The Complex Relationship Between Cooling Parameters and Neuroprotection in a Model of Selective Hypothermia.

Background: Hypothermia remains the best studied neuroprotectant. Despite extensive positive large and small animal data, side effects continue to limit human applications. Selective hypothermia is an efficient way of applying neuroprotection to the brain without the systemic complications of global hypothermia. However, optimal depth and duration of therapeutic hypothermia are still unknown. We analyzed a large animal cohort study of selective hypothermia for statistical relationships between depth or duration of hypothermia and the final stroke volume. Methods: A cohort of 30 swine stroke subjects provided the dataset for normothermic and selective hypothermic animals. Hypothermic parameters including duration, temperature nadir, and an Area Under the Curve measurement for 34 and 30°C were correlated with the final infarct volumes measured by MRI and histology. Results: Between group comparisons continue to demonstrate a reduction in infarct volume with selective hypothermia. Histologically-derived infarct volumes were 1.2 mm3 smaller in hypothermia-treated pigs (P = 0.04) and showed a similar, but non-significant reduction in MRI (P = 0.15). However, within the selective hypothermia group, more intense cooling, as measured through increased AUC 34 and decreased temperature nadir was associated with larger infarct proportions by MRI [Pearson's r = 0.48 (p = 0.05) and r = -0.59 (p = 0.01), respectively]. Reevaluation of the entire cohort with quadratic regression demonstrated a U-shaped pattern, wherein the average infarct proportion was minimized at 515 degree-minutes (AUC34) of cooling, and increased thereafter. In a single case of direct brain tissue oxygen monitoring during selective hypothermia, brain tissue oxygen strongly correlated with brain temperature reduction over the course of selective hypothermia to 23°C. Conclusions: In a large animal model of selective hypothermia applied to focal ischemia, there is a non-monotone relationship between duration and depth of hypothermia and stroke volume reduction. This suggests a limit to depth or duration of selective hypothermia for optimal neuroprotection. Further research is required to delineate more precise depth and duration limits for selective hypothermia.

Neuroprotection by selective endovascular brain cooling - the TwinFlo™ Catheter.

The neuroprotective effects of hypothermia have been demonstrated in experimental models and clinical trials. Experimental studies indicate that improved efficacy and broadened indications can be achieved with moderate to deep hypothermia. The TwinFlo catheter was designed to provide very rapid, deep and selective brain cooling with faster cooling rates, and temperatures much lower than those which can be achieved by any other hypothermia device and technique. This report describes the experimental in vivo studies and initial clinical experience with the TwinFlo catheter.

Improved outcome with novel device for low-pressure PTCA in de novo and in-stent lesions.

PURPOSE: Complex lesion morphology requiring the use of high pressure to effect lumen expansion and in-stent restenosis (ISR) remain two indications that challenge conventional PTCA balloons. We report on a new PTCA device that is designed to provide precise, low-pressure dilatation of both de novo and in-stent lesions. METHODS: The FX miniRAIL catheter (FX) has an integral wire positioned external to a dilating balloon and a short, 12-mm guidewire lumen distal to the balloon. The balloon inflates against the guidewire and the external wire to prevent slippage and to introduce high focal longitudinal stresses at low inflation pressures. In this initial study, the FX was used in 37 lesions (25 de novo, 12 in-stent; vessel reference diameter=2.73+/-0.49 mm) in 30 patients. A stepwise inflation protocol and QCA were used to determine the balloon pressure at which the stenosis was resolved (stenosis resolution pressure, SRP). RESULTS: All lesions (100%) were easily reached, crossed and dilated without complication. The SRP was 4.5+/-2.9 atm, and no balloon slippage was observed. Residual stenosis after FX was 26.39+/-13.29%. Minor dissections (Types A and B) were observed in eight lesions (21.6%). Target lesion revascularization (TLR) and target vessel revascularization (TVR) at follow-up (8.1+/-1.5 months) were 8.3% and 12.5%, respectively. CONCLUSION: The design of the FX is versatile and appears to provide for a safe, effective and improved low-pressure PTCA technique in de novo and in-stent lesions.

Focused force angioplasty: theory and application.

Focused force angioplasty is a technique in which the forces resulting from inflating an angioplasty balloon in a stenosis are concentrated and focused at one or more locations within the stenosis. While the technique has been shown to be useful in resolving resistant stenoses, its real value may be in minimizing the vascular trauma associated with balloon angioplasty and subsequently improving the outcome.