Hydrochlorothiazide abolishes the anti-atherosclerotic effect of quinapril.

1. Antihypertensive treatment has been demonstrated to result in persistent reductions in morbidity and mortality due to stroke. However, the coronary risk attributable to hypertension has been only partially reversed. We hypothesized that diuretics could have unfavourable effects on atherosclerosis. 2. New Zealand rabbits were fed a 0.5% cholesterol-enriched diet for 12 weeks, followed by a 0.1% cholesterol diet for another 12 weeks. During the last 12 week period, 40 animals were randomly assigned to one of four groups: (i) group I was the control group; (ii) group II received hydrochlorothiazide (10 mg/day); (iii) group III received quinapril (30 mg/day); and (iv) group IV was treated with hydrochlorothiazide (10 mg/day) plus quinapril (30 mg/day). 3. The treatments did not affect either the lipid profile or serum electrolytes and oxidative stress. However, endothelium-dependent vasorelaxation in isolated aortic rings was significantly improved with quinapril (group III) treatment (P < 0.001 vs other groups). In addition, therapy with quinapril promoted a significant reduction in atherosclerosis (intima area, intima/media ratio and perimeter of vessel with plaque; P < 0.05 vs other groups), as well as in cholesterol content of the aorta (P < 0.05 vs groups II and IV). 4. In conclusion, hydrochlorothiazide did not modify atherosclerosis and, when added to quinapril treatment, impaired the anti-atherosclerotic effect seen with quinapril alone.

Dietary magnesium improves endothelial dependent relaxation of balloon injured arteries in rats.

The purpose of the present study was to examine the importance of magnesium in endothelial function after arterial balloon injury. Male Wistar rats were fed normal, high or low concentrations of magnesium. Three weeks later the animals underwent endothelial injury of the thoracic aorta by a balloon catheter or a sham operation. Biochemical, histological and endothelial function analysis were performed 15 days after the surgical treatment. The animals fed a low magnesium diet presented the lowest level of serum magnesium and the highest ionized blood calcium levels. Histomorphometric analysis revealed no differences among groups neither regarding the magnitude of intimal thickening nor the recovery of endothelial coverage. However, when vasoreactivity responses were compared in the balloon-injured group, those animals fed a high magnesium diet had the better endothelium-dependent vascular relaxation. In conclusion, a higher magnesium level in the diet was beneficial to vessels that underwent endothelial injury by balloon catheter.

The influence of isotonic exercise on cardiac hypertrophy in arterial hypertension: impact on cardiac function and on the capacity for aerobic work.

Intense physical training through isotonic exercises has controversial effects in individuals with moderate to severe hypertension. In this study, normotensive Wistar rats and rats with renovascular hypertension (Goldblatt II) were subjected to intense physical exercise involving two 50-min swimming sessions per day for a period of 12 weeks. At the end of the study, we evaluated the effect of training on arterial pressure, the capacity for aerobic work and cardiac function. Our results demonstrate that intense physical training has no effect on the arterial blood pressure of normotensive rats or of animals with moderate renovascular hypertension. Hypertensive animals with cardiac hypertrophy require a greater period of training in order to attain the same capacity for aerobic work as normotensive rats. This difference may result from an inability of the former animals to increase cardiac compliance, thereby impeding more extensive usage of the Frank-Starling mechanism to subsequently increase the systolic cardiac performance. Cardiac hypertrophy induced by exercise did not summate with that induced by arterial hypertension. Physical exercise normalized the end-diastolic left ventricular pressure in hypertensive animals without any corresponding increase in the compliance of the chamber. The first derivative of left ventricular pulse pressure (+/- dP/dt) was greater in the hypertensive trained group than in the hypertensive sedentary rats. These observations suggest that a systolic dysfunction of the left ventricle involving an elevated residual volume secondary to arterial hypertension may be corrected by physical exercise such as swimming.

Progressive magnesium deficiency increases mortality from endotoxin challenge: protective effects of acute magnesium replacement therapy.

