Folic acid improves arterial endothelial function in adults with hyperhomocystinemia.

OBJECTIVES: To evaluate whether oral folic acid supplementation might improve endothelial function in the arteries of asymptomatic adults with hyperhomocystinemia. BACKGROUND: Hyperhomocystinemia is an independent risk factor for endothelial dysfunction and occlusive vascular disease. Folic acid supplementation can lower homocystine levels in subjects with hyperhomocystinemia; however, the effect of this on arterial physiology is not known. METHODS: Adults subjects were recruited from a community-based atherosclerosis study on healthy volunteers aged 40 to 70 years who had no history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease or family history of premature atherosclerosis (n = 89). Seventeen subjects (aged 54 +/- 10 years, 15 male) with fasting total homocystine levels above 75th percentile (mean, 9.8 +/- 2.8 micromol/liter) consented to participate in a double-blind, randomized, placebo-controlled and crossover trial; each subject received oral folic acid (10 mg/day) and placebo for 8 weeks, each separated by a washout period of four weeks. Flow-mediated endothelium-dependent dilation (percent increase in diameter) of the brachial artery was assessed by high resolution ultrasound, before and after folic acid or placebo supplementation. RESULTS: Compared with placebo, folic acid supplementation resulted in higher serum folate levels (66.2 +/- 7.0 vs. 29.7 +/- 14.8 nmol/liter; p < 0.001), lower total plasma homocystine levels (8.1 +/- 3.1 vs. 9.5 +/- 2.5 micromol/liter, p = 0.03) and significant improvement in endothelium-dependent dilation (8.2 +/- 1.6% vs. 6 +/- 1.3%, p < 0.001). Endothelium-independent responses to nitroglycerin were unchanged. No adverse events were observed. CONCLUSION: Folic acid supplementation improves arterial endothelial function in adults with relative hyperhomocystinemia, with potentially beneficial effects on the atherosclerotic process.

Chinese herbs and warfarin potentiation by 'danshen'.

Drug interactions with warfarin can be dangerous and although common drug interactions are now well recognized those with Chinese herbs are not widely appreciated. 'Danshen' is a herbal medicine often used for various complaints, particularly cardiovascular, in the Chinese community. We report a case of danshen-induced overcoagulation with severe and dangerous abnormalities of clotting in a patient with rheumatic heart disease.

The effect of transcutaneous electrical nerve stimulation on coronary and systemic haemodynamics in syndrome X.

BACKGROUND: Neurostimulation techniques have been shown to be beneficial in patients with angina and syndrome X but the mechanism remains unclear. We examined the effect of transcutaneous electrical nerve stimulation (TENS) on coronary artery blood flow in a group of patients with syndrome X. METHODS: Coronary blood flows were measured in 11 patients with angiographically normal coronary arteries, positive results from exercise tests and angina (syndrome X) using intracoronary Doppler catheters combined with quantitative coronary angiography. RESULTS: The mean coronary flow velocity did not increase in any patient during TENS therapy; in fact, there was a fall from 5.2 +/- 2.8 to 4.3 +/- 1.9 cm/s (P = 0.02) and the coronary blood flow index fell from 47 +/- 22 to 38 +/- 16 cm/s per mm2 (P = 0.007). This was associated with a fall in the rate x pressure product from 0.92 +/- 0.22 to 0.83 +/- 0.18 mmHg/min (P = 0.038). The coronary vascular resistance rose from 2.4 +/- 1.1 to 3.0 +/- 1.6 mmHg/cm per s per mm2 (P = 0.041). There were no major changes in the epicardial coronary artery diameter during TENS and there was no significant effect on the response to the cold-pressor test. CONCLUSIONS: In this group of patients with syndrome X, TENS produced a small but significant fall in coronary artery blood flow associated with a reduction in the rate x pressure product. TENS had no significant effect on coronary vasomotion during sympathetic stimulation by the cold-pressor test. Thus, TENS is unlikely to have a direct effect on coronary artery vasomotion or haemodynamics in syndrome X but reduces the rate x pressure product and thus myocardial oxygen consumption.

The effect of transcutaneous electrical nerve stimulation (TENS) on autonomic cardiovascular reflexes.

Transcutaneous electrical nerve stimulation (TENS) has been shown to have an anti-ischaemic effect in patients with angina and peripheral vascular disease that appears to be additional to any analgesic action. The mechanism for this anti-ischaemic effect is not known but it is possible that TENS interferes with the autonomic responses to ischaemia. To determine if TENS has any direct action on autonomic reflexes we have assessed the effect of high frequency TENS on a variety of standard tests of autonomic cardiovascular reflexes in 10 normal subjects. Tests were done on four consecutive days at the same time and TENS therapy or placebo was randomly allocated on 2 days each. Results of the tests were assessed by one person 'blinded' to the randomization order. These showed that TENS was associated with a significant reduction in the rise of the diastolic blood pressure (21.8 +/- 2.3 v. 17.6 +/- 17 mmHg; p < 0.05) during isometric exercise, using sustained Handgrip. There was no significant effect discernible on the changes of heart rate and blood pressure during the Valsalva manoeuvre, cold face stimulus or head-up tilt. Transcutaneous electrical nerve stimulation appears, therefore, to have a mild inhibitory action on those reflexes mediated predominantly by the sympathetic nervous system and this is more apparent when the stimulation may be greater, as during isometric exercise.

