Inhaled nitric oxide reverses cell-free hemoglobin-induced pulmonary hypertension and decreased lung compliance. Preliminary results

Background

In order to test the hypothesis that inhaled nitric oxide (NO) reverses the pulmonary hypertension induced by αα-diaspirin crosslinked hemoglobin (ααHb), were studied anesthetized pigs that were administered with a total dose of 200 mg/kg of 10% ααHb. Inhaled NO (5 ppm) was administered for 10 min, and then discontinued for 10 min. This cycle was then repeated with 10 ppm inhaled NO.

Results

ααHb caused pulmonary arterial pressure (PAP) to increase from 27 ± 1.7 to 40 ± 3.0 mmHg (P<0.05) and dynamic lung compliance to decrease from 29± 1.5 to 23± 1.6 ml/cmH₂O (P < 0.05). After both doses of inhaled NO, but particularly 10 ppm, PAP was reduced (P < 0.05) and lung compliance increased (P < 0.05) from the ααHb levels. When inhaled NO was discontinued PAP again increased and lung compliance decreased to levels significantly different from baseline (P < 0.05).

Conclusion

We conclude that cell-free hemoglobin-induced pulmonary hypertension and decreased lung compliance can be selectively counteracted by inhaled NO.     

多层螺旋CT灌注成像对肺栓塞-再灌注损伤的实验研究

目的应用CT灌注成像技术量化评价肺栓塞再灌注损伤,探讨肺栓塞再灌注损伤形成机制。方法选择14只健康杂种犬为实验对象。利用SwanGanz导管模拟肺膈叶动脉栓塞再灌注。栓塞前、栓塞24h和再通4h要分别进行肺动脉压测定、CT灌注成像和血清超氧化物歧化酶(SOD)的测定。结果再灌注肺损伤主要表现为急性渗透性肺水肿。再灌注损伤肺的BF[(325.69±134.00)ml·min-1·100g-1)]和MTT[(1.98±0.44)s]与栓塞前正常基线值[(409.58±88.42)ml·min-1·100g-1)和(1.87±0.48)s]的差异具有统计学意义(P<0.01和P<0.05)。再灌注4h的肺动脉压[(25.79±6.25)mmHg]和超氧化物歧化酶的平均值[(388.79±25.07)U/ml]与栓塞前正常基线值[(22.31±3.77)mmHg和(404.38±23.81)U/ml]相比均具有统计学差异(P<0.05和P<0.05)。再灌注损伤侧肺的湿/干重比率(6.29±1.23)显著大于对侧肺(4.54±1.19),其差异也具有统计学意义(P<0.01),说明再灌注水肿增加了肺组织的含水量。结论CT灌注成像有效反映肺栓塞再灌注损伤的血流动力学改变。氧自由基对肺栓塞再灌注损伤的形成起重要作用。     

A comparison of echocardiography to invasive measurement in the evaluation of pulmonary arterial hypertension in a rat model

Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by progressive elevation in pulmonary artery pressure (PAP) and total pulmonary vascular resistance (TPVR). Recent advances in imaging techniques have allowed the development of new echocardiographic parameters to evaluate disease progression. However, there are no reports comparing the diagnostic performance of these non-invasive parameters to each other and to invasive measurements. Therefore, we investigated the diagnostic yield of echocardiographically derived TPVR and Doppler parameters of PAP in screening and measuring the severity of PAH in a rat model. Serial echocardiographic and invasive measurements were performed at baseline, 21 and 35 days after monocrotaline-induction of PAH. The most challenging echocardiographic derived TPVR measurement had good correlation with the invasive measurement (r = 0.92, P < 0.001) but also more simple and novel parameters of TPVR were found to be useful although the non-invasive TPVR measurement was feasible in only 29% of the studies due to lack of sufficient tricuspid valve regurgitation. However, echocardiographic measures of PAP, pulmonary artery flow acceleration time (PAAT) and deceleration (PAD), were measurable in all animals, and correlated with invasive PAP (r = ?0.74 and r = 0.75, P < 0.001 for both). Right ventricular thickness and area correlated with invasive PAP (r = 0.59 and r = 0.64, P < 0.001 for both). Observer variability of the invasive and non-invasive parameters was low except in tissue-Doppler derived isovolumetric relaxation time. These non-invasive parameters may be used to replace invasive measurements in detecting successful disease induction and to complement invasive data in the evaluation of PAH severity in a rat model.     

