, Dex1.0, and Dex2.5 groups (all P<0.001). Slopes of end-diastolic pressure decrement and end-diastolic pressure-volume relationship did not differ among groups. Dexmedetomidine had no direct myocardial depressant effect in the rat heart in doses that are similar to those encountered under clinical conditions. Dexmedetomidine did not significantly alter the ability of the heart to cope with bradycardia and greatly increased afterload. Their potentially negative impact on cardiac output was effectively attenuated by improved myocardial contractility and preserved diastolic function in healthy subjects.

Pentobarbital-Induced Myocardial Stunning in Status Epilepticus Requiring Extracorporeal Membrane Oxygenation: A Case Report and Literature Review.

Introduction. Mild hypotension is a well-recognized complication of intravenous pentobarbital; however fulminant cardiopulmonary failure has not been previously reported. Case Report. A 28-year-old woman developed pentobarbital-induced cardiopulmonary failure that was successfully treated with maximal medical management including arteriovenous extracorporeal membrane oxygenation. She made an excellent cardiopulmonary and neurological recovery. Discussion and Conclusion. Pentobarbital is underrecognized as a potential cause of myocardial stunning. The mechanism involves direct myocardial depression and inhibition of autonomic neuroanatomical structures including the medulla and hypothalamus. Early recognition and implementation of aggressive cardiopulmonary support are essential to optimize the likelihood of a favorable outcome.

Bacillus anthracis edema but not lethal toxin challenge in rats is associated with depressed myocardial function in hearts isolated and tested in a Langendorff system

Although direct myocardial depression has been implicated in the lethal effects of Bacillus anthracis lethal toxin (LT), in hearts isolated from healthy rats and perfused under constant pressure, neither LT or edema toxin (ET) in typically lethal concentrations depressed myocardial function. In the present study, we challenged rats with LT and ET and performed in vivo and ex vivo heart measures. Sprague-Dawley rats infused over 24 h with LT (n = 94), ET (n = 99), or diluent (controls; n = 50) were studied at 8, 24, or 48 h. Compared with control rats (all survived), survival rates with LT (56.1%) and ET (37.3%) were reduced (P < 0.0001) similarly (P = 0.66 for LT vs. ET). LT decreased mean arterial blood pressure from 12 to 20 h (P ≤ 0.05), whereas ET decreased it progressively throughout (P < 0.05). On echocardiography, LT decreased left ventricular (LV) ejection fraction at 8 and 48 h but increased it at 24 h and decreased cardiac output (P ≤ 0.05 for the time interaction or averaged over time). ET decreased systolic and diastolic volumes and increased LV ejection fraction at 24 h (P ≤ 0.05). In isolated hearts perfused for 120 min under constant pressure, LT did not significantly alter LV systolic or developed pressures at any time point, whereas ET decreased both of these at 24 h (P < 0.0001 initially). ET but not LT progressively increased plasma creatine phosphokinase and cardiac troponin levels (P < 0.05). In conclusion, despite echocardiographic changes, in vivo lethal LT challenge did not produce evidence of myocardial depression in isolated rat hearts. While lethal ET challenge did depress isolated heart function, this may have resulted from prior hypotension and ischemia.

The Potential Contributions of Lethal and Edema Toxins to the Pathogenesis of Anthrax Associated Shock

Outbreaks of Bacillus anthracis in the US and Europe over the past 10 years have emphasized the health threat this lethal bacteria poses even for developed parts of the world. In contrast to cutaneous anthrax, inhalational disease in the US during the 2001 outbreaks and the newly identified injectional drug use form of disease in the UK and Germany have been associated with relatively high mortality rates. One notable aspect of these cases has been the difficulty in supporting patients once shock has developed. Anthrax bacilli produce several different components which likely contribute to this shock. Growing evidence indicates that both major anthrax toxins may produce substantial cardiovascular dysfunction. Lethal toxin (LT) can alter peripheral vascular function; it also has direct myocardial depressant effects. Edema toxin (ET) may have even more pronounced peripheral vascular effects than LT, including the ability to interfere with the actions of conventional vasopressors. Additionally, ET also appears capable of interfering with renal sodium and water retention. Importantly, the two toxins exert their actions via quite different mechanisms and therefore have the potential to worsen shock and outcome in an additive fashion. Finally, both toxins have the ability to inhibit host defense and microbial clearance, possibly contributing to the very high bacterial loads noted in patients dying with anthrax. This last point is clinically relevant since emerging data has begun to implicate other bacterial components such as anthrax cell wall in the shock and organ injury observed with infection. Taken together, accumulating evidence regarding the potential contribution of LT and ET to anthrax-associated shock supports efforts to develop adjunctive therapies that target both toxins in patients with progressive shock.

