piperidines and Ventricular-Dysfunction--Left

To compare hemodynamics, time to extubation, and costs of target-controlled infusion (TCI) with manually controlled infusion (MCI) of propofol in high-risk cardiac surgery patients.. Prospective, randomized.. Major community university-affiliated hospital.. Twenty patients undergoing first-time implantation of a cardioverter-defibrillator with severely reduced left ventricular function (left ventricular ejection fraction <30%).. Anesthesia was performed using remifentanil, 0.2 to 0.3 microg/kg/min, and propofol. Propofol was used as TCI (plasma target concentration, 2 to 3 microg x mL; n = 10) or MCI (2.5 to 3.5 mg/kg/hr; n = 10).. Hemodynamics were measured at 6 data points: T1, before anesthesia; T2, after intubation; T3, after skin incision; T4, after first defibrillation; T5, after third defibrillation; and T6, after extubation. There were no significant hemodynamic differences between the 2 groups. Dobutamine was required to maintain cardiac index >2 L/min/m(2) in significantly more patients of the TCI group than of the MCI group. Mean dose of propofol was higher in the TCI patients (6.0 +/- 1.0 mg/kg/hr) than in the MCI patients (3.0 +/- 0.4 mg/kg/hr) (p < 0.05), whereas doses of remifentanil did not differ. Time to extubation was significantly shorter in the MCI (11.9 +/- 2.4 min) versus the TCI group (15.6 +/- 6.8 min). Costs were significantly lower in MCI patients (34.73 dollars) than in TCI patients (44.76 dollars).. In patients with severely reduced left ventricular function, TCI and MCI of propofol in combination with remifentanil showed similar hemodynamics. TCI patients needed inotropic support more often than MCI-treated patients. Although extubation time was longer in TCI patients and costs were higher, both anesthesia techniques can be recommended for early extubation after implantation of a cardioverter-defibrillator.

Topics: Anesthesia, Intravenous; Anesthetics, Intravenous; Defibrillators, Implantable; Female; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Piperidines; Propofol; Prospective Studies; Remifentanil; Risk Factors; Ventricular Dysfunction, Left

ur preclinical findings replicated women's hypersensitivity to type-2 diabetes mellitus (T2DM)-evoked cardiac dysfunction along with demonstrating estrogen (E2)-dependent disruption of the cardiac adiponectin (APN)-connexin43 (Cx43) signaling. Whether the latter molecular anomaly underlies this women's cardiovascular health problem remains unknown. We hypothesized that restoration of the disrupted APN-Cx43 signaling alleviates this sex/E2-dependent cardiac dysfunction in diabetic female rats. To test this hypothesis, we administered the adiponectin receptor 1 (AdipoR1) agonist AdipoRon (30 mg/kg/d for 10 days) to female sham operated (SO) and ovariectomized (OVX) rats, which exhibited and lacked the T2DM left ventricular (LV) dysfunction, respectively, when fed high-fat diet and received low dose streptozotocin regimen; nondiabetic control SO and OVX rats received control diet and vehicle for streptozotocin. In T2DM SO rats, LV dysfunction, AdipoRon mitigated: (1) LV hypertrophy, (2) reductions in fractional shortening, LV developed pressure, dP/dtmax, dP/dtmin, and Tau. In LV tissues of the same rats, AdipoRon reversed reduction in Cx43 and elevations in TNFα, heme-oxygenase 1 (HO-1), and circulating cardiovascular risk factor asymmetric dimethylarginine. The findings also revealed ovarian hormones independent effects of AdipoRon, which included dampening of the pro-oxidant enzyme HO-1. These novel findings yield new insight into a causal role for compromised APN-Cx43 signaling in the E2-dependent hypersensitivity to T2DM-evoked cardiac inflammation and dysfunction. Equally important, the findings identify restoration of Cx43 signaling as a viable therapeutic modality for alleviating this women's cardiovascular health-related problem.

