L. Dembo

The effect of combined aerobic and resistance exercise training on vascular function in Type 2 diabetes

OBJECTIVES The purpose of this study was to examine whether exercise training stimulates a generalized improvement in vascular function in patients with type 2 diabetes mellitus. BACKGROUND Exercise is often recommended for patients with type 2 diabetes to improve physical conditioning and glycemic control. This study examined the effect of eight weeks of exercise training on conduit and resistance vessel function in patients with type 2 diabetes, using a randomized crossover design. METHODS Both resistance vessel endothelium-dependent and -independent functions were determined by forearm plethysmography and intrabrachial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, in 16 patients with type 2 diabetes. Conduit vessel endothelial function was assessed in 15 of these patients using high-resolution ultrasound and flow-mediated dilation of the brachial artery; glyceryl trinitrate (GTN) was used as an endothelium-independent dilator. RESULTS Flow-mediated dilation increased from 1.7 +/- 0.5% to 5.0 +/- 0.4% following training (p < 0.001). The forearm blood flow ratio to ACh was significantly improved (analysis of variance, p < 0.05). Responses to SNP and GTN were unchanged. Endothelium-dependent vasodilation was enhanced in both conduit and resistance vessels. CONCLUSIONS If endothelial dysfunction is an integral component of the pathogenesis of vascular disease, as currently believed, this study supports the value of an exercise program in the management of type 2 diabetes.

Exercise training, vascular function, and functional capacity in middle-aged subjects

PURPOSE The aim of this study was to investigate the effect of 8 wk of exercise training on functional capacity, muscular strength, body composition, and vascular function in sedentary but healthy subjects by using a randomized, crossover protocol. METHODS After familiarization sessions, 19 subjects aged 47 +/- 2 yr (mean +/- SE) undertook a randomized, crossover design study of the effect of 8 wk of supervised circuit training consisting of combined aerobic and resistance exercise. Peak oxygen uptake (.VO(2peak)), sum of 7 maximal voluntary contractions and the sum of 8 skinfolds and 5 segment girths were determined at entry, crossover, and 16 wk. Endothelium-dependent and -independent vascular function were determined by forearm strain-gauge plethysmography and intrabrachial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP) in 16 subjects. RESULTS Training did not alter ACh or SNP responses. .VO(2peak), (28.6 +/- 1.1 to 32.6 +/- 1.3 mL.kg(-1).min(-1), P < 0.001), exercise test duration (17.4 +/- 1.1 to 22.1 +/- 1.2 min, P < 0.001), and muscular strength (465 +/- 27 to 535 +/- 27 kg, P < 0.001) significantly increased after the exercise program, whereas skinfolds decreased (144 +/- 10 vs 134 +/- 9 mm, P < 0.001). CONCLUSION These results suggest that moderate intensity circuit training designed to minimize the involvement of the arms improves functional capacity, body composition, and strength in healthy, middle-aged subjects without significantly influencing upper limb vascular function. This finding contrasts with previous studies in subjects with type 2 diabetes and heart failure that employed an identical training program.

A prospective randomised longitudinal MRI study of left ventricular adaptation to endurance and resistance exercise training in humans

Non‐Technical Summary  This is the first study, to our knowledge, to use cardiac MRI before and after intensive and closely supervised resistance and endurance exercise training in humans. There is a long held belief that these different forms of training induce ‘concentric’ and ‘eccentric’ adaptation of the heart, but this concept is based on echocardiographic assessments and cross‐sectional comparison of different types of elite athletes. Our findings, using highly sensitive MRI methodology, suggest that concept may need to be reconsidered. This study is of fundamental importance to the understanding of the impact of exercise on human cardiac morphology and physiology.

Nitric oxide is not obligatory for radial artery flow-mediated dilation following release of 5 or 10 min distal occlusion.

