scholarly journals BPC 157 Therapy and the Permanent Occlusion of the Superior Sagittal Sinus in Rat: Vascular Recruitment

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 744
Author(s):  
Slaven Gojkovic ◽  
Ivan Krezic ◽  
Hrvoje Vranes ◽  
Helena Zizek ◽  
Domagoj Drmic ◽  
...  

We show the complex syndrome of the occluded superior sagittal sinus, brain swelling and lesions and multiple peripheral organs lesions in rat. Recovery goes centrally and peripherally, with the stable gastric pentadecapeptide BPC 157, which alleviated peripheral vascular occlusion disturbances, rapidly activating alternative bypassing pathways. Assessments were gross recording, venography, ECG, pressure, microscopy, biochemistry. The increased pressure in the superior sagittal sinus, portal and caval hypertension, aortal hypotension, arterial and venous thrombosis, severe brain swelling and lesions (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus), particular veins (azygos, superior mesenteric, inferior caval) dysfunction, heart dysfunction, lung congestion as acute respiratory distress syndrome, kidney disturbances, liver failure, and hemorrhagic lesions in gastrointestinal tract were all assessed. Rats received BPC 157 medication (10 µg/kg, 10 ng/kg) intraperitoneally, intragastrically, or topically to the swollen brain at 1 min ligation-time, or at 15 min, 24 h and 48 h ligation-time. BPC 157 therapy rapidly attenuates the brain swelling, rapidly eliminates the increased pressure in the ligated superior sagittal sinus and the severe portal and caval hypertension and aortal hypotension, and rapidly recruits collateral vessels, centrally ((para)sagittal venous collateral circulation) and peripherally (left superior caval vein azygos vein-inferior caval vein). In conclusion, as shown by all assessments, BPC 157 acts against the permanent occlusion of the superior sagittal sinus and syndrome (i.e., brain, heart, lung, liver, kidney, gastrointestinal lesions, thrombosis), given at 1 min, 15 min, 24 h or 48 h ligation-time. BPC 157 therapy rapidly overwhelms the permanent occlusion of the superior sagittal sinus in rat.

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1300
Author(s):  
Slaven Gojkovic ◽  
Ivan Krezic ◽  
Hrvoje Vranes ◽  
Helena Zizek ◽  
Domagoj Drmic ◽  
...  

We redefined Robert’s prototypical cytoprotection model, namely the intragastric administration of 96% alcohol in order to generate a general peripheral and central syndrome similar to that which occurs when major central or peripheral veins are occluded in animal models. With this redefinition, we used Robert’s model to examine the cytoprotective effects of the stable gastric pentadecapeptide BPC 157. The intragastric administration of alcohol induced gastric lesions, intracranial (superior sagittal sinus) hypertension, severe brain swelling and lesions, portal and vena caval hypertension, aortal hypotension, severe thrombosis, inferior vena cava and superior mesenteric vein congestion, azygos vein failure (as a failed collateral pathway), electrocardiogram disturbances, and heart, lung, liver and kidney lesions. The use of BPC 157 therapy (10 µg/kg or 10 ng/kg given intraperitoneally 1 min after alcohol) counteracted these deficits rapidly. Specifically, BPC 157 reversed brain swelling and superior mesenteric vein and inferior vena caval congestion, and helped the azygos vein to recover, which improved the collateral blood flow pathway. Microscopically, BPC 157 counteracted brain (i.e., intracerebral hemorrhage with degenerative changes of cerebral and cerebellar neurons), heart (acute subendocardial infarct), lung (parenchymal hemorrhage), liver (congestion), kidney (congestion) and gastrointestinal (epithelium loss, hemorrhagic gastritis) lesions. In addition, this may have taken place along with the activation of specific molecular pathways. In conclusion, these findings clarify and extend the theory of cytoprotection, offer an approach to its practical application, and establish BPC 157 as a prospective cytoprotective treatment.


Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1029
Author(s):  
Mario Knezevic ◽  
Slaven Gojkovic ◽  
Ivan Krezic ◽  
Helena Zizek ◽  
Hrvoje Vranes ◽  
...  

Background. Gastric pentadecapeptide BPC 157 therapy in rats compensated irremovable occlusion of various vessels and counteracted the consequent multiorgan dysfunction syndromes by activation of the corresponding collateral bypassing loops. Thus, we used BPC 157 therapy against the irremovable occlusion of the end of the superior mesenteric vein. Methods. Assessments, for 30 min (gross recording, venography, ECG, pressure, microscopy, biochemistry, and oxidative stress) include the portal and caval hypertension, aortal hypotension, and centrally, the superior sagittal sinus hypertension, systemic arterial and venous thrombosis, ECG disturbances, MDA-tissue increase, and heart, lung, liver, kidney and gastrointestinal tract, in particular, and brain (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus) lesions. Rats received BPC 157 medication (10 µg/kg, 10 ng/kg) intraperitoneally at 1 or 15 min ligation time. Results. BPC 157 rapidly activated the superior mesenteric vein–inferior anterior pancreati-coduodenal vein–superior anterior pancreaticoduodenal vein–pyloric vein–portal vein pathway, reestablished superior mesenteric vein and portal vein connection and reestablished blood flow. Simultaneously, toward inferior caval vein, an additional pathway appears via the inferior mesenteric vein united with the middle colic vein, throughout its left colic branch to ascertain alternative bypassing blood flow. Consequently, BPC 157 acts peripherally and centrally, and counteracted the intracranial (superior sagittal sinus), portal and caval hypertension, aortal hypotension, ECG disturbances attenuated, abolished progressing venous and arterial thrombosis. Additionally, BPC 157 counteracted multiorgan dysfunction syndrome, heart, lung, liver, kidney and gastrointestinal tract, and brain lesions, and oxidative stress in tissues. Conclusion. BPC 157 therapy may be specific management also for the superior mesenteric vein injuries.


Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1506
Author(s):  
Sanja Strbe ◽  
Slaven Gojkovic ◽  
Ivan Krezic ◽  
Helena Zizek ◽  
Hrvoje Vranes ◽  
...  

Due to endothelial impairment, high-dose lithium may produce an occlusive-like syndrome, comparable to permanent occlusion of major vessel-induced syndromes in rats; intracranial, portal, and caval hypertension, and aortal hypotension; multi-organ dysfunction syndrome; brain, heart, lung, liver, kidney, and gastrointestinal lesions; arterial and venous thrombosis; and tissue oxidative stress. Stable gastric pentadecapeptide BPC 157 may be a means of therapy via activating loops (bypassing vessel occlusion) and counteracting major occlusion syndromes. Recently, BPC 157 counteracted the lithium sulfate regimen in rats (500 mg/kg/day, ip, for 3 days, with assessment at 210 min after each administration of lithium) and its severe syndrome (muscular weakness and prostration, reduced muscle fibers, myocardial infarction, and edema of various brain areas). Subsequently, BPC 157 also counteracted the lithium-induced occlusive-like syndrome; rapidly counteracted brain swelling and intracranial (superior sagittal sinus) hypertension, portal hypertension, and aortal hypotension, which otherwise would persist; counteracted vessel failure; abrogated congestion of the inferior caval and superior mesenteric veins; reversed azygos vein failure; and mitigated thrombosis (superior mesenteric vein and artery), congestion of the stomach, and major hemorrhagic lesions. Both regimens of BPC 157 administration also counteracted the previously described muscular weakness and prostration (as shown in microscopic and ECG recordings), myocardial congestion and infarction, in addition to edema and lesions in various brain areas; marked dilatation and central venous congestion in the liver; large areas of congestion and hemorrhage in the lung; and degeneration of proximal and distal tubules with cytoplasmic vacuolization in the kidney, attenuating oxidative stress. Thus, BPC 157 therapy overwhelmed high-dose lithium intoxication in rats.


Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 609
Author(s):  
Mario Knezevic ◽  
Slaven Gojkovic ◽  
Ivan Krezic ◽  
Helena Zizek ◽  
Dominik Malekinusic ◽  
...  

Gastric pentadecapeptide BPC 157 therapy counteracts multiple organ dysfunction syndrome in rats, which have permanent occlusion of the superior mesenteric artery close to the abdominal aorta. Previously, when confronted with major vessel occlusion, its effect would rapidly activate collateral vessel pathways and resolve major venous occlusion syndromes (Pringle maneuver ischemia, reperfusion, Budd–Chiari syndrome) in rats. This would overwhelm superior mesenteric artery permanent occlusion, and result in local, peripheral, and central disturbances. Methods: Assessments, for 30 min (gross recording, angiography, ECG, pressure, microscopy, biochemistry, and oxidative stress), included the portal hypertension, caval hypertension, and aortal hypotension, and centrally, the superior sagittal sinus hypertension; systemic arterial and venous thrombosis; ECG disturbances; MDA-tissue increase; and multiple organ lesions and disturbances, including the heart, lung, liver, kidney, and gastrointestinal tract, in particular, as well as brain (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus). BPC 157 therapy (/kg, abdominal bath) (10 µg, 10 ng) was given for a 1-min ligation time. Results: BPC 157 rapidly recruits collateral vessels (inferior anterior pancreaticoduodenal artery and inferior mesenteric artery) that circumvent occlusion and ascertains blood flow distant from the occlusion in the superior mesenteric artery. Portal and caval hypertension, aortal hypotension, and, centrally, superior sagittal sinus hypertension were attenuated or eliminated, and ECG disturbances markedly mitigated. BPC 157 therapy almost annihilated venous and arterial thrombosis. Multiple organ lesions and disturbances (i.e., heart, lung, liver, and gastrointestinal tract, in particular, as well as brain) were largely attenuated. Conclusions: Rats with superior mesenteric artery occlusion may additionally undergo BPC 157 therapy as full counteraction of vascular occlusion-induced multiple organ dysfunction syndrome.


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 792
Author(s):  
Mario Knezevic ◽  
Slaven Gojkovic ◽  
Ivan Krezic ◽  
Helena Zizek ◽  
Dominik Malekinusic ◽  
...  

