Reidar J. Pettersen

Percutaneous left ventricular assist device can prevent acute cerebral ischaemia during ventricular fibrillation

AIMS A percutaneous left ventricular assist device has been shown to be able to perfuse cardiac and cerebral tissues during cardiac arrest and may be a useful supplement to current methods in resuscitation. We wished to assess device-assisted circulation during cardiac arrest with microspheres injections and continuous end-tidal CO(2) monitoring, and used cerebral microdialysis to detect ischaemia in the brain. METHODS 12 anaesthetised pigs had microdialysis and pressure catheters implanted via craniotomy. The percutaneous assist device was deployed transfemorally. Ventricular fibrillation was induced by angioplasty-balloon occlusion of the left coronary artery. Cerebral microdialysis samples representing 0-20 and 20-40 min of cardiac arrest with assisted circulation were analysed for markers of cerebral injury (glucose, pyruvate, lactate, and glycerol). RESULTS Microdialysis showed no ischaemic changes after 20 min of cardiac arrest (P=NS to Baseline for glucose, glycerol, lactate, pyruvate and lactate/pyruvate ratio) in subjects with maintained end-tidal CO(2) values above 1.3 kPa (10 mmHg). After 40 min only lactate showed a significant change compared to Baseline (P<0.05). Microspheres flow to the brain was 57% and myocardial flow was 72% compared to Baseline after 15 min (P<0.05). After 45 min flow declined to 22% and 40% of Baseline, respectively (P=NS vs. 15 min). CONCLUSIONS A percutaneous left ventricular assist device may prevent ischaemic cerebral injury during cardiac arrest for a limited time. Cerebral injury and tissue perfusion were indicated by end-tidal CO(2).

Sustained retention of tetradecylthioacetic acid after local delivery reduces angioplasty-induced coronary stenosis in the minipig.

OBJECTIVE The sulfur containing tetradecylthioacetic acid (TTA) has a profound effect on lipid metabolism and may also exert antioxidant and anti-inflammatory actions and thereby counteract coronary stenosis after angioplasty balloon injury. This study examined the possible modulatory effects of TTA, delivered locally, on coronary stenosis in minipigs and the underlying mechanisms of action. METHODS Coronary balloon angioplasty injury using an oversized balloon was performed to 40 coronary arteries (20 minipigs, Sus Scrofa, Gammelsroed) followed by delivery of placebo or TTA via a local drug delivery balloon catheter. TTA was radiolabelled in four pigs. Quantitative coronary angiography and intracoronary ultrasound (ICUS) were performed before and after injury, and after 4 weeks of follow-up. The arteries were examined with histomorphometry. The antioxidant and anti-inflammatory effects of TTA were examined on LDL oxidation and stimulated release of interleukin (IL)-2 and IL-10 in human peripheral blood mononuclear cells (PBMC), respectively. RESULTS Radioactive TTA was present in the coronary wall after 4 weeks. Angiographic minimal luminal diameter (mean+/-S.E.M.) in the placebo and TTA group was 1.3+/-0.1 vs. 2.2+/-0.2 mm (P<0.01) at follow-up, stenosis rate was 55 and 20% (P<0.01). Remodeling was -0.56+/-0.12 in the TTA group and -1.28+/-0.09 in the placebo group (P<0.01). TTA significantly prolonged the lag time of LDL oxidation. In phytohemagglutinin stimulated PBMC, TTA significantly decreased IL-2 levels and increased IL-10 levels suggesting a marked anti-inflammatory net effect. CONCLUSIONS Local delivery of TTA reduces coronary artery stenosis after PTCA as assessed by both angiographic, histomorphometric and ICUS examinations by influencing vessel remodeling rather than intimal hyperplasia. The underlying mechanism(s) seem to involve antioxidant and anti-inflammatory effects of this fatty acid analogue.

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.

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.

Tetradecylselenoacetic Acid, a PPAR Ligand With Antioxidant, Antiinflammatory, and Hypolipidemic Properties

Objective—Antioxidants protect against oxidative stress and inflammation, which, in combination with hyperlipidemia, are important mediators of atherogenesis. Here we present a selenium-substituted fatty acid, tetradecylselenoacetic acid (TSA), which is hypothesized to have antioxidant, antiinflammatory, and hypolipidemic properties. Methods and Results—We show that TSA exerts antioxidant properties by delaying the onset of oxidation of human low density lipoprotein (LDL), by reducing the uptake of oxidized LDL in murine macrophages, and by increasing the mRNA level of superoxide dismutase in rat liver. TSA also showed antiinflammatory effects by suppressing the release of interleukin (IL)-2 and -4, and by increasing the release of IL-10 in human blood leukocytes. In addition, TSA decreased the plasma triacylglycerol level and increased the mitochondrial fatty acid &bgr;-oxidation in rat liver. In pigs, TSA seemed to reduce coronary artery intimal thickening after percutaneous coronary intervention. In HepG2 cells TSA activated all peroxisome proliferator-activated receptors (PPARs) in a dose-dependent manner. Conclusions—Our data suggest that TSA exert potent antioxidant, antiinflammatory, and hypolipidemic properties, potentially involving PPAR-related mechanisms. Based on these effects, it is tempting to hypothesize that TSA could be an interesting antiatherogenic approach to atherosclerotic disorders.

Randomised comparison of percutaneous left ventricular assist device with open-chest cardiac massage and with surgical assist device during ischaemic cardiac arrest.

