Mohamed Salem

Percutaneous left ventricular assist in ischemic cardiac arrest.

Background: Ischemic cardiac arrest represents a challenge for optimal emergency revascularization therapy. A percutaneous left ventricular assist device (LVAD) may be beneficial. Objective: To determine the effect of a percutaneous LVAD during cardiac arrest without chest compressions and to assess the effect of fluid loading. Design: Totally, 16 pigs randomized to either conventional or intensive fluid with LVAD support during ventricular fibrillation (VF). Setting: Acute experimental trial with pigs under general anesthesia. Subjects: Farm pigs of both sexes. Interventions: After randomization for fluid infusion, VF was induced by balloon occlusion of the proximal left anterior descending artery. LVAD and fluid were started after VF had been induced. Measurements: Brain, kidney, myocardial tissue perfusion, and cardiac index were measured with the microsphere injection technique at baseline, 3, and 15 minutes. Additional hemodynamic monitoring continued until 30 minutes. Main results: At 15 minutes, vital organ perfusion was maintained without significant differences between the two groups. Mean cardiac index at 3 minutes of VF was 1.2 L·min−1·m2 (29% of baseline, p < 0.05). Mean perfusion at 3 minutes was 65% in the brain and 74% in the myocardium compared with baseline (p < 0.05), then remained unchanged during the initial 15 minutes. At 30 minutes, LVAD function was sustained in 11 of 16 animals (8 of 8 intensified fluid vs. 3 of 8 conventional fluid) and was associated with intensified fluid loading (p < 0.001). Conclusions: During VF, a percutaneous LVAD may sustain vital organ perfusion. A potential clinical role of the device during cardiac arrest has yet to be established.

Long-term results following percutaneous myocardial laser therapy

ObjectivesThe usefulness and safety of percutaneous myocardial laser therapy in selected patients have been identified in previous 1-year randomized trial reports, including that from a double-blind, sham-controlled trial we independently conducted. We aimed to determine whether the 1-year effects are maintained through a long-term, longitudinal follow-up. MethodsPatients (n=77) with chronic, stable, medically refractory angina (class III or IV) not amenable to conventional revascularization and with evidence of reversible ischemia, ejection fraction ≥25%, and myocardial wall thickness ≥8u2009mm were treated with percutaneous myocardial laser. After the 1-year follow-up and disclosure of all randomized assignments as prespecified in the respective study protocol, patients were followed up longitudinally for a mean of 3 years for angina class, left ventricular ejection fraction, medication usage, and adverse events. ResultsNo procedural mortality, myocardial infarction, or cerebral embolism occurred. Pericardiocentesis was required in two patients (2.6%). Cardiac event-free survival was 88% at 1 year and 66% at late follow-up. Mean Canadian Cardiovascular Society angina class was significantly improved from baseline (3.2±0.4) at 1 year (2.2±1.1, P<0.001) and at a mean of 3 years (1.9±1.2, P<0.001). Nitrate usage was significantly reduced at late follow-up; however, ejection fraction did not change over time. In a multivariate analysis, angina improvement at 1 year was found to be a significant independent predictor of both survival and angina improvement at late follow-up. ConclusionWe conclude that percutaneous myocardial laser therapy in selected patients with severe, medically refractory angina not treatable with conventional revascularization induces significant and sustained symptomatic benefit.

Pharmacology and safety of tetradecylthioacetic acid (TTA): phase-1 study.

