Richard J. Solomon

Ventricular Arrhythmias in Patients with Myocardial Infarction and Ischaemia

SummaryAlterations in serum electrolytes may frequently accompany ischaemic heart disease. Many of these patients are hypertensive and receive diuretic therapy which results in chronic lowering of serum potassium and magnesium. In addition, acute catecholamine-induced shifts of potassium into cells may also occur in the setting of acute myocardial ischaemia.An association between low serum potassium concentrations and ventricular arrhythmias has been observed by a number of investigators in patients with acute myocardial infarction. The increased frequency of ventricular fibrillation with low serum potassium concentrations is particularly relevant as this arrhythmia is associated with poor prognosis, even in the setting of a coronary care unit Ventricular fibrillation also occurs with increased frequency in patients with angina who have low serum potassium levels.The possibility that low serum potassium concentrations may be a risk factor in the increased incidence of sudden death in such patients should be considered. Diuretic-induced magnesium deficiency may be yet another factor favouring the emergence of ventricular arrhythmias in patients with ischaemic heart disease.While such electrolyte disturbances do not account for all of the ventricular irritability seen in patients with ischaemic heart disease, they represent easily identifiable and treatable risk factors. Primary prevention of these electrolyte disturbances in patients at risk for coronary ischaemia is recommended.RésuméDes modifications du taux sérique des électrolytes accompagnent souvent l’ischémie myocardique. La plupart des malades sont hypertendus et traités pur des diurétiques qui entraînent une perte du potassium et du magnésium. De plus, la réaction adrénergique qui accompagne le début d’une ischémie myocardique aiguë induit une inversion brutale du potassium intracellulaire.L’association d’un potassium sérique diminué et d’arythmies ventriculaires a souvent été notée par les cliniciens lors de la phase aiguë de l’infarctus du myocarde. La plus grande fréquence des fibrillations ventriculaires quand la kaliémie est basse est un fait particulièrement intéressant eu égard au mauvais pronostic de ce type d’arythmie même en unité de soins intensifs spécialisée. La fibrillation ventriculaire survient également avec une plus grande fréquence chez les angineux qui ont un taux sérique de potassium bas.Ce paramètre biologique pourrait donc être un facteur de risque de mort subite. Les diurétiques qui provoquent une perte de magnésium pourraient également être un facteur favorisant la survenue d’arythmies ventriculaires dans les ischémies myocardiques.Bien que les désordres électrolytiques ne rendent pas compte à eux seuls de l’augmentation de l’excitabilité myocardique observée dans l’ischémie, la facilité avec laquelle on peut en faire à la fois le diagnostic et la correction en font des paramètres qu’on doit penser à évaluer chez les patients à risque de maladie coronarienne.ZusammenfassungVeränderungen der Serumelektrolyte können bei ischämischer Herzkrankheit häufig sein. Viele dieser Patienten sind hypertensiv und erhalten eine zu einer chronischen Erniedrigung von Kalium und Magnesium im Serum führende diuretische Therapie. Auβerdem können auch Katecholamin-induzierte Kalium-Verschiebungen in die Zellen beim Auftreten von Myokardischämien erfolgen.Eine Assoziation zwischen niedrigen Serum-Kaliumkonzentrationen und ventrikulären Arrhythmien wurde von einer Anzahl von Untersuchern bei Patienten mit akutem Herzinfarkt festgestellt. Die höhere Häufigkeit von Kammerflimmern bei niedrigen Serum-Kaliumkonzentrationen ist besonders relevant, da diese Arrhythmien selbst auf koronaren Intensivstationen mit einer schlechten Prognose verbunden sind. Kammerflimmern tritt auch mit erhöhter Häufigkeit bei Patienten mit Angina pectoris auf, die niedrige Serum-Kaliumspiegel haben. Die Möglichkeit, daβ niedrige Serum-Kaliumkonzentrationen einen Risikofaktor für das gesteigerte Auftreten von plötzlichem Herztod bei solchen Patienten darstellen können, sollte in Betracht gezogen werden. Ein Diuretika-induzierter Magnesiummangel kann ein weiterer Faktor sein, der das Auftreten von Kammerflimmern bei Patienten mit ischämischer Herzkrankheit begünstigt.Wenn auch Elektrolytstörungen nicht für jede Art von gesteigerter ventrikulärer Erregbarkeit verantwortlich sind, stellen sie doch leicht erkennbare und behandelbare Risikofaktoren dar. Die primäre Verhütung dieser Elektrolytstörungen bei Patienten mit dem Risiko einer Koronarischämie ist zu empfehlen.SommarioAlterazioni degli elettroliti plasmatici possono frequentemente accompagnare una cardiopatia ischemica. Molti di questi pazienti sono ipertesi in terapia diuretica e quest’ultima comporta una riduzione cronica dei livelli plasmatici di potassio