The cardiovascular effects of normobaric hyperoxia in patients with heart rate fixed by permanent pacemaker

To investigate whether the established reductions in heart rate and cardiac output with hyperoxia in humans are primary effects or secondary to increases in systemic vascular resistance, we paced the hearts of nine patients with permanent pacemakers at a fixed rate when breathing either medical air (inspired O(2) fraction 0.21) or oxygen (inspired O(2) fraction 0.80) in a randomised, double-blind fashion. A thoracic bio-impedance machine was used to measure heart rate, stroke volume and blood pressure and calculate cardiac index and systemic vascular resistance index. Oxygen caused no change in cardiac index (p = 0.18), stroke index (p = 0.44) or blood pressure (p = 0.52) but caused a small (5.5%) increase in systemic vascular resistance index (p = 0.03). This suggests that hyperoxia has no direct myocardial depressant effects, but that the changes in cardiac output reported in previous studies are secondary to changes in systemic vascular resistance.

Cardiac arrest following naloxone in an extremely preterm neonate

Naloxone is a pure opioid antagonist specifically indicated for respiratory depression due to opioid exposure. There is not enough data on safety of naloxone, especially in extremely preterm neonates. We report the case of a preterm neonate (gestation 27 weeks and 3 days, birth weight 485 g) who developed cardiac arrest following treatment with naloxone (dose 100 mcg/kg) for a tenfold morphine overdose on day 7 while being ventilated for respiratory distress syndrome. Asystolic cardiac arrest occurred immediately after administering naloxone and required full resuscitation, including adrenaline and external chest compression. Recovery from the cardiac arrest was complete. However, the neonate died on day 45 of life due to unrelated causes. Reports of similar adverse effects of the drug in adults as well as data from animal models raise concerns about safety of naloxone, especially in preterm neonates, given the lack of data on the pharmacokinetics of the drug in this high-risk population. Possible explanations for the adverse event under such a scenario include an idiosyncratic reaction, hypoxia, direct myocardial depressant effect and sympathoadrenal interactions. Awareness of this rare but potentially lethal complication of naloxone is necessary to optimise the response to such an adverse event.

Intravenous Anesthesia for the Patient with Left Ventricular Dysfunction

Patients with heart failure have a diminished cardiac reserve capacity that may be further compromised by anesthesia. In addition to depression of sympathetic activity, most anaesthetics interfere with cardiovascular performance, either by a direct myocardial depression or by modifying cardiovascular control mechanisms. Etomidate causes the least cardiovascular depression. It is popular for induction of anesthesia in cardiac-compromised patients; however, it is not suitable for maintenance of anesthesia because it depresses adrenocortical function. Ketamine has a favorable cardiovascular profile related to central sympathetic stimulation and inhibition of neuronal catecholamine uptake. These counteract its direct negative inotropic effect. In patients with a failing myocardium, however, the negative inotropic effects may be unmasked, resulting in deterioration in cardiac performance and cardiovascular instability. Propofol is the most popular intravenous anesthetic for maintenance of anesthesia. It does have a negative inotropic effect, but the net effect on myocardial contractility is insignificant at clinical concentrations, probably because of a simultaneous increase in the sensitivity of the myofilaments to Ca2+. Propofol protects the myocardium against ischemia-reperfusion injury, an action derived from its antioxidant and free-radical-scavenging properties as well as the related inhibition of the mitochondrial permeability transition pore. For intravenous anesthesia, propofol is always combined with an opioid. Opioids have relatively few cardiovascular side effects and, in particular, do not cause myocardial depression. Indeed, they are cardioprotective, with antiarrhythmic activity, and induce pharmacologic preconditioning of the myocardium by a mechanism similar to the inhalational anesthetics.