Mental stress increases right heart afterload in severe pulmonary hypertension

Little is known about mental stress effects on the pulmonary circulation in health and disease. The current study was conducted to investigate whether pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) would further increase during standardized mental stress testing in patients with severe pulmonary hypertension. The study was a prospective analysis of seven patients (average age: 40 years, range from 21 to 56 years) with severe pulmonary hypertension (primary: n=4, secondary forms: n=3; resting mean pulmonary artery pressure ranged between 48 and 65 mmHg). Right heart catheterization for the determination of PAP, pulmonary capillary wedge pressure (PCW) and cardiac output (CO) was clinically indicated (diagnostic work‐up, acute drug testing). Patients accomplished a standardized 10 min mental stress test (computer based, adaptive complex reaction‐time task). Pulmonary haemodynamics during stress were compared to resting baseline. During mental stress mean PAP (±SEM) increased by 9·4 ± 2·1 mmHg (P<0·005). Pulmonary vascular resistance increased by 149 ± 25 dyne s cm^–5 (P<0·001). Stroke volume decreased by 6·6 ± 2·2 ml (P<0·03). The data show that moderate mental stress increases right heart afterload in patients with severe pulmonary hypertension owing to elevation of PVR.     

The role of endothelin-1 as a mediator of the pressure response after air embolism in blood perfused lungs

Objective: It is well known that lung embolism is associated with an increase in pulmonary vascular resistance. Since the mechanisms of pulmonary vascular reactions during embolism are still unclear, the aim of this study was to investigate the potential involvement of endothelin-1 (ET-1) and thromboxane A₂ (TXA₂) as mediators of the pulmonary artery pressure (PAP) increase after embolism using the selective ET_A receptor antagonist LU135 252 [1], the ET_B receptor antagonist BQ788 [2], and the cyclooxygenase inhibitor diclofenac. Design: Prospective experimental study in rabbits. Setting: Experimental laboratory in a university teaching hospital. Subjects: 36 adult rabbits of either sex. Interventions: The experiments were performed in 36 isolated and ventilated rabbit lungs which were perfused with a buffer solution containing 10 % of autologous blood. Embolism was induced by the injection of 0.75 ml air into the pulmonary artery. Measurements and results: PAP and lung weight, reflecting edema formation, were continuously recorded. Perfusate samples were drawn intermittently to determine TXA₂ and ET-1 concentrations. Air injection resulted in an immediate increase in PAP up to 22.8 ± 1.4 mm Hg at 2.5 min (control, n = 6), which was parallelled by an enhanced generation of TXA₂. No relevant edema formation occurred during the observation period. Pretreatment with the ET_A receptor antagonist LU135 252 significantly reduced the pressure reaction after air embolism (p < 0.001) whereas the ET_B receptor antagonist BQ788 (n = 6) was without marked effects. The administration of diclofenac (n = 6) did not alter the PAP increase 2.5 min after embolism, but significantly reduced the pressure reaction during the further observation period (p < 0.001). The application of LU135 252 and diclofenac together (n = 6) also significantly reduced the PAP increase from 2.5 min during the total observation period (p < 0.001). Conclusions: The acute pressure reaction after air embolism is mainly mediated via ET-1 by an ET_A receptor related mechanism. TXA₂ seems to maintain this reaction for a longer time. Received: 11 July 1997 Accepted: 27 February 1998     

The importance of trabecular hypertrophy in right ventricular adaptation to chronic pressure overload

To assess the contribution of right ventricular (RV) trabeculae and papillary muscles (TPM) to RV mass and volumes in controls and patients with pulmonary arterial hypertension (PAH). Furthermore, to evaluate whether TPM shows a similar response as the RV free wall (RVFW) to changes in pulmonary artery pressure (PAP) during follow-up. 50 patients underwent cardiac magnetic resonance (CMR) and right heart catheterization at baseline and after one-year follow-up. Furthermore 20 controls underwent CMR. RV masses were assessed with and without TPM. TPM constituted a larger proportion of total RV mass and RV end-diastolic volume (RVEDV) in PAH than in controls (Mass: 35 ± 7 vs. 25 ± 5 %; p < 0.001; RVEDV: 17 ± 6 vs. 12 ± 6 %; p = 0.003). TPM mass was related to the RVFW mass in patients (baseline: R = 0.65; p < 0.001; follow-up: R = 0.80; p < 0.001) and controls (R = 0.76; p < 0.001). In PAH and controls, exclusion of TPM from the assessment resulted in altered RV mass, volumes and function than when included (all p < 0.01). Changes in RV TPM mass (β = 0.44; p = 0.004) but not the changes in RVFW mass (p = 0.095) were independently related to changes in PAP during follow-up. RV TPM showed a larger contribution to total RV mass in PAH (~35 %) compared to controls (~25 %). Inclusion of TPM in the analyses significantly influenced the magnitude of the RV volumes and mass. Furthermore, TPM mass was stronger related to changes in PAP than RVFW mass. Our results implicate that TPM are important contributors to RV adaptation during pressure overload and cannot be neglected from the RV assessment.     