e di magnesio. Inoltre, in corso di ischemia miocardica acuta, si può verificare anche una variazione acuta del potassio intracellulare catecolamine-indotta.Numerosi ricercatori hanno osservato una correlazione fra basse concentrazioni di potassio e aritmie ventricolari in pazienti con infarto miocardico acuto. La maggiore frequenza di episodi di fibrillazione ventricolare in presenza dì basse concentrazioni plasmatiche di potassio è un dato di particolare interesse, dal momento che quest interesse aritma si associa ad una cattiva prognosi, anche nell’ambito di una unità di terapia intensiva coronarica. La fibrillazione ventricolare inoltre si verifica con una maggiore frequenza nei pazienti anginosi con bassi livelli di potassiemia. Dovrebbe essere considerata la possibilità che basse concentrazioni plasmatiche di potassio siano un fattore di rischio, data la maggiore incidenza di morte improvvisa in tali pazienti. Una carenza di magnesio diuretico-indotta potrebbe rappresentare un ulteriore fattore favorente il verificarsi di aritmie ventricolari in pazienti con cardiopatia ischemica. Anche se tali alterazioni elettrolitiche non possono spiegare completamente l’ipereccitabilità ventricolare osservata in pazienti con cardiopatia ischemica, esse rappresentano fattori di rischio di facile identificazione e terapia. Si raccomanda una prevenzione primaria di tali alterazioni elettrolitiche in pazienti a rischio per ischemia coronarica.ResumenLas alteraciones en los electrolitos śericos acompañan frecuentemente a la cardiopatía isquémica. Muchos de estos pacientes son hipertensos y, por tanto, son sometidos a tratamiento con diuréticos, lo cual lleva a que se registren niveles séricos de potasio y magnesio crónicamente bajos. A esto se añade que en el contexto de la isquemia miocárdica aguda pueden producirse también desplazamientos agudos, inducidos por catecolaminas, de potasio al interior de las células.Diversos investigadores han observado en pacientes de infarto agudo de miocardio la asociación entre concentraciones séricas bajas de potasio y la aparición de arritmias ventriculares. La mayor frecuencia de fibrilación ventricular concomitante a concentraciones bajas de potasio reviste una particular importancia, dado que este tipo de arritmia implica un mal pronóstico, incluso en el ambiente de una unidad de cuidados coronarios. La fibrilación ventricular también se présenta con mayor frecuencia en pacientes con angina que tienen niveles séricos bajos de potasio.Debe considerarse la posibilidad de que las concentraciones séricas bajas de potasio sean un factor de riesgo en relación con la mayor frecuencia de muerte súbita en tales pacientes. También el déficit de magnesio inducido por los diuréticos puede ser otro factor que favorezca la presentación de arritmias ventriculares en pacientes con cardiopatía isquémica.Si bien tales alteraciones electrolíticas no son las únicas responsables de la irritabilidad ventricular observada en pacientes de cardiopatía isquémica, sí son factores de riesgo de fácil detección y tratamiento. La prevención primaria de estas alteraciones electroliticas es aconsejable en los pacientes con riesgo de isquemia coronaria.ResumoAs doenças cardiacas isquêmicas podem ocorrer frequentemente acompanhadas de alterações nos eletrólitos contidos no sero. Muitos dos pacientes de doença cardíaca isquémica são hipertensos e recebem tratamento à base de diuréticos, o que resulta numa baixa crônica da concentração de potássio e magnésio no sero. Além disso, a deslocação aguda de potássio para o interior das células —o que é induzido por catecolaminas —também pode ocorrer na presença de uma isquemia aguda do miocárdio.Diversos investigadores puderam observar uma associação entre concentrações baixas de potássio e arritmias ventriculares, em pacientes de enfarte agudo do miocárdio. A maior ocorrência de fibrilaçào ventricular junto com concentrações baixas de potássio no sero é particularmente relevante visto que esta arritmia está associada a uma previsào deficiente, mesmo no quadro de um centro de tratamento intensivo. A fibrilação ventricular também ocorre com maior freqü’ência em pacientes com agina que têm concentrações de potássio no sero baixas.A possibilidade de que as baixas concentrações de potássio no sero possam constituir um fator de risco para uma maior incidência de mortes súbitas em tais pacientes deve ser considerada. A deficiência de magnésio induzida por diuréticos pode constituir um outro fator favorável à emergência de arritmias ventriculares em pacientes com doença cardíaca isquémica.Mesmo não respondendo pelo total da irritabilidade ventricular verificada em pacientes com doença cardíaca isquémica, estes distúrbios eletrolíticos representam fatores de risco facilmente identificáveis e tratáveis. Recomenda-se a prevenção primária destes distúrbios eletrolíticos em pacientes com doença cardíaca isquémica.