Spinal electrical stimulation for intractable angina--long-term clinical outcome and safety.

Spinal cord electrical stimulation is an alternative therapy for patients with chronic pain syndromes including angina. Although it has been shown to produce symptomatic relief and reduce ischaemia, doubts remain about its long-term safety. We report here for the first time the results of a follow-up study over a period of 62 months, mean 45 months (range 21-62), of 23 patients who had stimulator units implanted for intractable angina unresponsive to standard therapy. Symptomatic improvement was good and persisted in the majority with a mean (SD) change of NYHA grade from 3.1 (0.8) pre-operatively to 2.0 (0.9) (P < 0.01) immediately after operation and 2.1 (1.07) at the latest follow-up. GTN consumption fell markedly. Mean (SEM) treadmill exercise time increased from 407 (45) s with the stimulator off to 499 (46) s with the stimulator on (P < 0.01). Forty-eight hour ST segment monitoring in those with bipolar leads showed a reduction of total number and duration of ischaemic episodes. There were three deaths, none of which were sudden or unexplained and this mortality rate is acceptable for such a group of patients. Two patients had a myocardial infarction, which was associated with typical pain and not masked by the treatment. Complications related to earlier lead designs were frequent. This study confirms that spinal electrical stimulation is an effective and safe form of alternative therapy for the occasional patient whose angina is unresponsive to standard therapies.

Effects of spinal cord stimulation on myocardial ischaemia during daily life in patients with severe coronary artery disease. A prospective ambulatory electrocardiographic study.

BACKGROUND: Spinal cord stimulation (SCS) may be a useful additional therapy for pain in patients with therapeutically refractory angina pectoris. But doubts remain about whether it also relieves ischaemia. METHODS: Indices of ischaemia were studied with and without SCS in 10 patients with otherwise intractable angina and evidence of myocardial ischaemia on 48 h ambulatory electrocardiographic (ECG) recording. Primary end points assessed by 48 h ECG recordings were total ischaemic burden, number of ischaemic episodes, and duration of ischaemic episodes. In addition, symptoms were assessed by a diary of glyceryl trinitrate intake and angina attacks. RESULTS: During SCS the total ischaemic burden of the entire group was significantly reduced from a median of 27.9 (1.9-278.2) before SCS to 0 (0-70.2) mm x min with SCS (p < 0.03). In six out of the 10 patients there was no myocardial ischaemia during 48 h ambulatory ECG monitoring with SCS. The number of ischaemic episodes was reduced from a median of 3 (1-15) before SCS to 0 (0-9) with SCS (p < 0.04). The duration of ischaemic episodes decreased from a median of 20.6 (1.7-155.4) min before SCS to 0 (0-48.3) min with SCS (p < 0.03). This was accompanied by a significant improvement in symptoms with a reduction in daily glyceryl trinitrate intake from a median of 3.0 (0-10) before SCS to 0.3 (0-10) tablets per 48 h (p < 0.02) and a decrease in the frequency of anginal attacks from a median of 5.5 (2-14) before SCS to 1.0 (0-10) per 48 h with SCS (p < 0.03). CONCLUSIONS: SCS not only reduced symptoms but also myocardial ischaemia. Therefore, SCS appears to be both a safe and an effective therapy for patients with refractory angina.

Epidural spinal electrical stimulation for severe angina: a study of its effects on symptoms, exercise tolerance and degree of ischaemia.

The effectiveness of epidural spinal electrical stimulation has been studied in 14 patients with severe intractable angina unresponsive to standard therapies including bypass grafting. After implantation of the neurostimulator units the patients were assessed by a symptom questionnaire, treadmill exercise testing and right atrial pacing. There was a significant improvement of symptoms and GTN consumption fell markedly. With the neurostimulator on, exercise duration increased from a mean (CI) of 414 (153) to 478 (149) s, and total ST segment depression was less both at maximum exercise (7.1 (4.5) vs 5.6 (4.2) mm) and at 90% of the maximum control heart rate (3.5 (3.7) vs 2.6 (4.3) mm), with similar rate-pressure product at maximum exercise. With right atrial pacing the maximum heart rate reached before onset of angina was increased (143 (14) to 150 (7) b.min-1) and total ST segment depression was less at all heart rates. Benefit has persisted in some patients for over 2 years without any apparent adverse sequelae. Epidural spinal electrical stimulation is, therefore, an alternative therapy for some patients with intractable angina which has not responded to standard therapies.