Prediction of immediate ventricular arrhythmias after coronary artery ligation.

OBJECTIVES: Our aim was to test the hypothesis that increased beat to beat morphologic variations in the body surface electrocardiogram (ECG) are associated with fragmented diastolic electrical activity that appears after coronary artery ligation and to correlate the appearance of spontaneous ventricular fibrillation after coronary ligation with the magnitude of the ECG beat to beat variability. BACKGROUND: Unstable and variably delayed electrical activation precedes the development of ventricular fibrillation in dogs with acute ischemia. Detection of these highly variable low amplitude signals from the body surface is currently impossible. We have developed a system designed to measure the degree of beat to beat variability of the ECG. METHODS: With high fidelity electrocardiography, subtle beat to beat ECG morphologic variations were detected in epicardial and body surface electrograms and quantified as the variance of the ECG voltage at specific points of the cardiac cycle. The ratio of the variance at the QRS offset to that of the QRS onset (beat to beat variability index) was then calculated. RESULTS: Ventricular fibrillation developed in 12 of 27 dogs after left anterior descending coronary artery ligation. In 7 of the 12 dogs it occurred immediately (< 15 min) after ligation; in the other 5 it developed late (> 15 min) after ligation. Dogs with subsequently immediate ventricular fibrillation had a significantly higher beat to beat variability index than that of dogs with late or no ventricular fibrillation both before coronary ligation (4.7 +/- 1.4 vs. 1.1 +/- 0.2 and 0.8 +/- 0.1, respectively, p < 0.001) and after ligation (6.4 +/- 2.6, 1.0 +/- 0.6 and 1.2 +/- 0.6, respectively, p < 0.001). In dogs that developed ventricular fibrillation immediately after coronary ligation, the arrhythmia was preceded by fragmented diastolic electrical activity on the epicardial electrogram and a simultaneous increase in the beat to beat morphologic variability of the terminal portion of the body surface ECG QRS complex. CONCLUSIONS: Beat to beat QRS offset morphologic variations appear to be increased before and further increased after coronary artery ligation in dogs that develop ventricular fibrillation immediately after ligation. Increased beat to beat variability index may be associated with the presence of electrophysiologic instability and can predict early ventricular fibrillation.

Drug-induced hypoglycemic coma in 102 diabetic patients.

BACKGROUND: Hypoglycemic coma is a continuous threat for diabetic patients treated with insulin and/or oral hypoglycemic agents; it may be associated with substantial morbidity and mortality. METHODS: We retrospectively reviewed our clinical experience with drug-induced hypoglycemic coma during a 7-year period. RESULTS: The study consisted of 102 patients and included 61 females and 41 males. The median age was 72 years. Ninety-two patients suffered from type 2 diabetes mellitus; 10 patients had type 1 diabetes mellitus. The median lowest blood glucose level was 1.77 mmol/L (32 mg/dL). Drug-induced hypoglycemic coma occurred in 99 patients out of the hospital, while 3 patients developed it during hospitalization. Drug-induced hypoglycemic coma occurred in patients undergoing treatment with insulin, glyburide, and combined therapy with insulin and glyburide, insulin and metformin, or glyburide and metformin. Ninety-three patients had at least 1 of the following risk factors: age older than 60 years, renal dysfunction, decreased intake of energy, and infection. Fourteen patients concomitantly received drugs that potentiated hypoglycemia. Forty patients responded to treatment within the first 12 hours, while 62 patients had protracted hypoglycemia of 12 to 72 hours' duration. Morbidity included physical injuries in 7 patients, myocardial ischemia in 2 patients, and stroke in 1 patient. Death occurred in 5 patients. CONCLUSIONS: Hypoglycemic coma is a serious and not an uncommon problem among elderly patients with diabetes mellitus and treated with insulin and/or oral hypoglycemic drugs. Risk factors contribute substantially to the morbidity and mortality of patients with drug-induced hypoglycemic coma. Enhanced therapeutic monitoring may be warranted when hypoglycemic drugs are administered to an elderly patient with the above predisposing factors and potentiating drugs for hypoglycemia.