Topics: Adiponectin; Animals; Arginine; Connexin 43; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Estradiol; Estrogen Receptor alpha; Female; Heme Oxygenase (Decyclizing); Hypertrophy, Left Ventricular; Ovariectomy; Piperidines; Rats, Wistar; Receptors, Adiponectin; Receptors, G-Protein-Coupled; Signal Transduction; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase, has altered the treatment perspective of chronic lymphocytic leukemia and showed modest activity against several types of non-Hodgkin's lymphomas. According to phase studies and real-world data, reported serious adverse effects included atrial fibrillation, diarrhea, and bleeding diathesis. However, heart failure was not reported to be a probable adverse effect linked with ibrutinib.. In this paper, we present a 66-year-old female chronic lymphocytic leukemia patient who developed significant and symptomatic left ventricular dysfunction at the 13th month of ibrutinib treatment.. Following cessation of ibrutinib, ejection fraction and clinical findings of the left ventricular dysfunction alleviated.. Although the use of ibrutinib is generally well tolerated, cardiac functions should be monitored occasionally in all patients.

Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Aged; Cardiomyopathies; Female; Humans; Late Onset Disorders; Leukemia, Lymphocytic, Chronic, B-Cell; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Ventricular Dysfunction, Left

There are increasing evidence that left ventricle diastolic dysfunction is the initial functional alteration in the diabetic myocardium. In this study, we hypothesized that alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function and structure in diabetic rabbits.. A total of 30 rabbits were randomized into control group (CON, n = 10), alloxan-induced diabetic group (DM, n = 10) and alogliptin-treated (12.5 mg/kd/day for 12 weeks) diabetic group (DM-A, n = 10). Echocardiographic and hemodynamic studies were performed in vivo. Mitochondrial morphology, respiratory function, membrane potential and reactive oxygen species (ROS) generation rate of left ventricular tissue were assessed. The serum concentrations of glucagon-like peptide-1, insulin, inflammatory and oxidative stress markers were measured. Protein expression of TGF-β1, NF-κB p65 and mitochondrial biogenesis related proteins were determined by Western blotting.. DM rabbits exhibited left ventricular hypertrophy, left atrial dilation, increased E/e' ratio and normal left ventricular ejection fraction. Elevated left ventricular end diastolic pressure combined with decreased maximal decreasing rate of left intraventricular pressure (- dp/dtmax) were observed. Alogliptin alleviated ventricular hypertrophy, interstitial fibrosis and diastolic dysfunction in diabetic rabbits. These changes were associated with decreased mitochondrial ROS production rate, prevented mitochondrial membrane depolarization and improved mitochondrial swelling. It also improved mitochondrial biogenesis by PGC-1α/NRF1/Tfam signaling pathway.. The DPP-4 inhibitor alogliptin prevents cardiac diastolic dysfunction by inhibiting ventricular remodeling, explicable by improved mitochondrial function and increased mitochondrial biogenesis.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Diastole; Dipeptidyl-Peptidase IV Inhibitors; Fibrosis; Hypertrophy, Left Ventricular; Membrane Potential, Mitochondrial; Mitochondria, Heart; Nuclear Respiratory Factor 1; Oxidative Stress; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Piperidines; Rabbits; Reactive Oxygen Species; Signal Transduction; Stroke Volume; Transcription Factors; Uracil; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure; Ventricular Remodeling

Although OPC-28326, 4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate, was developed as a selective peripheral vasodilator with α2-adrenergic antagonist properties, it also reportedly exhibits angiogenic activity in an ischemic leg model. The purpose of this study was to examine the effect of OPC-28326 on the architectural dynamics and function of the infarcted left ventricle during the chronic stage of myocardial infarction. Myocardial infarction was induced in male C3H/He mice, after which the mice were randomly assigned into two groups: a control group receiving a normal diet and an OPC group whose diet contained 0.05% OPC-28326. The survival rate among the mice (n = 18 in each group) 4 wk postinfarction was significantly greater in the OPC than control group (83 vs. 44%; P < 0.05), and left ventricular remodeling and dysfunction were significantly mitigated. Histologically, infarct wall thickness was significantly greater in the OPC group, due in part to an abundance of nonmyocyte components, including blood vessels and myofibroblasts. Five days postinfarction, Ki-67-positive proliferating cells were more abundant in the granulation tissue in the OPC group, and there were fewer apoptotic cells. These effects were accompanied by activation of myocardial Akt and endothelial nitric oxide synthase. Hypoxia within the infarct issue, assessed using pimonidazole staining, was markedly attenuated in the OPC group. In summary, OPC-28326 increased the nonmyocyte population in infarct tissue by increasing proliferation and reducing apoptosis, thereby altering the tissue dynamics such that wall stress was reduced, which might have contributed to a mitigation of postinfarction cardiac remodeling and dysfunction.