OBJECTIVES: To study the effects of endotoxin on magnesium homeostasis; to determine if progressive magnesium deficiency alters outcome from endotoxin challenge; and to evaluate the efficacy of magnesium therapy in reducing endotoxin-induced mortality. DESIGN: Prospective, placebo-controlled, randomized, multiexperiment studies. SETTING: Research laboratory of a university hospital. SUBJECTS: Male Sprague Dawley rats (n = 299). INTERVENTIONS: Experiment 1 was designed to test if endotoxin alters magnesium homeostasis. Circulating total and ionized magnesium (estimated by ultrafilterable values) concentrations were determined in blood samples collected from animals after the randomized administration of placebo or 0.3, 3.0, or 30 mg/kg of endotoxin. A baseline blood sample was collected and then a second blood sample was obtained at 5, 15, 30, 60, 120, or 180 mins after endotoxin or placebo administration. In experiment 2, animals were randomized to receive magnesium-sufficient diets or magnesium-deficient diets for 6 wks. After 6 wks, the effects of the randomized administration of 3.0 mg/kg endotoxin or placebo were evaluated on mortality and analyte values (pH and blood gases, sodium, potassium, chloride, glucose, ionized calcium, hematocrit, total and ultrafilterable magnesium concentrations) in the three study groups (magnesium-sufficient, 3-wk magnesium-deficient, or 6-wk magnesium-deficient). In experiment 3, magnesium-deficient animals were randomized to receive 50 mmol/kg magnesium chloride or placebo, before or after the administration of 3.0 mg/kg of endotoxin. Baseline and 24-hr analyte determinations were performed and outcome was analyzed. MEASUREMENTS AND MAIN RESULTS: Experiment 1: Significant increases (p < .05) in circulating total magnesium concentrations were found in animals that received 30 mg/kg of endotoxin, at 120 mins (0.79 +/- 0.10 vs. 0.60 +/- 0.05 mmol/L), and 180 mins (0.74 +/- 0.04 vs. 0.56 +/- 0.04 mmol/L) compared with baseline values. Similarly, significant increases (p < .05) in ionized magnesium concentrations were observed 120 and 180 mins after 3.0 and 30 mg/kg of endotoxin compared with baseline values. Experiment 2: Magnesium deficiency was strongly (p < .02) associated with increased mortality from endotoxin challenge. Endotoxin administration (3.0 mg/kg) was lethal in 10 (43%) of 23 magnesium-sufficient animals, 15 (65%) of 23 3-wk magnesium-deficient animals, and 20 (83%) of 24 6-wk magnesium-deficient animals. Experiment 3: In magnesium-deficient animals, rats treated with magnesium replacement therapy had significantly increased survival from endotoxin administration (15 [52%] of 29 vs. five [17%] of 29, p < .01) compared with placebo-treated animals. CONCLUSIONS: a) Endotoxin challenge causes significant increases in circulating total and ionized magnesium concentrations. b) Progressive magnesium deficiency is strongly associated with increased lethality, and magnesium replacement therapy provides significant protection from endotoxin challenge. c) These experimental results support the concept that cellular injury is probably associated with increases in circulating magnesium concentrations. Furthermore, these experimental findings suggest that magnesium deficiency predisposes to worse outcome from endotoxin challenge, and that replacement therapy in the setting of magnesium deficiency may be warranted, especially in critically ill subjects.

[A cardiac lesion secondary to paraquat]. / Lesão cardíaca secundária ao paraquat.

PURPOSE: To evaluate cardiac alterations secondary to exogenous intoxication by paraquat. METHODS: We performed analysis of clinical and laboratory data of 25 patients with acute paraquat poisoning admitted in our ICU from November 1983 to January 1991. RESULTS: There were purposeful overdoses in 24 cases (96%). The mortality rate was 56%. The lung involvement was 96%, renal was 92%, gastrointestinal tract was 72%, hepatic was 56%, and cardiac involvement was 40%. CONCLUSION: Cardiac involvement due to paraquat is frequent (40%). The clinical picture of this involvement has a wide spectrum, ranging from minimal changes in the ECG to acute and extensive myocardial necrosis.

[Enalapril and myocardial protection from stress by cold]. / Enalapril e proteção do miocárdio ao estresse pelo frio.

PURPOSE: To evaluate the myocardial protective effect of enalaprilat in rats submitted to stress by cold. METHODS: Fifteen adults, male rats were studied. They were allocated into four groups: group A received unrestricted diet + intraperitoneal (IP) diluent; group B: unrestricted diet + IP enalaprilat 1.0 mg/kg; group C: high salt diet (HD) for seven days + IP indomethacin 1.0 mg/kg and group D received high salt diet for seven days + IP indomethacin 1.0 mg/kg + IP enalaprilat 1.0 mg/kg. Three animals were the control group. The animals of the groups A, B, C and D were then submitted to stress by cold. Fragments of the left ventricle were obtained for electron microscopy and the occurrence of mitochondrial lysis or preservation of the mitochondrial ultrastructure were considered as parameter for myocardial protective effect evaluation. RESULTS: Crystolysis (partial or total) was observed in 16.2% group A; 19.5% of group C; 3.2% of group B and in 8.8% of group D. CONCLUSION: Enalaprilat protects the cardiomyocyte from the stress by cold.

[Electrocardiographic changes in accidental hypothermia]. / Alterações eletrocardiográficas na hipotermia acidental.

PURPOSE: Electrocardiographic alterations were evaluated in a group of accidental hypothermia patients, and correlated with values of core temperature, pH and plasmatic concentrations of Na+, K+ and Cl-. METHODS: Conventional 12-lead surface electrocardiograms were obtained in a group of 32 patients with accidental hypothermia after involuntary cold exposure. Cardiac arrhythmias, QRS configuration, ST-T segment and T wave alterations were analyzed. pH, Na+, K+ and Cl- serum concentrations were simultaneously measured. Electrocardiogram and electrolyte abnormalities were then correlated with the core temperature. RESULTS: Twenty-eight patients had abnormal electrocardiogram (90.6%). Sinus bradycardia and idioventricular rhythm were observed in 11 and 3 patients respectively. QT interval enlargement was found in 24 patients and Osborn wave in 28 cases. Altered T waves expressing an abnormal repolarization were observed in 23 cases. A significant negative correlation was obtained when J wave amplitude was correlated with core temperature levels. CONCLUSION: Hypothermia produces electrocardiographic abnormalities characterized by Osborn waves. Other minor findings include sinus bradycardia, idioventricular rhythm and long QT intervals.

