Modifying pulmonary ischemia-reperfusion injury by altering ventilatory strategies during ischemia.

We used an intact in vivo canine model of pulmonary ischemia-reperfusion (IR) injury to evaluate the differential effects of alveolar hypoxia and ventilation during 2 h of unilateral warm lung ischemia. Serial measurements of regional pulmonary blood flow, extravascular density (EVD), and transcapillary protein flux were made after reperfusion with the quantitative imaging technique of positron emission tomography. Twenty-seven animals were divided into five experimental groups: VENT O2 (n = 5) in which the left lung was ventilated with 40% O2 during ischemia, STATIC O2 (n = 4) in which the left lung was statically inflated with 40% O2 during ischemia, VENT N2 (n = 5) in which the left lung was ventilated with 100% N2 during ischemia, VENT N2/CO2 (n = 5) in which the left lung was ventilated with 95% N2-5% CO2 during ischemia, and STATIC N2 (n = 8) in which the left lung was statically inflated with 100% N2 during ischemia. These groups were compared with a control group (CONT, = 3) that was studied previously. Protein flux was significantly increased in the previous ischemic lung only for the STATIC N2 group [median 175 x 10(-4) min-1 (range 53-1,217) for the STATIC N2 group vs. 50 x 10(-4) min-1 (range 40-56) for the CONT group] 0.25 h after reperfusion and did not change over 3 h. EVD also increased but not significantly. Protein flux and EVD in the other groups were not different from CONT.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fistula from left main coronary artery to pulmonary trunk

Netherlands Heart Journal -     

Banding of the pulmonary artery in infancy: selection of patients and results of main pulmonary artery banding in the treatment of congenital heart disease.

Patterns of blood flow were examined in the surface vessels of the surgically exposed brain by intracarotid injection of 1% fluorescein and rapid serial photographs timed by a photo-cell signal. Matching colour filters were used for black and white or Ektachrome film.As developed in cats and monkeys, and applied in five patients during craniotomy, the technique gave a picture of flow patterns in the pial and cortical vascular bed, demonstrating “water-shed” areas bordering major arterial territories, laminar flow in veins, and, in particular, the details of filling and clearing in the fine pial vessels, the superficial cortical capillary bed and in the vascular beds of tumours.Since these features are rendered in finer detail and sharper contrast than by standard x-ray angiography, the method affords a new means of more adequately examining the epicerebral circulation in man during craniotomy for a variety of lesions.     

Opening the pericardium during pulmonary artery constriction improves cardiac function.

During acute pulmonary hypertension, both the pericardium and the right ventricle (RV) constrain left ventricular (LV) filling; therefore, pericardiotomy should improve LV function. LV, RV, and pericardial pressures and RV and LV dimensions and LV stroke volume (SV) were measured in six anesthetized dogs. The pericardium was closed, the chest was left open, and the lungs were held away from the heart. Data were collected at baseline, during pulmonary artery constriction (PAC), and after pericardiotomy with PAC maintained. PAC decreased SV by one-half. RV diameter increased, and septum-to-LV free wall diameter and LV area (our index of LV end-diastolic volume) decreased. Compared with during PAC, pericardiotomy increased LV area and SV increased 35%. LV and RV compliance (pressure-dimension relations) and LV contractility (stroke work-LV area relations) were unchanged. Although series interaction accounts for much of the decreased cardiac output during acute pulmonary hypertension, pericardial constraint and leftward septal shift are also important. Pericardiotomy can improve LV function in the absence of other sources of external constraint to LV filling.     

Assessment of brachial artery blood flow across the cardiac cycle: retrograde flows during cycle ergometry.

We describe a novel software system that utilizes automated algorithms to perform edge detection and wall tracking of high-resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, to calculate conduit arterial blood flow (BF) across the cardiac cycle. Furthermore, we describe changes in brachial arterial BF to the resting forearm during incremental cycle ergometry in eight subjects. During exercise, peak BF during the cardiac cycle increased at each workload (P < 0.001), because of increased velocity in the presence of unaltered cross-sectional area. In contrast, mean BF calculated across each cardiac cycle decreased at lower workloads before increasing at 100 and 160 W (P < 0.001). Differences in the pattern of peak and mean cardiac cycle flows were due to the influence of retrograde diastolic flow, which had a larger impact on mean flows at lower workloads. In conclusion, BF can be measured with high temporal resolution across the cardiac cycle in humans. Resting brachial arterial flow, including retrograde flow, increases during lower limb exercise.     