This study investigated the nitric oxide (NO) dependence of radial artery (RA) flow-mediated dilation (FMD) in response to three different reactive hyperemia (RH) shear stimulus profiles. Ten healthy males underwent the following three RH trials: 1) 5 min occlusion (5 trial), 2) 10 min occlusion (10 trial), and 3) 10 min occlusion with cuff reinflation at 30 s (10-30 trial). Trials were performed during saline infusion and repeated during N(G)-monomethyl-L-arginine (L-NMMA) infusion in the brachial artery. RA blood flow velocity was measured with Doppler ultrasound, and B-mode RA images were analyzed using automated edge detection software. Shear rate estimation of shear stress was calculated as the blood flow velocity/vessel diameter. L-NMMA decreased baseline vascular conductance by 35%. L-NMMA infusion did not affect the peak shear rate stimulus (P = 0.681) or the area under the curve (AUC) of shear rate to peak FMD (P = 0.088). The AUC was significantly larger in the 10 trial vs. the 10-30 or 5 trial (P < 0.001). Although percent FMD (%change in diameter) in the 10 trial was larger than that in the 5 trial (P = 0.035), there was no significant difference in %FMD between the saline and L-NMMA conditions in any trial: 5 trial, 5.62 +/- 1.48 vs. 5.63 +/- 1.27%; 10 trial, 9.07 +/- 1.16 vs. 11.22 +/- 2.21%; 10-30 trial, 6.52 +/- 1.43 vs. 7.98 +/- 1.51% for saline and L-NMMA, respectively (P = 0.158). We conclude the following: 1) RH following 10 min of occlusion results in an enhanced stimulus and %FMD compared with 5 min of occlusion. 2) When the occlusion cuff is reinflated 30 s postrelease of a 10 min occlusion, it does not result in an enhanced %FMD compared with that which results from RH following 5 min of occlusion. 3) The lack of effect of L-NMMA on FMD suggests that NO may not be obligatory for radial artery FMD in response to either 5 or 10 min of occlusion in healthy volunteers.

Management Options to Treat Gastrointestinal Bleeding in Patients Supported on Rotary Left Ventricular Assist Devices: A Single‐Center Experience

Gastrointestinal (GI) bleeding in ventricular assist devices (VADs) has been reported with rotary devices. The pathophysiological mechanisms and treatments are in evolution. We performed a retrospective review of GI bleeding episodes for all VADs implanted at our institution. Five male patients experienced GI bleeding-age 63.6 ± 3.64 years. VAD type VentrAssist n = 1, Jarvik 2000 n = 2, and HeartWare n = 2. All patients were anticoagulated as per protocol with antiplatelet agents (aspirin and/or clopidogrel bisulfate [Plavix] and warfarin (therapeutic international normalized ratio 2.0-3.5). There was no prior history of gastric bleeding in this group. Ten episodes of bleeding requiring blood transfusion occurred in five patients. Some patients had multiple episodes (1 × 5, 1 × 2, 3 × 1). The events occurred at varying times post-VAD implantation (days 14, 21, 26, 107, 152, 189, 476, 582, 669, and 839). Octreotide (a long-acting somatostatin analogue that reduces splanchnic arterial and portal blood flow) was administered subcutaneously or intravenously. Three patients received infusions of adrenaline at 1 µg/min to enhance pulsatility. Anticoagulation was interrupted during bleeding episodes but successfully introduced post bleeding event. GI bleeding is a significant complication of VAD therapy. In this article, we discuss diagnosis and management options.

Successful treatment of rotary pump thrombus with the glycoprotein IIb/IIIa inhibitor tirofiban.

Despite advances in blood pump technology, thrombus formation within left ventricular assist devices (LVADs) is a life-threatening complication with few therapeutic options. A 38-year-old woman who underwent rotary LVAD implantation as a bridge to cardiac transplant developed labile flows (4 to >10 liters), associated with power spikes (4 to 12 watts) and an increase in plasma free hemoglobin (0.86 g/liter), consistent with pump thrombus at Day 140 post-LVAD implantation, despite thromboprophylaxis with aspirin and warfarin. Within 12 hours of commencing an intravenous infusion of tirofiban at a rate of 0.1 mug/kg/min, there were signs of improvement of pump dysfunction, and complete resolution was evident at Day 4 with, stable flows, power consumption and normalization of plasma free hemoglobin. Tirofiban may be considered as an alternative thrombolytic treatment strategy in rotary pump thrombus to avoid the need for LVAD replacement.

Repeated infusions of levosimendan: well tolerated and improves functional capacity in decompensated heart failure - a single-centre experience.

