M. St. John Sutton

Effects of acute hyperglycaemia on cardiac function: an echocardiographic study of monozygotic twins

BACKGROUND A major cause of morbidity in type I diabetes is congestive heart failure due predominantly to left ventricular diastolic dysfunction. The mechanism of diastolic dysfunction remains unknown and does not relate to blood pressure, microvascular complications and glycated haemoglobin. Hyperglycaemia is the hallmark of diabetes and is a potential determinant of left ventricular diastolic dysfunction. OBJECTIVE To determine whether acute hyperglycaemia can induce changes in left ventricular diastolic function in normal subjects similar to those observed in insulin-dependent diabetes mellitus (IDDM). DESIGN Cross-sectional study. SETTING London teaching hospital. SUBJECTS Sixteen twins from eight identical twin pairs discordant for IDDM (age 18-38 years, five male) were studied; none had a history or evidence of myocardial ischaemia, valvular or primary heart muscle disease, systemic hypertension or nephropathy. INTERVENTIONS Non-diabetic twins underwent a hyperglycaemic clamp at 10 mmol/l. MAIN OUTCOME MEASURES Doppler echocardiography was performed in basal condition in identical twin pairs discordant for IDDM and repeated in the non-diabetic twins during hyperglycaemia. Blood glucose, insulin and catecholamines were measured at baseline and during hyperglycaemia. RESULTS Transmitral Doppler E/A velocity ratio was significantly lower in diabetic than non-diabetic twins at baseline (1.44 (0.38) vs. 1.51 (0.19), P<0.05). Glucose infusion in the non-diabetic twins resulted in an increase in their E/A ratio (1.51 (0.19) vs. 1.82 (0. 47), P<0.05) due to an increase in E velocity (68 (12) to 64.7 (10. 7), P<0.05) and a decrease in the peak A velocity (42.7 (3.85) to 38. 0 (4.1), P<0.05). No significant changes were observed in peak E velocity or isovolumic relaxation time in the non-diabetic twins between baseline and hyperglycaemia. CONCLUSIONS The alterations in left ventricular diastolic function induced by acute hyperglycaemia and consequent increase in plasma catecholamines do not mimic those demonstrated in IDDM patients.

560 Differential activation of natriuretic peptides in human heart failure and relationship to cardiac function: evidence for peptide deficiency

Contraction-relaxation cycle characteristics and sensitivity to cholinergic stimulation suggest involvement of the Gs-adenylyl cyclase-pathway. The concentration response curves to 5-HT were shifted to higher concentrations by 0.5 nM of the 5-HT4 selective antagonist GR113808, with pEC50-values of 7.62 ± 0.06 (SEM, n = 6) and 7.32 ± 0.06 (SEM, n = 6, p < 0.005), respectively, and the derived pKb value of 9.5 for GR113808 documents involvement of 5-HT4 receptors. Quantitative RT-PCR revealed a 4-fold increase of 5-HT4(b) mRNA expression in ventricles from CHF rat hearts compared to SHAM rat hearts.