Elevated nicotine levels in patients undergoing hemodialysis: A role in cardiovascular mortality and morbidity?

The incidence of cardiovascular disease in patients with end-stage renal disease undergoing long-term maintenance hemodialysis is excessively high. The reason for this excess morbidity and mortality has remained unclear. Cigarette smoking is one factor that has been associated with increased cardiovascular risk. To learn more about the effects of tobacco smoking in these patients, nicotine levels were assayed in the serum of 10 patients with end-stage renal disease undergoing maintenance hemodialysis. Specimens were obtained before and after smoking one cigarette and following dialysis or an equivalent period in control subjects. Serum nicotine levels (+/-SEM) in control subjects measured 19.0 +/- 7.2 ng/ml initially, 36.1 +/- 8.2 ng/ml after smoking, and 9.3 +/- 3.5 ng/ml after a period of 4.35 hours. These compare with respective values of 76.6 +/- 16.8 ng/ml (p less than 0.004), 132.9 +/- 19.7 ng/ml (p less than 0.001), and 51.9 +/- 10.5 ng/ml (p less than 0.001) in patients undergoing hemodialysis. These data demonstrate markedly higher nicotine levels in hemodialysis patients compared with control subjects, which may have serious implications regarding morbidity and mortality.

Electrocardiographic Changes following Dialysis

We investigated electrocardiographic changes occurring after hemodialysis in 20 male patients with chronic renal failure. Changes in the configuration of T wave, ST segment and R wave consistent with ischemia were found in 30, 45, and 75%, respectively. Contrary to prior speculation the R wave height did not vary with the volume changes of body fluid occurring in dialysis. It is concluded that ischemic-appearing changes of uncertain significance are common in the postdialysis population.

THE DIURNAL RHYTHM OF PLASMA POTASSIUM : RELATIONSHIP TO DIURETIC THERAPY

Summary: Plasma potassium levels have been implicated in the genesis of cardiac arrhythmias, particularly in patients receiving diuretic therapy. The present study was undertaken to evaluate the stability of plasma potassium levels throughout a 28-h period. Normal volunteers (n = 8) and subjects with essential hypertension (n = 10) were studied in a clinical research center while receiving controlled dietary intakes. Plasma potassium followed a diurnal rhythm in both groups, with a peak level at 12 h and a trough level at 24 h. The average peak-to-trough difference was 0.62 × 0.05 mmol/L. Urinary potassium excretion also followed a diurnal rhythm, with the lowest excretory rate during the evening hours, when plasma potassium reached its nadir. Subjects with essential hypertension were restudied after 4 weeks of hydrochlorothiazide (50 mg/day) and then after an additional 4 weeks of hydrochlorothiazide (50 mg/day) and amiloride (5 mg/day). Hydrochlorothiazide alone reduced plasma potassium at all times of measurement without altering the diurnal rhythm. The combination of hydrochlorothiazide and amiloride resulted in higher plasma potassium levels in the morning, but did not significantly affect evening plasma potassium levels. The frequency of hypokalemia (K × 3.0 mmol/L) was related to the time at which the plasma potassium was measured. We conclude that plasma potassium undergoes a diurnal rhythm and that diuretics shift this rhythm to uniformly lower values. This rhythm must be considered when defining the frequency of hypokalemia.

Thallium-201 Myocardial Imaging in Patients on Chronic Hemodialysis

10 long-term hemodialysis patients had immediate and redistribution thallium-201 myocardial imaging performed after a course of hemodialysis. Subjects had EKGs done on the same day before and after dialysis. 3 of the 10 subjects had resting thallium-201 myocardial imaging obtained on non-dialysis days. 60% of the electrocardiograms showed changes with dialysis. All 13 thallium studies were abnormal, showing multiple transient filling defects at rest. Most subjects had permanent filling defects as well. It is concluded that hemodialysis patients have a high frequency of abnormal thallium-201 myocardial images at rest. The cause of these abnormal studies is uncertain.