Attenuation of the side effect profile of regadenoson: a randomized double-blind placebo-controlled study with aminophylline in patients undergoing myocardial perfusion imaging and have severe chronic kidney disease—the ASSUAGE-CKD trial

A subgroup analysis of the ASSUAGE trial suggested that the standardized intravenous aminophylline administration following regadenoson-stress leads to substantial attenuation of regadenoson adverse-effects in patients with severe chronic kidney disease (CKD). In a randomized, double-blinded, placebo-controlled clinical trial of patients with stage 4 and 5 CKD, we compared the frequency and severity of regadenoson adverse-effects in those who received 75 mg of intravenous aminophylline versus a matching placebo administered 90 s post-radioisotope injection. Consecutive 300 patients with severe CKD (36 % women; 86 % end-stage renal disease; age 55 (±13) years) were randomized to receive aminophylline (n = 150) or placebo (n = 150). In the aminophylline arm, there was 65 % reduction in the incidence of the primary endpoint of diarrhea (9 (6.0 %) vs. 26 (17.3 %), P = 0.002), 51 % reduction in the secondary endpoint of any regadenoson adverse-effect (47 (31.3 %) vs. 96 (64 %), P < 0.001) and 70 % reduction in headache (16 (10.7 %) vs. 54 (36 %), P < 0.001). The stress protocol was better tolerated in the aminophylline group (P = 0.008). The quantitative summed difference score, as a measure of stress-induced ischemic burden, was similar between the study groups (P = 0.51). In conclusion, the routine standardized administration of intravenous aminophylline in patients with severe CKD substantially reduces the frequency and severity of the adverse-effects associated with regadenoson-stress without changing the ischemic burden. [NCT01336140]     

Assessment of pulmonary arterial stiffness in obstructive sleep apnea

Pulmonary hypertension (PH) is one of the major complications of obstructive sleep apnea syndrome (OSAS). Pulmonary arterial stiffness (PAS) can be used in determination of PH. The aim of the present study was to evaluate the PAS and cardiac function of patients with OSAS and analyses the relationship between OSAS severity and PAS. Sixty newly diagnosed patients with OSAS (mean age 49.6 ± 11.7 years) and 30 healthy controls (mean age 46.4 ± 14 years) were enrolled. Right ventricle (RV) and left ventricle (LV) echocardiographic parameters and PAS values of study groups were compared. There were no significant differences in terms of LV ejection fraction, LV Tei-index and tricuspid annular plane systolic excursion. PAS, mean pulmonary arterial pressure (PAP) and RV Tei-index were significantly higher but tricuspid annulus early diastolic myocardial velocity was lower in patients with OSAS than control subjects (respectively p < 0.001, p < 0.001, p = 0.001, p = 0.001). Moreover, we found a higher PAS in OSAS patients without PH compared to controls (p < 0.001). When we investigated the relationship between polysomnographic variables and echocardiographic parameters, we found positive correlations between apnea hypopnea index and total oxygen desaturation with PAS and mean PAP (r = 0.384, p < 0.001; r = 0.404, p < 0.001; r = 0.36, p < 0.001; r = 0.349, p = 0.001 respectively). PAS and mean PAP were increased in patients with OSAS. Pulmonary vascular bed may be affected due to the fluctuation of PAP during day and night time. Therefore, assessment of PAS can be more useful than PAP in OSAS patients.     

Infusion of ultrafiltrate from endotoxemic pigs depresses myocardial performance in normal pigs