Topics: Angiogenesis Inducing Agents; Aniline Compounds; Animals; Cell Proliferation; Heart; Ki-67 Antigen; Mice; Myocardial Infarction; Myocardium; Myofibroblasts; Nitric Oxide Synthase Type III; Piperidines; Proto-Oncogene Proteins c-akt; Survival Rate; Vasodilator Agents; Ventricular Dysfunction, Left; Ventricular Remodeling

We described the anesthetic management of a 17-year-old male patient with Fukuyama congenital muscle dystrophy (FCMD) who underwent surgical repair for scoliosis under total intravenous anesthesia. The patient had severe constructive lung disease (%VC 18.6%). Left ventricular wall motion was reduced (left ventricular ejection fraction 40%). Propofol and remifentanil were continuously infused to maintain anesthesia, but we did not use any muscle relaxant throughout the course. We used arterial pressure-based cardiac output and stroke volume variation as a guide for circulatory management. We could not find any congestion on chest X-ray after the surgery. The emergence and recovery from the anesthesia was rapid and muscle strength was enough, and we could extubate the patient just after the end of the surgery. No respiratory and cardiac complications occurred during the postoperative period. Even though he was in the young age in FCMD, respiratory and cardiac complications were severely impaired. For successful anesthetic management in FCMD patient, we should take care of rapid emergence from anesthesia and also we should not impair muscle strength for good postoperative respiratory function. Appropriate hemodynamic monitoring to avoid postoperative cardiac congestion is also required.

Topics: Adolescent; Anesthesia, Intravenous; Humans; Lung Diseases, Obstructive; Male; Monitoring, Intraoperative; Perioperative Care; Piperidines; Propofol; Remifentanil; Scoliosis; Stroke Volume; Ventricular Dysfunction, Left; Walker-Warburg Syndrome

An 81-year-old man with cardiac sarcoidosis was scheduled for an open colectomy and partial resection of liver metastasis. He had undergone implantation of a permanent cardiac pacemaker for complete atrioventricular block 5 years before. Preoperative echocardiography revealed severely reduced left ventricular function, with an ejection fraction of 30%. General anesthesia was induced and maintained with remifentanil 0.2 microg x kg(-1) x min(-1), along with a target-controlled infusion of propofol combined with intermittent administrations of low-dose fentanyl. Perioperative hemodynamic monitoring with a pulmonary artery catheter and transesophageal echocardiography was useful for management of cardiac function and control of infusion volume. The surgery was conducted uneventfully and the patient entered the ICU without endotracheal intubation. Thereafter, the postoperative course was stable without major complications. Cardiac sarcoidosis is characterized by a high incidence of complete atrioventricular block, ventricular arrhythmia, and cardiac dysfunction. We consider that a combination of remifentanil and propofol is useful for careful anesthetic management of patients with cardiac sarcoidosis.

Topics: Aged, 80 and over; Anesthesia, Intravenous; Cardiomyopathies; Colectomy; Hepatectomy; Humans; Male; Piperidines; Propofol; Remifentanil; Sarcoidosis; Ventricular Dysfunction, Left