Normothermic ischaemic cardiac arrest of isolated working rat heart: effects of reserpine and propranolol on functional, metabolic and morphological recovery.

The ability to preserve myocardial structural and functional integrity during extended periods of total ischaemia has practical clinical significance. The role of endogenous catecholamines in the onset of irreversible damage in global ischaemia of the isolated rat heart was assessed by beta-blockade or catecholamine depletion. The effects of propranolol and reserpine pretreatment on myocardial ultrastructure, function and metabolism were studied during normothermic ischaemic arrest (NICA) and reperfusion of the isolated working rat heart. beta-Blockade as well as catecholamine depletion resulted in an increase in the percentage of totally ischaemic hearts which recovered mechanically upon reperfusion. In these studies mechanical recovery during reperfusion was associated with reversal of ultrastructural ischaemic alterations, but without an improvement in mitochondrial function. These findings support the concept that failure of mitochondria to recover functionally upon reperfusion is not the cause of either irreversible mechanical failure or ultrastructural damage of the ischaemic myocardium.

Effect of hypertonicity on contractility of isolated working rat left ventricle.

OBJECTIVE: The aim was to evaluate the effect of hypertonic perfusate on isolated left ventricular mechanical and energetic characteristics. METHODS: An isolated working rat heart model was perfused with a hyponatraemic Krebs-Heinseleit bicarbonate buffer (240 mOsmol.litre-1). To this buffer was added increasing amounts of mannitol to achieve 280, 320, and 360 mOsmol.litre-1 perfusates. RESULTS: Left ventricular peak pressure, maximum time derivative of left ventricular pressure (dP/dtmax), and end systolic pressure were all increased to a maximum value at 280 or 320 mOsmol.litre-1 perfusate tonicity. A similar response was evident with cardiac output, which changed from 33.7(SEM 0.6) to 43.5(0.8) ml.min-1 following changing the perfusate tonicity from 240 to 280 mOsmol.litre-1 (p less than or equal to 0.003). However, increasing perfusate tonicity further decreased cardiac output to 36.5(1.3) ml.min-1 at 360 mOsmol.litre-1. Maximal left ventricular elastance remained unchanged during perfusion with increasing perfusate tonicities. CONCLUSIONS: Changing perfusate osmolality using mannitol has a positive inotropic effect at low osmolalities and a negative inotropic effect at perfusate osmolality greater than 320 mOsm.litre-1.

Value of direct fine needle aspirative cytology in diagnosing palpable abdominal masses.

PURPOSE: Fine needle aspirative cytology is a well-established diagnostic tool for evaluating tumor masses. The goal of the current study was to determine the diagnostic accuracy of direct (nonimaging-guided) fine needle aspiration of palpable abdominal masses excluding the liver. PATIENTS AND METHODS: Direct aspiration of a palpable abdominal mass was performed in 190 patients in order to confirm or to rule out malignancy. Based on histologic, cytologic, and clinical findings, final diagnoses were reached in 165 patients, of whom 130 had a malignant abdominal mass and 35 a benign abdominal mass. The cytologic findings were verified by correlation with histologic, cytologic, and clinical findings. RESULTS: Among the 130 patients with a malignant abdominal mass, the cytologic findings failed to reveal malignancy in 12 patients (9.2%), but did reveal suspected malignancy in five (3.8%) and malignancy in 113 patients (86.9%). Among all 35 patients with a benign abdominal mass, the cytologic findings were reported as nonmalignant. The overall sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of cytologic findings were 90.8%, 100%, 100%, 74.5%, and 92.7%, respectively. A nonfatal case of bile peritonitis and a case of localized peritonitis that, in retrospective, could have been avoided were the only major complications that followed the fine needle aspirative procedure. CONCLUSION: With careful patient selection and meticulous attention to the proper procedure, direct fine needle cytology is a simple, safe, and highly accurate method for diagnosing palpable abdominal masses.

Cardiac valvular vegetations in cancer patients: a prospective echocardiographic study of 200 patients.