Effect of menstrual cycle phase on the ventilatory response to rising body temperature during exercise

To examine the effect of menstrual cycle on the ventilatory sensitivity to rising body temperature, ten healthy women exercised for ~60 min on a cycle ergometer at 50% of peak oxygen uptake during the follicular and luteal phases of their cycle. Esophageal temperature, mean skin temperature, mean body temperature, minute ventilation, and tidal volume were all significantly higher at baseline and during exercise in the luteal phase than the follicular phase. On the other hand, end-tidal partial pressure of carbon dioxide was significantly lower during exercise in the luteal phase than the follicular phase. Plotting ventilatory parameters against esophageal temperature revealed there to be no significant menstrual cycle-related differences in the slopes or intercepts of the regression lines, although minute ventilation and tidal volume did significantly differ during exercise with mild hyperthermia. To evaluate the cutaneous vasodilatory response, relative laser-Doppler flowmetry values were plotted against mean body temperature, which revealed that the mean body temperature threshold for cutaneous vasodilation was significantly higher in the luteal phase than the follicular phase, but there were no significant differences in the sensitivity or peak values. These results suggest that the menstrual cycle phase influences the cutaneous vasodilatory response during exercise and the ventilatory response at rest and during exercise with mild hyperthermia, but it does not influence ventilatory responses during exercise with moderate hyperthermia.     

Chronic hypoxia-induced spontaneous and rhythmic contractions in the rat main pulmonary artery

The effect of chronic hypoxia (CH; 1-4 wk) on the electromechanical properties of the rat main pulmonary artery (MPA) was investigated. MPA rings obtained from rats exposed for 14 days to hypobaric (50.5 kPa) CH exhibited spontaneous and rhythmic contractions (SRCs) that were never observed in control (normoxic) rats. SRCs were unaffected by tetrodotoxin, phentolamine, BQ-123 and BQ-788, N-nitro-L-arginine methyl ester, or endothelium removal. CH depolarized smooth muscle cells from -58.8 +/- 9 to -38.6 +/- 5.4 mV and increased the resting cytosolic Ca2+ concentration from 67.3 +/- 11.9 to 112.5 +/- 16.4 nM. CH also induced spontaneous spikelike depolarizations. All of these effects were inhibited by external Ca2+ removal or nifedipine (1 microM). Moreover, depletion of intracellular Ca2+ stores with ryanodine (1-5 microM) or cyclopiazonic acid (3 microM) progressively attenuated SRCs. This study demonstrates that CH switches the MPA from a quiescent to a spontaneously active mechanical state. Finally, the fact that SRCs precede the development of right ventricle hypertrophy and disappear when this hypertrophy reaches a maximal value (after 3-4 wk of CH) suggests that SRCs may play a role in the adaptive process of the pulmonary circulation to CH.     

Improved pulmonary artery buffering function during phenylephrine-induced pulmonary hypertension

The goal of this study was to determine the in vivo pulmonary arterial buffering function (BF) during acute and moderate pulmonary hypertension achieved by phenylephrine-induced smooth muscle activation.Pulmonary pressure (Konigsberg P7) and diameter (sonomicrometry) were measured in nine anesthetized sheep. Transit pulmonary arterial hypertension was induced by mechanical occlusion of the pulmonary artery (HP) and by phenylephrine infusion (5 g/kg/min) (PHE). A viscoelastic Kelvin-Voigt model was used. By increasing the values of the viscous modulus, the pressure-diameter hysteresis area was reduced to a minimum in order to obtain the purely elastic pressure-diameter relationship. The elastic index (E) was calculated as the first derivative of the exponential model of the purely elastic pressure-diameter relationship at the mean pressure point.Systolic, diastolic, mean and pulse pressures were similar during HP and PHE, but significantly higher with regard to control steady state. In HP, E and arterial diameter (both its minimum and maximum values) increased significantly. In contrast, when pulmonary hypertension was induced by VSM activation, E was maintained concomitantly with pulmonary artery vasoconstriction.Pulmonary hypertension produced by occlusion of the pulmonary artery increases elasticity. Smooth muscle activation may offset the deleterious effect of pulmonary hypertension on arterial wall elasticity by reducing E and impeding arterial dilatation and collagen recruitment, maintaining BF during pulmonary hypertension.     

