Objective: Pulmonary ischemia-reperfusion (IR) injury causes cardiac damage through inflammation related to hypoxic conditions. Dexpanthenol (DEX) has an anti-inflammatory action in various tissues such as lung, liver, and kidney. This study aimed to show the effects of DEX on myocardial damage secondary to pulmonary IR injury.Material and Method: Thirty two rats were randomly divided into four groups as sham, IR, DEX (500 mg/kg, intraperitoneally, single dose), and IR+DEX. After left thoracotomy, non-traumatic vascular clamping was applied for 60 minutes, followed by 60 minutes of reperfusion to create a lung IR model. After sacrification, heart tissues were collected and placed in formaldehyde solution for histopathological and immunohistochemical analyses. Hyperemia, hemorrhage, and degeneration were examined, Immunostainings of cyclooxygenase-1 (COX-1), hypoxia-inducible factor 2 alpha (HIF-2α), and interferon alpha (IFα) were performed.Results: Cardiomyocytes in the sham group appeared elongated, branching, and of normal size with well-defined intercalated discs. Delicate endomysium sheaths surrounding the cardiac cells were observed, along with a dense capillary network surrounding the cells. In contrast, the IR group exhibited alterations in cardiac tissue, including hyperemia, hemorrhage, and disruption of the cross-striated banding pattern of the cardiac cells. Also; COX-1, EPAS-1/HIF-2α, and IFα expressions were elevated in the IR group. Treatment with DEX resulted in a reduction of these pathological outcomes.Conclusions: In the context of pulmonary IR, damage is likely to occur not only in lung tissue but also in other organs. This is attributed to the dissemination of immunomodulatory cytokines developed within the tissue to other organs through the bloodstream. DEX is a derivative of pantothenic acid, recognized for its tissue-protective effects. In this study, it was histopathologically and immunohistochemically shown that DEX could be protective against lung IR-induced cardiac damage.