We previously showed a beneficial effect of hemofiltration on hemodynamics of endotoxic shock pigs. To test the hypothesis that this effect of hemofiltration is caused by convective removal of factors that adversely effect hemodynamics during endotoxemia, we infused ultrafiltrate from endotoxic shock pigs into healthy pigs. Their hemodynamics were compared with those of pigs who were infused with ultrafiltrate from healthy pigs. Twelve anesthetized and ventilated pigs were hemodynamically monitored for 150 minutes following the infusion of 2 L of ultrafiltrate from 12 donor pigs. The acceptor pigs were randomly divided into two groups; group 1 received ultrafiltrate from pigs who were hemofiltered after the infusion of 0.5 mg/kg endotoxin over 30 minutes; group 2 served as a control group, receiving ultrafiltrate from healthy donor pigs. Group 1 showed a decrease in mean arterial pressure of 28 ± 7 mm Hg (mean ± SEM) versus an increase of 17 ± 3 mm Hg in group 2 (P < .04). Mean pulmonary artery pressure increased more in group 1 than in group 2 (9 ± 2 mm Hg versus 1 ± 1 mm Hg, P < .04). The decrease in cardiac output in group 1 was greater than in group 2 (3.3 ± 0.2 L/ min v 0.3 ± 0.3 L /min, P < .02) and was due to a decrease in stroke volume. The decrease in right ventricular ejection fraction was also greater (0.15 ± 0.02 v 0.01 ± 0.00, P < .01). Systemic vascular resistance, right atrial pressure, right ventricular end-diastolic volume, pulmonary wedge pressure and heart rate did not differ between groups. In contrast to ultrafiltrate from healthy pigs, ultrafiltrate from endotoxic shock pigs contains soluble, filtrable factors that increase pulmonary artery pressure and depress cardiac performance.     

Left atrial appendage: morphology and function in patients with paroxysmal and persistent atrial fibrillation

The anatomical and functional characteristics of the left atrial appendage (LAA) and its relationships with anatomical remodeling and ischemic stroke in patients with atrial fibrillation (AF) have not been clearly established. The purpose of this study was to determine whether functional and morphological features of the LAA independently predict clinical outcome and stroke in patients with AF who underwent catheter ablation (CA). Two hundred sixty-four patients with AF, including 176 with paroxysmal AF (PAF, 54.0 ± 11.4 years old, M:F = 138:38) and 88 with persistent AF (PeAF, 56.4 ± 9.6 years old, M:F = 74:14) were studied. Of these patients, 31 (11.7 %) had a history of stroke/TIA (transient ischemic attack). The LA and LAA volumes were 124.0 ± 42.4 and 24.9 ± 4.3 ml in PeAF, these values were greater than those in PAF (81.2 ± 24.8 ml and 21.2 ± 5.1 ml, P < 0.001). The AF type (P = 0.016) and AF duration (P = 0.005), and anti-arrhythmic drugs use (P < 0.001) were significant predictors of AF recurrence after CA in all patients. Compared with patients without history of stroke, stroke patients had larger LA volume (106.9 ± 23.0 vs. 94.0 ± 38.9 ml, P = 0.004) and had lower LAA EF (50.0 ± 11.0 vs. 65.7 ± 13.4 %, P < 0.001). The independent predictors of stroke were age (P = 0.002) and LAA EF (P < 0.001) in PAF patients and that was only age (P = 0.001) in PeAF patients. In anatomical and morphological parameters of the LA and LAA, only depressed systolic function of the LAA was significantly related to stroke/TIA and recurrence of AF after CA in paroxysmal AF patients. Further large scaled prospective study is required for validation.     

Dual-energy CT for differentiating acute and chronic pulmonary thromboembolism: an initial experience

The purpose of this study was to prospectively evaluate the diagnostic capability of single-phase dual-energy CT (DECT) angiography to differentiate acute and chronic pulmonary thromboembolism (APTE, CPTE). We prospectively enrolled 26 patients (M:F = 9:17; mean age, 61 years old) with a filling defect in the pulmonary artery on DECT angiography. They were divided into two groups—APTE and CPTE—based on the clinical criteria. Two investigators quantitatively measured the following parameters at the embolism and main pulmonary artery: CT attenuation density [Hounsfield unit (HU) values], iodine-related HU value (IHU), and iodine concentration (IC, mg/ml). These parameters of the embolism and their ratio divided by those of the main pulmonary artery were compared between APTE and CPTE groups. Among 26 patients, 15 were categorized into the APTE group and 11 into the CPTE group. The mean HU, IHU, and IC values of emboli were significantly different between the APTE and CPTE groups (32.2 ± 17.0 vs. 52.1 ± 13.6 HU; P = 0.016, 7.2 ± 2.8 vs. 27.3 ± 12.7 HU; P < 0.001, and 0.57 ± 0.23 vs. 1.56 ± 0.67; P < 0.001). The mean HU, IHU, and IC ratios between emboli and main pulmonary arteries were also significantly different between the two groups (0.085 ± 0.046 vs. 0.156 ± 0.064 HU; P = 0.003, 0.023 ± 0.013 vs. 0.099 ± 0.053; P < 0.001, and 0.048 ± 0.035 vs. 0.130 ± 0.064; P = 0.001). DECT angiography using a quantitative analytic methodology can be used to differentiate between APTE and CPTE.     