Argatroban for Anti-Coagulation during Plasma Exchange in a Patient with Cardiac Transplant Rejection and HIT.

INTRODUCTION:Plasma exchange has been used with anecdotal success in patients diagnosed with acute humoral rejection after cardiac transplantation. Historically, these exchanges have been performed using citrate as an anti-coagulant. However, citrate can have adverse metabolic effects due to its effect on calcium homeostasis and direct myocardial depression. These adverse effects may result in further reduction of cardiac function in patients already compromised from acute rejection. Heparin is a reasonable alternative, but its use may lead to heparin-induced thrombocytopenia (HIT). Argatroban is a direct thrombin inhibitor which may serve as an alternative to citrate or heparin anti-coagulation when plasma exchange is performed in patients with depressed myocardial function where heparin is not a viable option. We report a case in which a continuous infusion of Argatroban was used as an anti-coagulant during plasma exchange in a cardiac transplant patient with a history of HIT and with a diagnosis of acute humoral rejection and cardiopulmonary collapse.CASE REPORT:The patient is a 15 year old male with a history of single ventricle physiology who underwent multiple surgical corrections and who required temporary VAD implantation with two different devices and was bridged to cardiac transplant in June 2003. At the time of heart transplantation, he was diagnosed with HIT. He was readmitted to the ICU in April 2004 in respiratory distress, cardiovascular collapse and renal failure. His ejection fraction (EF) was 15%. The diagnosis of acute humoral rejection was made. Multiple supportive measures were required including ventilatory support, inotropic support, dialysis, and the placement of an intra-aortic balloon pump. Plasma exchange was performed for four consecutive days. On each day one plasma volume was exchanged using 5% albumin for the first half of the exchange and FFP for the second. A continuous Argatroban infusion was introduced into the COBE system via a 3-way stopcock at the access port. Coagulation parameters (PT, aPTT, and INR) were measured before the exchange and at one hour after the initiation of the procedure (Table 1). The patient tolerated the procedures well. There were no hemostatic problems and the EF increased to 50% by day 4. At the end of the plasma exchange treatment, monoclonal anti-rejection treatment was initiated.CONCLUSION:Plasma exchange may be used as a therapeutic option to treat acute humoral graft rejection in cardiac transplant patients. When there are issues precluding the use of either citrate or heparin as an anti-coagulant, a reasonable alternative may be Argatroban. This direct thrombin inhibitor has been used in other settings including cardiopulmonary bypass, dialysis and ECMO. In these settings its use was monitored with the activated clotting time. An ideal infusion regimen and monitoring protocol have not been established. In the described case a continuous infusion was used, and progress was monitored with the aPTT. We believe that this case is the first published example of the use of Argatroban in therapeutic plasma exchange and the first example of using continuous infusion with aPTT monitoring.Coagulation Parameters (Table 1)DayRate (mg/hr)Pre-procedure PT (INR)/PT (INR) at 1 hourPre-procedure aPTT/aPPT at 1 hour1733 (5.2) / 28.7 (4.1)31.5/51.320.577 (23) / 38.6 (6.9)115.6/77.43225.3 (3.3) / 30.4 (4.5)61.5/76.44226.9 (3.5) / 28.2 (4.0)74/70

Cardiopulmonary effects of the novel neuromuscular blocking drug GW280430A (AV430A) in dogs.

This investigation determined the cardiopulmonary side effects of a novel nondepolarizing neuromuscular blocking drug with an ultrashort duration of action in anesthetized male beagles. The ED95 for GW280430A was first determined in four animals. These data were then used to guide bolus dosing in multiples of ED95 in six dogs instrumented for hemodynamic measurements as well as inspiratory pressure and pulmonary compliance. Cardiopulmonary data were compared before and after the conclusion of a 60- to 90-min GW280430A infusion and in response to subsequent incremental bolus dosing starting with 3.125 x ED95. An adverse response was regarded as an alteration of 10% or greater in any variable. Arterial blood was obtained for histamine analysis before and 1 min after each dose. The ED95 of GW280430A was 0.064 +/- 0.01 mg/kg, and stable neuromuscular blockade was maintained with infusion of 0.012 +/- 0.002 mg.kg(-1).min(-1). With the exception of a late 14% increase in heart rate, there were no cardiopulmonary changes during infusion. Bolus dosing produced no cardiopulmonary change until a decrease in mean arterial pressure was elicited in four of six dogs at 25 x ED95. This response was modest, transient, and associated with a concomitant increase in plasma histamine concentration. There were no accompanying changes indicative of direct myocardial depression, pulmonary vasoconstriction, or bronchospasm. These data indicate that GW280430 does not produce demonstrable cardiovascular effects in the anesthetized dog until doses far in excess of the ED95 are administered as a bolus.

