Photodynamic therapy with acridine orange in musculoskeletal sarcomas.

Limb salvage involving wide resection and reconstruction is now well established for managing musculoskeletal sarcomas. However, involvement of major nerves and vessels with a large volume of muscle and skin may result in a useless limb, contributing to depression and a low quality of life. We have been studying alternative treatments for musculoskeletal sarcoma since 1990, and have recently established a regime using photodynamic surgery with cells labelled with acridine orange, photodynamic therapy with cells treated similarly and radiodynamic treatment using the effect of X-rays on such cells. These techniques have been used after marginal or intralesional resection of tumours since 1999 and have enabled maintenance of excellent limb function in patients with sarcomas.

The impact of lesion length and vessel size on outcomes after sirolimus-eluting stent implantation for in-stent restenosis.

OBJECTIVES: We evaluated the predictors of recurrent restenosis and the impact of lesion length and vessel size on outcomes in patients treated with routine sirolimus-eluting stent (SES) implantation for in-stent restenosis (ISR) of bare-metal stent (BMS). METHODS: In this study, 250 consecutive patients with 275 lesions after SES implantation for ISR of BMS were enrolled. Follow-up angiogram was obtained in 239 patients with 258 lesions eight months after implantation (follow-up rate: 95.6%). We compared characteristics of patients and lesions between the two groups (the recurrent restenosis group and the no-restenosis group). RESULTS: Recurrent restenosis was angiographically documented in 43 lesions (16.7%). Recurrent restenosis was found in 30.4% with small vessel lesions (reference diameter of less than 2.5 mm, 92 lesions) and 23% with the diffuse type lesions (106 lesions). Seventy-two per cent of patients had a focal pattern of recurrent restenosis. Previously recurrent ISR lesions (odds ratio (OR) 1.94, 95% confidence interval (CI) 0.94 to 4.06, p = 0.05), reference diameter of less than 2.5 mm (OR 2.41, CI 1.05 to 5.41, p = 0.03), diffuse type restenosis (OR 4.48, CI 2.12 to 9.94, p = 0.0001) and dialysis patients (OR 4.72, CI 1.42 to 15.7, p = 0.01) were independent predictors of recurrent restenosis. CONCLUSIONS: Small vessels, diffuse type restenosis and dialysis patients were still the predictors of recurrent restenosis in patients treated with SES for ISR of BMS.

Cardiovascular beneficial effects of electroacupuncture at Neiguan (PC-6) acupoint in anesthetized open-chest dog.

Neiguan (PC-6) is a traditional acupoint in the bilateral forearms, overlying the median nerve trunk. Neiguan electroacupuncture (EA) has been believed to affect cardiovascular function and used in traditional Chinese medicine to improve or treat a wide range of health conditions and diseases, including angina pectoris, myocardial infarction, hypertension, and hypotension. However, few physiological studies have assessed the beneficial effects of Neiguan EA on the cardiovascular function. In the present study, we investigated its effects on the cardiovascular function in normal open-chest dogs under pentobarbital and fentanyl anesthesia. We also obtained left ventricular (LV) pressure-volume (P-V) data with a micromanometer catheter and a volumetric conductance catheter. Mean arterial pressure, end-diastolic volume, heart rate, stroke volume, cardiac output, and end-systolic pressure gradually decreased by 5 to 10% over 1.5 h without Neiguan EA. Neiguan EA at 40 Hz, however, increased these cardiovascular variables by 10 to 15%, especially end-systolic elastance (Ees) by 40% (p<0.05) over 15 to 60 min. After Neiguan EA was stopped at 1 h, these facilitated cardiovascular variables decreased below the pre-EA level. This beneficial effect of electroacupuncture may contribute to the effectiveness of the acupuncture in Chinese medicine.

A new integrative method to quantify total Ca2+ handling and futile Ca2+ cycling in failing hearts.

Ca2+ handling in excitation-contraction coupling requires considerable O2 consumption (VO2) in cardiac contraction. We have developed an integrative method to quantify total Ca2+ handling in normal hearts. However, its direct application to failing hearts, where futile Ca2+ cycling via the Ca2+-leaky sarcoplasmic reticulum (SR) required an increased Ca2+ handling VO2, was not legitimate. To quantify total Ca2+ handling even in such failing hearts, we combined futile Ca2+ cycling with Ca2+ handling VO2 and the internal Ca2+ recirculation fraction via the SR. We applied this method to the canine heart mechanoenergetics before and after intracoronary ryanodine at nanomolar concentrations. We found that total Ca2+ handling per beat was halved after the ryanodine treatment from approximately 60 micromol/kg left ventricle before ryanodine. We also found that futile Ca2+ cycling via the SR increased to >1 cycle/beat after ryanodine from presumably zero before ryanodine. These results support the applicability of the present method to the failing hearts with futile Ca2+ cycling via the SR.

Effects of thapsigargin and KCl on the O2 use of the excised blood-perfused rat heart.