Acute improvement in arterial-ventricular coupling after transcatheter aortic valve implantation (CoreValve) in patients with symptomatic aortic stenosis

The recent development of transcatheter aortic valve implantation (TAVI) to treat severe aortic stenosis (AS) offers a viable option for high-risk patients categories. Our aim is to evaluate the early effects of implantation of CoreValve aortic valve prosthesis on arterial-ventricular coupling by two dimensional echocardiography. Sixty five patients with severe AS performed 2D conventional echocardiography before, immediately after TAVI, at discharge (mean age: 82.6?±?5.9?years; female: 60%). The current third generation (18-F) CoreValve Revalving system (Medtronic, Minneapolis, MN) was used in all cases. Vascular access was obtained by percutaneous approach through the common femoral artery; the procedure was performed with the patient under local anesthesia. We calculated, apart the conventional parameters regarding left ventricular geometry and the Doppler parameters of aortic flow (valvular load), the vascular load and the global left ventricular hemodynamic load. After TAVI we showed, by echocardiography, an improvement of valvular load. In particular we observed an immediate reduction of transaortic peak pressure gradient (P?<?0.0001), of mean pressure gradient (P?<?0.0001) and a concomitant increase in aortic valve area (AVA) (0.97?±?0.3?cm²). Left ventricular ejection fraction improved early after TAVI (before: 47?±?11, after: 54?±?11; P?<?.0001). Vascular load, expressed by systemic arterial compliance, showed a low but significant improvement after procedure (P?<?0.01), while systemic vascular resistances showed a significant reduction after procedure (P?<?0.001). As a global effect of the integrated changes of these hemodynamic parameters, we observed a significant improvement of global left ventricular hemodynamic load, in particular through a significant reduction of end-systolic meridional stress (before: 80?±?34 and after: 55?±?29, P?<?0.0001). The arterial-valvular impedance showed a significant reduction (before: 7.6?±?2 vs after: 5.8?±?2; P?<?0.0001. Furthermore we observed a significant reduction with a normalization of arterial-ventricular coupling (P?<?0.005). With regard to left ventricular (LV) efficiency, we observed, after the procedure, a significant reduction of stroke work (P?<?0.001) and potential energy (P?<?0.001), with a significant increase of work efficiency early after the procedure (P?<?0.001). Our results showed that the TAVI procedure was able to determine an early improvement of the global left ventricular hemodynamic load, allowing a better global LV performance. Further follow-up investigations are needed to evaluate these results in a more prolonged time observation.     

Time course of myocardial and cerebral blood flow during stable but hemodynamically compromising ventricular tachycardias

Myocardial and cerebral blood flow were determined with radiolabeled microspheres in 20 Sprague-Dawley rats during sinus rhythm and during stable but hemodynamically compromising ventricular tachycardias. In addition, in 10 animals the measurements were performed at hypotension induced by exsanguination. In controls (n=10), myocardial and cerebral blood flow were 5.14±0.6 and 1.03±0.3 ml/g per minute, respectively. The range of myocardial blood flow values was markedly enlarged after onset of tachycardia induced by epicardial pacing. The mean values of myocardial blood flow were 5.80±1.9 ml/g per minute (n.s.) after 1 min and 7.46±3.9 ml/g per minute (n.s.) after 5 min. Cerebral blood flow, however, significantly decreased after 1 min (0.57±0.1 ml/g per minute,P<0.01) and after 5 min (0.71±0.3 ml/per minute,P<0.05). In contrast, 1 min after exsanguination myocardial blood flow signifcantly decreased (4.03±1.5 ml/g per minute,P<0.05) and recovered after 5 min (6.06±1.2 ml/g per minute, n.s.) Cerebral blood flow was below control levels 1 min (0.70±0.2 ml/g per minute,P<0.05) after onset of hypotension due to exsanguination and returned to normal values with the next 4 min (0.90±1 ml/g per minute, n.s.). The results suggest that stable but hemodynamically compromising ventricular tachycardias markedly affect cerebral blood flow, whereas in most cases myocardial blood flow is maintained within normal ranges, or even increases. An augmented myocardial autoregulation can be concluded from the autoregulatory index. This maintainance of regulatory ability might be due to the increase of myocardial oxygen consumption at decreased coronary perfusion pressures during tachycardias. In contrast, during hypovolemic hypotension, myocardial as well as cerebral blood flow decreased. During stable but hemodynamically compromising ventricular tachycardias, cerebral blood flow initially drops drastically and recovers slowly over the next 5 min. This finding contrasts with the results of hypovolemic and drug-induced hypotension models.     