BACKGROUND Levosimendan is a novel agent used in the treatment of patients with decompensated heart failure to enhance cardiac contractility. Recent clinical studies have demonstrated that single doses of levosimendan have positive symptomatic and haemodynamic benefits, few have explored the efficacy and safety of intermittent repeated doses of levosimendan. AIMS In this prospective study we document our single-centre experience of repeated administration of levosimendan to patients with decompensated heart failure. METHODS Prospective data were collected and analysed with respect to New York Heart Association (NYHA) class, mean arterial pressure (MAP), brain natriuretic peptide levels (BNP) and adverse events. RESULTS Forty-four consecutive patients with decompensated heart failure received repeated doses of levosimendan. The mean dosing interval was 66.2 (12) days. All patients had documented evidence of impaired left ventricular function, with a mean ejection fraction (EF) of 23.7% (2.2). Fifty-eight percent were NYHA class IV, mean age 50 (2.4), 82% were male. A significant drop in BNP levels and improvement in NYHA class was seen post-infusion. In general, levosimendan was well tolerated with 130 (83.5%) infusions completed without an adverse event. Twenty-five percent of patients were bridged to cardiac transplant or left ventricular assist device (LVAD) insertion. Four patients received 12 infusions, in total in the community. CONCLUSION The majority of repeated levosimendan infusions were well tolerated, reduced BNP and improved NYHA functional class. In selected patients it can be administered in the community. Further investigation is required to assess the efficacy and safety of this approach.

Successful Heart Transplant after Ten Hours Out-of-body Time using the TransMedics Organ Care System

OBJECTIVE We report the successful transplantation of a heart following an out-of-body time of 611 minutes into a recipient with dilated cardiomyopathy and left ventricular assist device implant. PATIENTS Our patient was urgently waiting for a cardiac transplant whilst receiving LVAD support. Recurrent VF and repeated AICD shocks necessitated this action. RESULTS Although requiring ECMO and inotropic support in the first 17 hours post-transplant, the patient was discharged from hospital on day 15 post-transplant with normal cardiac function. CONCLUSION We report some of the salient points of the process and discuss the utility of this technology to an Australian transplant unit.

Is the soleus a sentinel muscle for impaired aerobic capacity in heart failure

PURPOSE Skeletal muscle wasting is well documented in chronic heart failure (CHF). This article provides a more detailed understanding of the morphology behind this muscle wasting and the relation between muscle morphology, strength, and exercise capacity in CHF. We investigated the effect of CHF on lower limb lean mass, detailed muscle-tendon architecture of the individual triceps surae muscles (soleus (SOL), medial gastrocnemius, and lateral gastrocnemius) and how these parameters relate to exercise capacity and strength. METHODS Eleven patients with CHF and 15 age-matched controls were recruited. Lower limb lean mass was assessed by dual energy x-ray absorptiometry and the architecture of skeletal muscle and tendon properties by ultrasound. Plantarflexor strength was assessed by dynamometry. RESULTS Patients with CHF exhibited approximately 25% lower combined triceps surae volume and physiological cross-sectional area (PCSA) compared with those of control subjects (P < 0.05), driven in large part by reductions in the SOL. Only the SOL volume and the SOL and medial gastrocnemius physiological cross-sectional area were statistically different between groups after normalizing to lean body mass and body surface area, respectively. Total lower limb lean mass did not differ between CHF and control subjects, further highlighting the SOL specificity of muscle wasting in CHF. Moreover, the volume of the SOL and plantarflexor strength correlated strongly with peak oxygen uptake (V˙O2peak) in patients with CHF. CONCLUSIONS These findings suggest that the SOL may be a sentinel skeletal muscle in CHF and provide a rationale for including plantarflexor muscle training in CHF care.

A cardiac magnetic resonance imaging study of electrocardiographic Q waves in type 2 diabetes : The Fremantle Diabetes Study

To investigate the evolution and significance of Q waves in type 2 diabetes, we studied 36 patients of mean (+/-S.D.) age 69.9+/-7.1 years from the longitudinal observational Fremantle Diabetes Study (FDS). All had (i) neither history/symptoms of coronary heart disease (CHD) nor pathological Q waves at FDS recruitment between 1993 and 1996, (ii) five consecutive annual assessments by FDS close-out in 2001, and (iii) contrast-enhanced cardiac magnetic resonance imaging in 2005. At this latter assessment, there were (i) 9 with no history of CHD or Q waves during follow-up (Group 1), (ii) 13 with Q waves on >/=1 electrocardiogram but no CHD history/symptoms (Group 2), and (iii) 14 with CHD history/symptoms irrespective of electrocardiographic status (Group 3). Of 20 episodes of new Q waves in 17 Group 2 or Group 3 patients during FDS follow-up, 17 (85%) resolved within 2 years. A myocardial infarction (MI) was detected by CMR in three patients (8.3%; one subendocardial in Groups 1 and 3, one non-full-thickness in Group 3) but these did not correlate with electrocardiographic appearances. Q waves may have unreliable pathological significance in type 2 diabetes, including as a marker of silent MI.