Ventriclar Arrhythmias in Patients with Myocardial Infarction and Ischaemia The Role of Serum Potassium

SummaryAn association between low serum potassium concentrations and ventricular arrhythmias has been observed by a number of investigators in patients with both acute myocardial infarction and symptomatic angina. The increased frequency of ventricular fibrillation in patients with low serum potassium concentrations has not been attributable to differences in the size or location of the infarct or concomitant digitalis administration. Although prior diuretic usage is frequently associated with a low serum potassium concentration, diuretic usage in the absence of significant changes in serum electrolytes is not associated with an increase in malignant ventricular arrhythmias.It is not clear whether the alterations in serum potassium are important in the pathogenesis of the arrhythmias or merely a marker for other arrhythmogenic factors. To the extent that changes in serum potassium contribute to the production of serious ventricular arrhythmias, efforts should be directed at the correction of such electrolyte disturbances.Attempts to increase the serum potassium in acute cases do not appear to be successful in preventing ventricular arrhythmias in this setting. Primary prevention of electrolyte disturbances would seem to offer more effective protection against serious arrhythmias. Long term studies with β-blockers support this premise.RésuméNombre d’investigateurs ont trouvé une association entre concentrations sériques de potassium basses et arythmies ventriculaires chez les malades qui présentent un infarctus aigu du myocarde et un angor symptomatique. L’augmentation de fréquence de la fibrillation ventriculaire chez les malades qui ont des concentrations de potassium sérique basses n’a pas été attribuée à des différences de localisation de l’infarctus ou d’administration concomittante de digitaliques. Bien que l’utilisation non contrôlée de diurétiques soit fréquemment associée à un potassium sérique bas, l’emploi de diurétiques en l’absence de modifications significatives des électrolytes sériques n’est pas associée à une augmentation des arythmies ventriculaires malignes.On ne sait pas clairement si les altérations du potassium sérique sont un facteur important dans la pathologie des arythmies ou simplement un marqueur d’autres facteurs arythmogènes. Dans la mesure où les changements du potassium sérique contribuent à la formation d’arythmies ventriculaires graves, on doit s’efforcer de corriger de tels désordres électrolytiques.Les tentatives faites pour augmenter le potassium sérique dans les cas aigus ne paraissent pas couronnées de succès pour prévenir les arythmies ventriculaires dans ce contexte. La prévention primaire des désordres électrolytiques semblerait offrir une protection plus efficace contre les arythmies graves. Des études à long terme avec les β bloqueurs étayent cette façon de voir.ZusammenfassungEine Assoziation zwischen niedrigen Serumkonzentrationen von Kalium und ventrikulären Arrhythmien wurde durch eine Anzahl von Untersuchern sowohl bei Patienten mit akutem Myokardinfarkt als auch symptomatischer Angina beobachtet. Die gesteigerte Häufigkeit einer ventrikulären Fibrillation bei Patienten mit niedrigen Kalium-Konzentrationen im Serum wurde auf Unterschiede in der Gröβe oder Lokalisation des Infarkts oder einer gleichzeitigen Gabe von Digitalis zurückgeführt. Obwohl eine vorherige Verwendung von Diuretika häufig mit niedrigen Serumkonzentrationen des Kalium einhergehen, ist eine diuretische Verwendung in Abwesenheit von signifikanten Veränderungen bei den Serum-Elektrolyten nicht mit einem Anstieg von malignen ventrikulären Arrhythmien assoziiert.Es ist nicht klar, ob die Veränderungen im Serum-Kalium für die Pathogenese der Arrhythmien wichtig oder nur ein Zeichen für andere arrhythmogene Faktoren sind. Falls Veränderungen des Serum-Kalium an der Erzeugung von schweren ventrikulären Arrhythmien beitragen, sollten die Bemühungen auf eine Korrektur solcher Elektrolyt-Störungen gerichtet sein.Versuche, das Kalium im Serum bei akuten Fällen zu erhöhen, scheinen zur Verhinderung ventrikulärer Arrhythmien unter diesen Umständen nicht erfolgreich zu sein. Eine vorherige Verhinderung von Elektrolyt-Störungen sollte einen wirksameren Schutz gegen schwere Arrhythmien bieten. Langzeitstudien mit Beta-Blockern stützen diese Annahme.ResumenVarios investigadores han observado una asociación entre concentraciones bajas de potasio sérico y arritmias ventriculares en pacientes de infarto de miocardio agudo y angor sintomático. La mayor frecuencia de fribilación ventricular en los casos de concentraciones bajas de potasio sérico no ha sido atribuible a diferencias de tamaño o localizacion del infarto ni a la administración concomitante de digital. Aunque el uso previo de diuréticos va unido frecuentemente a una concentración baja de potasio sérico, en su empleo en ausencia de