Dietary nitrate supplementation opposes the elevated diaphragm blood flow in chronic heart failure during submaximal exercise.

Chronic heart failure (CHF) results in a greater cost of breathing and necessitates an elevated diaphragm blood flow (BF). Dietary nitrate (NO3‾) supplementation lowers the cost of exercise. We hypothesized that dietary NO3‾ supplementation would attenuate the CHF-induced greater cost of breathing and thus the heightened diaphragm BF during exercise. CHF rats received either 5days of NO3‾-rich beetroot (BR) juice (CHF+BR, n=10) or a placebo (CHF, n=10). Respiratory muscle BFs (radiolabeled microspheres) were measured at rest and during submaximal exercise (20m/min, 5% grade). Infarcted left ventricular area and normalized lung weight were not significantly different between groups. During submaximal exercise, diaphragm BF was markedly lower for CHF+BR than CHF (CHF+BR: 195±28; CHF: 309±71mL/min/100g, p=0.04). The change in diaphragm BF from rest to exercise was less (p=0.047) for CHF+BR than CHF. These findings demonstrate that dietary NO3‾ supplementation reduces the elevated diaphragm BF during exercise in CHF rats thus providing additional support for this therapeutic intervention in CHF.

Suitability of the pericardiophrenic veins for phrenic nerve stimulation: an anatomic study.

OBJECTIVE: The objective of this study was to assess the potential of the pericardiophrenic veins (PPVs) as conduits for transvenous stimulation of the phrenic nerves. Modulating respiration with transvenous phrenic nerve stimulation via the PPVs might reduce or eliminate the adverse effects of central sleep apnea in heart failure. METHODS: Forty-eight fixed cadavers were dissected to study the anatomic characteristics of the PPVs and related neurovascular structures. RESULTS: The right PPV, found in only 1 of 35 cadavers, was <0.5 mm diameter. The left PPV, located in all 48 cadavers, drained into the left brachiocephalic vein (BCV) directly or into the BCV via the superior intercostal vein (SICV). Mean ± SD SICV trunk diameter was 4 ± 2 mm. Mean ± SD left PPV diameter was 2 ± 1 mm. The length between the point of separation of the left PPV from the phrenic nerve to its junction with the BCV or SICV trunk ranged from 6 to 40 mm. The angle of approach, defined as the angle formed by the intersection of the longitudinal axis of the BCV and the longitudinal axis of the PPV or SICV trunk, and which represents the angle that would need to be navigated when inserting a stimulation lead into the PPV using a peripheral cannulation approach, was 99 ± 28 degrees. Valves were identified in 54% of left PPVs. CONCLUSIONS: Because of its extremely small size, the right PPV appears unsuitable for transvenous phrenic nerve stimulation. In contrast, the left PPV may be accessible via the left BCV using standard transvenous catheterization techniques; however, the small caliber of the left PPV and the frequent presence of valves within it might pose challenges in navigating the vessel to achieve transvenous phrenic nerve stimulation.

Interleukin-6 causes myocardial failure and skeletal muscle atrophy in rats.

BACKGROUND: The impact of interleukin (IL)-6 on skeletal muscle function remains the subject of controversy. METHODS AND RESULTS: The effects of 7-day subcutaneous administration of recombinant human IL-6 were examined at 3 doses, 50, 100, or 250 microg x kg(-1) x d(-1), in rats. Skeletal muscle mass decreased dose-dependently (with increasing dose: in the diaphragm, -10%, P=NS; -15%, P=0.0561; and -15% P<0.05; and in the gastrocnemius, -9%, P=NS; -9%, P=NS; and -18%, P<0.005) because of decreases in cross-sectional area of all fiber types without alterations in diaphragm contractile properties. Cardiovascular variables showed a dose-dependent heart dilatation (for end-diastolic volume: control, 78 microL; moderate dose, 123 microL; and high dose, 137 microL, P<0.001), reduced end-systolic pressure (control, 113 mm Hg; moderate dose, 87 mm Hg; and high dose, 90 mm Hg; P=0.037), and decreased myocardial contractility (for preload recruitable stroke work: control, 79 mm Hg; moderate dose, 67 mm Hg; and high dose, 48 mm Hg; P<0.001). Lung edema was confirmed by an increased wet-to-dry ratio (control, 4.2; moderate dose, 4.6; and high dose, 4.5; P<0.001) and microscopy findings. These cardiovascular alterations led to decreases in organ blood flow, particularly in the diaphragm (control, 0.56 mL x min(-1) x g(-1); moderate dose, 0.21 mL x min(-1) x g(-1); and high dose, 0.23 mL x min(-1) x g(-1); P=0.037). In vitro recombinant human IL-6 administration did not cause any alterations in diaphragm force or endurance capacity. CONCLUSIONS: IL-6 clearly caused ventilatory and peripheral skeletal muscle atrophy, even after short-term administration. Blood flow redistribution, resulting from the myocardial failure induced by IL-6, was likely responsible for this muscle atrophy, because IL-6 did not exert any direct effect on the diaphragm.

