The research team, working at the Laboratory Animal Center of Shanghai University of Traditional Chinese Medicine, set out to answer two linked questions. First, could they establish a stable and reproducible rat model of lung injury driven by myocardial ischemia and reperfusion? Second, could pretreatment with electroacupuncture reduce that injury, and if so, did the HMGB1/RAGE pathway, a pair of molecules long implicated in acute lung inflammation, sit at the center of the mechanism? Their answer to both questions, based on a series of five carefully controlled experiments in male Sprague-Dawley rats, was yes.

Building the model required calibrating the injury. The researchers ligated the left anterior descending coronary artery in anesthetized rats for 30 minutes, 45 minutes, or one hour, then released the snare to allow 24 hours of reperfusion, confirming ischemia by visible cyanosis of the ventricular wall and ST-segment elevation on the electrocardiogram. Only the one-hour ischemia protocol produced consistent, measurable lung damage. In those animals, arterial oxygen partial pressure and the oxygenation index fell significantly, the alveolar-arterial oxygen gradient rose, and the lung wet-to-dry weight ratio, a standard gauge of pulmonary edema, climbed sharply. Under the microscope, the lungs showed alveolar collapse, hemorrhage, thickened septa, and dense inflammatory infiltration, and immunostaining revealed abundant cleaved caspase-3, a hallmark of apoptosis. Shorter ischemic periods produced weaker or statistically insignificant changes, establishing one hour of ischemia followed by 24 hours of reperfusion as the reliable model.

With the model in hand, the team turned to electroacupuncture. They stimulated two classical acupoints, Zusanli (ST36) on the hind limb and Feishu (BL13) on the back near the lungs, using a 2/20 Hz dense-disperse waveform for 30 minutes per session. The critical variable was timing. A single 30-minute session immediately before ischemia did essentially nothing: blood gas values, edema measures, injury scores, and apoptotic cell counts in that group were indistinguishable from the untreated ischemia-reperfusion group. But when the same stimulation was repeated over three consecutive days before the procedure, the picture changed dramatically. Oxygenation improved, the wet-to-dry ratio dropped, lung injury scores fell, and cleaved caspase-3 staining diminished significantly compared with injured animals that received no pretreatment.

The protective effect was accompanied by a clear anti-inflammatory signature. Quantitative PCR showed that ischemia-reperfusion drove up the messenger RNA of the pro-inflammatory cytokines IL-1β and IL-6 and the chemokines CXCL1 and CXCL2 in lung tissue. Three days of electroacupuncture pretreatment significantly reduced all four transcripts at four hours of reperfusion, with IL-6 and CXCL1 still suppressed at 24 hours. Immunohistochemistry told a parallel story at the cellular level: myeloperoxidase-positive neutrophils and F4/80-positive macrophages, the two dominant infiltrating populations, flooded the injured lungs after reperfusion but were markedly fewer in the pretreated animals at both early and late time points.

The molecular centerpiece of the study was HMGB1, a nuclear non-histone protein that escapes from stressed cells and acts as a danger signal when it binds transmembrane receptors, most notably RAGE and the Toll-like receptors. Western blotting and PCR revealed that ischemia-reperfusion significantly increased both HMGB1 and RAGE in lung tissue, and electroacupuncture pretreatment brought both back down at four and 24 hours of reperfusion. Because HMGB1 is known to recruit and activate inflammatory cells in many forms of acute lung injury, the authors reasoned that this axis could be the plausible bridge between the systemic inflammatory surge triggered by cardiac ischemia and the pulmonary damage that follows.

A key question was where the lung HMGB1 actually came from. The injured heart itself is an obvious suspect. Yet when the researchers measured HMGB1 expression in heart tissue, they found it elevated only in the earliest phase of inflammation and essentially normal by 24 hours of reperfusion, precisely when lung HMGB1 remained high. Moreover, electroacupuncture reduced lung HMGB1 without changing myocardial infarct size, measured by triphenyltetrazolium chloride staining, indicating that the treatment was not simply shrinking the cardiac wound and thereby sending fewer danger signals. The accumulating HMGB1 in the lungs, the data suggested, was generated locally rather than imported from the heart.

To test causality more directly, the team delivered recombinant HMGB1 protein directly into the lungs via intubation-mediated intratracheal administration before reperfusion. Adding the protein to injured animals worsened respiratory dysfunction, edema, and histological injury to some degree. More tellingly, in rats that had received the three-day electroacupuncture pretreatment, intratracheal recombinant HMGB1 significantly raised lung HMGB1 and RAGE expression, lowered oxygenation indices, increased the wet-to-dry ratio, worsened injury scores, and boosted apoptotic cell counts. In other words, flooding the lungs with the very molecule the therapy suppresses partially reversed its benefits, evidence that HMGB1 is not merely a bystander but a functional target of the electroacupuncture effect.

