Background: This study evaluated physiological responses to repeated handling and blood collection in laboratory rabbits using infrared thermography, serum cortisol, and faecal cortisol metabolites (FCMs), and assessed responses in non-handled rabbits housed in the same room. Methods: Sixteen healthy adult rabbits were randomly allocated to experimental (n = 8) and non-handled control (n = 8) groups. Experimental rabbits underwent nine blood collections over 5 h as part of a pharmacokinetic study, with periocular surface temperature measured by infrared thermography before each collection. Controls underwent thermography at identical time points without handling or blood sampling. Serum cortisol was measured in experimental rabbits, whereas FCMs were analysed in both groups. Results: Following the first blood collection, periocular temperature increased by 1.0 °C in experimental and 1.3 °C in control rabbits. Experimental serum cortisol increased from 13.6 ± 5.5 to 23.7 ± 7.3 ng/mL at 30 min and declined to 8.1 ± 2.1 ng/mL at final sampling. FCMs increased approximately 9 h after the first collection in both groups and remained elevated for up to three days in experimental rabbits. Conclusions: Repeated handling and blood collection elicited measurable physiological responses. Changes in controls suggest that procedure-related environmental cues may also influence nearby non-handled rabbits.

Enhancing the fibrinolysis efficacy of recombinant tissue plasminogen activators (r-tPA) may be achieved by increasing the blood plasminogen levels. This study evaluated the effect of plasminogen (PLG) addition to a clinically relevant alteplase (r-tPA) dose on fibrinolysis. Sixty nine Wistar albino rats were divided into 7 groups; control (n = 10), r-tPA 0.9 mg/kg (0.9r-tPA) (n = 10), r-tPA 0.9 mg/kg + PLG 8 IU/kg (0.9r-tPA+8PLG) (n = 10), r-tPA 0.9 mg/kg + PLG 16 IU/kg (0.9r-tPA+16PLG) (n = 10), r-tPA 0.6 mg/kg + PLG 8 IU/kg (0.6r-tPA+8PLG) (n = 10), r-tPA 0.6 mg/kg + PLG 16 IU/kg (0.6r-tPA+16PLG) (n = 10), and r-tPA 0.9 mg/kg + PLG 8 IU/kg (0.9r-tPA+8PLG60) (n = 9) with the PLG administered 60 min before the r-tPA administration. In all groups, systemic embolism was induced by application of three barium sulfate-labeled artificial clots in abdominal aorta. Artificial clots were visualized under micro-fluoroscopy, and radiographs were captured every 5 min during fibrinolytic/saline infusion. The measurement of clot area was used to calculate fibrinolysis rate (%/min) and the area under the curve (AUC; %*min). Results show that all PLG combinations enhanced fibrinolysis relative to untreated controls (p < 0.001). At the clinical 0.9 mg/kg dose, PLG supplementation significantly increased the fibrinolysis rate compared with r-tPA alone (r-tPA: 0.8 ± 0.5%/min; 8 IU/kg, p = 0.025; 16 IU/kg, p < 0.001), and this benefit was retained when PLG was administered 60 min in advance (p = 0.024). Differences between PLG doses were not statistically significant. Systemic plasminogen supplementation therefore enhances r-tPA-mediated fibrinolysis in vivo at a clinically relevant dose and regimen, without requiring catheter-directed delivery.