Hon Kan Yip

Systemic combined melatonin–mitochondria treatment improves acute respiratory distress syndrome in the rat

Despite high in‐hospital mortality associated with acute respiratory distress syndrome (ARDS), there is no effective therapeutic strategy. We tested the hypothesis that combined melatonin–mitochondria treatment ameliorates 100% oxygen‐induced ARDS in rats. Adult male Sprague‐Dawley rats (n = 40) were equally categorized into normal controls, ARDS, ARDS‐melatonin, ARDS with intravenous liver‐derived mitochondria (1500 μg per rat 6 hr after ARDS induction), and ARDS receiving combined melatonin–mitochondria. The results showed that 22 hr after ARDS induction, oxygen saturation (saO2) was lowest in the ARDS group and highest in normal controls, significantly lower in ARDS‐melatonin and ARDS‐mitochondria than in combined melatonin–mitochondria group, and significantly lower in ARDS‐mitochondria than in ARDS‐melatonin group. Conversely, right ventricular systolic blood pressure and lung weight showed an opposite pattern compared with saO2 among all groups (all P < 0.001). Histological integrity of alveolar sacs showed a pattern identical to saO2, whereas lung crowding score exhibited an opposite pattern (all P < 0.001). Albumin level and inflammatory cells (MPO+, CD40+, CD11b/c+) from bronchoalveolar lavage fluid showed a pattern opposite to saO2 (all P < 0.001). Protein expression of indices of inflammation (MMP‐9, TNF‐α, NF‐κB), oxidative stress (oxidized protein, NO‐1, NOX‐2, NOX‐4), apoptosis (mitochondrial Bax, cleaved caspase‐3, and PARP), fibrosis (Smad3, TGF‐β), mitochondrial damage (cytochrome C), and DNA damage (γ‐H2AX+) exhibited an opposite pattern compared to saO2 in all groups, whereas protein (HO‐1, NQO‐1, GR, GPx) and cellular (HO‐1+) expressions of antioxidants exhibited a progressively increased pattern from normal controls to ARDS combined melatonin–mitochondria group (all P < 0.001). In conclusion, combined melatonin–mitochondrial was superior to either treatment alone in attenuating ARDS in this rat model.

Long-term effects of baroreflex function after stenting in patients with carotid artery stenosis

Baroreflex sensitivity is recognized for its prognostic relevance to cardio-vascular and cerebro-vascular risks. However, little is known about the long-term outcome of baroreflex function in patients with carotid stenosis undergoing carotid stenting. Heart rate variability and cardio-vascular autonomic function, including baroreflex sensitivity, were examined using non-invasive methods in 22 adult patients who underwent carotid stenting. They were compared with the normal control group with 22 sex- and age-matched normal volunteers and the risk control group with 10 adult patients with severe stenosis or even total occlusion of the carotid artery without stenting. The groups of patients with stenting and risk controls had significantly reduced valsalva ratio and baroreflex sensitivity measured by the valsalva method compared to normal controls. However, there was no significant difference between patients with stenting and risk controls. There was significant decrease in heart rate response to deep breathing and to head-up tilt in patients with carotid stenting compared to normal controls. Other parameters of cardio-vascular autonomic function showed no difference among the three groups. Reduced baroreceptor function in patients with carotid stenting may be due to underlying diseases rather than the stenting itself. There was no short-term parasympathetic hyperactivity after the stenting, suggesting that the effect is transient rather than permanent.

Enhancement of Wound Healing by Non-Thermal N2/Ar Micro-Plasma Exposure in Mice with Fractional-CO2-Laser-Induced Wounds

Micro-plasma is a possible alternative treatment for wound management. The effect of micro-plasma on wound healing depends on its composition and temperature. The authors previously developed a capillary-tube-based micro-plasma system that can generate micro-plasma with a high nitric oxide-containing species composition and mild working temperature. Here, the efficacy of micro-plasma treatment on wound healing in a laser-induced skin wound mouse model was investigated. A partial thickness wound was created in the back skin of each mouse and then treated with micro-plasma. Non-invasive methods, namely wound closure kinetics, optical coherence tomography (OCT), and laser Doppler scanning, were used to measure the healing efficiency in the wound area. Neo-tissue growth and the expressions of matrix metallopeptidase-3 (MMP-3) and laminin in the wound area were assessed using histological and immunohistochemistry (IHC) analysis. The results show that micro-plasma treatment promoted wound healing. Micro-plasma treatment significantly reduced the wound bed region. The OCT images and histological analysis indicates more pronounced tissue regrowth in the wound bed region after micro-plasma treatment. The laser Doppler images shows that micro-plasma treatment promoted blood flow in the wound bed region. The IHC results show that the level of laminin increased in the wound bed region after micro-plasma treatment, whereas the level of MMP-3 decreased. Based on these results, micro-plasma has potential to be used to promote the healing of skin wounds clinically.

