A novel mechanism of heart failure with normal ejection fraction.

BACKGROUND: Patients with heart failure and a normal left ventricular ejection fraction have significantly reduced left ventricular long-axis function. This paper proposes an explanation for this apparent paradox and suggests a new mechanism of "diastolic" heart failure. METHOD: The effect of changes in left ventricular hypertrophy on stroke volume and ejection fraction in non-dilated left ventricles was calculated using the area-length method. Further, the effect of a reduction in long-axis shortening on these parameters was determined. RESULTS: Increasing left ventricular hypertrophy resulted in augmentation of systolic wall thickening and ejection fraction but not stroke volume when long-axis shortening was normal. In the presence of abnormal long-axis function, stroke volume was reduced but ejection fraction was preserved. CONCLUSION: The model predicts that the normal ejection fraction in patients with heart failure may be explained by the presence of left ventricular hypertrophy. The resulting amplified radial thickening in the setting of reduced long-axis shortening explains the preservation of ejection fraction. The reduced stroke volume in the precompensated state rather than diastolic dysfunction may be the cause of heart failure.

Platypnoea-orthodeoxia syndrome in association with an ascending aortic aneurysm.

Platypnoea-orthodeoxia syndrome is a uncommon condition presenting with dyspnoea and cyanosis that are characteristically worse in the upright posture and improved by lying supine. We present the case of a patient with a thoracic aortic aneurysm and a patent foramen ovale who presented with platypnoea-orthodeoxia syndrome. Diagnosis was established using transoesophageal echocardiography. We suggest a mechanism for the development of dyspnoea and hypoxia in patients with this disorder.

Constrictive pericarditis and pleuropulmonary fibrosis secondary to cabergoline treatment for Parkinson's disease.

A 63 year old man with a six year history of Parkinson's disease presented with signs of right heart failure following a knee replacement. Constrictive pericarditis was diagnosed and a radical pericardectomy performed. Six months later, the patient remained unwell with raised inflammatory markers. An inflammatory fibrotic reaction caused by cabergoline was diagnosed. He improved after cessation of cabergoline.

A depressed myocardium.

BACKGROUND: Venlafaxine is a potent neuronal serotonin and noradrenaline re-uptake inhibitor, and to a lesser extent an inhibitor of dopamine reuptake. Paroxetine is a potent selective inhibitor of serotonin reuptake. CASE REPORT: A 27-year-old man ingested 1987.5 mg of venlafaxine and 360 mg of paroxetine. He subsequently developed systolic and diastolic hypertension, transient electrocardiographic abnormalities, and an area of persistent myocardial damage. He recovered from his overdose with his blood pressure and electrocardiogram returning to normal. The area of myocardial damage was documented on echocardiogram as an area of marked hypokinesia at the basal anterior septum. Despite the absence of confirming blood levels or the absolute exclusion of cocaine, this case indicates that venlafaxine and paroxetine have the potential for serious cardiotoxicity when taken in overdose.

Effect of experimental hypertension on phosphoinositide hydrolysis and proto-oncogene expression in cardiovascular tissues.

Products of inositol lipid hydrolysis and levels of c-myc, c-fos and H-ras mRNAs were measured in rat left ventricle and vascular tissues 72 h and 9 days after the induction of aortic coarctation in order to examine inositol phosphate and proto-oncogene signals during the development of pressure-related cardiac and vascular structural changes. There was a significant increase in left ventricular and proximal aortic mass at both time points but no change in mesenteric resistance artery morphology in rats with coarctation. At 72 h there was a significant increase in c-myc, c-fos and H-ras mRNAs in the left ventricle of rats with coarctation, and this was accompanied by increased levels of inositol (1,4,5)-trisphosphate. Similar results were obtained in the proximal but not the distal aorta. In resistance arteries inositol phosphate production and proto-oncogene mRNA expression were unchanged. The results indicate that at 72 h aortic coarctation induced structural thickening in the left ventricle and proximal aorta and was associated with increased inositol phosphate production and stimulation of specific proto-oncogene mRNAs. By 9 days following surgery much of the structural change in these tissues was completed, and these raised cellular signals were no longer observed. The results suggest that both increased inositol lipid hydrolysis and a rise in the expression of these proto-oncogenes are important processes in the development of vascular hypertrophy seen in this model of hypertension.

