Chest Pain and Wide QRS Tachycardia.

This case report presents the electrocardiogram findings of a patient in their 70s with diabetes who presented with 3 hours of chest pain.

A puzzling overnight change in the QRS morphology.

Pacemakers set in a bipolar pacing mode often result in no discernible spikes on surface 12­lead ECG registrations. In this situation, left axis deviation combined with wide QRS can help to identify the paced ECG morphology. We present a case of a non-pacemaker dependent patient whose normal atrioventricular conduction also appeared as atypical left axis deviation with wide QRS on the ECG. These two depolarization-repolarization morphologies, and the switch between the two raised differential diagnostic questions. The case also illustrates a paced ECG demonstrating the concept of Littmann: a close relationship between leads V2 and aVL.

Therapeutic hypothermia-induced QT prolongation and "torsade de pointes" ventricular tachycardia / Terápiás hypothermia okozta QT-megnyúlás és "torsade de pointes" kamrai tachycardia.

Összefoglaló. A szerzok egy 44 éves, autoimmun betegségben szenvedo nobeteg kórlefolyását ismertetik. A váratlan kórházi kamrafibrillációt követo sikeres resuscitatio után a beteg comatosus állapotban maradt, ezért terápiás hypothermiában részesült. A hypothermiás kezelés hatására jelentos QT-megnyúlás és "torsade de pointes" kamrai tachycardia lépett fel. A hypothermia okozta szívritmuszavar oka a homérséklet-csökkenés kiváltotta QT-megnyúlás és korai utódepolarizációs mechanizmusú triggerelt aktivitás. A szerzok felhívják a figyelmet arra, hogy jelen tudásunk szerint enyhe hypothermiát javasolt alkalmazni az ajánlásban szereplo hypothermiás tartományon belül. Orv Hetil. 2022; 163(13): 523-526. Summary. The authors describe the course of disease in a 44-year-old female patient with autoimmune disease. After successful resuscitation following unexpected hospital ventricular fibrillation, the patient remained in a comatose state and therefore received therapeutic hypothermia. Hypothermic treatment resulted in significant QT prolongation and "torsade de pointes" ventricular tachycardia. The probable cause of arrhythmia is the QT prolongation caused by the hypothermia and the consequential early afterdepolarization and triggered activity. The authors draw attention to the fact that - to the best of our knowledge - milder hypothermia is recommended within the preset hypothermic range. Orv Hetil. 2022; 163(13): 523-526.

[T-wave alternans and atrial tachycardia]. / T-hullám-alternáns és pitvari tachycardia.

A 70-year-old male patient presented with acute respiratory failure. ECG at admission showed atrial tachycardia with macro T-wave alternans that disappeared as soon as normal sinus rhythm had returned. This ECG shape was not accompanied by either QT-prolongation or acute ischaemia. This case draws attention to atrial tachycardia (provoked here in a context of respiratory insufficiency) that may be the sole reason for macro T-wave alternans. Orv Hetil. 2020; 161(7): 275-277.

[Differential diagnostic dilemmas after use of an out-of-date antihypertensive medication. Case report]. / Az ügyeleti ellátás útvesztoi egy korszerutlen készítmény okozta iatrogenia kapcsán.

Hydrochlorothiazide became one of the most commonly prescribed first-line antihypertensive medication, though its use is often complicated with serious side-effects. A 66-year-old female patient with a history of hypertension had suffered a transient loss of consciousness, and referred to our cardiology unit with an ST-segment elevation and giant negative T-waves in V1-2 ECG leads, long QT-segment and elevated serum creatine-kinase (5392 U/L) and troponin I (4,357 ng/ml) levels. Acute myocardial infarction was not proven (later coronarography revealed preserved coronary circulation), but severe hyponatraemia and hypokalaemia was detected, explaining a possible symptomatic seizure, and which could be accounted for a 25 mg daily hydrochlorothiazide antihypertensive treatment and - as a precipitating insult - a one-week history of gastroenteritis. The case-report presents a unique differential diagnostic question where thiazide-induced hyponatraemia and hypokalaemia resulted in a clinical picture sharing some similarities with acute myocardial infarction. This case underlines the serious side-effects of an inappropriately used common antihypertensive medication. Orv. Hetil., 2017, 158(11), 426-431.