modificaciones significativas de los electrólitos del suero no se asocia a un aumento de las arritmias ventriculares malignas. No está claro si las alteraciones del potasio sérico son importantes en la patogenia de las arritmias o se trata de meros marcadores de otros factores arritmógenos. En la medida en que las modificaciones del potasio sérico contribuyan a laproducción de arritmias ventriculares graves, será preciso esforzarse por corregir dichos trastornos electrolíticos.Los intentos de aumentar el potasio sérico en los casos agudos no parecen dar resultado para prevenir las arritmias ventriculares en estas condiciones. La prevención primaria de los trastornos electrolíticos parecen ofrecer más protectión efectica contra las arritmias graves. Estudios prolongados con β-bloqueadores respaldan esta afirmación.ResumoFoi observada por uma série de investigadores uma associação entre baixas concentrações de potássio no soro e arritmias ventriculares em patientes portadores tanto de enfarto agudo do miocárdio como de angina sintomática. Não se atribui a maior frequência de fibrilação ventricular em patientes com baixas concentrações de potássio no soro a diferenças de tamanho ou localização do enfarto, nem à aplicação concomitante de digital. Embora o uso precedente de diuréticos esteja frequentemente associado a baixas concentrações de potássio no soro, o uso de diuréticos, na ausência de mudanças significativas nos electrólitos no soro, não está associado a urn aumento nas arritmias ventriculares malignas.Não está claro se as alterações nas concentrações de potássio no soro são importantes na patogênese das arritmias, ou se elas apenas funcionam como sinal de outros fatores arritmogênicos. Contudo, visto que as mudanças nas concentrações de potássio no soro contribuem para a formação de sérias arritmias do ventnículo, deve-se desenvolver esforços no sentido de se corrigir tais distúrbios eletrolíticos.As tentativas de se aumentar a concentração de potássio no soro em casos agudos não conseguiram prevenir as arritmias do ventrículo num tal quadro. A prevenção primária de distúrbios eletrolíticos parece oferecer proteção mais efetiva contra arritmias graves. Estudos a longo prazo com beta-bloqueadores sustentam esta premissa.RiassuntoUna associazione tra bassi livelli sierici di potassio e aritmie ventricolari è stata osservata da numerosi ricercatori sia in pazienti con infarto miocardico acuto che con angina sintomatica. Non è stato possibile attribuire l’aumentata frequenza di fibrillazione ventricolare in pazienti con ipopotassiemia a differenze di dimensione o di sede dell’infarto o a contemporanea sontministrazione di digitale. Sebbene un precedente trattamento diuretico sia frequentemente associato ad ipopotassiemia, l’uso di un diuretico in assenza di significative modificazioni di elettroliti sierici, non è associato ad un aumento di aritmie ventricolari maligne. Non è chiaro se le modificazioni del potassio sierico siano importanti nella patogenesi delle aritmie o siano solo un marker di altri fattori aritmogenici. Poichè variazioni del potassio sierico contribuiscono alla produzione di serie aritmie ventricolari, un grande impegno dovrebbe essere diretto alla correzione di tali anomalie elettrolitiche. Tentativi di aumentare il potassio sierico in casi acuti non sembrano efficaci nel prevenire aritmie ventricolari. La prevenzione primaria delle alterazioni elettrolitiche sembrerebbe offrire una protezione più efficace nei confronti delle aritmie gravi. Studi a lungo termine con beta-bloccanti confermano questa tesi.

Urinary Kininogen: A Possible Regulator of Kinin Formation in Normal Individuals and Subjects with Essential Hypertension, End-Stage Renal and Liver Disease

Most previous studies have not significantly correlated urinary kallikrein to urinary kinins. We investigated whether urinary kininogen might influence kinin formation within the urine. On an ad-lib diet the 24 hour excretion of total and intact kininogen, kinins and kallikrein was determined in 24 control subjects, 20 untreated essential hypertensives, 12 with end-stage renal disease and 8 subjects with liver disease. Kallikrein and kinins were measured by a direct radioimmunoassay. Total kininogen was determined from the sum of preformed kinins and kinins generated after trypsin (intact kininogen). Cross reactivity between purified human low molecular weight kininogen and bradykinin antiserum was 3%. Total and intact kininogen were significantly correlated with kinins in controls, essential hypertension and liver disease. In essential hypertension, end-stage renal and liver diseases kinins were significantly decreased. This was associated with a reduction in kininogen but not kallikrein in essential hypertension and liver disease, and a reduction in kallikrein but not kininogen in end-stage renal disease. Thus, renal kinin generation in various states may be affected by either or both kininogen and kallikrein.