PR interval as a predictor of syncope in tilt-up testing in adolescents and young adults.

BACKGROUND: Syncope, as the most frequent consciousness disorder, is very common in young individuals. The aim of this study was to analyze ECG parameters and clinical properties obtained during tilt-up testing in 12 to 30-year-old subjects. We enrolled a total of 142 patients from our outpatient clinic (39 males, 103 females) with a true positive tilt-up test and analyzed ECG records obtained during tilt-testing. Data were stratified according to the age, gender, and type of syncope. RESULTS: PR interval shortening preceding syncope was found in all syncope types, irrespective of the gender. All types of syncope were more frequent in women (72.5%). Mixed syncope type was found to be the most common (47.18%). Male and female subjects differed in initial heart rate (71.56 vs 76.23/min, p=0.05), as well as heart rate dynamics during tilt-up testing. A gender difference was also found in systolic blood pressure (116.92 vs 110.44 mmHg, p<0.01), time to syncope onset (20.77 vs. 16.44 min, p=0.03), and the total number of syncopal episodes in patient history (2.79 vs. 4.62, p<0.05). Subjects with cardioinhibitory syncope had the longest PR interval (average 154.3 ms). PR interval prolongation and loss of variability during tilt-up testing positively correlated with aging (r=0.22, p<0.05). Nodal rhythm was found in 8 patients. CONCLUSION: PR interval shortening on ECG tracings during a tilt-up test can be found in all subtypes of vasovagal syncope, thereby contrasting previous reports that these changes are a hallmark of the cardioinhibitory type of syncope. PR shortening, if observed during ECG monitoring, could be a potential predictor of syncope.

Stress in Gastrointestinal Tract and Stable Gastric Pentadecapeptide BPC 157. Finally, do we have a Solution?

Selye's syndrome produced by diverse nocuous agents and "response to damage as such" means Selye's stress triad in stress coping response to reestablish homeostasis. Logically, from the gastrointestinal tract viewpoint, such organoprotective/healing response implies the angiogenic growth factors that commonly signify the healing. Thereby, the gastric pentadecapeptide BPC 157-organoprotection (huge range of beneficial effects) signifies the Selye's stress concept/stress coping response implemented in and from gastrointestinal tract, and BPC 157 as an integrative mediator that integrates the adaptive bodily response to stress. In clinical trials without side effects, LD1 not achieved, BPC 157 healing in gastrointestinal tract, and particularly the healing of the extragastrointestinal tissues (i.e., skin/tendon/ligament/muscle/bone; nerve; cornea/ brain) were referred throughout its integrative capabilities (i.e., ulcerative colitis/multiple sclerosis model equally counteracted), native in gastrointestinal tract, stability in human gastric juice (and thereby, strong efficacy and applicability), its relevance for dopamine-system function (and thereby, counteracting effects of dopamine-system dysfunction and overfunction, centrally and peripherally (mucosa maintenance); interaction with serotonin- and GABA-system)), afforded cytoprotection/adaptive cytoprotection/organoprotection (and thereby, beneficial effects on gastric and whole intestinal tract lesions and adaptation, wounds and fistulas healing, blood vessels, somatosensory neurons, NSAIDs-side effects (including also pancreas, liver, brain lesions, and blood disturbances, prolonged bleeding, thrombocytopenia, thrombosis)). Further, we combine such gut-brain axis and the NO-system where BPC 157 counteracts complications of either L-NAME application (i.e., various lesions aggravation, hypertension) or Larginine application (i.e., hypotension, prolonged bleeding, thrombocytopenia). Also, BPC 157 particularly affects genes functions (i.e., Fos, c-Jun, Egr-1), all together suggestive for an indicative generalization. Thus, we could suggest gastric pentadecapeptide BPC 157 and BPC 157 induced-organoprotection as integrative mediator that integrates the adaptive bodily response to stress, and thereby practically applied in further therapy and in effective realization of Selye's stress response.

Stable gastric pentadecapeptide BPC 157 and bupivacaine.