Acute Coronary Syndrome in Cisatracurium-induced Anaphylactic Shock: Kounis Syndrome

In this case report, we describe a 70-year-old male patient who sustained Kounis syndrome induced by cisatracurium administration immediately following induction of general anesthesia. Acute coronary syndrome combined with anaphylactic shock, termed Kounis syndrome, should be investigated in percutaneous coronary intervention to solve this complex and life-threatening condition. A team effort by cardiologist and anesthesiologist is essential for successful resuscitation. In general, the incidence of an anaphylactic reaction to cisatracurium is low, but a high serum IgE level in combination with a positive skin prick test in our patient was strongly suggestive of cisatracurium-induced Kounis syndrome. In addition, a cross-reaction between cisatracurium and rocuronium is reported.

Transradial retrograde approach rescuing iatrogenic long spiral dissection during chronic total occlusion intervention

Percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) is one of the greatest challenges in coronary interventions. A retrograde approach via the collateral channel has been recently proposed to improve the success rate of PCI in CTO lesions of the coronary arteries. We describe an accidental complication encountered during transradial PCI to recanalize right coronary artery CTO in a patient with unstable angina. A long spiral dissection has been created by antegrade wiring and extended from the ostium all the way down to mid RCA segment. Subsequent attempts with antegrade wiring into the true lumen were unsuccessful. Ad‐hoc retrograde recanalization has been employed to rescue the vessel via septal collateral from left anterior descending artery. Retrograde wiring and dilatation were performed followed by successful antegrade wiring into the true lumen under IVUS guidance, which revealed significant intramural hematoma extending distally to the posterolateral branch. Bailout stenting was achieved with sealing of the multiple entry and exit sites created by the spiral dissection and complete coverage of the intramural hematoma. This report highlights the role of the retrograde approach as a rescue option in the setting of complicated antegrade approach and to improve the success rate of CTO‐PCI. Moreover, IVUS was a valuable tool to confirm the true lumen course of the successful wire and to guide the stenting procedure.

Aspirin for Stroke Prevention Taken in the Evening? * Response:

To the Editor: We read the article by Yip et al1 with great interest, in which they demonstrated that platelet activation significantly increases in acute ischemic stroke and subtantially decreases thereafter. The lesser long-term pharmacodynamic potency of aspirin relative to clopidogrel raises the prospect of the need for more effective antiplatelet agents or a synergistic combination therapy for stroke prevention in the future.1 Their results are very impressive and raise some ideas, particularly associated with the prevention’s procedures. According to World Health Organization data, in 1996 4.6 million people in the world died because of cerebrovascular manifestation of atherothrombosis.2 In Hungary, nearly 18 000 people suffer stroke every year, half of whom die within a year. In cases of both cardiovascular and cerebrovascular diseases the significant decrease of morbidity/mortality can only be achieved by increasing the effect of prevention. A major form of secondary prevention is the administration of drugs inhibiting the aggregation of platelets. Aspirin is one of the most common, useful, and inexpensive tools for prevention. The effect of aspirin on platelets is irreversible lasting for the duration of the platelet’s life span (≈10 days). Aspirin-mediated inhibition of platelet function occurs within 60 minutes of ingestion.3 The incidence of stroke assessed by onset of clinical symptoms exhibits a marked circadian variation with a peak period during the morning. Stroke usually occurs unexpectedly and more frequently in early morning …

Impact of Combined Adipose-Derived Mesenchymal Stem Cell (ADMSC) and Low-Energy of Extracorporeal Shock Wave Therapy on Protecting Brain Death-Induced Remote Organ Damage in Rat