The authors are candid about the limits of their work. The validation relied on recombinant protein challenge rather than genetic knockout, which leaves some causal uncertainty, and the sample sizes were small, with five rats per group. All experiments were conducted in male animals, and no clinical data exist yet to confirm that the findings translate to patients awaiting cardiac surgery. Larger, multicenter human studies will be needed before electroacupuncture pretreatment can be recommended as a standard element of perioperative lung protection.

Even so, the study adds a compelling piece to a growing body of evidence that neuromodulation through acupuncture-like stimulation can precondition distant organs against surgical stress. Previous work has shown electroacupuncture protecting the lungs during cardiopulmonary bypass by dampening inflammasome activation and oxidative stress pathways, and the new findings extend that logic to the specific HMGB1/RAGE axis in the setting of myocardial ischemia and reperfusion. If the mechanism holds in humans, a low-side-effect intervention delivered in the days before surgery could help reduce the burden of postoperative pulmonary complications, aligning with the principles of enhanced recovery after surgery and broadening the toolkit of perioperative organ protection.

Subject of Research: Electroacupuncture pretreatment and protection against myocardial ischemia/reperfusion-induced lung injury via the HMGB1/RAGE pathway in rats

Article Title: Electroacupuncture pretreatment alleviates myocardial ischemia/reperfusion‐induced lung injury by inhibiting the expression of HMGB1/RAGE in male rats

Article References: Xie, C., Zhang, J., Zhang, Y., Chi, H., Yong, Y., & Song, J. (2026). Electroacupuncture pretreatment alleviates myocardial ischemia/reperfusion‐induced lung injury by inhibiting the expression of HMGB1 / RAGE in male rats. Physiological Reports, 14(18), Article e71066. https://doi.org/10.14814/phy2.71066

Image Credits: AI Generated

DOI: 10.14814/phy2.71066

Keywords: electroacupuncture, myocardial ischemia-reperfusion, lung injury, HMGB1, RAGE, inflammation, acute lung injury, cardiac surgery, pulmonary complications, rat model, preconditioning, enhanced recovery after surgery

The patient, a Nepalese man with well-controlled asthma and hypertension, first sought medical attention in 2017 after experiencing mild, intermittent hemoptysis—the coughing up of blood. A contrast-enhanced computed tomography (CT) scan revealed a large, compartmentalized collection along the right pleural space, the thin cavity between the lung and chest wall. The mass measured approximately 13.7 by 6.5 by 7 centimeters and appeared consistent with an organized pleural hematoma. Ultrasound-guided drainage produced altered, old blood rather than evidence of active hemorrhage. Tests found no acid-fast bacteria or other bacteria in the fluid, and cytological analysis showed no malignant cells. Because his symptoms were mild and his condition stabilized with oral tranexamic acid, a medication that helps prevent clot breakdown, he declined surgical removal.

The hematoma did not disappear. When the patient returned after another episode of hemoptysis in 2020, imaging showed new pockets of gas inside the otherwise blood-filled lesion. The finding was particularly concerning because he had undergone no intervening pleural procedure and had no documented infection that could readily explain gas formation. Clinicians suspected a bronchopleural fistula, an abnormal passage connecting the bronchial tree to the pleural cavity. Such a connection can allow air from the respiratory tract to enter the hematoma and, in the opposite direction, enable blood or infected material to reach the airways. The patient then returned to Nepal and was lost to medical follow-up for five years, leaving the suspected communication untreated while the encapsulated mass continued its slow evolution.

By late 2025, he re-presented with chest pain and severely elevated blood pressure. A CT angiogram ruled out an acute aortic dissection, but showed that the pleural hematoma had grown to 14.0 by 7.8 by 8.4 centimeters. Its outer capsule also contained more dystrophic calcification, a process in which calcium deposits accumulate in chronically damaged tissue. The increase in size was modest in some dimensions, but clinically important: a lesion occupying much of one side of the chest can compress adjacent lung tissue, restrict its expansion and impair the diaphragm’s movement. The patient also had new-onset atrial fibrillation, an irregular heart rhythm that increases the risk of stroke. After his blood pressure was controlled, clinicians began apixaban, an anticoagulant prescribed to reduce that risk.