AIMS A percutaneous left ventricular assist device can maintain blood flow to vital organs during ventricular fibrillation and may improve outcomes in ischaemic cardiac arrest. We compared haemodynamic and clinical effects of a percutaneous left ventricular assist device with a larger device deployed via endovascular prosthesis and with open-chest cardiac massage during ischaemic cardiac arrest. METHODS Eighteen swine were randomised into three groups. After thoracotomy, coronary ischaemia and ventricular fibrillation was induced. Cardiac output was measured with transit-time flowmetry. Tissue perfusion was measured with microspheres. Defibrillation was performed after 20 min. RESULTS Cardiac output with cardiac massage was 1129 mL min⁻¹ vs. 1169 mL min⁻¹ with the percutaneous- and 570 mL min⁻¹ with the surgical device (P < 0.05 surgical vs. others). End-tidal CO₂ was 3.3 kPa with cardiac massage vs. 3.2 kPa with the percutaneous- and 2.3 kPa with the surgical device (P < 0.05 surgical vs. others). Subepicardial perfusion was 0.33 mL min⁻¹ g⁻¹ with cardiac massage vs. 0.62 mL min⁻¹ g⁻¹ with both devices (P < 0.05 devices vs. massage), cerebral perfusion was comparable between groups (all reported values after 3 min cardiac arrest, all P<0.05 vs. baseline, all P = NS for 3 min vs. 15 min). Return of spontaneous circulation was achieved in 5/6 subjects with cardiac massage vs. 6/6 with the percutaneous- and 4/6 with the surgical device (P = NS). CONCLUSION The percutaneous device improved myocardial perfusion, maintained cerebral perfusion and systemic circulation with similar rates of successful defibrillation vs. cardiac massage. Increased delivery was not obtained with the surgical device during cardiac arrest.

Ketorolac (Toradol®) as an analgesic in swine following transluminal coronary angioplasty

Post-procedure pain is a common complication in swine following survival angioplastic procedures. Ketorolac and buprenorphine have been used to control pain in these animals. Time from completion of procedure-extubation to onset of feeding was used as an indicator for analgesic effect. The onset of feeding following extubation occurs within 6 to 20 h in animals given ketorolac compared to 30 plus hours in animals given buprenorphine.

Treatment of cardiogenic shock with left ventricular assist device combined with cardiac resynchronization therapy: A case report

Cardiogenic shock has a poor prognosis with established treatment strategies. We report a 62 years old man with heart failure exacerbating into refractory cardiogenic shock successfully treated with the combination of a percutaneous left ventricular assist device (LVAD) and subacute cardiac resynchronization therapy (CRT) implantable cardioverter-defibrillator device (CRT-D).

Long-term retention of a novel antioxidant sulphur-substituted fatty acid analogue after local delivery in porcine coronary arteries.

OBJECTIVE Antioxidants have been suggested to reduce restenosis after balloon angioplasty. A novel sulphur-containing fatty acid, tetradecylthioacetic acid (TTA), with antioxidant properties, is efficiently incorporated into cellular phospholipids. We have determined the uptake and retention of TTA after local coronary artery delivery in 20 pigs. DESIGN Radiolabelled TTA was delivered to 40 main coronary arteries via a multiporous coronary angioplasty balloon catheter inflated before, after, or without overstretch vessel injury. The animals were killed at intervals of up to 6 weeks post-procedure. The radioactivity of the tissue sections was determined as nmol TTA/g tissue. RESULTS Concentrations of TTA in the coronary arteries were 1.84 +/- 0.45 nmol/g up to 24 h, 1.50 +/- 0.96 nmol/g at 2 weeks, 0.22 +/- 0.11 nmol/g at 4 weeks and a trace was present at 6 weeks (p-value for trend <0.01). The arterial wall uptake at the delivery site was higher than distal to delivery (1.84 +/- 0.37 vs 0.55 +/- 0.13 nmol/g, p = 0.006) and perivascular fat (p < 0.01) but not higher than in the myocardium. Infusion before, after or without vessel injury was not important for tissue concentration. CONCLUSIONS After local coronary artery delivery, the antioxidant TTA is taken up by the arterial wall in which it is retained for at least 4 weeks.Objective: Antioxidants have been suggested to reduce restenosis after balloon angioplasty. A novel sulphurcontaining fatty acid, tetradecylthioacetic acid (TTA), with antioxidant properties, is efficiently incorporated into cellular phospholipids. We have determined the uptake and retention of TTA after local coronary artery delivery in 20 pigs. Design: Radiolabelled TTA was delivered to 40 main coronary arteries via a multiporous coronary angioplasty balloon catheter inflated before, after, or without overstretch vessel injury. The animals were killed at intervals of up to 6 weeks post-procedure. The radioactivity of the tissue sections was determined as nmol TTA/g tissue. Results:

Percutaneous Catheter-based Intracoronary Infusion of Insulin - A Dose Finding Study in the Porcine Model

Insulin given at immediate reperfusion reduces myocardial infarct size in the in vitro and the ex vivo rat heart. In vivo, insulin may cause hypoglycaemia, hypokalaemia and elevation of catecholamines, potentially harmful during an acute myocardial infarction. The purpose of this study was to evaluate tolerance and safety of intracoronary insulin infusions in a porcine model applying percutaneous intervention techniques.