Levosimendan Administration in Limb Ischemia: Multicomponent Signaling Serving Kidney Protection.

AIMS AND OBJECTIVES: Acute renal failure is a severe complication of lower extremity major arterial reconstructions, which could even be fatal. Levosimendan is a dual-acting positive inotropic and vasodilatory agent, which is suspected to have protective effects against cardiac ischemia. However, there is no data available on lower limb or remote organ ischemic injuries therefore the aim of the study was to investigate the effect of levosimendan on lower limb ischemia-reperfusion injury and the corollary renal dysfunction. METHODS: Male Wistar rats underwent 180 min bilateral lower limb ischemia followed by 4 or 24 hours of reperfusion. Intravenous Levosimendan was administered continuously (0.2µg/bwkg/min) throughout the whole course of ischemia and the first 3h of reperfusion. Results were compared with sham-operated and ischemia-reperfusion groups. Hemodynamic monitoring was performed by invasive arterial blood pressure measurement. Kidney and lower limb muscle microcirculation was registered by a laser Doppler flowmeter. After 4h and 24h of reperfusion, serum, urine and histological samples were collected. RESULTS: Systemic hemodynamic parameters and microcirculation of kidney and the lower limb significantly improved in the Levosimendan treated group. Muscle viability was significantly preserved 4 and 24 hours after reperfusion. At the same time, renal functional laboratory tests and kidney histology demonstrated significantly less expressive kidney injury in Levosimendan groups. TNF-α levels were significantly less elevated in the Levosimendan group 4 hours after reperfusion. CONCLUSION: The results claim a protective role for Levosimendan administration during major vascular surgeries to prevent renal complications.

Postconditioning in major vascular surgery: prevention of renal failure.

BACKGROUND: Postconditioning is a novel reperfusion technique to reduce ischemia-reperfusion injuries. The aim of the study was to investigate this method in an animal model of lower limb revascularization for purpose of preventing postoperative renal failure. METHODS: Bilateral lower limb ischemia was induced in male Wistar rats for 3 hours by infrarenal aorta clamping under narcosis. Revascularization was allowed by declamping the aorta. Postconditioning (additional 10 sec reocclusion, 10 sec reperfusion in 6 cycles) was induced at the onset of revascularization. Myocyte injury and renal function changes were assessed 4, 24 and 72 hours postoperatively. Hemodynamic monitoring was performed by invasive arterial blood pressure registering and a kidney surface laser Doppler flowmeter. RESULTS: Muscle viability studies showed no significant improvement with the use of postconditioning in terms of ischemic rhabdomyolysis (4 h: ischemia-reperfusion (IR) group: 42.93 ± 19.20% vs. postconditioned (PostC) group: 43.27 ± 27.13%). At the same time, renal functional laboratory tests and kidney myoglobin immunohistochemistry demonstrated significantly less expressed kidney injury in postconditioned animals (renal failure index: 4 h: IR: 2.37 ± 1.43 mM vs. PostC: 0.92 ± 0.32 mM; 24 h: IR: 1.53 ± 0.45 mM vs. PostC: 0.77 ± 0.34 mM; 72 h: IR: 1.51 ± 0.36 mM vs. PostC: 0.43 ± 0.28 mM), while systemic hemodynamics and kidney microcirculation significantly improved (calculated reperfusion area: IR: 82.31 ± 12.23% vs. PostC: 99.01 ± 2.76%), and arterial blood gas analysis showed a lesser extent systemic acidic load after revascularization (a defined relative base excess parameter: 1(st) s: IR: 2.25 ± 1.14 vs. PostC: 1.80 ± 0.66; 2(nd) s: IR: 2.14 ± 1.44 vs. PostC: 2.44 ± 1.14, 3(rd) s: IR: 3.99 ± 3.09 vs. PostC: 2.07 ± 0.82; 4(th) s: IR: 3.28 ± 0.32 vs. PostC: 2.05 ± 0.56). CONCLUSIONS: The results suggest a protective role for postconditioning in major vascular surgeries against renal complications through a possible alternative release of nephrotoxic agents and exerting a positive effect on hemodynamic stability.