Reactive oxygen species (ROS) and intracellular Ca(2+) overload play key roles in myocardial ischemia-reperfusion (IR) injury but the relationships among ROS, Ca(2+) overload and LV mechanical dysfunction remain unclear. We tested the hypothesis that H(2)O(2) impairs LV function by causing Ca(2+) overload by increasing late sodium current (I(Na)), similar to Sea Anemone Toxin II (ATX-II). Diastolic and systolic Ca(2+) concentrations (d[Ca(2+)](i) and s[Ca(2+)](i)) were measured by indo-1 fluorescence simultaneously with LV work in isolated working rat hearts. H(2)O(2) (100 microM, 30 min) increased d[Ca(2+)](i) and s[Ca(2+)](i). LV work increased transiently then declined to 32% of baseline before recovering to 70%. ATX-II (12 nM, 30 min) caused greater increases in d[Ca(2+)](i) and s[Ca(2+)](i). LV work increased transiently before declining gradually to 17%. Ouabain (80 microM) exerted similar effects to ATX-II. Late I(Na) inhibitors, lidocaine (10 microM) or R56865 (2 microM), reduced effects of ATX-II on [Ca(2+)](i) and LV function, but did not alter effects of H(2)O(2). The antioxidant, N-(2-mercaptopropionyl)glycine (MPG, 1 mM) prevented H(2)O(2)-induced LV dysfunction, but did not alter [Ca(2+)](i). Paradoxically, further increases in [Ca(2+)](i) by ATX-II or ouabain, given 10 min after H(2)O(2), improved function. The failure of late I(Na) inhibitors to prevent H(2)O(2)-induced LV dysfunction, and the ability of MPG to prevent H(2)O(2)-induced LV dysfunction independent of changes in [Ca(2+)](i) indicate that impaired contractility is not due to Ca(2+) overload. The ability of further increases in [Ca(2+)](i) to reverse H(2)O(2)-induced LV dysfunction suggests that Ca(2+) desensitization is the predominant mechanism of ROS-induced contractile dysfunction.

Topics: Animals; Anti-Arrhythmia Agents; Benzothiazoles; Calcium; Calcium Channel Blockers; Cardiotonic Agents; Cnidarian Venoms; Hydrogen Peroxide; Ion Transport; Lidocaine; Male; Myocardial Reperfusion Injury; Myocardium; Organ Culture Techniques; Ouabain; Oxidants; Piperidines; Rats; Rats, Sprague-Dawley; Ventricular Dysfunction, Left

The role of neuronal nitric oxide synthase (nNOS) in regulating contractile function remains controversial, and in regulating myocardial perfusion is uninvestigated. We used magnetic resonance imaging (MRI) to phenotype nNOS(-/-) and wild-type (WT) mice regarding left ventricular (LV) structure, baseline function, beta-adrenergic responsiveness, and perfusion reserve.. Cine MRI showed higher LV mass to end-diastolic volume ratio (2.3 +/- 0.2 mg/microL nNOS(-/-) vs. 1.7 +/- 0.1 mg/microL WT; P=0.032) and LV ejection fraction (64.9 +/- 2.1% nNOS(-/-) vs. 55.8 +/- 1.1% WT; P = 0.003) in nNOS(-/-). Myocardial tagging demonstrated similar baseline systolic circumferential strain (Ecc) in nNOS(-/-) and WT. With dobutamine, the normal change in Ecc was nearly absent in nNOS(-/-) (-0.5 +/- 0.3% nNOS(-/-) vs. -2.2 +/- 0.3% WT; P = 0.001), and the systolic strain rate (dEcc/dt) response to dobutamine seen in WT was reduced in nNOS(-/-) (-29 +/- 13%/s nNOS(-/-) vs. -106+/-16%/s WT; P = 0.001). Diastolic strain rate increased significantly with dobutamine only in WT. Arterial spin labelling showed that baseline perfusion and perfusion reserve with either dobutamine or an adenosine receptor agonist are normal in nNOS(-/-).. MRI provides non-invasive in vivo evidence that nNOS does not play a role in basal contractile function or myocardial perfusion, but is required for increasing cardiac inotropy and lusitropy upon beta-adrenergic stimulation.