This study describes the clinical, hematological, and biochemical safety of tetradecylthioacetic acid (TTA). A total of 18 healthy volunteers were included. Subjects were randomly assigned into 3 groups according to the daily given dose of TTA: group 1 (200 mg), group 2 (600 mg), and group 3 (1000 mg). TTA was given as a single oral dose for 7 consecutive days. Safety was evaluated by following the adverse events, vital signs, and hematological and biochemical parameters in blood and urine samples. Efficacy was estimated through its effects on plasma lipids profile. Few adverse events of mild severity were reported. No clinically significant changes were observed in the hematological or clinical chemical parameters in blood/urine. TTA did not induce significant changes in the blood lipids or free fatty acids, but it did result in an increase in plasma concentration of Δ9 desaturated TTA (TTA: 1n-8). Serum concentration pattern of TTA at day 1 showed a 1.5-hour lag time followed by a rapid absorption and a slower elimination phase. The median peak values were 2.9 mg/L (range, 1.1 to 5.4 mg/L), 11.5 mg/L (range, 4 to 35 mg/L), and 11 mg/L (range, 5 to 25 mg/L), in groups 1, 2, and 3, respectively (P = 0.006). The time to peak levels were 3.5 hours (range, 2.5 to 6.5 hours), 2.5 hours (range, 2.5 to 4.5 hours), and 4.5 hours (range, 2.5 to 12 hours), respectively (P = 0.2). TTA is safe and well tolerated.

Effects of local delivery of Tetradecylthioacetic acid within the injured coronary vessel wall

Abstract Objectives. Inflammation is involved in cell proliferation and collagen deposition causing vessel wall remodeling and restenosis after plain balloon angioplasty. Local drug delivery of bioactive agents that reduce the incidence of adverse wall remodeling is of considerable interest concerning treatment strategies for coronary vessel disease and could alter the need of repeated revascularization. Design. In this study, 34 domestic pigs undergoing coronary balloon injury were randomly assigned to Tetradecylthioacetic acid (TTA) or placebo delivered locally. After four weeks, vessel wall collagen density, inflammatory markers and lipid fractions were assessed as well as cell proliferation. Results. Collagen particle count was lower after TTA compared to placebo, 177 ± 11 n/area versus 225 ± 13 n/area (p = 0.007). Interleukin-2 (IL-2) concentration was reduced, 1.6 ± 0.02 pg/ml versus 2.6 ± 0.5 pg/ml, (p = 0.01). The anti-inflammatory index was increased after TTA, 46.28 ± 12.1 versus 34.66 ± 4.5, (p = 0.025). There were no differences between TTA and placebo with regard to cell proliferation. Conclusions. Local delivery of TTA reduced the local inflammatory response and collagen accumulation. Local balloon delivery of TTA into the vessel wall may represent an alternative antiproliferative strategy for preventing restenosis, in particular for vessels with obstructive disease not available for stent implantation.

Only transient increase of vascular growth factors and microvascular density after percutaneous myocardial laser.

ObjectiveWe tested the hypothesis that percutaneous myocardial laser may stimulate microvascular growth in areas surrounding the laser channels. MethodsWe conducted a study of 24 domestic pigs, which underwent percutaneous myocardial laser to left ventricular myocardium using holmium:YAG laser. The pigs were sacrificed in groups of four after one day, 3–4 days, one week, three weeks and six weeks. Frozen sections from both normal and treated myocardium were prepared for immunofluorescence microscopy and stained with antibodies against von Willebrand factor, vascular endothelial growth factor (VEGF) and Extra Domain-A cellular fibronectin (ED-AcFN). Microvascular density (MVD) and vascular area (VA) were determined in sections stained with antibodies against von Willebrand factor VIII using a digitised image analysis system. When determined in laser treated areas, channel core remnants were excluded from analysis. ResultsWithin the laser channel remnants and in the tissue closely surrounding these, expression of VEGF and ED-AcFN increased significantly after treatment at one, 3–4, and seven days and decreased to normal at three and six weeks. Expression of ED-AcFN was detected adjacent to endothelial cells of microvessels. The original laser channels were rapidly invaded by granulation tissue. There was no sign of recanalization at any stage during the six weeks. Morphometric analysis showed no increase in MVD and VA in the myocardium surrounding the laser channels. ConclusionAn increase of VEGF and ED-AcFN after myocardial laser is transient and is not associated with increase of MVD or VA in myocardium not involving laser channel remnants.