Antiarrhythmic Sotalol, Occlusion/Occlusion-like Syndrome in Rats, and Stable Gastric Pentadecapeptide BPC 157 Therapy

Abstract

We focused on the first demonstration that antiarrhythmics, particularly class II and class III antiarrhythmic and beta-blocker sotalol can induce severe occlusion/occlusion-like syndrome in rats. In this syndrome, as in similar syndromes with permanent occlusion of major vessels, peripheral and central, and other similar noxious procedures that severely disable endothelium function, the stable gastric pentadecapeptide BPC 157-collateral pathways activation, was a resolving therapy. After a high dose of sotalol (80 mg/kg intragastrically) in 180 min study, there were cause-consequence lesions in the brain (swelling, intracerebral hemorrhage), congestion in the heart, lung, liver, kidney, and gastrointestinal tract, severe bradycardia, and intracranial (superior sagittal sinus), portal and caval hypertension, and aortal hypotension, and widespread thrombosis, peripherally and centrally. Major vessels failed (congested inferior caval and superior mesenteric vein, collapsed azygos vein). BPC 157 therapy (10 µg, 10 ng/kg given intragastrically at 5 min or 90 min sotalol-time) effectively counteracted sotalol-occlusion/occlusion-like syndrome. In particular, eliminated were heart dilatation, and myocardial congestion affecting coronary veins and arteries, as well as myocardial vessels; eliminated were portal and caval hypertension, lung parenchyma congestion, venous and arterial thrombosis, attenuated aortal hypotension, and centrally, attenuated intracranial (superior sagittal sinus) hypertension, brain lesions and pronounced intracerebral hemorrhage. Further, BPC 157 eliminated and/or markedly attenuated liver, kidney, and gastrointestinal tract congestion and major veins congestion. Therefore, azygos vein activation and direct blood delivery were essential for particular BPC 157 effects. Thus, preventing such and similar events, and responding adequately when that event is at risk, strongly advocates for further BPC 157 therapy.

The Stable Gastric Pentadecapeptide BPC 157 Pleiotropic Beneficial Activity and Its Possible Relations with Neurotransmitter Activity

“…By BPC 157 therapy, the principle of upgrading minor vessels by prompt activation of the vascular collaterals (i.e., azygos vein direct blood flow delivery) is commonly operative to counteract the occlusion/occlusion-like syndrome, major vascular and multiorgan failure peripherally and centrally induced in rats [ 26 , 27 ]. These were induced with permanent major vessel occlusions, central [ 38 , 39 ] and peripheral [ 40 , 41 , 42 , 43 , 44 , 45 , 46 ], similar noxious procedures [ 47 , 48 , 49 , 50 ], and agents’ applications [ 51 , 52 , 53 , 54 , 55 , 56 ]. These all severely affect endothelium function.…”

“…Disabling heart failure recovery as a whole [ 4 ] (myocardial infarction [ 53 ], heart failure [ 87 ], pulmonary hypertension [ 88 ], arrhythmias [ 40 , 41 , 42 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 60 , 81 , 89 , 90 , 91 ], and thrombosis presentation [ 40 , 41 , 42 , 43 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]) was reviewed [ 3 , 4 ]. Smooth muscle function recovery was also reviewed [ 3 , 4 ] (i.e., sphincter dysfunction (pupil [ 86 ], lower esophageal and pyloric sphincter [ 92 , 93 , 94 , 95 , 96 , 97 , 98 , …”

“…Finally, for encephalopathies therapy (see Chapter Nerve-Nerve), acting simultaneously in both the periphery and central nervous system, BPC 157 counteracted various encephalopathies and stomach and liver lesions in non-steroidal anti-inflammatory drugs (NSAIDs)-rats [ 61 , 105 , 106 , 107 , 108 , 109 ] and insulin-rats [ 62 ]. Noteworthy, these were recently combined with the mentioned evidence that BPC 157 therapy by rapidly activated collateral pathways (azygos vein direct blood flow delivery) goes as a particular therapy effect, as counteracted the vascular and multiorgan failure concomitant to various major vessel occlusion and similar various noxious procedures and various agents’ application [ 40 , 41 , 42 , 43 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. This specifically reversed the initiated multicausal noxious circuit of the occlusion/occlusion-like syndrome as a general effect.…”

“…Counteracted were the severe lesions and hemorrhage in the brain, lungs, liver, kidney, and gastrointestinal tract. In particular, progressing thrombosis, both peripherally and centrally, and heart arrhythmias and infarction that would consistently occur were fully counteracted and/or almost annihilated [ 40 , 41 , 42 , 43 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. With these capabilities (already advanced Virchow triad circumstances were counteracted), BPC 157 therapy is effective in conditions of ischemia [ 40 , 41 , 42 , 43 , 47 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ] and in conditions of reperfusion [ 38 , 48 , 76 , 77 , 110 ].…”

“…This also includes counteraction of anaphylactoid reaction [ 132 ]. It also acts as a free radical scavenger [ 8 , 11 , 75 , 110 , 133 , 134 , 135 ] in vascular occlusion/occlusion-like failure studies, in particular [ 40 , 41 , 42 , 43 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ], associated with its function as a stabilizer of cellular junction [ 11 ], leading to the significantly mitigated leaky gut syndrome [ 11 ]. There, in the vessel wall, the rapid change in the lipid contents and protein secondary structure conformation, produced instantly via BPC 157 therapy [ 136 ] (Fourier transform infrared spectroscopy), supported the vessel function even in the worst circumstances.…”