Attenuation of skeletal muscle and renal injury to the lower limb following ischemia-reperfusion using mPTP inhibitor NIM-811.

INTRODUCTION: Operation on the infrarenal aorta and large arteries of the lower extremities may cause rhabdomyolysis of the skeletal muscle, which in turn may induce remote kidney injury. NIM-811 (N-metyl-4-isoleucine-cyclosporine) is a mitochondria specific drug, which can prevent ischemic-reperfusion (IR) injury, by inhibiting mitochondrial permeability transition pores (mPTP). OBJECTIVES: Our aim was to reduce damages in the skeletal muscle and the kidney after IR of the lower limb with NIM-811. MATERIALS AND METHODS: Wistar rats underwent 180 minutes of bilateral lower limb ischemia and 240 minutes of reperfusion. Four animal groups were formed called Sham (receiving vehicle and sham surgery), NIM-Sham (receiving NIM-811 and sham surgery), IR (receiving vehicle and surgery), and NIM-IR (receiving NIM-811 and surgery). Serum, urine and histological samples were taken at the end of reperfusion. NADH-tetrazolium staining, muscle Wet/Dry (W/D) ratio calculations, laser Doppler-flowmetry (LDF) and mean arterial pressure (MAP) monitoring were performed. Renal peroxynitrite concentration, serum TNF-α and IL-6 levels were measured. RESULTS: Less significant histopathological changes were observable in the NIM-IR group as compared with the IR group. Serum K+ and necroenzyme levels were significantly lower in the NIM-IR group than in the IR group (LDH: p<0.001; CK: p<0.001; K+: p = 0.017). Muscle mitochondrial viability proved to be significantly higher (p = 0.001) and renal function parameters were significantly better (creatinine: p = 0.016; FENa: p<0.001) in the NIM-IR group in comparison to the IR group. Serum TNF-α and IL-6 levels were significantly lower (TNF-α: p = 0.003, IL-6: p = 0.040) as well as W/D ratio and peroxynitrite concentration were significantly lower (p = 0.014; p<0.001) in the NIM-IR group than in the IR group. CONCLUSION: NIM-811 could have the potential of reducing rhabdomyolysis and impairment of the kidney after lower limb IR injury.

Muscle fiber viability, a novel method for the fast detection of ischemic muscle injury in rats.

Acute lower extremity ischemia is a limb- and life-threatening clinical problem. Rapid detection of the degree of injury is crucial, however at present there are no exact diagnostic tests available to achieve this purpose. Our goal was to examine a novel technique - which has the potential to accurately assess the degree of ischemic muscle injury within a short period of time - in a clinically relevant rodent model. Male Wistar rats were exposed to 4, 6, 8 and 9 hours of bilateral lower limb ischemia induced by the occlusion of the infrarenal aorta. Additional animals underwent 8 and 9 hours of ischemia followed by 2 hours of reperfusion to examine the effects of revascularization. Muscle samples were collected from the left anterior tibial muscle for viability assessment. The degree of muscle damage (muscle fiber viability) was assessed by morphometric evaluation of NADH-tetrazolium reductase reaction on frozen sections. Right hind limbs were perfusion-fixed with paraformaldehyde and glutaraldehyde for light and electron microscopic examinations. Muscle fiber viability decreased progressively over the time of ischemia, with significant differences found between the consecutive times. High correlation was detected between the length of ischemia and the values of muscle fiber viability. After reperfusion, viability showed significant reduction in the 8-hour-ischemia and 2-hour-reperfusion group compared to the 8-hour-ischemia-only group, and decreased further after 9 hours of ischemia and 2 hours of reperfusion. Light- and electron microscopic findings correlated strongly with the values of muscle fiber viability: lesser viability values represented higher degree of ultrastructural injury while similar viability results corresponded to similar morphological injury. Muscle fiber viability was capable of accurately determining the degree of muscle injury in our rat model. Our method might therefore be useful in clinical settings in the diagnostics of acute ischemic muscle injury.

