Impact of therapeutic hypothermia on coronary flow.

Mild hypothermia therapy (HT) improves survival and neurologic outcome after sudden cardiac death (SCD) [1]. Despite the controversy between the relation of HT and stent thrombosis (ST) [2], our group reported an increased risk of ST in patients treated with HT [3]. Increased platelet activation and a potential inefficiency of antiplatelet therapy may explain the increased riskof ST inHT.Nonetheless, recentdata suggest that other etiologic mechanisms may play a role in the occurrence of thrombotic events. Experimental models have demonstrated a relationship between HT and endothelial dysfunction [4]. Endothelial disorders have been associated with coronary-flow impairment and therefore thrombotic events [5,6]. The objective of our study was to analyze the impact of HT on coronary microcirculation by comparing the coronary flow measured by thrombolysis in Myocardial Infarction frame count (TFC) with and without HT. From January 2010 to March 2013, 55 patients with out-of-hospital SCD were admitted in our institution and treated with HT (mean age 55.4 ± 15 years, 67% male). Of them, 39 (70.9%) patients had STsegment elevation myocardial infarction (STEMI) and underwent primary PCI. The HT protocol was accomplished as previously described [2]. We selected those patients in whom two coronary angiographies (with and without HT) were performed (see Table 1). Five patients (12.9%) were included in the analysis. In every patient, a clear distal anatomic landmarkwas selected as the region of interest to quantify the TFC, andmeasurementswere repeated in both normothermia andHT. In case of STEMI or ST, the coronary flow was always measured in a noninfarct related artery. Coronary angiography technique including catheter shape, catheter diameter, automatic contrast injection flow, and projection were the same for every paired angiography. An experienced reviewer blinded to the temperature condition assessed the TFC. TFC values were compared using t-test for repeated measures with SPSS ® v.18.0 (IBM Corp., Armonk, NY, USA). Patient characteristics, clinical status and TFC are summarized in Table 1. Patients with cardiogenic shock were treated with IV norepinephrine and/or dobutamine infusion according to guidelines. Coronary angiography in normothermiawas performed after SCDwith a diagnosis of STEMI in 80% of patients. Coronary angiography in HT was indicated in 80% of patients because a suspicion of ST. Despite the small number of patients, a noteworthy trend towards a higher TFCwas observed in hypothermia compared to normothermia (11.6 vs. 8.0; p = 0.066) (Fig. 1). VanGenderen et al. [7] reporteda significantmicrocirculatory disorder after HTas a result of changes in body temperature rather than changes in systemic hemodynamic variables. Accordingly, Ergenekon observed that newborn patients treated with hypothermia for hypoxic ischemic encephalopathy presented a sluggish peripheral flow when compared to controls [8]. Recently, Zoerner et al. [4] demonstrated that mild HT is associated with higher plasmatic levels of endothelin-1 (ET-1). ET-1, a potent vasoconstrictor isolated from endothelial cells, has a biological effect that includes platelet activation and vascular dysfunction and is associated with a lower endothelial progenitor cell mobilization after myocardial infarction [9]. High ET-1 levels have been linked to impaired coronary circulation including slow coronary flow and even no-reflow. Slow coronary flow is a recognized predictor of thrombotic events, althoughother factorsmayalsoplaya role. The results of our studysuggest thatmildHTmight slowdown coronaryflowand endothelial dysfunction seems to be the most plausible explanation considering the previous published data [4,7]. The identification of other potential pro-thrombotic mechanisms besides the coagulation and platelet disorders seems to be of pivotal importance when designing strategies for preventing thrombotic events. In this sense, the present manuscript should be considered as hypothesis generating and encourage future research. Although the small number of patients is the main limitation of the study, the strong trend towards a reduced TFC despite the limited sample and the difficulties finding patients with SCD with two coronary angiographies (with and without HT) should be taken into consideration.