Taquicardia atrial e funçäo renal / Atrial tachycardia and renal function

A taquicardia atrial induzida artificialmente em cäo produziu nas nossas condiçöes, alteraçäo importante da funçäo renal. Essa alteraçäo se manifestou por significativo aumento do volume urinário por minuto (1,3 ñ 0,12 no controle para 3,2 ñ 0,6ml/min no experimental) e da fraçäo de excreçäo de sódio (FENa) (de 2,3 ñ 0,3 no controle para 3,6 ñ 0,5), na presença de queda significante do fluxo sanguíneo renal (317 ñ 30,9 para 232 ñ 26,7 ml/min), sem alterar o ritmo de filtraçäo glomerular (66,1 ñ 6,7 no controle para 70,6 ñ 6,5 ml/min no experimental). Quanto à hemodinâmica sistêmica, observamos queda signficante do débito cardíaco e aumentos significantes da resistência vascular sistêmica e da pressäo de capilar pulmonar. Esses resultados demonstram que possivelmente fatores näo relacionados à hemodinâmica sistêmica, mas relacionados a alteraçöes hormonais, sejam responsáveis por estas alteraçöes

Hypomagnesemia is a frequent finding in the emergency department in patients with chest pain.

STUDY OBJECTIVE: To evaluate the frequency of low blood levels of total and ultrafilterable magnesium (total and ultrafilterable hypomagnesemia) in patients with chest pain in the emergency department, and to determine if hypomagnesemia is associated with other clinically important diagnostic and outcome variables in cardiac care. SETTING: An emergency department of a university teaching hospital. DESIGN: Prospective study of extracellular magnesium homeostasis in patients with chest pain in the emergency department and a cohort of patients without chest pain with a clinical indication for blood sampling. PATIENTS: During a 4-month period, 147 patients presenting to the emergency department were studied: 67 patients (mean +/- SD age, 61.4 +/- 13 years) with a chief complaint of chest pain (study group) and 80 patients (55.6 +/- 19 years) with other diagnoses (control group). RESULTS: Total and ultrafilterable hypomagnesemia occurred more frequently in patients with chest pain (20/67 [30%] and 9/67 [13%]) than in the control group (12/80 [15%] and 3/80 [4%]). Patients with a chief complaint of chest pain who were receiving diuretic medications were hypomagnesemic more frequently (9/16 [56%]) than patients not receiving diuretics (12/51 [23%]). In patients with chest pain admitted to the hospital with a diagnosis of "rule out" myocardial infarction, the frequency of hypokalemia was greater among hypomagnesemic patients (6/14 [43%]) than normomagnesemic patients (3/31 [10%]). A similar frequency of hypomagnesemia was noted in patients with a final diagnosis of myocardial infarction (4/15 [27%]) when compared with other patients admitted with chest pain (10/31 [32%]) in whom myocardial infarction was excluded. No association was noted among hypomagnesemia and length of hospital stay or the occurrence of hypotension or dysrhythmias. CONCLUSIONS: Total and ultrafilterable hypomagnesemia are frequent occurrences in patients with and without chest pain in the emergency department. Diuretic use is associated with hypomagnesemia in patients presenting with chest pain in the emergency department. These results support the concept that hypomagnesemia is common in patients with chest pain in the emergency department and is associated with hypokalemia but is not predictive of whether the patient with chest pain has had an acute myocardial infarction.

Reliability of right atrial pressure monitoring to assess left ventricular preload in critically ill septic patients.

Right atrial pressure (RAP) can be used as a guide to fluid therapy in critical care settings. RAP and pulmonary capillary wedge pressure (WP) were measured in 27 septic patients without cardiac disease and on mechanical ventilation. An r of .61 was obtained with a regression line defined by the equation WP = 7.38 + (0.53 x RAP) +/- 3.15. However, a large SD of data points can invalidate the clinical usefulness of this equation. The reliability of various RAP interval values in predicting optimal WP was then studied in these patients. We concluded that RAP values less than or equal to 5 mm Hg were highly specific (97%) in predicting low or normal WP (less than or equal to 12 mm Hg).

[Acute pulmonary edema secondary to pheochromocytoma. A case report]. / Edema agudo de pulmáo secundário a feocromocitoma. Relato de caso.

Authors report a case of a patient with abdominal pheochromocytoma who presented recurrent episodes of acute pulmonary edema. No cardiopathy was detected either by clinical examination or by electrocardiogram, echograms or invasive cineventricleangiograma. They concluded that a non cardiogenic etiology is possible for the referred clinical manifestations.