Rapidly progressing fatal reperfusion syndrome caused by acute critical ischemia of the lower limb.

The most severe complication of ischemia-reperfusion injury following lower limb arterial surgery is reperfusion syndrome. Therefore, our aim was to describe the extent of muscle damage and the reperfusion syndrome-related remote organ lesions in detail, through a well-documented case of long-lasting infrarenal aorta thrombosis. After urgent revascularization, several clinical signs of multiple organ dysfunction were detectable, including the circulatory, urinary, respiratory, gastrointestinal, and hemostatic systems. Upon histological examination, intraoperative muscle biopsy showed severe muscle damage. Muscle fiber viability was assessed with a special nitroblue tetrazolium staining-based viability test developed by our team; the obtained results indicated significant degree of muscle damage before this was confirmed by conventional histological methods. Thorough postmortem examination confirmed the presence of remote organ damage. The pathological findings included acute tubular necrosis, myocardial and jejunal infarctions, ischemic pancreatitis, and diffuse alveolar damage with hyaline membrane formation in the lungs and focal centrilobular liver necrosis. By using special staining techniques, the presence of myoglobin and lipofuscin deposits was confirmed in the kidney samples. In this paper, we present a patient who developed all major complications following long-lasting arterial occlusion. We also introduce a novel method to assess the degree of ischemic injury, which may be suitable in the near future for the rapid detection of irreversible muscle injury. Therefore, the mortality of the disease might be reduced.

[Postconditioning can reduce long-term lung injury after lower limb ischemia-reperfusion]. / Alsó végtagi ischaemiás-reperfusiós károsodás hosszú távú tüdoszövodményeinek megelozése posztkondicionálással.

INTRODUCTION: Operation on the infrarenal aorta could cause ischemic-reperfusion (IR) injury in local tissues and remote organs (e.g. the lung). OBJECTIVES: Our aim was to reduce long-term lung damage, after lower limb IR with postconditioning. MATERIALS AND METHODS: Male Wistar rats underwent 180 minutes of bilateral lower limb ischemia. Animals were divided into three groups: Sham-operated, IR, Postconditioned (PostC) and further to two subgroups according to reperfusion time: 24 h and 72 h. Serum free radical and IL-6 levels, histological changes, Wet/Dry (W/D) ratio, tissue myeloperoxidase (MPO) activity and Hsp72 levels were investigated. RESULTS: Postconditioning can reduce histological changes in the lung. Free radical levels are significantly lower in PostC groups than in IR groups (42.9 ± 8.0 vs. 6.4 ± 3.4; 27.3 ± 4.4 vs. 8.3 ± 4.0 RLU%; p < 0.05). IL-6 level (238.4 ± 31.1 vs. 209.1 ± 18.8; 190.0 ± 8.8 vs. 187.0 ± 14.9 pg/ml) and Hsp72 expression did not show any significant difference. Compared to the IR group, lung MPO activity did not change in the PostC groups. W/D ratio in PostC groups is significantly lower at all measured time-points (68% vs. 65%; 72% vs. 68%; p < 0.05). CONCLUSION: Postconditioning may reduce long-term damages of the lung after lower limb ischemic-reperfusion injury.

Therapeutic option for managing lung injury induced by infrarenal aortic cross-clamping.

