A Khayat’s research while affiliated with AHEPA University Hospital and other places

We describe successful use of a minimal extracorporeal circulation circuit (MECC) as an alternative to conventional cardiopulmonary bypass (CPB) for the implantation of left ventricular assist device (LVAD) in a 65-year-old patient with ischemic dilated cardiomyopathy. A Jarvik 2000 was implanted through a median sternotomy with the outflow graft anastomosed to the ascending aorta. MECC circuit provides optimal circulatory support throughout the procedure and prevents hemodynamic instability caused by marked displacement of the heart for exposure of the left ventricular apex, while minimizing the adverse effects of conventional CPB.

We challenge the hypothesis of enhanced myocardial reperfusion after implanting a left ventricular assist device together with bone marrow mononuclear stem cells in patients with end-stage ischemic cardiomyopathy. Irreversible myocardial loss observed in ischemic cardiomyopathy leads to progressive cardiac remodelling and dysfunction through a complex neurohormonal cascade. New generation assist devices promote myocardial recovery only in patients with dilated or peripartum cardiomyopathy. In the setting of diffuse myocardial ischemia not amenable to revascularization, native myocardial recovery has not been observed after implantation of an assist device as destination therapy. The hybrid approach of implanting autologous bone marrow stem cells during assist device implantation may eventually improve native cardiac function, which may be associated with a better prognosis eventually ameliorating the need for subsequent heart transplantation. The aforementioned hypothesis has to be tested with well-designed prospective multicentre studies.

We tested the hypothesis that a miniaturised axial flow pump with infection-resistant power delivery could improve longevity and quality of life (QOL) in advanced heart failure patients deemed unsuitable for transplantation. The study included all non-United States Jarvik 2000 patients (n=46), where a skull-pedestal-based power line was employed with the intention of long-term support. Patient age ranged from 29 to 80 years. Of the 46 patients, 42 were male. All were New York Heart Association (NYHA) IV predominantly with idiopathic dilated (n=22) or ischaemic (n=18) cardiomyopathy. The experience (2000-2008) included the learning curve of 10 centres. The internal components are imperceptible. The power/control system is user friendly, allowing excellent QOL. There has been no pump malfunction. The Kaplan-Meier survival analysis is shown. The longest event-free survival is 7.5 years. Support exceeded 3 years in five cases. The cumulative experience exceeds 50 years. Three patients were transplanted, and two pumps were replaced at 90 and 203 days. Nineteen cases are ongoing (mean: 663 days), while 22 died during support (mean survival: 402 days), of which five from non-device-related diseases. Temporary local infection occurred in three pedestals, and there has been no pump infection. Incidence of thrombo-embolic events showed wide variation between centres. From this learning-curve experience, both left ventricular assist device (LVAD) and power delivery are reliable and promising for destination therapy. Early mortality is similar to other studies and relates to the severity of illness. Pump infection has not occurred and prolonged event-free survival is clearly possible with expert medical management.

Isoflurane and sevoflurane have been shown to elicit myocardial postconditioning, but the effect of desflurane remain unknown. The authors studied the mechanisms involved in desflurane-induced myocardial postconditioning. Contracting isolated human right atrial trabeculae (34 degrees C, stimulation frequency 1 Hz) were exposed to 30-min hypoxia followed by 60-min reoxygenation. Desflurane at 3%, 6%, and 9% was administered during the first 5-min of reoxygenation. Postconditioning with 6% desflurane was studied in the presence of 1 microM calphostin C, a protein kinase C inhibitor; 800 mm 5-hydroxydecanoate, a mitochondrial adenosine triphosphate-sensitive potassium channels antagonist; 1 microM Akt inhibitor; 20 microM PD89058, an extracellular-regulated kinase 1/2 inhibitor; and 1 microM SB 202190, a p38 mitogen-activated protein kinase inhibitor. The force of contraction at the end of the 60-min reoxygenation period was compared (mean +/- SD). The p38 mitogen-activated protein kinase phosphorylation was studied using Western blotting. Desflurane at 3% (77 +/- 10% of baseline), 6% (90 +/- 14% of baseline), and 9% (86 +/- 11% of baseline) enhanced the recovery of force after 60 min of reoxygenation as compared with the control group (51 +/- 9% of baseline; P < 0.001). Calphostin C (55 +/- 3% of baseline), 5-hydroxydecanoate (53 +/- 3% of baseline), Akt inhibitor (57 +/- 8% of baseline), PD89058 (64 +/- 6% of baseline), and SB 202190 (61 +/- 3% of baseline) abolished desflurane-induced postconditioning. Western blot analysis showed that 6% desflurane increased p38 mitogen-activated protein kinase phosphorylation. In vitro, desflurane postconditioned human atrial myocardium through protein kinase C activation, opening of mitochondrial adenosine triphosphate-sensitive potassium channels, Akt and extracellular-regulated kinase 1/2 activation, and p38 mitogen-activated protein kinase phosphorylation.

