F-19 MR imaging of glucose metabolism in the rabbit

Noninvasive metabolic magnetic resonance (MR) imaging reflecting glucose metabolism in the aldose-reductase-sorbitol (ARS) pathway was performed in the rabbit head; after administration of the fluorinated glucose analogue 3-fluoro-3-deoxy-D-glucose (3FD-glucose), fluorine-19 images were generated. Images of 3FD-glucose showed significant 3FD-glucose uptake by adipose tissue, indicating its buffering effects in case of excess loads of glucose. Images of 3-fluoro-3-deoxy-D-sorbitol (3FD-sorbitol) demonstrated the spatial distribution of aldose reductase activities and significant sorbitol accumulation in the lens. Images of 3-fluoro-3-deoxy-D-fructose (3FD-fructose) showed preferential uptake of fructose by muscle tissue. The extremely low toxicity of 3FD-glucose indicates promise for its clinical application in metabolic imaging.     

Abnormal circulating levels of metalloprotease 9 and its tissue inhibitor 1 in angiographically proven peripheral arterial disease: relationship to disease severity

BACKGROUND: Peripheral arterial disease (PAD) is associated with adaptive changes in the vascular and muscle extracellular matrix (ECM) in response to reduced blood flow. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), are key modulators of ECM turnover. We hypothesized that patients with intermittent claudication (with low ankle-brachial blood pressure index, <0.8), and critical ischaemia would have raised circulating levels of MMP-9, TIMP-1 and TIMP-2 compared with healthy controls, reflecting an increase in proteolytic activity which may be related to ECM turnover in PAD. METHODS: We studied 36 patients (23 males; 65 +/- 9 years) with intermittent claudication and 43 (25 males; 68 +/- 12) patients with critical ischaemia. All patients had angiographic evidence confirming significant PAD. RESULTS: Circulating levels of MMP-9 and TIMP-1 were higher (both P < 0.0001) in the PAD patient groups compared with the controls. Patients with critical ischaemia had MMP-9 and TIMP-1 levels that were significantly higher than those with intermittent claudication. There were no differences in circulating TIMP-2 levels between patients and controls. There was a modest positive correlation between the white cell count (WCC) and MMP-9, both patients with intermittent claudication (Spearman, r = 0.398, P = 0.016) and critical ischaemia (r = 0.378, P = 0.014). CONCLUSION: We demonstrate higher levels of circulating MMP-9 and TIMP-1 in patients with intermittent claudication and critical ischaemia. Circulating concentrations of both markers can be related to disease severity, being higher in critical ischaemia compared with levels in intermittent claudication.     

Tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9 levels in patients with hypertension Relationship to tissue Doppler indices of diastolic relaxation

BACKGROUND: Hypertension, hypertensive heart disease, and left ventricular (LV) hypertrophy are integral to symptomatic diastolic heart failure. Tissue inhibitor of metalloproteinase-1 (TIMP-1) is linked to extracellular matrix fibrosis and is elevated in hypertension. We hypothesized a link between circulating TIMP-1, matrix metalloproteinase-9 (MMP-9), and resting echocardiographic LV filling parameters using tissue Doppler parameters of diastolic (dys)function. METHODS: Circulating MMP-9 and TIMP-1 levels were measured in citrated plasma by ELISA in 74 patients with hypertension (58 men, mean age 58 +/- 11 years) and 34 controls (23 men, mean age 53 +/- 13 years). All had confirmed normal short axis systolic contractility, with no significant wall motion abnormalities; the LV mass and standard resting tissue Doppler echocardiographic indices of diastolic function were also recorded. RESULTS: Both MMP-9 and TIMP-1 levels were higher in the hypertensive group (P =.0039 and P =.0054, respectively). When compared to controls, hypertensive patients had a greater LV mass (P =.0054), and differences in many of the parameters reflecting diastolic dysfunction (controls versus hypertensives: E: 0.71 +/- 0.15 v 0.81 +/- 0.15 m/sec, P =.004; A: 0.66 +/- 0.12 v 0.81 +/- 0.16 m/sec, P <.0001; e': 0.12 (0.09-0.14) v 0.09 (0.07-0.10) m/sec, P =.0017; e'/a': 1.20 (1.00-1.80) v 0.88 (0.71-1.05), P <.0001; E/e': 6.54 (4.75-7.14) v 8.89 (7.55-10.75), P <.0001, respectively). Within the hypertensive cohort, only TIMP-1 levels correlated with LV mass (r = 0.271, P =.024), LV mass index (r = 0.323, P =.007), and tissue Doppler parameters of diastolic dysfunction, including e' (r = -0.338, P =.005), a' (r = -0.350, P =.005), and E/e' (r = 0.334, P =.005). CONCLUSIONS: TIMP-1 is thought to increase tissue concentrations of collagen type I by preventing its breakdown by MMPs. Our findings therefore add weight to a hypothesis suggesting that TIMP-1 may be a key mediator of LV diastolic dysfunction through definition of ventricular matrix composition.     