Increased Prevalence of Patent Foramen Ovale in Patients with Severe Chronic Obstructive Pulmonary Disease

This study was designed to assess the prevalence of patent foramen ovale (PFO) in patients with severe chronic obstructive pulmonary disease (COPD) and the magnitude of any effects of right-to-left interatrial PFO shunting on systemic arterial oxygen desaturation after the Valsalva maneuver. The prevalence of PFO was compared between a group of 20 patients with severe chronic obstructive pulmonary disease (FEV₁ % <50%; FEV₁ /FVC <50%) and 20 control subjects (FEV₁ % >70%; FEV₁ /FVC >70%) by contrast transesophageal echocardiography during the Valsalva maneuver with simultaneous measurement of systemic arterial oxygen saturation (SaO₂ ) by pulse oximetry. Patients with severe COPD (FEV₁ = 27.2% ± 8.4%; FEV₁ /FVC = 44.3% ± 11.0%) had a significantly higher pulmonary artery systolic pressure (38.3 ± 7.3 vs 21.0 ± 2.4 mm Hg; P < .005), higher prevalence of PFO (14/20 = 70% vs 7/20 = 35%; P < .05), and greater systemic arterial desaturation after Valsalva (Sao₂ change: –2.6% ± 1.4% vs –1.1% ± 0.9%; P < .005) than control subjects. In the severe COPD group, the degree of systemic arterial desaturation after Valsalva in patients with PFO was significantly greater than in patients without PFO (Sao₂ change: –3.1% ± 1.4% vs –1.5% ± 0.5%; P < .05). Significant systemic arterial oxygen desaturation was observed after Valsalva in 45% of patients with interatrial PFO shunting and severe COPD. This significantly correlated with the degree of pulmonary hypertension (r = 0.6; P < .05). We conclude (1) that patients with severe COPD have an increased prevalence of PFO and (2) that approximately one half of subjects with severe COPD and PFO demonstrate statistically significant systemic arterial oxygen desaturation after the Valsalva maneuver. (J Am Soc Echocardiogr 1999;12:99-105.)     

Acute hyperventilation increases oxygen consumption and decreases peripheral tissue perfusion in critically ill patients

PurposeThis study aimed to evaluate the effects of acute hyperventilation on central venous-to-arterial carbon dioxide tension difference (Pv-aCO₂), central venous oxygen saturation (ScvO₂), central venous-to-arterial CO₂ difference/arterial-central venous O₂ difference ratio (CO₂GAP-Ratio), and peripheral perfusion index (PI) in hemodynamically stable critically ill patients.MethodsFifty-four mechanically ventilated patients were evaluated. The cardiac index, Pv-aCO₂, ScvO₂, CO₂GAP-Ratio, PI, and arterial and venous blood gas parameters were measured in the first set of measurements. Then, alveolar ventilation was increased by raising the respiratory rate (10 breaths/min). After a 30 min hyperventilation period, the second set of measurements was recorded.ResultsAcute hyperventilation induces an increase in Pv-aCO₂ (from 3.87 ± 1.31 to 8.44 ± 1.81 mmHg, P < 0.001) and a decrease in ScvO₂(from 71.78 ± 4.82 to 66.47 ± 5.74%, P < 0.001). The CO₂GAP-Ratio was significantly increased(from 0.97 ± 0.40 to 1.74 ± 0.46, P < 0.001), and the PI showed a remarkable decrease caused by acute hyperventilation(from 1.82 ± 1.14 to 1.40 ± 0.99，P = 0.04). Hyperventilation-induced ∆_Pv-aCO₂ was negatively correlated with ∆PaCO₂(r = −0.572, P<0.001). The change in ∆_PaCO₂ was correlated with ∆_ScvO₂(r = 0.450, P<0.001). However, the left ventricular outflow tract velocity time integral (LVOT-VTI) remained unchanged during hyperventilation.ConclusionsAcute hyperventilation induced an increase in oxygen consumption and decreased peripheral tissue perfusion in patients. For critical care patients, it is necessary to pay attention to the influence of hyperventilation on peripheral tissue perfusion indices and oxygen consumption indices.     