PURPOSE: Nonbacterial thrombotic endocarditis can complicate various malignancies and may cause morbidity and mortality mainly as a result of systemic embolism. The antemortem diagnosis of nonbacterial thrombotic endocarditis is rare. The purpose of our study was to assess the frequency, echocardiographic characteristics, and clinical correlation of nonbacterial thrombotic endocarditis in cancer patients. PATIENTS AND METHODS: A prospective echocardiographic screening of 200 nonselected ambulatory patients with solid tumors was performed. Patients were evaluated for evidence of thromboembolic events and for plasma D-dimer levels. A cohort of 100 consecutive patients without overt heart disease referred to echocardiography for the detection of an occult arterial embolic source served as a control group. It consisted of 52 males and 48 females, median age 60 years. RESULTS: The study group included 87 women and 113 men, median age 64 years (range 21 to 91). The frequent malignancies were lymphoma (26%), carcinoma of the gastrointestinal tract (20%), and carcinoma of the lung (16%). Cardiac valvular vegetations were found in 38 patients (19%) compared with only in 2 patients in the control group (2%, P < 0.001). Vegetations were found on the mitral or on the aortic valve in 19 and 18 patients, respectively. Isolated tricuspid valve vegetation was found in 1 patient. Valvular lesions were mostly common in patients with carcinoma of the pancreas (3 of 6, 50%), carcinoma of the lung (9 of 32, 28%), and lymphoma (10 of 52, 19%). Thromboembolism was diagnosed in 22 (11%) patients (12 deep vein thrombosis, 4 emboli to extremities, 2 cerebrovascular accidents, and 4 "silent" segmental left ventricular wall motion abnormalities on echocardiography). Thromboembolism was noticed in 9 of 38 patients (24%) with vegetations compared with 13 of 162 patients without vegetations (8%; P = 0.013). Plasma D-dimer level was examined in a subgroup of 170 patients. D-dimer level was increased in 19 of 21 patients (90%) with thromboembolism compared with 76 of 149 patients without thromboembolism (51%; P = 0.001). CONCLUSIONS: This study demonstrated a high prevalence of cardiac valvular lesions in patients with solid tumors. Vegetations were associated with thromboembolism. Plasma D-dimer level was significantly increased in patients with thromboembolism.

Beat-to-beat morphologic variability of the electrocardiogram for the evaluation of chest pain in the emergency room.

The value of electrocardiographic, morphologic variability in the early diagnosis of acute myocardial infarction (AMI) and myocardial ischemia was evaluated in 49 nonselected patients presenting to the emergency room with chest pain. High-resolution electrocardiography was used to determine the morphologic variability of consecutive electrocardiographic complexes, and the ratio of the variance of the QRS onset to that of the entire electrocardiogram was calculated. A final diagnosis of AMI was confirmed in 8 patients, acute coronary insufficiency in 8, angina pectoris in 19, and a noncardiac origin for chest pain in 14. Patients with AMI had a significantly higher beat-to-beat electrocardiographic morphologic variability of the QRS onset (1.4 +/- 0.2) than did those with acute coronary insufficiency (1.1 +/- 0.2), angina pectoris (0.9 +/- 0.1) or noncardiac chest pain (0.8 +/- 0.1) (p < 0.05). The sensitivity of the clinical presentation, typical electrocardiographic changes and creatine phosphokinase levels for the diagnosis of an acute ischemic event on admission to the emergency room was 62, 25 and 37.5%, respectively. Relative variance of the QRS onset of > 0.86 had a sensitivity of 75% and a specificity of 61% for diagnosing an acute ischemic event. Logistic regression of these variables showed that the QRS onset relative variability is an independent predictor for an acute ischemic event. It is concluded that an increased beat-to-beat electrocardiographic variability in patients with AMI is present on admission to the emergency room and may assist in establishing the diagnosis in this setting.

Beat-to-beat electrocardiographic morphology variation in healed myocardial infarction.