Resting and exercise ventilatory chemosensitivity across the menstrual cycle

We hypothesized that resting and exercise ventilatory chemosensitivity would be augmented in women when estrogen and progesterone levels are highest during the luteal phase of the menstrual cycle. Healthy, young females (n = 10; age = 23 ± 5 yrs) were assessed across one complete cycle: during early follicular (EF), late follicular (LF), early luteal, and mid-luteal (ML) phases. We measured urinary conjugates of estrogen and progesterone daily. To compare values of ventilatory chemosensitivity and day-to-day variability of measures between sexes, males (n = 10; age = 26 ± 7 yrs) were assessed on 5 nonconsecutive days during a 1-mo period. Resting ventilation was measured and hypoxic chemosensitivity assessed using an isocapnic hypoxic ventilatory response (iHVR) test. The hypercapnic ventilatory response was assessed using the Read rebreathing protocol and modified rebreathing tests. Participants completed submaximal cycle exercise in normoxia and hypoxia. We observed a significant effect of menstrual-cycle phase on resting minute ventilation, which was elevated in the ML phase relative to the EF and LF phases. Compared with males, resting end-tidal CO(2) was reduced in females during the EF and ML phases but not in the LF phase. We found that iHVR was unaffected by menstrual-cycle phase and was not different between males and females. The sensitivity to chemical stimuli was unaffected by menstrual-cycle phase, meaning that any hormone-mediated effect is of insufficient magnitude to exceed the inherent variation in these chemosensitivity measures. The ventilatory recruitment threshold for CO(2) was generally lower in women, which is suggestive of a hormonally related lowering of the ventilatory recruitment threshold. We detected no effect of menstrual-cycle phase on submaximal exercise ventilation and found that the ventilatory response to normoxic and hypoxic exercise was quantitatively similar between males and females. This suggests that feed-forward and feed-back influences during exercise over-ride the effects of naturally occurring changes in sex hormones.     

Effect of the mechanical ventilatory cycle on thermodilution right ventricular volumes and cardiac output.

The purpose of this study was to evaluate right ventricular (RV) loading and cardiac output changes, by using the thermodilution technique, during the mechanical ventilatory cycle. Fifteen critically ill patients on mechanical ventilation, with 5 cmH(2)O of positive end-expiratory pressure, mean respiratory frequency of 18 breaths/min, and mean tidal volume of 708 ml, were studied with help of a rapid-response thermistor RV ejection fraction pulmonary artery catheter, allowing 5-ml room-temperature 5% isotonic dextrose thermodilution measurements of cardiac index (CI), stroke volume (SV) index, RV ejection fraction (RVEF), RV end-diastolic volume (RVEDV), and RV end-systolic volume (RVESV) indexes at 10% intervals of the mechanical ventilatory cycle. The ventilatory modulation of CI and RV volumes varied from patient to patient, and the interindividual variability was greater for the latter variables. Within patients also, RV volumes were modulated more by the ventilatory cycle than CI and SV index. Around a mean value of 3.95 +/- 1.18 l. min(-1). m(-2) (= 100%), CI varied from 87.3 +/- 5.2 (minimum) to 114.3 +/- 5.1% (maximum), and RVESV index varied between 61.5 +/- 17.8 and 149.3 +/- 34.1% of mean 55.1 +/- 17.9 ml/m(2) during the ventilatory cycle. The variations in the cycle exceeded the measurement error even though the latter was greater for RVEF and volumes than for CI and SV index. For mean values, there was an inspiratory decrease in RVEF and increase in RVESV, whereas a rise in RVEDV largely prevented a fall in SV index. We conclude that cyclic RV afterloading necessitates multiple thermodilution measurements equally spaced in the ventilatory cycle for reliable assessment of RV performance during mechanical ventilation of patients.