Bupivacaine toxicity following accidental overdose still lacks therapeutic solution. However, there are major arguments for testing BPC 157 against bupivacaine toxicity in vivo in rats, in particular, and then finally, in vitro. These are: the lack of any known BPC 157 toxicity, a lifesaving effect via the mitigation of arrhythmias in rats underwent hyperkalemia or digitalis toxicity, the elimination of hyperkalemia and arrhythmias in rats underwent succinylcholine toxicity and finally, the reduction of potassium-induced depolarization in vitro (in HEK293 cells) in severe hyperkalemia. Most importantly, BPC 157 successfully prevents and counteracts bupivacaine cardiotoxicity; BPC 157 is effective even against the worst outcomes such as a severely prolonged QRS complex. Here, rats injected with bupivacaine (100mg/kg IP) exhibited bradycardia, AV-block, ventricular ectopies, ventricular tachycardia, T-wave elevation and asystole. All of the fatalities had developed T-wave elevation, high-degree AV-block, respiratory arrest and asystole. These were largely counteracted by BPC 157 administration (50µg/kg, 10µg/kg, 10ng/kg, or 10pg/kg IP) given 30min before or 1min after the bupivacaine injection. When BPC 157 was given 6min after bupivacaine administration, and after the development of prolonged QRS intervals (20ms), the fatal outcome was markedly postponed. Additionally, the effect of bupivacaine on cell membrane depolarization was explored by measuring membrane voltages (Vm) in HEK293 cells. Bupivacaine (1mM) alone caused depolarization of the cells, while in combination with BPC 157 (1µm), the bupivacaine-induced depolarization was inhibited. Together, these findings suggest that the stable gastric pentadecapeptide BPC 157 should be a potential antidote for bupivacaine cardiotoxicity.

Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications.

BACKGROUND: Brain-gut interaction involves, among others, peptidergic growth factors which are native in GI tract and have strong antiulcer potency and thus could from periphery beneficially affect CNS-disorders. We focused on the stable gastric pentadecapeptide BPC 157, an antiulcer peptidergic agent, safe in inflammatory bowel disease trials and now in multiple sclerosis trial, native and stable in human gastric juice. METHODS: Review of our research on BPC 157 in terms of brain-gut axis. RESULTS: BPC 157 may serve as a novel mediator of Robert's cytoprotection, involved in maintaining of GI mucosa integrity, with no toxic effect. BPC 157 was successful in the therapy of GI tract, periodontitis, liver and pancreas lesions, and in the healing of various tissues and wounds. Stimulated Egr-1 gene, NAB2, FAK-paxillin and JAK-2 pathways are hitherto implicated. Initially corresponding beneficial central influence was seen when BPC 157 was given peripherally and a serotonin release in particular brain areas, mostly nigrostriatal, was changed. BPC 157 modulates serotonergic and dopaminergic systems, beneficially affects various behavioral disturbances that otherwise appeared due to specifically (over)stimulated/damaged neurotransmitters systems. Besides, BPC 157 has neuroprotective effects: protects somatosensory neurons; peripheral nerve regeneration appearent after transection; after traumatic brain injury counteracts the otherwise progressing course, in rat spinal cord compression with tail paralysis, axonal and neuronal necrosis, demyelination, cyst formation and rescues tail function in both short-terms and long-terms; after NSAIDs or insulin overdose or cuprizone encephalopathies were attenuated along with GI, liver and vascular injuries. CONCLUSION: BPC 157, a gastric peptide, may serve as remedy in various CNS-disorders.

Mortal hyperkalemia disturbances in rats are NO-system related. The life saving effect of pentadecapeptide BPC 157.

We demonstrate the full counteracting ability of stable gastric pentadecapeptide BPC 157 against KCl-overdose (intraperitoneal (i), intragastric (ii), in vitro (iii)), NO-system related. (i) We demonstrated potential (/kg) of: BPC 157 (10ng, 10µg ip, complete counteraction), l-arginine (100mg ip, attenuation) vs. L-NAME (5mg ip, deadly aggravation), given alone and/or combined, before or after intraperitoneal KCl-solution application (9mEq/kg). Therapy was confronted with promptly unrelenting hyperkalemia (>12mmol/L), arrhythmias (and muscular weakness, hypertension, low pressure in lower esophageal and pyloric sphincter) with an ultimate and a regularly inevitable lethal outcome within 30min. Previously, we established BPC 157-NO-system interaction; now, a huge life-saving potential. Given 30min before KCl, all BPC 157 regimens regained sinus rhythm, had less prolongation of QRS, and had no asystolic pause. BPC 157 therapy, given 10min after KCl-application, starts the rescue within 5-10min, completely restoring normal sinus rhythm at 1h. Likewise, other hyperkalemia-disturbances (muscular weakness, hypertension, low sphincteric pressure) were also counteracted. Accordingly with NO-system relation, deadly aggravation by L-NAME: l-arginine brings the values to the control levels while BPC 157 always completely nullified lesions, markedly below those of controls. Combined with l-arginine, BPC 157 exhibited no additive effect. (ii) Intragastric KCl-solution application (27mEq/kg) - (hyperkalemia 7mmol/L): severe stomach mucosal lesions, sphincter failure and peaked T waves were fully counteracted by intragastric BPC 157 (10ng, 10µg) application, given 30min before or 10min after KCl. (iii). In HEK293 cells, hyperkalemic conditions (18.6mM potassium concentrations), BPC 157 directly affects potassium conductance, counteracting the effect on membrane potential and depolarizations caused by hyperkalemic conditions.

Detecting volume responders prior to implantation of a cardiac resynchronization therapy device via minithoracotomy: the septal flash as a predictor of immediate left ventricular reverse remodeling.