Using high-fidelity electrocardiographic (ECG) amplifiers, we measured subtle beat-to-beat ECG morphologic variations at different phases of the ECG complex. The electrocardiograms were recorded from 49 men with a documented Q-wave myocardial infarction and from 30 age-matched normal men. Forty consecutive beats were averaged to achieve an average ECG signal from which variance could be calculated. The relative variance, defined as the ratio between the integrated variance of the examined window and the integrated variance of the ECG signal that was close to full cycle length, was calculated at QRS onset and at offset in 2 frequency bands (4 to 40 and 60 to 120 Hz). Patients with healed infarction had a relative variance of 2.1 +/- 0.5 (mean +/- standard deviation [SD]) at QRS offset (a window of 40 ms), which was significantly lower than that of the healthy volunteers: 2.5 +/- 0.33 (mean +/- SD; p less than 0.02) at the low-frequency band. At the high-frequency band, patients with healed infarction had a significantly higher relative variance than the control subjects at QRS onset: 1.95 +/- 0.58 vs 1.55 +/- 0.35 (mean +/- SD; p less than 0.005). A model based on the numerous minor conduction abnormalities that exist in the chronically ischemic myocardium is presented to explain the changes in variance at the onset and offset of the QRS. The variance changes described can eventually serve as quantitative indexes of myocardial injury and electrical stability in patients with ischemic heart disease.

Pericardial rub in pericardial effusion: lack of correlation with amount of fluid.

The relation between the amount of pericardial fluid and the presence of a pericardial rub was examined in 76 patients with echocardiographic evidence of pericardial effusion. A pericardial rub was noted in 4 of 13 patients with small pericardial effusion (less than 100 ml), in 23 of 40 patients with moderate effusion (100 to 500 ml), and in ten of 23 patients with a large effusion. No difference in the amount of fluid was demonstrated in the group of patients with a rub when compared to the group without one. There was a statistically significant relation between the presence of a rub and the cause of the effusion. No inference as to the amount of pericardial fluid should be drawn from the presence or absence of a pericardial rub.

Talcosis presenting as pulmonary infiltrates in an HIV-positive heroin addict.

A case of an HIV-positive young drug addict presenting with fever, respiratory distress, and pulmonary infiltrates is reported. Pulmonary talcosis was diagnosed by transbronchial biopsy. The differential diagnosis of pulmonary infiltrates in HIV-positive patients is reviewed and the predisposition of drug addicts to develop both HIV infection, as well as pulmonary talcosis, is discussed. Pulmonary talcosis must be considered in the differential diagnosis of pulmonary infiltrates of HIV-positive drug addicts.

Long-term prognosis of acute pulmonary oedema--an ominous outcome.

BACKGROUND: Acute pulmonary oedema (APOE) is a major health problem, leading to poor hospital and long-term outcomes. There is a relative paucity of studies describing prognosis of consecutive unsolicited patients diagnosed with APOE and hospitalized in internal medicine departments. AIMS: To describe the clinical profile and outcome (in hospital and 1-year prognosis) of successive unselected patients with APOE, in a prospective observational study. METHODS AND RESULTS: The study population included 150 consecutive unsolicited patients (90 men, 60 women; median age 75 years) with APOE all hospitalized in an internal medicine department, in a 900-bed care centre. Ischaemic heart disease (IHD), hypertension and diabetes were present in 85%, 70% and 52% of patients, respectively. The most common precipitating factors for APOE included high blood pressure (29%), rapid atrial fibrillation (29%), unstable angina pectoris (25%), infection (18%) and acute myocardial infarction (MI; 15%). Eighteen patients (12%) died in hospital, with 82% of these deaths attributed to cardiac pump failure. Predictors for an increased in-hospital mortality included: diabetes (P<0.05), orthopnoea (P<0. 05), echocardiographic finding of depressed global left ventricular systolic function (P<0.001), acute MI during hospital stay (P<0.001), hypotension/shock (P<0.05), and the need for mechanical ventilation (P<0.001). After a median hospital stay of 10 days, 132 patients were discharged home. The 1-year mortality was 40%. Only the presence of pleural effusion was found as a predictor for 1-year mortality. CONCLUSION: Most patients with APOE in this study are elderly, and have IHD, hypertension, diabetes and a previous history of APOE. The overall mortality is high (in-hospital, 12%: 1-year, 40%). Left ventricular dysfunction was associated with high in-hospital mortality, but not with long-term prognosis.

