Abnormal Myocardial Free Fatty Acid Utilization Deteriorates With Morphological Changes in the Hypertensive Heart.

Abstract

n essential hypertension, changes in the morphology of the left ventricle (LV) are commonly observed, and are considered to be the result of adaptation to pressure overload. The changes have been classified into 4 geometric patterns based on the LV mass and wall thickness. 1 These geometric changes are consistent with progression of heart failure in an experimental model, 2 and furthermore, are considered to reflect the course of hypertensive heart failure. 3,4 On the other hand, it has been speculated that a disorder of myocardial energetic metabolism relates to progression of heart failure. 123 I-15-p-iodophenyl-3-(R,S)-methylpentadecanoic acid (I-123 BMIPP) is a radioisotope used for assessment of myocardial free fatty acid (FFA) metabolism and abnormal myocardial uptake of BMIPP has been reported in patients with heart failure. 13 However, Japanese Circulation Journal Vol.65, September 2001 it has not been clarified whether the pathophysiological adaptation of changing the LV morphology in hypertensive hearts is related to changes in myocardial FFA metabolism. MethodsThirty-five patients (21 men, 14 women; mean age: 61±11 years) who had a history of essential hypertension (blood pressure ≥160 mmHg at systole or 90 mmHg at diastole according to the WHO criteria) were enrolled. The patients were free of any symptoms of ischemic heart disease, valvular heart disease, or concomitant important diseases such as diabetes mellitus. Two patients with symptomatic congestive heart failure (New York Heart Association class II-III) who took some diuretics were included. The evaluations, including a detailed medical history, 12-lead ECG, urinalysis, and serum levels of urea nitrogen, creatinine, glucose, cholesterol, sodium, potassium and calcium, were performed in all subjects. An echocardiogram of adequate quality to assess LV morphologic characteristics was also obtained from all subjects. Patients who showed LV asymmetrical hypertrophy on the echocardiogram were excluded, as were patients with diabetes mellitus or renal failure. All patients in the study gave written informed consent.Echocardiography was performed using an ultrasonic sector scanner with 2.5-and 3.75-MHz transducers (SONOLAYER SSH-160A Toshiba Co, Japan The left ventricle's morphological adaptation to high blood pressure is classified into 4 patterns based on mass and wall thickness. The geometric changes caused by maladaptation to pressure overload possibly relate to progression of contractile dysfunction with abnormal energy metabolism. The present study assessed whether the geometric adaptation of the left ventricle (LV) to high blood pressure relates to changes in myocardial energy metabolism, especially free fatty acid (FFA) utilization. Thirty-five patients with essential hypertension underwent echocardiography and dual isotopes myocardial scintigraphy using iodine-123 labeled 15-p-iodophenyl-3-(R,S)-methylpentadecanoic acid (BMIPP, an analogue of a FFA) and . Systolic (endocardial fractional shortening; %FS) and diastolic indices (the ratio o...

Cardioprotective effects of gallic acid in diabetes-induced myocardial dysfunction in rats

“…The elevated circulating FFA produces inhibition of glucose oxidation, abnormal high oxygen requirements during FFA metabolism, and the intracellular accumulation of potentially toxic intermediates of FFA, all of which lead to impaired myocardial performance and severe morphological changes. [229] Thus, strategy to be employed to produce improvement in cardiac function is to improve upon these metabolic disarrangements. Chronic treatment with gallic acid in diabetic rats decreased elevated lipid profiles.…”

Diabetic cardiomyopathy: understanding the molecular and cellular basis to progress in diagnosis and treatment

“…Moreover, in addition to the FFAinduced inhibition of glucose oxidation, high circulating and cellular FFA levels may result in intracellular accumulation of potentially toxic intermediates of FFA (lipotoxicity), besides the abnormally high oxygen requirements during FFA metabolism. All these lead to morphological changes [140,169,223] and impaired myocardial performance [3,125,197]. Since the ischemic myocardium depends upon anaerobic metabolism of glucose, increased glucose uptake and metabolism are necessary for the maintenance of myocardial function [193,219].…”

Metabolic Planar Imaging Using ¹²³I-<i>β</i>-Methyl-Iodophenyl Pentadecanoic Acid Identifies Myocardial Ischemic Memory After Intracoronary Acetylcholine Provocation Tests in Patients With Vasospastic Angina

“…The uptake of 123 I-BMIPP was signifi cantly lower in patients with VSA than in hypertensive controls, although myocardial fatty acid metabolism in the hypertensive heart is considered abnormal. 30,31) The H/M ratios and washout rate may have been affected by the extension, severity, duration of spasm, and medication. The discrepancy between the SPECT and planar imaging must be considered, however, no data to explain the discrepancy in the present study is also a limitation.…”