BACKGROUND: Operations on the infrarenal aorta can cause ischemic-reperfusion (IR) injury in local tissues, which could result in remote organ (e.g., lung) damage. Treatment of such injuries remains an unresolved problem. OBJECTIVES: Our aim was to reduce remote lung damage after lower limb IR by means of postconditioning. MATERIALS AND METHODS: Male Wistar rats were divided into three groups: Sham-operated, IR, and Postconditioned (PostC). In the latter two groups rats underwent 180 min of exclusion of the infrarenal aorta. The reperfusion time was 4 h. Serum-free radical levels, tumor necrosis factor-α and interleukin-6 concentrations, histologic changes in the lung, wet/dry-ratio, myeloperoxidase activity, heat shock protein 72 level and blood gas changes were investigated. RESULTS: Postconditioning reduced histological damage in the lung (P < 0.05). Free radical levels and tumor necrosis factor-α concentrations were significantly lower in the PostC group than in the IR group (P < 0.05 and P < 0.01, respectively). Interleukin-6 concentrations did not significantly differ in the PostC group. Compared with the IR group, lung myeloperoxidase activity was lower in the PostC group. Decreased pulmonary heat shock protein 72 level was observed in the PostC group compared with the IR group and the wet/dry-ratio was also significantly lower in the PostC group (P < 0.05). A noticeably higher arterial pO2 level was manifest in the PostC group after 2 and 4 h of reperfusion (P < 0.05). CONCLUSIONS: Postconditioning reduced lung damage under experimental conditions, in the early period of reperfusion after lower limb IR injury.

Interaction of SSR161421, a novel specific adenosine A(3) receptor antagonist with adenosine A(3) receptor agonists both in vitro and in vivo.

A novel adenosine A(3) receptor antagonist (SSR161421) was characterized by both receptor binding assays and pharmacological tests. Binding studies on cloned human adenosine receptors showed that SSR161421 has high affinity for adenosine hA(3) receptors (K(i)=0.37 nM) with at least 1000-fold selectivity compared to hA(1), hA(2A) and hA(2B) receptors. The receptor antagonist nature of SSR161421 was determined in a functional study on Chinese hamster ovarian cells (CHO) cells expressing human adenosine A(3) receptors. SSR161421 competitively antagonized the effect of 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methylcarboxamide (Cl-IB-MECA) on cAMP production with a pA2 value in a luciferase reporter gene construct. In mice, intravenously administered SSR161421 inhibited the N6-(4-aminobenzyl)-adenosine-5'-N-methyl-uronamide dihydrochloride (AB-MECA) induced increase in plasma histamine levels (ED(50)=2.0mg/kg) and the Cl-IB-MECA evoked plasma extravasation (ID(50)=2.9 mg/kg) and oedema formation (ID(50)=4.6 mg/kg) in mouse ear.

Evaluation of SSR161421, a novel orally active adenosine A3 receptor antagonist on pharmacology models.

The effects of a novel adenosine A(3) receptor antagonist, SSR161421, were examined on both antigen per se and adenosine receptor agonist-increased airway responses in antigen-sensitized guinea pigs. Adenosine (10(-5)M) and AB-MECA [N6-(4-aminobenzyl)-adenosine-5'-N-methyl-uronamide dihydrochloride] (10(-7)M) increased the antigen response up to 61 ± 3.0% and 88 ± 5.2% of maximal contraction, respectively. The agonists of adenosine A(1) and A(2) adenosine receptors NECA [1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-b-d-ribofuranuronamide-5'-N-ethylcarboxamidoadenosine], R-PIA [N(6)-R-phenylisopropyladenosine], and CGS21680 (10(-7)M) were ineffective. In vivo intravenous adenosine (600 µg/kg) and AB-MECA (30 µg/kg) increased the threshold antigen dose-induced bronchoconstriction by 214 ± 13.0% and 220 ± 15.2%, respectively. SSR161421 in vitro (IC(50)=5.9 × 10(-7)M) inhibited the AB-MECA-enhanced antigen-induced airway smooth muscle contractions and also in vivo the bronchoconstriction following either intravenous (ED(50)=0.008 mg/kg) or oral (ED(50)=0.03 mg/kg) administration in sensitized guinea pigs. Antigen itself could evoke tracheal contraction in vitro and bronchoconstriction in vivo in antigen-sensitized guinea pigs. SSR161421 (3 × 10(-6)M) decreased the AUC of the antigen-induced contraction-time curve to 20.8 ± 5.4% from the 100% control level. SSR161421 effectively reversed the antigen-induced bronchoconstriction, plasma leak and cell recruitment with EC(50) values of 0.33 mg/kg p.o., 0.02 mg/kg i.p. and 3 mg/kg i.p., respectively.