Heart energetic efficiency in O2-exposed rats studied in isolated working heart.

Death in normobaric hyperoxia was related in the past to pulmonary insufficiency of the edematous lung. However, high arterial O2 tension on final collapse led to the suggestion that the heart and not the lung is the first organ that fails. We measured aortic flow, coronary flow, left ventricular pressure, affluent and effluent PO2, PCO2, and pH in the working heart excised from control and normobaric O2-exposed rats (51-63 h). The oxygen consumption (VO2) of experimental hearts was not different from control, but mechanical power output (PVAP) (calculated from pressure-volume area) was reduced as a function of O2 exposure time. Myocardial contractility indexes, maximal elastance and maximal time derivative of pressure, increased as a function of O2 exposure time, being below control values after 50 h and above control values after 60 h. The individual slopes for the regression of VO2 vs. PVAP rose as a function of exposure time from values below control after 50 h exposure to values above control after 60 h. Energetic efficiency (PVAP/VO2) decreased as a function of O2 exposure time and points to possible heart failure in the intact animal. After 50 h O2 exposure the heart was energetically more efficient than the control. Possible changes in the heart are discussed.

An integrative physiological approach to polyuria and hyponatraemia: a 'double-take' on the diagnosis and therapy in a patient with schizophrenia.

A patient with a history of schizophrenia was brought to the emergency department with extensive self-inflicted soft tissue injuries. Primary polydipsia was evident on admission, because he had a maximally dilute urine, a urine flow rate of 10 ml/min, and hyponatraemia (100 mmol/l). During an imaginary consultation with Professor McCance in which he applied basic principles of integrative physiology and a deductive analysis in quantitative terms, other reasons for the polyuric state were considered. Moreover, based on the very low value for the concentration of urea in plasma (< 0.7 mmol/l, BUN 1 mg /dl), the goals of therapy to prevent osmotic demyelination became evident. Applying this simple approach, a more comprehensive and accurate differential diagnosis, and a plan for therapy to avoid serious complications was compiled.

Severe degree of hyperglycaemia: insights from integrative physiology.

We illustrate how the application of principles of integrative physiology at the bedside can reveal novel insights that have been largely overlooked to this day. In this didactic exercise, modern-day physicians seek an imaginary medical consultation with Professor Sir Hans Krebs because of an unusual finding in his area of expertise: a very severe degree of hyperglycaemia. Although Professor Krebs is restricted to data prior to World War II, this does not prevent him from making novel discoveries. First, he illustrates how an occult factor, rapid absorption of glucose from the intestinal tract, was a critical feature in explaining the basis of the severe degree of hyperglycaemia without obvious ketoacidosis in a 16-year-old patient with type 1 diabetes mellitus in poor control. Second, by examining simple principles of renal and gastrointestinal physiology in a quantitative fashion, Professor Krebs speculates as to how cerebral oedema might occur before therapy in a patient with a severe degree of hyperglycaemia. We hope that readers and educators will appreciate the value of applying principles of integrative physiology in a quantitative fashion at the bedside.

Hyponatraemia and hyperglycaemia during laproscopic surgery.

The aim of this masterclass is to develop a rational plan of therapy to deal with a severe degree of hyponatraemia (90 mmol/l) and hyperglycaemia (100 mmol/l) that occurred 100 min after the start of laproscopic surgery in a young woman. The lavage fluid used in this procedure was 10% dextrose.H(2)O in water (505 mmol glucose/l). To focus attention on specific issues, three questions are posed to the reader, as they were to a panel of 59 modern-day experts. Two imaginary consultants from the past were asked the same (and additional) questions. Their responses were restricted to knowledge available before the molecular era, to show the power of integrative physiology at the bedside. An analysis of intracellular events was helpful in answering the first question: 'Is an infusion of hypertonic saline required to treat her acute hyponatremia?' Similarly, a quantitative analysis of changes in the composition of the extracellular fluid compartment was helpful in answering the second question: 'Is an infusion of isotonic saline required to treat her hypotension?' A metabolic analysis was used to answer the third question, 'Should insulin be administered?'