ABSTRACT Objective: This study tested the hypothesis that allogenic adipose-derived mesenchymal stem cell (ADMS) and extracorporeal shock wave (ECSW) therapy could attenuate brain death (BD)-induced remote cardiac organ damage in rat. Methods: Adult-male SD rats (n=30) were equally divided into group 1 (sham control); group 2 (BD); group 3 [BD + ECSW (0.15 mJ/mm2/300 impulses applied to skull surface 3 h after BD induction)]; group 4 [BD + ADMSC (1.2 x 106 cell) by intravenous injection 3 h after BD induction]; and group 5 (BD-ECSW-ADMSC). Animals were sacrificed by 6 h after BD induction and the heart specimens harvested. Results: ELISA analysis showed that the circulating level of inflammation (IL-6/MPO/TNF-α) was lowest in group 1, highest in group 2, significantly lower in groups 5 than in groups 3 and 4, and significantly lower in group 4 than in group 3 (all p<0.0001). Flow cytometry demonstrated that circulating inflammatory (Ly6G+) cells and circulating/splenic immune (CD3/CD4+/CD3/CD8+) exhibited an identical pattern whereas Treg+ cells expressed an opposite pattern of inflammatory biomarkers (all p<0.001). The protein expressions of inflammatory (IL-1s/MMP-9/TNF-α/NF-κB/), and apoptotic (cleaved/caspase-3/PARP/ mitochondrial Bax), oxidative-stress (NOX-1/NOX-2/oxidized protein) biomarkers exhibited an identical pattern, whereas the protein expressions of mitochondrial integrity (mitochondrial cytochrome C) and anti-inflammatory (IL-4/IL-10) biomarkers exhibited an opposite pattern to inflammatory biomarkers among the five groups (all p<0.0001). The expressions of myocardial inflammatory (CD14+/CD68+) and immune (CD3+/CD4+) cells displayed an identical pattern of inflammatory biomarkers among the five groups (all p<0.0001). Conclusion: ECSW-ADMSC therapy effectively protected the remote cardiac organ against BD-induced damage.

Transradial retrograde approach rescuing iatrogenic long spiral dissection during chronic total occlusion intervention: Retrograde Approach as a Rescue Option

Percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) is one of the greatest challenges in coronary interventions. A retrograde approach via the collateral channel has been recently proposed to improve the success rate of PCI in CTO lesions of the coronary arteries. We describe an accidental complication encountered during transradial PCI to recanalize right coronary artery CTO in a patient with unstable angina. A long spiral dissection has been created by antegrade wiring and extended from the ostium all the way down to mid RCA segment. Subsequent attempts with antegrade wiring into the true lumen were unsuccessful. Ad‐hoc retrograde recanalization has been employed to rescue the vessel via septal collateral from left anterior descending artery. Retrograde wiring and dilatation were performed followed by successful antegrade wiring into the true lumen under IVUS guidance, which revealed significant intramural hematoma extending distally to the posterolateral branch. Bailout stenting was achieved with sealing of the multiple entry and exit sites created by the spiral dissection and complete coverage of the intramural hematoma. This report highlights the role of the retrograde approach as a rescue option in the setting of complicated antegrade approach and to improve the success rate of CTO‐PCI. Moreover, IVUS was a valuable tool to confirm the true lumen course of the successful wire and to guide the stenting procedure.

Aspirin for stroke prevention taken in the evening? [8] (multiple letters)

To the Editor: We read the article by Yip et al1 with great interest, in which they demonstrated that platelet activation significantly increases in acute ischemic stroke and subtantially decreases thereafter. The lesser long-term pharmacodynamic potency of aspirin relative to clopidogrel raises the prospect of the need for more effective antiplatelet agents or a synergistic combination therapy for stroke prevention in the future.1 Their results are very impressive and raise some ideas, particularly associated with the prevention’s procedures. According to World Health Organization data, in 1996 4.6 million people in the world died because of cerebrovascular manifestation of atherothrombosis.2 In Hungary, nearly 18 000 people suffer stroke every year, half of whom die within a year. In cases of both cardiovascular and cerebrovascular diseases the significant decrease of morbidity/mortality can only be achieved by increasing the effect of prevention. A major form of secondary prevention is the administration of drugs inhibiting the aggregation of platelets. Aspirin is one of the most common, useful, and inexpensive tools for prevention. The effect of aspirin on platelets is irreversible lasting for the duration of the platelet’s life span (≈10 days). Aspirin-mediated inhibition of platelet function occurs within 60 minutes of ingestion.3 The incidence of stroke assessed by onset of clinical symptoms exhibits a marked circadian variation with a peak period during the morning. Stroke usually occurs unexpectedly and more frequently in early morning …