Pulmonary complications after hepatic artery chemoembolization or infusion via the inferior phrenic artery for primary liver cancer.

PURPOSE: The purpose of this study was to determine the frequency, patterns of disease, and risk factors for development of pulmonary complications after liver chemoembolization via the inferior phrenic artery (IPA). MATERIALS AND METHODS: Forty-four selective transcatheter hepatic chemoembolization (THCE) procedures via the IPA were performed in patients with primary liver cancers with use of a mixture of anticancer agents and iodized oil (Lipiodol) with or without transcatheter arterial embolization. The grades of pulmonary complications were assessed on triphasic helical computed tomographic (CT) images after THCE and were correlated with angiographic findings of the IPA, infused dosages of Adriamycin and Lipiodol, and hepatic venous tumor thrombus on triphasic CT images before THCE. RESULTS: THCE via the IPA frequently resulted in lung CT changes: Lipiodol accumulation in the lung field (52%), consolidation (68%), and pleural effusion (41%). Among 44 patients, two (5%) developed respiratory symptoms. An excellent correlation was shown between Lipiodol accumulation and the presence of angiographic abnormalities of the IPA (P <.005). A significant correlation was also shown between the grades of pulmonary complications and the numbers of angiographic abnormalities (P <.01). The grades of pulmonary complications increased according to the infused dosage of Adriamycin and Lipiodol (P <.05). CONCLUSIONS: Angiographic abnormalities such as arteriovenous shunts, dilated anastomotic branches, and dense pleural staining are important risk factors for pulmonary complications of THCE via the IPA. Embolization for shunts may be required to prevent such complications, especially in cases with shunts to pulmonary vessels or hepatic veins.

Effect of alpha-adrenoreceptor stimulation on the diaphragmatic oxygen delivery-consumption relationship.

PURPOSE: In the vascularly isolated canine hemidiaphragm, we tested the hypothesis that alpha-adrenoreceptor stimulation may influence diaphragmatic function and O2 extraction during reductions in O2 delivery (QO2di). METHODS: The diaphragm was perfused using a constant flow pump with blood diverted from the left femoral artery. QO2di was reduced in a stepwise fashion by progressive reductions in pump flow. The tension generated by the contracting diaphragm (3 Hz), the critical O2 delivery (QO2di,c) below which O2 consumption (VO2di) becomes dependent on O2 supply and the oxygen extraction ratio at this critical point (ERc) were assessed in two groups of animals. Phenylephrine (10(-5) mol/L) was infused into the phrenic artery in one group and saline was infused in another group. RESULTS: In the contracting diaphragm, VO2di was higher in the phenylephrine infused group than in the control group (5.2 +/- 0.5 vs 2.11 +/- 0.3 mL/min/100 g). QO2di,c and ERc were also higher in the phenylephrine group than in the control group (6.16 +/- 0.43 vs 3.1 +/- 0.5 mL/min/100 g and 0.87 +/- 0.035 vs 0.63 +/- 0.05, respectively). In the resting diaphragm, VO2di was not significantly different between the two groups and no critical oxygen delivery could be identified in either group. CONCLUSIONS: These results indicate that alpha-adrenoreceptor activation may increase the tension generated by the diaphragm as well as its oxygen consumption and oxygen extraction. Although this may be beneficial during moderate reductions in oxygen delivery, in more severe shock states, activation of these receptors by endogenous or exogenously administered catecholamines may hasten the development of delivery limitation of VO2di and compromise the ability to sustain ventilation.