We examined the effects of etomidate on recovery of contractile function after hypoxia reoxygenation and hypoxic preconditioning in vitro using isolated human myocardium. Human right atrial myocardium were obtained at the time of cardiac surgery from 38 adults patients. We recorded isometric force of contraction (FoC) of atrial trabeculae suspended in an oxygenated Tyrode's solution (34 degrees C, stimulation frequency 1 Hz). In all groups, a 30-min hypoxic period was followed by 60 min of reoxygenation (HR). In separate groups, muscles were exposed to etomidate (10(-7), 10(-6), 10(-5) M) 10 min before and throughout the HR periods. Hypoxic preconditioning was induced by 4-min hypoxia followed by 7-min reoxygenation applied before HR periods. Etomidate 10(-5) M was administered before, throughout, and after the hypoxic preconditioning stimulus. Recovery of FoC (expressed as % of baseline value) at the end of HR was compared among groups. Compared with the control group (FoC: 52%+/-10%), etomidate 10(-7) M (FoC: 57%+/-9%; P=0.24), 10(-6) M (FoC: 61%+/-11%; P=0.10), and 10(-5) M (FoC: 54%+/-9%; P=0.29) did not modify the recovery of FoC after HR. Hypoxic preconditioning-induced increase in the recovery of FoC (87%+/-5%; P<0.001 vs control group) was not modified in the presence of etomidate 10(-5) M (FoC: 86%+/-7%; P=0.74 vs hypoxic preconditioning group). Etomidate did not modify the in vitro FoC of human myocardium exposed to HR. Furthermore, etomidate did not modify the protective effect of hypoxic preconditioning.

We examined the role of reactive oxygen species (ROS) in sevoflurane- and desflurane-induced preconditioning on isolated human right atrial myocardium. We recorded isometric contraction of human right atrial trabeculae suspended in an oxygenated Tyrode's solution (34 degrees C, stimulation frequency 1 Hz). In all groups, a 30-min hypoxic period was followed by 60 min of reoxygenation. Ten minutes before hypoxia reoxygenation, muscles were exposed to 5 min of sevoflurane 2% or desflurane 6%. In separate groups, the sevoflurane 2% (Sevo + N-(2-mercaptopropionyl)-glycine [MPG]) or desflurane 6% (Des + MPG) was administered in the presence of 0.1 mM MPG, a ROS scavenger. The effect of 0.1 mM MPG alone was tested. Recovery of force after a 60-min reoxygenation period was compared between groups (mean +/- sd). Preconditioning with sevoflurane 2% (85% +/- 4% of baseline) or desflurane 6% (86% +/- 7% of baseline) enhanced the recovery of the force of myocardial contraction after 60 min reoxygenation compared with the control group (53% +/- 11% of baseline, P < 0.001). This effect was abolished in the presence of MPG (56% +/- 12% of baseline for Sevo + MPG, 48% +/- 13% of baseline for Des + MPG). The effect of MPG alone on the recovery of force was not different from the control group (57% +/- 7% of baseline versus 53% +/- 11%; P = NS). In vitro, sevoflurane and desflurane preconditioned human myocardium against hypoxia through a ROS-dependent mechanism.

The authors reported a case involving a young patient with a cardiogenic shock associated to an acute pulmonary oedema. According to the seriousness of the shock, an external ventricular assist device (VAD) was initially inserted and replaced thereafter because of the cardiovascular instability, by an external pneumatic biventricular assist device. A cardiogenic shock induced by an acute adrenergic myocarditis due to a phaeochromocytoma was diagnosed. The patient was weaned from the VAD on day 84 and was scheduled for elective surgery of the phaeochromocytoma on day 93. The authors discussed the time of the surgery according to the anticoagulation therapy necessary to the VAD and the necessary caution taken if a cardiogenic shock appeared around surgery.

The authors reported a case involving a young patient with a cardiogenic shock associated to an acute pulmonary oedema. According to the seriousness of the shock, an external ventricular assist device (VAD) was initially inserted and replaced thereafter because of the cardiovascular instability, by an external pneumatic biventricular assist device. A cardiogenic shock induced by an acute adrenergic myocarditis due to a phaeochromocytoma was diagnosed. The patient was weaned from the VAD on day 84 and was scheduled for elective surgery of the phaeochromocytoma on day 93. The authors discussed the time of the surgery according to the anticoagulation therapy necessary to the VAD and the necessary caution taken if a cardiogenic shock appeared around surgery.