BACKGROUND: Although cardiac resynchronization therapy (CRT) is well established as an adjunctive heart failure treatment, a 30% rate of nonresponders poses a challenge to improve the detection of potential responders prior to device implantation. A previously proposed mechanism-based approach to patient selection suggests in part that the septal flash is a sign of intraventricular dyssynchrony, which is predictive of CRT responsiveness. METHODS: In this pilot study, data from 5 consecutive patients (2 women and 3 men; mean + or - SD age, 62 + or - 9 years) referred for CRT device implantation via a minithoracotomy were analyzed. Intraoperative transthoracic and/or transesophageal echocardiography data, as well as Doppler myocardial imaging data, were acquired before and after CRT device activation. The septal flash was defined as an early ventricular inward and outward septal motion within the isovolumic contraction period and was imaged with grayscale imaging or tissue Doppler color M-mode. Reverse remodeling was defined as a reduction in the left ventricular end-systolic volume (LVESV) of > or =10%. The right atrial and right ventricular leads were placed transvenously, and the LV screw-in lead was positioned epicardially on the lateral wall. RESULTS: The septal flash was detected preoperatively in all patients and resolved immediately after the onset of biventricular pacing. Immediately following pacemaker activation, we measured a significant reduction in the LVESV (248 + or - 99 mL versus 190 + or - 100 mL, P = .01) and an increase in the ejection fraction (19% + or - 5% versus 28% + or - 5%, P = .01) in all patients. Likewise, a significant increase in the postactivation dP/dt (rate of LV pressure change) measured noninvasively from the mitral regurgitation trace was noted in all patients (298.6 + or - 58.0 mm Hg/s versus 601.7 + or - 111.2 mm Hg/s, P = .001). CONCLUSION: The preoperative presence of the septal flash is a valid predictor of the response to CRT. Immediately after CRT device activation, the septal flash disappears, and LV reverse remodeling and an increase in contractility are observed.

Inhibition of methyldigoxin-induced arrhythmias by pentadecapeptide BPC 157: a relation with NO-system.

Pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419) reversed congestive heart failure and various arrhythmias, influenced the NO-system and showed no proarrhythmic effect. In therapy analogy, we challenged rats with digitalis, to show attenuation by BPC 157 and the relation between the NO-system and digitalis toxicity. (i). BPC 157 prophylactic effect. Development of cumulative intravenous digitalis toxicity, BPC 157 (50 microg, 10 microg, 10 ng/kg applied intravenously immediately before a methyldigoxin increment regimen (2.0/1.5/1.5/1.0 mg/kg at 15 min-intervals, total dose 6.0 mg/kg/45 min)) reduced the number of ventricular premature beats, prolonged the time before onset of ventricular tachycardia, reduced ventricular tachycardia and AV-block duration (microg-regimes) or reduced mainly the AV-block duration (ng-regimen). (ii). BPC 157 therapy. Advanced methyldigoxin toxicity (6.0 mg/kg i.v. bolus). BPC 157 applied at the 20th second of the grade 3 AV-block shortened AV-blocks, mitigated a further digitalis toxicity course. Ventricular tachycardias were either avoided (50 microg), or markedly reduced (10 microg, 10 ng). Fatal outcome was either avoided (50 microg), reduced (10 microg), or only delayed (10 ng) (iii) BPC 157, L-NAME, l-arginine, L-NAME+l-arginine application. L-NAME-application (5 mg/kg i.p.) aggravated methyldigoxin-arrhythmias. l-arginine (200 mg/kg i.p.) alone had no effect but blunted L-NAME-exaggeration (L-NAME+l-arginine). In this respect, BPC 157 (50 microg/kg i.p.) was prophylactically and therapeutically more effective: the antagonism of L-NAME with BPC 157 produced an effect similar to BPC 157 alone. In conclusion, digitalis-induced arrhythmias in rats could be prevented and counteracted by pentadecapeptide BPC 157, mainly through an interaction with the NO-system.

[Endocarditis associated with atrial and ventricular cardiac pacing leads. Case report]. / Endokarditis na atrijskoj i ventrikulskoj elektrodi trajnog elektrostimulatora srca. Prikaz bolesnika.

The infection of a transvenous lead implanted for cardiac stimulation is a rare, but serious complication. We report observation of a 25-year old man whose Staphylococcus epidermidis sepsis linked to endocarditis was related to atrial and ventricular pacing leads, and was diagnosed after two months of medical treatment. The most important role during the diagnostic process was played by the echocardiographic examination, especially transoesophageal, which revealed the large vegetations on atrial as well as ventricular pacing lead. The diagnosed condition was treated by complete removal of pacing system using open chest surgery and cardiopulmonary pump. After four weeks of vigorous antibiotic treatment, a new DDDR pacing system was implanted, but with epicardial leads.