Topics: Adrenergic beta-Agonists; Animals; Blood Pressure; Cardiac Volume; Coronary Circulation; Dobutamine; Heart Ventricles; Magnetic Resonance Angiography; Magnetic Resonance Imaging, Cine; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide Synthase Type I; Phenotype; Piperidines; Purinergic P1 Receptor Agonists; Systole; Vasodilation; Ventricular Dysfunction, Left

Dahl salt-sensitive (DS) rats fed high-salt diet exert compensated left ventricular (LV) hypertrophy and eventually develop heart failure. Oxidative stress has been shown to be involved in myocardial remodeling and failure and thus might play an important role in this transition from hypertrophy to failure. We measured the amount of reactive oxygen species (ROS) in the myocardium from DS rats by using electron spin resonance spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (hydroxy-TEMPO) and also examined the effects of chronic angiotensin-converting enzyme (ACE) inhibition on the transition. We divided DS rats (5 weeks old, 150-200 g) into three groups: low-salt (0.3% NaCl) diet for 10 weeks (LS group), high-salt (8% NaCl) diet for 10 weeks (HS-10+V group), and high-salt diet and cilazapril (10 mg/kg body weight per day) started after 5 weeks of high-salt diet and maintained for 5 weeks (HS-10+Cil group). Systolic blood pressure (mm Hg) was significantly elevated in the HS-10+V (229+/-5) and HS-10+Cil (209+/-5) groups compared with the LS group (141+/-2). The amount of myocardial ROS was not changed after 5 weeks of high-salt diet, but significantly increased in HS-10+V rats compared with LS rats, and was abolished in the HS-10+Cil group. HS-10+V rats exerted the clinical signs of heart failure, including increased lung weight and pleural effusion, associated with LV hypertrophy and LV cavity dilatation. In the HS-10+Cil group, signs of heart failure were significantly attenuated despite only a modest reduction in systolic blood pressure (-20 mm Hg). The progression of LV failure after hypertrophy in high-salt-loaded DS hypertensive rats was associated with increased myocardial ROS, and ACE inhibitor could prevent this transition from compensated hypertrophy to failure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Cilazapril; Electron Spin Resonance Spectroscopy; Heart Failure; Hypertrophy, Left Ventricular; Male; Oxidative Stress; Piperidines; Rats; Rats, Inbred Dahl; Reactive Oxygen Species; Sodium Chloride, Dietary; Survival Rate; Ventricular Dysfunction, Left

The anaesthetic management of an elderly patient with severely impaired left ventricular function undergoing thoracotomy and lobectomy is described. Total intravenous anaesthesia (TIVA) with remifentanil and target-controlled infusion of propofol titrated according to the bispectral index (BIS) was used, with thoracic epidural anaesthesia commenced at the end of surgery providing postoperative analgesia. Avoidance of intraoperative epidural local anaesthetics and careful titration and dose reduction of propofol using the BIS was associated with excellent haemodynamic stability. The rapid offset of action of remifentanil and low-dose propofol facilitated early recovery and tracheal extubation. The BIS was a valuable monitor in optimal titration of TIVA.

Topics: Aged; Analgesia, Epidural; Anesthesia Recovery Period; Anesthesia, Intravenous; Anesthetics, Intravenous; Carcinoma, Squamous Cell; Cardiomyopathy, Dilated; Electroencephalography; Hemodynamics; Humans; Infusions, Intravenous; Intubation, Intratracheal; Lung Neoplasms; Male; Monitoring, Intraoperative; Piperidines; Pneumonectomy; Propofol; Remifentanil; Signal Processing, Computer-Assisted; Thoracotomy; Titrimetry; Ventricular Dysfunction, Left

