Biomedical subjects

Brian A Mullan

Publications and source records attributed to Brian A Mullan.

3 recordsLinked to original sources

PubMed2004

Protective effects of ascorbic acid on arterial hemodynamics during acute hyperglycemia.

Mortality increases when acute coronary syndromes are complicated by stress-induced hyperglycemia. Early pulse wave reflection can augment central aortic systolic blood pressure and increase left ventricular strain. Altered pulse wave reflection may contribute to the increase in cardiac risk during acute hyperglycemia. Chronic ascorbic acid (AA) supplementation has recently been shown to reduce pulse wave reflection in diabetes. We investigated the in vivo effects of acute hyperglycemia, with and without AA pretreatment, on pulse wave reflection and arterial hemodynamics. Healthy male volunteers were studied. Peripheral blood pressure (BP) was measured at the brachial artery, and the SphygmoCor pulse wave analysis system was used to derive central BP, the aortic augmentation index (AIx; measure of systemic arterial stiffness), and the time to pulse wave refection (Tr; measure of aortic distensibility) from noninvasively obtained radial artery pulse pressure (PP) waveforms. Hemodynamics were recorded at baseline and then every 30 min during a 120-min systemic hyperglycemic clamp (14 mmol/l). The subjects, studied on two separate occasions, were randomized in a double-blind, crossover manner to placebo or 2 g intravenous AA before the initiation of hyperglycemia. During hyperglycemia, AIx increased and Tr decreased. Hyperglycemia did not change peripheral PP but did magnify central aortic PP and diminished the normal physiological amplification of PP from the aorta to the periphery. Pulse wave reflection, as assessed from peripheral pulse wave analysis, is enhanced during acute hyperglycemia. Pretreatment with AA prevented the hyperglycemia-induced hemodynamic changes. By protecting hemodynamics during acute hyperglycemia, AA may have therapeutic use.

Acute Disease↗

PubMed2002

Ascorbic acid reduces blood pressure and arterial stiffness in type 2 diabetes.

Experimental evidence suggests that acute parenteral administration of high-dose ascorbic acid has beneficial vascular effects in type 2 diabetes. We studied the hemodynamic effects of chronic oral supplementation in this condition. Thirty patients, 45 to 70 years of age, with type 2 diabetes, were randomly assigned in a double-blind manner to receive 500 mg ascorbic acid daily by mouth or placebo. Patients were studied at baseline and after 4 weeks of assigned treatment. The central aortic augmentation index (AgIx) and the time to wave reflection (Tr) were derived from radial artery pulse wave analysis data. AgIx and Tr were used as measures of systemic arterial stiffness and aortic stiffness, respectively. Ascorbic acid decreased brachial systolic blood pressure from 142.1+/-12.6 (SD) to 132.3+/-12.1 mm Hg (difference [95% CI] 9.9 [4.7, 15.0]; P<0.01), brachial diastolic pressure from 83.9+/-4.8 to 79.5+/-6.0 mm Hg (4.4 [1.8, 7.0]; P<0.01), and AgIx from 26.8+/-5.5% to 22.5+/-6.8% (4.3 [1.5, 7.1]; P<0.01). Tr increased from 137.1+/-12.6 to 143.4+/-9.2 ms (-6.3 [-10.1, -2.5]; P<0.01). Placebo had no hemodynamic effects, and this difference between treatments was significant (P<0.01 for blood pressure and Tr, P=0.03 for AgIx). We have therefore shown that after 1 month, oral ascorbic acid lowered arterial blood pressure and improved arterial stiffness in patients with type 2 diabetes. As strict control of blood pressure reduces cardiovascular risk in diabetes, ascorbic acid supplementation may potentially be a useful and inexpensive adjunctive therapy. Larger and longer studies now need to be performed.

Administration, Oral↗

PubMedDate not supplied

Pretreatment with intravenous ascorbic acid preserves endothelial function during acute hyperglycaemia (R1).

1. Acute hyperglycaemia may impair endothelial function. Ascorbic acid (AA), administered intra-arterially, has been reported to improve endothelium-dependent vasodilatation during a forearm hyperglycaemic clamp. Using a randomized, double-blind, placebo-controlled, cross-over study, we investigated the potential for intravenous ascorbic acid to modify the endothelial response to acute systemic hyperglycaemia in humans. 2. Nine healthy male volunteers were recruited from the hospital staff. Endothelial function was determined by measuring the forearm blood flow responses to intrabrachial infusions of endothelium-dependent (ED) and endothelium-independent (EID) vasodilators. The endothelial function index (EFI) was derived from the ratio of ED and EID vasodilatation. Haemodynamic and endothelial function measurements were performed at baseline and then repeated 2 h after a systemic hyperglycaemic clamp (14 mmol/L). The subjects, studied on two separate occasions, were randomized to placebo or 2 g intravenous ascorbic acid prior to the initiation of hyperglycaemia. 3. After systemic hyperglycaemia with placebo pretreatment, the EFI fell from 1.08 +/- 0.21 to 0.74 +/- 0.13 (difference (95% confidence interval): 0.34 (0.20, 0.47); P < 0.001). When subjects were pretreated with ascorbic acid, the EFI was not affected by hyperglycaemia (1.11 +/- 0.21 to 1.12 +/- 0.17; P = 0.938). This difference between placebo and ascorbic acid was significant (P < 0.001). Plasma ascorbate concentrations decreased during hyperglycaemia and correlated directly with the reduction in the EFI (r = 0.798; P < 0.001). 4. Pretreatment with an intravenous bolus of ascorbic acid can prevent endothelial dysfunction during acute systemic hyperglycaemia. Therefore, ascorbic acid may have potential therapeutic use in clinical situations where acute hyperglycaemia may be a complication.

Acute Disease↗