Direct myocardial depressant effect of naloxone: mechanical and electrophysiological actions in vitro.

Naloxone, an opioid antagonist, has a cardiovascular pressor effect and has been used in various types of shock states. The aim was to determine the non-opioid effect on direct cardiac muscle contractility and explore the mechanism using guinea pig right ventricular papillary muscles. With institutional approval, isometric contractile force was measured in modified normal and 26 mM K+ Tyrode solution at various stimulation rates. The effects of naloxone on sarcoplasmic recticulum function were evaluated by measuring rested-state contraction in low Na+ (25 mM) Tyrode solution and rapid cooling contracture in modified normal Tyrode solution. Normal and slow action potentials (APs) were measured using conventional microelectrode technique. Patch clamp study was performed to examine the direct effect on Ca2+ current in cardiac ventricular myocytes. Naloxone (50, 100, and 200 microM) caused a concentration-dependent depression of peak force and maximal rate of force development. Modest depression, approximately 20%, was shown in rested-state contraction in low Na+ Tyrode solution. Naloxone (100 microM) modestly depressed the rapid cooling contracture to 80 +/- 3% of baseline, accompanied by prolongation of time to peak contracture by approximately 37%. In 26 mM K+ Tyrode solution, naloxone (100 microM) markedly and selectively depressed the late force development. While naloxone (100 microM) did not alter the amplitude and dV/dt-max in normal and slow APs at 0.25 Hz, AP duration was prolonged significantly. In patch clamp experiment, naloxone (50 microM) depressed Ca2+ current by approximately 50%. The direct myocardial depressant effect of naloxone appeared to be in part caused by depression of Ca2+ influx through cardiac membrane. Sarcoplasmic reticulum function appeared to be modestly depressed.

This Month in ANESTHESIOLOGY

This Month in ANESTHESIOLOGY

Direct myocardial depressant effect of methylmethacrylate monomer: mechanical and electrophysiologic actions in vitro.

The present study explored the mechanism of direct myocardial depression by methylmethacrylate monomer (MMA). Isometric contraction of isolated guinea pig right ventricular papillary muscle was measured in modified normal and 26 mm K+ Tyrode solutions at various stimulation rates. Normal and slow action potentials were evaluated by conventional microelectrode technique. MMA effects on various aspects of sarcoplasmic reticulum function were evaluated by its effect on rapid-cooling contractures, rested-state contraction in rat papillary muscle in modified normal Tyrode solution, and in guinea pig papillary muscle under low Na+ (25 mm) Tyrode solution. Whole cell patch clamp techniques were applied to measure the inward Ca2+ currents (I(Ca)). MMA (0.5, 1.5, and 4.7 mm) caused concentration-dependent depression of peak force and maximal rate of force development to approximately 70, 50, and 20% of baseline from rested state to 3 Hz stimulation rates, respectively. Depression of peak force and maximal rate of force development by MMA was dependent on stimulation frequency, with less depression at higher stimulation rates. In low Na+ Tyrode solution, 1.5 mm MMA depressed peak force of rat and guinea pig myocardium by 20-30%. In 26 mm K+ Tyrode solution, 0.5 and 1.5 mm MMA caused selective and marked concentration-dependent depression of late force development (0.5 mm: approximately 60% of baseline, 1.5 mm: approximately 30% of baseline) with no alteration in early force development. MMA (1.5 mm) depressed rapid-cooling contracture to 53 +/- 10% of baseline, accompanied by approximately 63% prolongation of time to peak contracture. In patch clamp studies, MMA reduced I(Ca) in a concentration-dependent manner. The direct myocardial depressant effect of MMA seems to be caused in part by depression of Ca2+ influx through cardiac membrane, while depolarization-activated sarcoplasmic reticulum Ca2+ release appears modestly depressed.

