A Pilot Study of Rapid Cooling by Cold Saline and Endovascular Cooling Before Reperfusion in Patients With ST-Elevation Myocardial Infarction
ABSTRACT Experimental studies have shown that induction of hypothermia before reperfusion of acute coronary occlusion reduces infarct size. Previous clinical studies, however, have not been able to show this effect, which is believed to be mainly because therapeutic temperature was not reached before reperfusion in the majority of the patients. We aimed to evaluate the safety and feasibility of rapidly induced hypothermia by infusion of cold saline and endovascular cooling catheter before reperfusion in patients with acute myocardial infarction.
Twenty patients with acute myocardial infarction scheduled to undergo primary percutaneous coronary intervention were enrolled in this prospective, randomized study. After 4 ± 2 days, myocardium at risk and infarct size were assessed by cardiac magnetic resonance using T2-weighted imaging and late gadolinium enhancement imaging, respectively. A core body temperature of <35°C (34.7 ± 0.3°C) was achieved before reperfusion without significant delay in door-to-balloon time (43 ± 7 minutes versus 40 ± 6 minutes, hypothermia versus control, P=0.12). Despite similar duration of ischemia (174 ± 51 minutes versus 174 ± 62 minutes, hypothermia versus control, P=1.00), infarct size normalized to myocardium at risk was reduced by 38% in the hypothermia group compared with the control group (29.8 ± 12.6% versus 48.0 ± 21.6%, P=0.041). This was supported by a significant decrease in both peak and cumulative release of Troponin T in the hypothermia group (P=0.01 and P=0.03, respectively).
The protocol demonstrates the ability to reach a core body temperature of <35°C before reperfusion in all patients without delaying primary percutaneous coronary intervention and that combination hypothermia as an adjunct therapy in acute myocardial infarction may reduce infarct size at 3 days as measured by MRI.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00417638.
SourceAvailable from: Erik Kulstad
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ABSTRACT: The mode of protection against cardiac reperfusion injury by mild hypothermia and TRO40303 was investigated in various experimental models and compared to MitoQ in vitro. In isolated cardiomyocytes subjected to hypoxia/reoxygenation, TRO40303, MitoQ and mild hypothermia delayed mPTP opening, inhibited generation of mitochondrial superoxide anions at reoxygenation and improved cell survival. Mild hypothermia, but not MitoQ and TRO40303, provided protection in a metabolic starvation model in H9c2 cells and preserved respiratory function in isolated rat heart mitochondria submitted to anoxia/reoxygenation. In the Langendorff-perfused rat heart, only mild hypothermia provided protection of hemodynamic function and reduced infarct size following ischemia/reperfusion. In biopsies from the left ventricle of pigs subjected to in vivo occlusion/reperfusion, TRO40303 specifically preserved respiratory functions in the peri-infarct zone whereas mild hypothermia preserved both the ischemic core area and the peri-infarct zones. Additionally in this pig model, only hypothermia reduced infarct size. We conclude that mild hypothermia provided protection in all models by reducing the detrimental effects of ischemia, and when initiated before occlusion, reduced subsequent reperfusion damage leading to a smaller infarct. By contrast, although TRO40303 provided similar protection to MitoQ in vitro and offered specific protection against some aspects of reperfusion injury in vivo, this was insufficient to reduce infarct size. Copyright © 2015. Published by Elsevier B.V.European journal of pharmacology 04/2015; 760. DOI:10.1016/j.ejphar.2015.04.009 · 2.68 Impact Factor
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ABSTRACT: An increasing number of conditions appear to benefit from control and modulation of temperature, but available techniques to control temperature often have limitations, particularly in smaller patients with high surface to mass ratios. We aimed to evaluate a new method of temperature modulation with an esophageal heat transfer device in a pediatric swine model, hypothesizing that clinically significant modulation in temperature (both increases and decreases of more than 1°C) would be possible. Three female Yorkshire swine averaging 23 kg were anesthetized with inhalational isoflurane prior to placement of the esophageal device, which was powered by a commercially available heat exchanger. Swine temperature was measured rectally and cooling and warming were performed by selecting the appropriate external heat exchanger mode. Temperature was recorded over time in order to calculate rates of temperature change. Histopathology of esophageal tissue was performed after study completion. Average swine baseline temperature was 38.3°C. Swine #1 exhibited a cooling rate of 3.5°C/hr; however, passive cooling may have contributed to this rate. External warming blankets maintained thermal equilibrium in swine #2 and #3, demonstrating maximum temperature decrease of 1.7°C/hr. Warming rates averaged 0.29°C/hr. Histopathologic analysis of esophageal tissue showed no adverse effects. An esophageal heat transfer device successfully modulated the temperature in a pediatric swine model. This approach to temperature modulation may offer a useful new modality to control temperature in conditions warranting temperature management (such as maintenance of normothermia, induction of hypothermia, fever control, or malignant hyperthermia).BMC Anesthesiology 02/2015; 15(1). DOI:10.1186/1471-2253-15-16 · 1.33 Impact Factor