Postconditioning of the lower limb--protection against the reperfusion syndrome.

BACKGROUND: Postconditioning-alternating brief cycles of reperfusion/reocclusion applied at the beginning of revascularization-is a potent therapeutic technique, attenuating ischemia-reperfusion injury. Vascular surgery on the lower limb with ischemia-reperfusion injury may give rise to serious systemic complications [organ dysfunction syndrome (MODS), systemic inflammatory response syndrome (SIRS)], a phenomenon called reperfusion-syndrome. MATERIAL AND METHODS: We studied the effects of postconditioning on reperfusion-syndrome in a rodent experimental model. Wistar rats underwent 180 min of bilateral lower limb ischemia using an infrarenal crossclamping of the abdominal aorta. Postconditioning consisted of six cycles of 10-s aortic occlusion/10-s declamping at the beginning of reperfusion. Microcirculation of the lower limb was detected with laser Doppler flowmeter. After 4 h of reperfusion, plasma, urine, and histologic samples were collected. RESULTS: One hundred eighty-minute ischemia resulted in significant hemodynamic changes after reperfusion. Postconditioning affected the character of the microcirculatory flow, the limb circulation stabilized with hyperemia during reperfusion. Postconditioning caused a significant reduction in systemic inflammatory response (TNF-α, oxygen-derived free radicals). The laboratory and histologic samples implied a significant decrease in distant organ (lung and renal) dysfunctions after postconditioning. CONCLUSION: Postconditioning proves to be capable of conferring protection against different organ injuries caused by longer circulatory occlusions during elective major vascular operations.

[Acute and critical ischemia of the lower limb]. / Akut kritikus ischaemia az alsó végtagon.

Acute limb arterial occlusion has great clinical significance due to its high mortality and complication rates. Its diagnosis is easy; however staging after long-term occlusions can be very difficult with lack of exact criteria. It is crucial, since reversible stage should undergo revascularization, while with irreversible stage only amputation is curative. Due to occlusion, long-term ischemia occurs, resulting in injury of the muscle fibers and endothelial cells. In case of revascularization the reperfusion causes more damage, than ischemia alone locally and initiates a remote organ injury. The aim of the review is to summarize the knowledge and fact and focus on some exact methods or parameters which can determine the degree of injury. One of these methods is a new approach which is the use of enzyme-histochemical reactions, and could give rapid, precise results even preoperatively regarding tissue viability. Routine clinical application of it is predictable after proper standardization.

[Long ischemic period of the lower limb--study of skeletal muscle viability in experimental animal models]. / Hosszú ideju végtagi veroér-elzáródás és izomszövet-életképesség vizsgálata kísérletes állatmodellben.

INTRODUCTION: Surgical treatment for acute limb ischemia is revascularization or - when the limb is in a critical stage - amputation. Correct staging of the disease is relatively difficult, therefore complication and mortality rates are extremely high. Our aim was to invesitigate acute critical ischemia in rats and to test postconditioning on this model. METHODS: Experiment I: male Wistar rats underwent 4, 6, 8 hours of bilateral lower limb ischemia without reperfusion. Experiment II: suspected critical ischemia was followed by 2 hours of reperfusion with or without postconditioning. Histological samples were collected for routine staining and nitroblue-tetrazolium (NBT) enzyme-histochemistry. In Experiment II the microcirculatory changes were measured by laser Doppler flowmetry and blood samples were collected for laboratory testing (kreatin-kinase, CK). RESULTS: Experiment I: After an eight-hour-obstruction, severe ischemic lesions were detectable, with rutine and NBT stainings, therefore 8 hours of ischemia was chosen for further testing. Experiment II: The CK levels showed significant (p < 0.05) drop, quantitative evaluation of enzyme-histochemisty resulted in significantly (p < 0.001) less viability depletion and microcirculation showed significant (p < 0.05) amelioration of the reperfusion parameters in the postconditioned group compared to the control. CONCLUSIONS: Eight hours of lower limb ischemia is a suitable model to investigate acute critical ischemia in rats. Postconditioning could be a feasible technique to reduce IR injury associated with acute lower limb ischemia.