Background. We investigated the occluded essential vessel tributaries, both arterial and venous, occluded superior mesenteric vein and artery in rats, consequent noxious syndrome, peripherally and centrally. As therapy, we hypothesized the rapidly activated alternative bypassing pathways, arterial and venous, and the stable gastric pentadecapeptide BPC 157 since it rapidly alleviated venous occlusion syndromes. Methods. Assessments were performed for 30 min (gross recording, venography, ECG, pressure, microscopy, biochemistry, and oxidative stress), including portal hypertension, caval hypertension, aortal hypotension, and centrally, the superior sagittal sinus hypertension; systemic arterial and venous thrombosis, ECG disturbances, MDA-tissue increase, the multiple organs lesions, heart, lung, liver, kidney and gastrointestinal tract, including brain (swelling, and cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus lesions). Rats received BPC 157 medication (10 µg/kg, 10 ng/kg) intraperitoneally at 1 min ligation-time. Results. BPC 157 rapidly activated collateral pathways. These collateral loops were the superior mesenteric vein-inferior anterior pancreaticoduodenal vein-superior anterior pancreaticoduodenal vein-pyloric vein-portal vein pathway, an alternative pathway toward inferior caval vein via the united middle colic vein and inferior mesenteric vein through the left colic vein, and the inferior anterior pancreaticoduodenal artery and inferior mesenteric artery. Consequently, BPC 157 counteracted the superior sagittal sinus, portal and caval hypertension, aortal hypotension, progressing venous and arterial thrombosis peripherally and centrally, ECG disturbances attenuated. Markedly, the multiple organs lesions, heart, lung, liver, kidney, and gastrointestinal tract, in particular, as well as brain lesions, and oxidative stress in tissues were attenuated. Conclusions. BPC 157 therapy rapidly recovered rats, which have complete occlusion of the superior mesenteric vein and artery.


2001 ◽  
Vol 94 (1) ◽  
pp. 130-132 ◽  
Author(s):  
Cheng-Shyuan Rau ◽  
Chun-Chung Lui ◽  
Cheng-Loong Liang ◽  
Han-Jung Chen ◽  
Yeh-Lin Kuo ◽  
...  

✓ There is a wide variety of disorders associated with thrombosis of the superior sagittal sinus (SSS), including infectious disease, noninfectious conditions such as vasculitis and hypercoagulable states, and complications arising from pregnancy or use of oral contraceptive medications. Despite these well-defined associations, approximately 25% of the cases remain idiopathic. In this article the authors describe a patient who was found to have SSS thrombosis while experiencing a thyrotoxic phase of Graves disease. The patient presented with intracerebral hemorrhage, subarachnoid hemorrhage, seizure, coma, a raised fibrinogen concentration, low protein C activity, and atrial fibrillations. Thrombolysis was successfully performed despite the coexistence of thrombosis and intracranial hemorrhage. Patients with thyrotoxicosis and a diffuse goiter may be predisposed to the development of SSS thrombosis, as a result of hypercoagulation and stasis of local venous blood flow. In the present case, a patient in whom thrombosis coexisted with intracranial hemorrhage was successfully treated using thrombolytic therapy.


Author(s):  
Rajendra Chavan ◽  
Shreya Sethi ◽  
Harsha Sahu ◽  
Neeraj Rao ◽  
Shivani Agarwal

AbstractDural arteriovenous fistulas (DAVFs) located within superior sagittal sinus (SSS) wall with direct cortical venous drainage are rare. They are also known as variant DAVF (vDAVF) and form a special subgroup of DAVFs. Their chance of presenting with aggressive features is high compared with transverse sigmoid sinus fistula. They drain directly into cortical veins (Borden type 3, Cognard type III and IV). A systematic English literature review of SSS vDAVF was made. Systematic literature review revealed a total of 31 published cases. These were commonly seen in male population, (24 males, 77.41%, 24/31). Average age of patients was 54 years. A total of 24 patients (77.41%, 24/31) had aggressive clinical presentations with 13 patients (41.93%, 13/31) having intracranial hemorrhages (ICH). Two patients had rebleeding (15.38%, 2/13). Middle portion of SSS was commonly involved (15 cases, 75%). A total of 25 (96.15%, 25/26) cases had patent SSS. Most of the fistulas were idiopathic (65.38%, 17/26), with trauma being a frequent etiological factor (26.92%, 7/26). Venous ectasia was seen in 19 patients (59.37%, 19/32). Middle meningeal arterial (MMA) supply was seen in all patients (100%, 26/26), with bilateral MMA supply in 21 cases (80.76%), and unilateral in 5 cases (19.23%). Twenty patients (62.50%, 20/32) received only endovascular treatment (EVT), while four patients had EVT followed by surgery (12.5%, 4/32). Transarterial route via MMA was the preferred treatment option (79.16%). Complete obliteration of fistulas was noted in all cases (100%, 30/30). No immediate complication was noted after EVT. As much as 92.30% patients showed good recovery. Thus, SSS vDAVF forms a special subgroup of DAVF, with aggressive presentation, and warrants urgent treatment. EVT is effective treatment option and can produce complete obliteration.


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