Testosterone and cyproterone acetate modulate peripheral but not central benzodiazepine receptors in rats.

Sixteen days of testosterone acetate (TA) treatment in male rats induced an increase in the densities of peripheral benzodiazepine receptors (PBR) in the adrenal and Cowper's glands and a decrease in PBR density in the testis. TA did not alter PBR density in the heart, cerebral cortex, or pituitary, or central benzodiazepine receptor (CBR) density in the cerebral cortex or hypothalamus. The antiandrogenic agent cyproterone acetate induced a decrease in PBR density in the testis, adrenal, and pituitary, but did not affect PBR density in Cowper's glands, heart, or cerebral cortex, or CBR density in the cerebral cortex or hypothalamus. In all of the above organs, affinity values did not change following the treatment with both agents. The receptoral changes may be relevant to the physiological and neurobehavioral effects of the chronic exogenous androgenic and antiandrogenic treatment.

Echocardiography in nonbacterial thrombotic endocarditis: from autopsy to clinical entity.

Bacteria-free verrucae, frequently termed "non-bacterial thrombotic endocarditis," have been recognized in autoimmune disorders as well as in neo-plastic diseases. The antemortem diagnosis of non-bacterial thrombotic endocarditis is rare, and most existing data result from postmortem examinations. In 3 prospective echocardiographic studies we found typical cardiac valvular lesions in patients with primary antiphospholipid syndrome, myelo-proliferative disorders, and solid malignant tumors. Cardiac lesions associated with these 3 different entities had common echocardiographic appearance and correlated positively with thromboembolic events. The possibility of common pathogenesis is suggested, and clinical significance is discussed.

A fatal case of Behçet's disease associated with multiple cardiovascular lesions.

Behçet's disease is recognised as a chronic multisystem disorder with vasculitis as its underlying pathological process. Cardiac involvement is rare and often associated with poor prognosis. A large right atrial thrombus, pulmonary aneurysms and aortic pseudoaneurysm that developed 17 years after surgery for bilateral renal artery stenosis is presented in a 26-year-old Behçet's disease patient. He was admitted to the hospital with fever of unknown origin associated with chest pain, dyspnea, cough, haemoptysis and pulmonary opacity in chest X-ray. Initial pulmonary CT demonstrated small subpleural infiltrates bilaterally, one of which was round and suspected as being metastatic. Examination of open lung biopsy demonstrated haemorrhagic infarct surrounded by some occluded pulmonary arteries. Subsequent CT showed pulmonary aneurysms compatible with Behçet's disease. Echocardiography demonstrated a large pedunculated mass in the right atrium. Injection of urographin showed a right atrial mass and a large right pulmonary artery aneurysm. The atrial mass was completely excised during open heart surgery and was identified as being an organising thrombus. Eight weeks later while taking prednisone, he was readmitted because of an infected mid sternal wound. CT showed slight separation of the stemum, retrosternal fluid, pulmonary arteries aneurysm and ascending aorta aneurysm. The next day, the patient died from massive bleeding from his ruptured ascending aortic pseudoaneurysm. Bizarre presentation of arterial and venous thromboses or arterial aneurysm formation, particularly in young patients, should suggest Behçet's disease.

Acute transient chylous ascites associated with acute biliary pancreatitis.

We report a case of acute chylous ascites secondary to acute biliary pancreatitis, the first such case reported in the literature. Surprisingly, chylous ascites was detected during elective cholecystectomy. The pathogenesis and management of this problem is discussed.

Left hydronephrosis caused by Crohn disease successfully treated conservatively.

We report the case of a 35-year-old man who presented with fever, diarrhea, and a left abdominal mass. Diagnostic studies confirmed Crohn disease and revealed an abdominal mass obstructing the left ureter with hydroureter and hydronephrosis. The patient was successfully treated conservatively, with corticosteroids and mesalamine, A review of the literature indicates a predominance of right ureteral involvement in Crohn disease, associated with a high incidence of ileocecal disease. Most of these patients were treated surgically, with resection of ileocecal lesion and/or ureterolysis. Ureteral obstruction as a complication of Crohn disease is discussed, with emphasis on conservative treatment.