Soon afterward, he developed life-threatening hemoptysis and type 2 respiratory failure, in which inadequate ventilation causes carbon dioxide to accumulate in the blood. Apixaban was immediately stopped, but the bleeding was severe enough to require emergency intubation and mechanical ventilation in an intensive-care unit. Bronchoscopy, in which a camera is passed through the breathing tube, showed blood oozing from the right lower-lobe bronchus—the airway anatomically closest to the hematoma. This localization strengthened the suspicion that the expanding pleural lesion had begun bleeding into or communicating with the bronchial system. Respiratory testing also detected Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus, prompting treatment with levofloxacin and vancomycin. However, CT bronchial arteriography did not show enlarged or abnormal bronchial arteries that could explain the hemorrhage, suggesting that the bleeding might have arisen from fragile vessels within the chronic inflammatory capsule rather than from a readily embolized arterial source.

The biology of CEH helps explain why such a mass can enlarge long after the original bleeding event. As hemoglobin and other blood products break down, they irritate surrounding tissues and maintain a low-grade inflammatory response. The body attempts to contain the collection by forming granulation tissue and a thick fibrous capsule. That capsule is not inert: it can develop a network of small, abnormal blood vessels. These newly formed capillaries are structurally fragile and vulnerable to repeated microhemorrhage. Each tiny bleed adds more blood to the lesion, while further inflammation and organization thicken the capsule, creating a self-perpetuating cycle. Over years, the result can be a heterogeneous pleural mass containing layers of different-aged clot, fibrous tissue, inflammatory cells and calcification. The same cycle has been proposed in other chronic expanding hematomas, including those occurring after tuberculosis-related pleural disease or old thoracic operations.

The clinical team considered the standard definitive treatment: surgical evacuation of the clot together with capsulectomy, or removal of the constricting fibrous shell. Surgery is generally favored because simply draining a CEH may leave behind the vascularized capsule that drives further bleeding and expansion. In some high-risk patients, selective arterial embolization may be performed before surgery to reduce blood loss. The operation, however, can itself be hazardous because the capsule may adhere tightly to the lung, chest wall and major vessels, and reports have described substantial intraoperative blood loss. In this patient, persistent type 2 respiratory failure, severely restricted lung volumes, poor diaphragmatic excursion and frailty made major thoracic surgery too dangerous. An attempt to aspirate the mass through a needle also failed: the blood had become so densely organized that no fluid could be withdrawn.

Mechanical ventilation introduced another complication. Positive pressure increased the pressure within the airways and apparently worsened the suspected bronchopleural air leak, producing subcutaneous emphysema—air trapped beneath the skin of the chest and neck. The swelling was managed conservatively and eventually resolved without insertion of an intercostal chest drain. Yet the underlying problem remained. Recurrent bleeding required frequent bronchoscopic suctioning and airway clearance, while the large hematoma continued to compromise respiratory mechanics. The patient repeatedly failed attempts to come off the ventilator and ultimately underwent an elective tracheostomy to provide longer-term ventilatory support. Two months later, despite intensive supportive treatment, he developed hospital-acquired pneumonia and died from progressive respiratory failure.

A post-mortem examination finally provided definitive confirmation. The pleural lesion contained dense fibrous tissue, dystrophic calcification, patchy chronic inflammation, mature fibroadipose tissue and organized blood clots—the characteristic mixture expected in a chronic expanding hematoma. There was no histological evidence of tuberculosis, cancer or acute infection. The authors emphasize that CEH should be considered when CT reveals a slowly enlarging, heterogeneous pleural mass surrounded by a thick, sometimes calcified capsule, particularly after more common explanations such as malignancy and active infection have been excluded. The case also demonstrates why early recognition matters: a patient with mild symptoms may later develop airway bleeding, bronchopleural fistula, infection, lung compression and respiratory collapse. Because treatment decisions involve radiologists, pulmonologists, intensivists and cardiothoracic surgeons, the report argues for multidisciplinary assessment and early consideration of definitive surgery before the lesion becomes too organized or the patient too medically fragile to survive it.

Subject of Research: Chronic expanding thoracic hematoma complicated by life-threatening hemoptysis, bronchopleural fistula and respiratory failure

Article Title: Chronic Expanding Hematoma Complicated by Life Threatening Hemoptysis and Respiratory Arrest—A Case Report

Article References: Yu A. S.-y., Cheung C. Y., Ng C. T., et al., “Chronic Expanding Hematoma Complicated by Life Threatening Hemoptysis and Respiratory Arrest—A Case Report,” Respirology Case Reports 14, no. 7 (2026): e70665. Original research article

Image Credits: AI Generated

DOI: 10.1002/rcr2.70665

Keywords: chronic expanding hematoma, thoracic hematoma, life-threatening hemoptysis, bronchopleural fistula, respiratory failure, pleural disease, organized blood clot, dystrophic calcification