To determine the cardiocirculatory effects of total intravenous anesthesia (TIVA) using remifentanil and propofol in high-risk cardiac surgical patients.. Prospective study of 20 patients undergoing first-time implantation of a cardioverter-defibrillator (ICD).. Major, community, university-affiliated hospital.. In 20 patients with severely reduced left ventricular function (left ventricular ejection fraction <30%) undergoing first-time implantation of an ICD, TIVA using remifentanil and propofol was performed.. Extensive hemodynamic monitoring using a pulmonary artery catheter was performed: (T1) before induction of anesthesia, (T2) after intubation, (T3) after skin incision, (T4) after first defibrillation, and (T5) 10 minutes after extubation. Propofol, 3.0 +/- 0.6 mg/kg/h (range, 1.9 to 4.4 mg/kg/h), and remifentanil, 0.30 +/- 0.05 microg/kg/min (range, 0.21 to 0.40 microg/kg/min), were used. Total costs added up to US $44.60 per patient. Patients could be extubated within 12.5 +/- 4.2 minutes after stopping anesthesia. There were significant decreases in heart rate (HR; from 77 +/- 12 to 57 +/- 10 beats/min [T3]), mean arterial blood pressure (MAP; from 98 +/- 14 to 70 +/- 12 mmHg [T2]), and systemic vascular resistance (from 1,551 +/- 309 to 1,233 +/- 274 dyne x s x cm(-5) [T2]). Cardiac index (CI) slightly decreased only at T3 (from 2.46 +/- 0.42 to 1.92 +/- 0.29 L/min/m2; p = 0.04). The decrease in MAP could easily be treated by volume infusion in most patients (17 patients). Sixty-five percent of the patients needed dobutamine to increase CI to greater than 2.0 L/min/m2 (mean dose, 2.2 +/- 1.8 microg/kg/min). Dobutamine could be stopped before extubation in all patients. No patient needed sustained inotropic or ventilatory support and intensive care therapy could be avoided.. TIVA using remifentanil and propofol in patients with severely reduced left ventricular function is safe, well-controllable, and allows early extubation after implantation of an ICD. Because patients without complications did not need a postoperative intensive care stay, costs may be considerably reduced.

Topics: Aged; Anesthesia, Intravenous; Anesthetics, Combined; Anesthetics, Intravenous; Arrhythmias, Cardiac; Cardiotonic Agents; Defibrillators, Implantable; Dobutamine; Female; Hemodynamics; Humans; Male; Middle Aged; Monitoring, Intraoperative; Piperidines; Propofol; Remifentanil; Risk Factors; Ventricular Dysfunction, Left

Impairment of myocardial contraction ("myocardial stunning") occurs during reperfusion after short ischemic periods. Substance P (SP) is widely distributed in heart and can be released by various stimuli including myocardial hypoxia. Our previous study shows SP has a negative inotropic effect in guinea pig heart. The objective of this study was to investigate whether SP contributes to the myocardial stunning after brief global ischemia. Guinea pig hearts in a Langendorff preparation were subjected to 15 min of global ischemia followed by 60 min reperfusion. Experiments were performed without and with pretreatment with neurokinin-1 (NK1) receptor antagonists, spantide (10(-6)M) or CP-99,994-01 (10(-6)M) in order to study the role of SP. Experiments were also performed in hearts which were perfused with atropine, phentolamine, and nadolol (10(-6)M each) to examine the role of neurotransmitters and autonomic receptors. A group of hearts obtained from capsaicin-pretreated guinea pigs was also investigated. Left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), heart rate, and perfusion pressure were monitored. At the end of reperfusion, the LVDP of control hearts recovered to only 55 +/- 6% (+/- SEM) of preischemic baseline and the LVEDP increased significantly (P > 0.05). With pretreatment with spantide or CP-99,994-01, LVDP recovered to 88 +/- 2% or 78 +/- 2% of the preischemic baseline, respectively. The LVEDP of these hearts was not different from preischemic baseline and much smaller than in control hearts. There were no differences in heart rate and perfusion pressure compared to baseline among all groups. Similar results were obtained in hearts perfused with autonomic blockers. However, recoveries of LVDP and LVEDP were faster in hearts perfused with autonomic blockers during the first 10 min of reperfusion. Pretreatment with capsaicin also significantly improved recovery of LVDP and LVEDP. In conclusion, substance P is involved in postischemic myocardial dysfunction and neurokinin-1 receptors mediate this action. The NK1 receptor antagonists may be useful in prevention of "myocardial stunning".

Topics: Analgesics; Animals; Capsaicin; Guinea Pigs; Heart Rate; Male; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Stunning; Piperidines; Substance P; Ventricular Dysfunction, Left