We have already reported a curvilinear end-systolic pressure-volume relation and a linear oxygen consumption per beat (Vo2)-systolic pressure-volume area (PVA) relation of the left ventricle in the rat blood-perfused whole heart preparation. Recently, we have proposed that a PVA at an appropriate left-ventricular end-diastolic volume (0.15 ml/g), such as PVA0.15 and the Vo2 intercept (minimally loaded Vo2) of the Vo2-PVA relation, can be good indexes for assessing rat left-ventricular mechanoenergetics. The minimally-loaded Vo2 would mainly consist of Vo2 for Ca 2+ handling in the excitation-contraction (E-C) coupling and basal metabolism. However, the fraction of the Vo2 by the sarcoplasmic reticulum (SR) Ca2+-ATPase in the total Ca2+ handling Vo2 has not yet been examined. To study this for the first time, we investigated the effects of thapsigargin and KCl on left-ventricular mechanoenergetics. Blockade of the SR Ca2+ pump by thapsigargin (2.5 micromol/l) decreased PVA 0. 15 by 65% and decreased the Vo2 intercept by 40% without a change in the slope of the Vo2-PVA relation. We measured the basal metabolic Vo2 by intracoronary KCl and found a 75% decrease in the Vo2 intercept. We conclude that the minimally-loaded Vo2 mainly consists of Vo2 for Ca2+ handling in the E-C coupling (at least 40% is consumed by the SR Ca2+ ATPase) and basal metabolism (25%).

Linear O2 use-pressure-volume area relation from curved end-systolic pressure-volume relation of the blood-perfused rat left ventricle.

We measured rat left ventricular pressure, volume, and oxygen consumption ( = arteriovenous oxygen content differencexcoronary flow) to establish a new evaluation of its mechanoenergetics in the whole heart preparation by using the cross-circulation method. We obtained a curved end-systolic pressure-volume relation in contrast to a linear end-systolic pressure-volume relation in dogs, rabbits, and humans. However, we obtained a linear oxygen consumption per beat (VO2)-systolic pressure-volume area (PVA, a measure of left ventricular total mechanical energy per beat) relation as in other species. Thus PVA can be a good index for assessing rat left ventricular mechanoenergetics. The VO2 intercept and slope of the linear VO2-PVA relation correspond to those in other species. Intracoronary calcium elevated the curved end-systolic pressure-volume relation and significantly increased PVA at 0.15 ml/g of left ventricular end-diastolic volume (PVA0.15) by 50%. Calcium also significantly increased the VO2 intercept of the VO2-PVA relation by 30% without a change in its slope. We conclude that the rat left ventricular end-systolic pressure-volume relation is curved, but the VO2-PVA relation is linear, and that the VO2 intercept is mainly composed of PVA-independent VO2, presumably VO2 for Ca2+ handling in the excitation-contraction coupling and basal metabolism. Therefore we propose PVA at an appropriate left ventricular volume and the VO2 intercept as good rat left ventricular mechanoenergetic indexes despite the nonlinearity of the end-systolic pressure-volume relation.

Calcium equally increases the internal calcium recirculation fraction before and after beta-blockade in canine left ventricles.

We studied whether intracoronary Ca administration after beta-blockade would increase the internal Ca recirculation fraction (RF) analogously to the Ca administration before beta-blockade. This was performed in excised cross-circulated canine hearts. We analyzed the exponential decay component of the postextrasystolic potentiation (PESP) following a spontaneous extrasystole. All the PESPs decayed in alternans with atrial pacing at a constant rate. We obtained the time constant (tau(e)) of the monoexponential decay component of the alternans PESP. An increment of intracoronary Ca by 1.5 mmol/l enhanced the left ventricular contractility index Emax (end-systolic maximum elastance) by 2.5 times before and after beta-blockade with propranolol. The intracoronary Ca after beta-blockade slightly but significantly increased tau(e), and hence increased RF calculated from tau(e) by RF = exp(-1/tau(e)). This was analogous to the slightly increased tau(e) and RF with Ca before beta-blockade. We speculate that the myocardial cyclic AMP-dependent phosphorylation level would not significantly alter the effect of intracoronarily administered Ca on myocardial Ca handling, in terms of tau(e) and RF.

Ryanodine decreases internal Ca2+ recirculation fraction of the canine heart as studied by postextrasystolic transient alternans.

We tested our hypothesis that the O2 wasting of Ca2+ handling in the excitation-contraction (E-C) coupling in ryanodine-treated failing hearts could be reflected by a decrease in the internal Ca2+ recirculation fraction (RF). We have reported, using canine excised cross-circulated hearts, that intracoronary ryanodine (40 nmol/l blood) halved left ventricular contractility without decreasing myocardial O2 consumption for the E-C coupling. We previously suspected this mechanoenergetic state to manifest energy wasting of Ca2+ handling due to ryanodine causing leakage of Ca2+ from the sarcoplasmic reticulum. To test this hypothesis, we analyzed all the sporadic spontaneous cases of postextrasystolic potentiation (PESP) obtained during the ryanodine experiments. We calculated RF from the beat constant of the exponential decay component of not only the monotonic type but also the transient alternans type of PESP. Results showed that ryanodine significantly decreased the beat constant in both types of PESP from about 2 to 1.5 beats and hence RF from 0.6 to 0.5 on the average, supporting the hypothesis. This organ-level systems approach to Ca2+ handling using transient alternans PESP as well as monotonic PESP may help obtain better insights into the mechanoenergetics of failing hearts.