Endothelin‐1: increased plasma clearance,pulmonary affinity and renal vasoconstriction in young smokers

Pulmonary and renal haemodynamics and elimination of endothelin‐1 (ET‐1) were studied in six young smokers in response to 20 min intravenous infusion of ET‐1 (4 pmol kg^–1 min^–1) after smoking. At 20 min of ET‐1 infusion fractional ET‐1 extractions in the lungs and kidneys were 60 ± 2 and 60 ± 7%, respectively. Cardiac output and renal blood flow (RBF) fell by 18 ± 4% (P<0·05) and 34 ± 5% (P<0·01). Mean systemic arterial pressure increased (P<0·05) whereas pulmonary pressures were unchanged. Compared with previously published data in non‐smokers ( 38 , 39 ) basal arterial ET‐1 and ET‐1‐values during ET‐1 infusion were lower with a more rapid return to basal value. Smokers had higher pulmonary extraction of ET‐1 at the same pulmonary arterial concentration (P<0·05). RBF reduction was more pronounced (P<0·05). Systemic vascular resistance increased while pulmonary vascular resistance did not increase as in non‐smokers. Increased plasma clearance and more efficient pulmonary elimination of ET‐1 lowers the arterial level in young smokers. In addition ET‐1 evokes more pronounced renal vasoconstriction in these individuals.     

Nifedipine and diltiazem reduce pulmonary edema formation during postischemic reperfusion of the rabbit lung

A protective effect of calcium antagonists in pulmonary preservation for transplantation has been observed recently. This report focuses on the potential use of diltiazem and nifedipine in the early phase of reperfusion after normothermic pulmonary ischemia. Rabbits weighing 4–5 kg were tracheotomized and ventilated with 50% oxygen. In a control group (group I,n=7), the hilus of the right lung was clamped for 210 min without ischemia of the left lung. Lung ischemia was created in a second group (n=7) by clamping the left hilum for 2 h. Subsequently, reperfusion of the left lung was maintained for 210 min, while the right hilus was kept occluded. In group III (n=6) and group IV (n=8) the conditions were the same as in group II, but either diltiazem (62.5 μg/kg i.v., group III) or nifedipine (3 μg/kg i.v., group IV) was administered during the first 20 min of reperfusion. After 210 min of reperfusion, the pulmunary vascular resistance was elevated in group II (×: 5120 dyn·sec·cm⁻⁵), group III (5518 dyn·sec·cm⁻⁵), and group IV (4324 dyn·sec·cm⁻⁵), compared with group I (3390; n.s.). Arterial oxygenation showed no significant differences among group I (×: 257 mmHg), group II (261 mmHg), group III (208 mmHg), and group IV (247 mmHg). Pulmonary ischemia resulted in an increased extravascular lung water content in group II as compared to group I (73 and 64 g/g wet weight;P<0.0125 vs group I). No such increase was seen in groups III and IV (53 and 54 g/g wet weight respectively;P<0.001 vs group II). In this model of normothermic left lung ischemia, the application of diltiazem or nifedipine during the early phase of reperfusion limits formation of pulmonary edema. In constrast to previous findings using verapamil, both substances do not show significant influence on pulmonary vascular resistance. They may be of use in clinical lung transplantation by reducing fluid accumulation in the lung parenchyma.     

Effects of dibutyryl cyclic adenosine monophosphate on hypercapnic depression of diaphragmatic contractility in pentobarbital-anesthetized dogs

Background: Hypercapnia is associated with diaphragm muscle dysfunction that causes a reduction of diaphragmatic force generated for a constant elective myographic activity. No published data are available concerning hypercapnic depression of diaphragmatic contractility during dibutyryl cyclic adenosine monophospate (DBcAMP) administration.Objective: The aim of this study was to assess the effects of DBcAMP on hypercapnic depression of diaphragmatic contractility in pentobarbital-anesthetized dogs.Methods: This experimental study was conducted from July to December 2008 at the Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. Adult (aged >5 years) mongrel dogs weighing 10 to 15 kg were randomly divided into 3 equal groups. Hypercapnia (80-90 mm Hg) was induced with 10% carbon dioxide added to the inspired gas. When hypercapnia was established, group 1 was infused with low-dose DBcAMP (0.05 mg/kg/min); group 2 was infused with high-dose DBcAMP (0.2 mg/kg/min); and group 3 received placebo (saline). Study drug was administered intravenously for 60 minutes. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi) at baseline, induction of hypercapnia, and study drug administration.Results: Twenty-one dogs were divided into 3 groups of 7. There were no significant differences observed at baseline. In the presence of hypercapnia, Pdi (mean [SD], cm H₂O) at low- (20-Hz) and high-frequency (100-Hz) stimulation was significantly decreased from baseline in each group (all, P = 0.001). In groups 1 and 2, Pdi at both stimuli was significantly increased during DBcAMP administration compared with hypercapnia-induced values (group 1: 20-Hz, 13.5 [2.2] vs 15.0 [2.4], respectively, P = 0.001, 100-Hz, 21.2 [1.6] vs 22.5 [1.6], P = 0.001; group 2: 20-Hz, 13.7 [1.4] vs 19.2 [1.7], P = 0.001, 100-Hz, 21.0 [2.4] vs 27.2 [2.5], P = 0.001). The Pdi at both stimuli during DBcAMP administration was significantly higher in group 2 than in group 1 (20-Hz, 19.2 [1.7] vs 15.0 [2.4], P = 0.001, 100-Hz, 27.2 [2.5] vs 22.5 [1.6], P = 0.003). In group 3, Pdi did not significantly change in regard to either stimulus from hypercapnia-induced values.Conclusion: DBcAMP, in a dose-dependent manner, was associated with improved hypercapnic depression of diaphragmatic contractility in these pentobarbital-anesthetized dogs.     