Blood pressure response to the first dose of angiotensin-converting enzyme inhibitors in congestive heart failure

Angiotensin-converting enzyme (ACE) inhibitors improve survival in heart failure and delay progression to clinical heart failure in patients with left ventricular dysfunction after myocardial infarction. Increasing numbers of older patients are being considered for such treatment. However, there are reports of excessive and prolonged decreases in blood pressure (BP) after the first dose of some ACE inhibitors. We have studied the hemodynamics, pharmacokinetics, and neurohumoral responses to the first dose of oral captopril 6.25 mg, enalapril 2.5 mg, perindopril 2.0 mg, intravenous enalaprilat 1.5 mg, and perindoprilat 1.0 mg, compared with oral or intravenous placebo in 6 parallel groups of 12 elderly patients each with moderate-to-severe (New York Heart Association classes II-IV) heart failure. Oral dosing with active drugs led to different temporal responses. After captopril, there was an early short-lived decrease in BP. Enalapril led to a later long-lasting decrease, but perindopril was not different from placebo. Intravenous enalaprilat and intravenous perindoprilat each lowered BP to a similar extent. The doses of drugs used appeared to be comparable because plasma ACE inhibition was similar following perindopril or enalapril and also comparing perindoprilat and enalaprilat. These studies indicate that oral ACE inhibitors have different profiles of acute BP changes after the first dose. The explanation is not clear, but could include physicochemical differences in the interaction between prodrug ester and diacid metabolites leading to differences in tissue distribution and local enzyme inhibition.     

A cause for conversion of laparoscopic splenectomy: splenic candidiasis

Laparoscopic splenectomy (LS) is now considered the procedure of choice for removal of the spleen in several hematologic and traumatic splenic conditions. Perisplenitis is still considered a relative contraindication. We report a rare case of isolated splenic candidiasis treated by laparoscopic splenectomy. The technical challenges of the laparoscopic approach in cases of perisplenitis are outlined. Because of dense adhesions to the diaphragm, the LS was converted to open splenectomy, and the procedure was completed through a small subcostal incision. This case report suggests the need for and effectiveness of splenectomy in patients whose fungal infection is suspected to be localized to the spleen. Laparoscopic removal of the spleen in these cases is very difficult to accomplish because of the risk for diaphragm injuries and the technical problems encountered.     

Acquired coropulmonary and bronchopulmonary anastomoses occurring in association with pulmonary arterial occlusion and veno-occlusive disease generating potential coronary steal

The development of collateral circulation is a general vascular response which is well characterised in the heart. The most common precipitant of this is ischaemia and the most common manifestation is intra coronary collateralisation. Collateral flow between the heart and other thoracic structures is also documented albeit rarely and can be congenital or acquired. In this case report we define a unique case of collateral flow between the coronary and pulmonary circulations in a complex case of mediastinal fibrosis.