Intracellular pH in rat resistance arteries during the development of experimental hypertension.

1. In order to examine the effects of experimental hypertension on intracellular pH in mesenteric resistance arteries, intracellular pH was measured in mesenteric resistance arteries from rats with coarctation 72 h, 9 days and 28 days after the aorta was partially constricted between the origins of the renal arteries. Carotid arterial pressure was significantly raised at all time points. 2. Second-order mesenteric resistance arteries were mounted in a myograph and were loaded with the acetoxymethyl ester of the pH-sensitive dye 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein. Morphological measurements demonstrated that arteries from rats with coarctation had an increased media volume at 9 days and at 28 days compared with vessels from sham-operated control animals, but this was only statistically significant at 28 days. 3. Resting intracellular pH was not significantly different at any time point in arteries from rats with coarctation compared with control animals, although there was a rise in intracellular pH in both groups of rats between 72 h and 9 days. The application of 4,4-di-isothiocyanatostilbene-2,2'-disulphonic acid produced a fall in intracellular pH which was significantly greater in the sham-operated rats at 9 days; this difference was not found at 28 days. Blockade of Na+/H+ exchange with 60 mumol/l ethylisopropylamiloride led to a similar fall in intracellular pH in both groups of rats at 9 days but a significantly greater fall in intracellular pH in arteries of rats with coarctation at 28 days. Activation with noradrenaline (10 mumol/l) induced acid changes in intracellular pH that were similar in both groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of short chain fatty acid supplementation on membrane electrolyte transport and blood pressure.

Eleven normotensive subjects with no family history of essential hypertension took part in a double-blind randomized placebo-controlled crossover study to examine the effects of supplementing a normal omnivore diet with miglyol. This resulted in a fall in diastolic blood pressure in both the supine and standing positions, achieving statistical significance for the standing diastolic pressures, following miglyol treatment. Miglyol is rich in caprylic (8:0) and capric acids (10:0), both short chain saturated fatty acids, and supplementation with this produced a significant fall in erythrocyte membrane oleic and linoleic acid (P less than 0.01 compared to placebo for each fatty acid), as well as a fall in the saturated fat palmitic acid (16:0) (P less than 0.01). These changes were not associated with any alterations in total erythrocyte sodium influx, bumetanide sensitive influx or sodium red cell intracellular or potassium content. In addition, body weight and urinary excretion of sodium and potassium did not change. These data indicate that this dietetic manipulation with an oil rich in short chain saturated fatty acids lowers diastolic blood pressure but not as a result of changes in membrane sodium handling. It is possible that the short chain fats displace the longer carbon chain fatty acids which are metabolically important to cellular integrity and it is in this way that blood pressure falls.

Predicting future treatment of diabetes mellitus from characteristics available at presentation.

This study was designed to identify the clinical features of a newly diagnosed diabetic patient that are most useful in deciding treatment. A secondary aim was to formulate a statistical model for predicting subsequent treatment. The following features were considered in 289 patients: age, sex, severity and duration of symptoms, degree and duration of weight loss, glycosuria, ketonuria, blood glucose concentration, body mass index (BMI), and family history of diabetes. Three treatment groups, 6 months after diagnosis, were defined: diet alone, diet with oral hypoglycaemic agent(s), and insulin-treated. Univariate analysis showed that symptom severity, glycosuria, ketonuria, glucose concentration, weight loss, and BMI were significantly different between the three groups. Age and rate of weight loss were significantly different between the insulin-treated and non-insulin-treated groups. Multivariate analysis gave a model to calculate the probability of requiring each of the three treatments given certain characteristics. A second cohort of 174 patients was used to assess the accuracy of the model. The model predicted the actual treatment at 6 months correctly in 72%.