Transcutaneous electrical nerve stimulation as a novel method of remote preconditioning: in vitro validation in an animal model and first human observations.

Remote ischemic preconditioning (rIPC) induced by transient limb ischemia (li-rIPC) leads to neurally dependent release of blood-borne factors that provide potent cardioprotection. We hypothesized that transcutaneous electrical nerve stimulation (TENS) is a clinically relevant stimulus of rIPC. Study 1: seven rabbits were subjected to lower limb TENS; six to li-rIPC, and six to sham intervention. Blood was drawn and used to prepare a dialysate for subsequent analysis of cardioprotection in rabbit Langendorff preparation. Study 2: 14 healthy adults underwent upper limb TENS stimulation on one study day, 10 of whom also underwent li-rIPC on another study day. Blood was drawn before and after each stimulus, dialysate prepared, and cardioprotective activity assessed in mouse Langendorff preparation. The infarct size and myocardial recovery were measured after 30 min of global ischemia and 60 or 120 min of reperfusion. Animal validation: compared to control, TENS induced marked cardioprotection with significantly reduced infarct size (TENS vs. sham p < 0.01, rIPC vs. sham p < 0.01, TENS vs. rIPC p = ns) and improved functional recovery during reperfusion. Human study: compared to baseline, dialysate after rIPC (pre-rIPC vs. post-rIPC, p < 0.001) and TENS provided potent cardioprotection (pre-TENS vs. post-TENS p < 0.001) and improved myocardial recovery during reperfusion. The cardioprotective effects of TENS dialysates were blocked by pretreatment of the receptor heart with the opioid antagonist naloxone. TENS is a novel method for inducing cardioprotection and may provide an alternative to the limb ischemia stimulus for induction of rIPC clinically.

Dose-related effects of red wine and alcohol on hemodynamics, sympathetic nerve activity, and arterial diameter.

The cardiovascular benefits of light to moderate red wine consumption often have been attributed to its polyphenol constituents. However, the acute dose-related hemodynamic, vasodilator, and sympathetic neural effects of ethanol and red wine have not been characterized and compared in the same individual. We sought to test the hypotheses that responses to one and two alcoholic drinks differ and that red wine with high polyphenol content elicits a greater effect than ethanol alone. Thirteen volunteers (24-47 yr; 7 men, 6 women) drank wine, ethanol, and water in a randomized, single-blind trial on three occasions 2 wk apart. One drink of wine and ethanol increased blood alcohol to 38 +/- 2 and 39 +/- 2 mg/dl, respectively, and two drinks to 72 +/- 4 and 83 +/- 3 mg/dl, respectively. Wine quadrupled plasma resveratrol (P < 0.001) and increased catechin (P < 0.03). No intervention affected blood pressure. One drink had no heart rate effect, but two drinks of wine increased heart rate by 5.7 +/- 1.6 beats/min; P < 0.001). Cardiac output fell 0.8 +/- 0.3 l/min after one drink of ethanol and wine (both P < 0.02) but increased after two drinks of ethanol (+0.8 +/- 0.3 l/min) and wine (+1.2 +/- 0.3 l/min) (P < 0.01). One alcoholic drink did not alter muscle sympathetic nerve activity (MSNA), while two drinks increased MSNA by 9-10 bursts/min (P < 0.001). Brachial artery diameter increased after both one and two alcoholic drinks (P < 0.001). No beverage augmented, and the second wine dose attenuated (P = 0.02), flow-mediated vasodilation. One drink of ethanol dilates the brachial artery without activating sympathetic outflow, whereas two drinks increase MSNA, heart rate, and cardiac output. These acute effects, which exhibit a narrow dose response, are not modified by red wine polyphenols.

Improvement in exercise duration and capacity after conversion to nocturnal home haemodialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) have a reduced exercise capacity as assessed by peak oxygen uptake (VO2peak). Nocturnal haemodialysis (NHD) augments uraemic clearance and vascular responsiveness to nitric oxide and lowers blood pressure (BP) and peripheral resistance. METHODS: To assess the impact of NHD on exercise duration and capacity, 13 consecutive ESRD patients [age: 41 +/- 3; (mean +/- SEM)] and healthy normal subjects (n = 14) matched for age and body mass index exercised to peak effort (VO2peak) as determined by open-circuit spirometry during a graded cycle ergometer test with a ramp increase in work rate (by 17 watts/min). RESULTS: Exercise was performed before, 2 and 3-6 months after conversion from conventional haemodialysis (CHD) (3 sessions per week; 4 h per session) to NHD (5-6 sessions per week; 6-8 h per session). Exercise duration increased progressively [from 617 +/- 50 (CHD) to 634 +/- 47 (NHD 2 months) to 682 +/- 55 [NHD 3-6 months], P = 0.03) as did exercise capacity, expressed as percent of predicted (based on age, sex and body size) VO2peak, [from 66 +/- 8 (CHD) to 72 +/- 6 (NHD 2 months) to 75 +/- 6% (NHD 3-6 months), P < 0.05). CONCLUSION: Enhanced uraemia control by NHD improved both exercise duration and capacity. When coupled with augmented uraemia management, an increase in physical activity, perhaps due to more effective oxygen delivery or improved muscle metabolism, has the potential to improve the quality of life of patients with ESRD.