Evaluation neointimal coverage in patients with coronary artery aneurysm formation after drug-eluting stent implantation by optical coherence tomography

The neointimal coverage in patients with coronary artery aneurysms (CAA) formation after drug eluting stent (DES) implantation is not clear. Total of 175 patients who had been implanted DES were identified. Patients were divided into the CAA group (n = 31) and non-CAA group (n = 144) based on the results of the coronary angiography. The cardiac events including angina and acute myocardial infarction were noted, in addition, the neointimal thickness and the frequence of strut malapposition and strut uncoverage were noted. A greater proportion of incomplete neointimal coverage (17.17 vs. 1.9 %, P < 0.001) and malapposition struts (18.2 vs. 1.38%, P < 0.001) were observed in the CAA group. 8 patients in CAA group underwent OCT examination twice in the period of follow-up. The proportion of incomplete neointimal coverage increased significantly as compared the second OCT results with the first examination (18.45 vs. 2.66 %, P < 0.001). Hyperplasia neointimal desquamated from struts and acquired struts incomplete neointimal coverage were detected. Patients with CAA had a higher frequency of cardiac events including angina pectoris (25.81 vs. 6.25 %, P = 0.001) and acute myocardial infarction (9.68 vs. 0.13 %, P = 0.002) and thrombosis (16.13 vs. 0.69 %, P < 0.001). The longitudinal length of CAA in cardiac event group was significantly longer than no cardiac event group (20.0 ± 9.07 vs. 12.05 ± 5.38 mm, P = 0.005). CAA formation after DES implantation frequently associated with cardiac events as a result of stent malapposition and incomplete neointimal coverage. Acquired incomplete neointimal coverage associated with CAA formation.     

Effects of Multimodal Inpatient Rehabilitation vs Conventional Pulmonary Rehabilitation on Physical Recovery After Esophageal Cancer Surgery

ObjectiveTo determine the effects of multimodal rehabilitation initiated immediately after esophageal cancer surgery on physical recovery compared with conventional pulmonary rehabilitation.DesignRetrospective study.SettingPrivate quaternary care hospital.ParticipantsFifty-nine inpatients (N=59) who participated in either conventional pulmonary rehabilitation (n=30) or in multimodal rehabilitation (n=29) after esophageal cancer surgery were included.InterventionsBoth groups performed pulmonary exercises, including deep breathing, chest expansion, inspiratory muscle training, coughing, and manual vibration. In the conventional pulmonary rehabilitation group, light-intensity mat exercise, stretching, and walking were performed. The multimodal rehabilitation group performed resistance exercises and moderate- to high-intensity aerobic interval exercises using a bicycle.Main Outcome MeasuresThe European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30), pain, 6-minute walk test (6MWT), 30-second chair stand test, and grip strengths were assessed before and after the rehabilitation programs.ResultsSymptom scales of pain, dyspnea, and insomnia in the EORTC QLQ-C30 as well as 6MWT improved significantly after each program (P<.05). 6MWT (73.1±52.6 vs 28.4±14.3, P<.001, d=1.15), 30-second chair stand test (3.5±3.9 vs 0.35±2.0, P<.001, d=1.06), and left grip strength (1.2±1.3 vs 0.0±1.5, P=.002, d=0.42) improved significantly in the multimodal rehabilitation group compared with the pulmonary rehabilitation group. While right grip strength also showed more improvement for those undergoing the multimodal program, the mean strength difference was not clinically meaningful.ConclusionsA multimodal inpatient rehabilitation program instituted early after esophageal cancer surgery improved endurance for walking more than conventional pulmonary rehabilitation as measured by the 6MWT and the 30-second chair stand test.