Direct Myocardial Depressant Effect of Desflurane: Mechanical and Electrophysiological Actions in Vitro

Background: Desflurane actions on myocardial contractility and cellular electrophysiologic behavior were studied in isolated guinea pig and rat right ventricular papillary muscles. Methods: The isometric force of isolated guinea pig ventricular papillary muscles was studied in normal and 26 mM Tyrode's solution at various stimulation rates. Experiments using rat papillary muscles under normal Tyrode's solution at the rested-state (RS) and using guinea pig papillary muscles under low Tyrode's solution (25 mM) were performed to evaluate the effect of release from the sarcoplasmic reticulum (SR). Effects of desflurane on SR function in situ were examined by its effect on rapid cooling contractures (RCCs). Normal and slow action potentials (APs) were evaluated by using a conventional microelectrode technique. Finally, currents of isolated guinea pig ventricular myocytes were examined using the whole cell patch clamp technique. Results: 1 MAC (minimum alveolar concentration: 6%) and 2 MAC desflurane were applied. 1 MAC and 2 MAC desflurane depressed guinea pig myocardial contractions by 30% and 60%, respectively, from RS to 3 Hz stimulation rates. 1 MAC (1.15%) and 2 MAC isoflurane depressed peak force by 25% and 45%, respectively. Contractile force after rest in rat and guinea pig myocardium under low Tyrode's solution showed modest depression. In the partially depolarized, adrenergically stimulated myocardium, 1 MAC and 2 MAC desflurane caused a marked depression of the late peak force (1 MAC:60%, 2 MAC:80%) with moderate changes of the early peak force (1 MAC: 20%, 2 MAC: 40%). RCCs were abolished at 1 MAC desflurane. Desflurane did not alter the peak amplitude or maximum depolarization rate of normal and slow APs, however, AP duration was significantly prolonged. In isolated guinea pig myocytes at room temperature, 1 MAC and 2 MAC desflurane caused a 28% and 55% decrease in currents, respectively. Conclusions: These results indicate that desflurane causes a dose-dependent depression of contractile force in isolated myocardium, which is comparable to that of isoflurane. The depression seems to be related, at least in part, to its ability to reduce inward currents through the cardiac membrane. Therefore, it is likely that various methods employed to enhance inward current may improve the hemodynamic depression induced by desflurane.

Drug chirality in anesthesia.

Drug chirality in anesthesia.

General anaesthesia for emergency surgery during acute organophosphate poisoning

General anaesthesia for emergency surgery during acute organophosphate poisoning

The Direct Myocardial Depressant Effect of Methylmethacrylate Monomer in vitro: Mechanical and Electrophysiological Actions

The Direct Myocardial Depressant Effect of Methylmethacrylate Monomer in vitro: Mechanical and Electrophysiological Actions

Comparative effects of etomidate, ketamine, propofol, and fentanyl on myocardial contractility in dogs.

The present study was carried out to determine the direct effects of etomidate, ketamine, propofol, and fentanyl on myocardial contractility, and whether fentanyl would enhance the myocardial depression caused by propofol. The anesthetics were injected directly into the circuit that supplied blood to the left circumflex coronary artery (LCX) in anesthetized open-chest dogs. Myocardial contractility was evaluated from measurements of percent segmental shortening (%SS). Etomidate, ketamine, and propofol significantly reduced %SS in a dose-dependent manner. The %SS values with 1.6 and 3.2 mg of etomidate were similar to those with 3.2 and 6.4 mg of ketamine, respectively, and the %SS value with 6.4 mg of propofol was similar to those with 3.2 and 6.4 mg of ketamine. Fentanyl alone had no effects on myocardial performance and did not influence the effect of propofol on %SS. On the basis of clinical doses, the direct myocardial depressant effect of ketamine is more than twice as potent as that of etomidate and slightly more than that of propofol. Fentanyl has no inotropic effect and does not enhance the direct myocardial depressant effect of propofol.