Lung angiotensin converting enzyme activity in chronically hypoxic rats.

A study was carried out to test the hypothesis that the reduced lung angiotensin converting enzyme (ACE) activity which occurs in chronic hypoxia is related to the development of pulmonary hypertension rather than to hypoxia per se. Right ventricular mean systolic pressure (Prvs, mm Hg) and ACE activity (nmol/mg protein/min) in lung tissue homogenates were measured in seven groups of four rats placed in a hypobaric chamber (380 mm Hg; 51 kPa) for two to 24 days. Identical measurements were made on 11 groups of four rats, which were placed in the chamber for 24 days and then allowed to recover in room air for one to 153 days. After two days of hypoxia the mean Prvs (25.5 (SD 3.7] and the mean lung ACE activity (56 (4.6] did not differ significantly from control values. Exposure to hypoxia for four to 24 days caused a progressive increase in mean Prvs to 44.4 (5.9) and a progressive reduction in mean lung ACE activity to 34 (4.0). During recovery lung ACE activity increased and Prvs decreased, so that normal values were achieved by 15 and 56 days respectively. Decreased lung ACE activity may be related to haemodynamic factors associated with pulmonary hypertension rather than to hypoxia.     

Assessment of cardiac performance using Tei indices in patients undergoing pulmonary thromboendarterectomy

BACKGROUND: This study was designed to evaluate left and right ventricular performance using Tei indices in patients with severe chronic thromboembolic pulmonary hypertension undergoing pulmonary thromboendarterectomy (PTE). The Doppler-derived indices are easily measurable indicators of ventricular function based on nongeometric assessment, which helps overcome some of the difficulties entailed in the geometric assessment of left ventricular (LV) and right ventricular (RV) function in pulmonary hypertension. METHODS: The indices were derived for 24 patients (aged 54+/-14 years) before and after PTE. Calculation of these indices was based on the duration of two time intervals using the formula (A - B)/B, where A is the interval between cessation and onset of mitral inflow (or tricuspid inflow) and B is LV or RV ejection time. In addition, LV and RV end-diastolic and end-systolic chamber areas were determined using two-dimensional echocardiography, and systolic function was calculated. Mean pulmonary artery pressure was determined invasively. RESULTS: PTE led to a significant reduction of mean pulmonary artery pressure (46+/-10 versus 25+/-6 mm Hg; p < 0.05). LV and RV indices were abnormally high before surgery, declined significantly afterwards, and then almost matched normal values (0.61+/-0.26 versus 0.37+/-0.18; p < 0.05 and 0.55+/-0.22 versus 0.37+/-0.13; p < 0.05). Geometric assessment of the left and right ventricle also showed impaired systolic function before PTE, with significant improvement after surgery. CONCLUSIONS: LV and RV Tei indices allow a quantitative assessment of ventricular function in patients undergoing PTE. Lower indices after surgery reflect an improvement of the previously impaired cardiac function. Our results emphasize the value of PTE in the treatment of chronic thromboembolic pulmonary hypertension.     

Single lung transplantation in rats with chemically induced pulmonary hypertension.

Physiologic effects of single lung transplantation on pulmonary hypertension were studied in rats with monocrotaline-induced pulmonary hypertension. Inbred rats treated with monocrotaline (40 mg/kg) received a left lung isograft from a normal donor 2 weeks later, when pulmonary hypertension became significant (transplant group; n = 6). These rats and control rats treated with monocrotaline (mediated control group; n = 11) or vehicle alone (normal control group; n = 9) were followed up weekly by metabolic treadmill testing for exercise tolerance and oxygen consumption up to 6 weeks after monocrotaline (4 weeks after transplantation), when all rats underwent hemodynamic and histologic examinations. Whereas maximal oxygen consumption and exercise tolerance consistently deteriorated in the medicated control group of rats, indices in the transplant group stopped deteriorating 2 weeks after lung transplantation and remained at levels similar to those of normal control rats. Severe pulmonary hypertension (68 +/- 19 mm Hg) and right ventricular hypertrophy (right ventricular/left ventricular weight ratio, 0.95 +/- 0.19) were confirmed in medicated control rats in contrast to transplant animals, in which these two indices remained at normal control levels. Whereas left-to-right lung perfusion ratio was constant among rats not receiving transplants (0.69 +/- 0.16), it was significantly elevated (2.27 +/- 0.65; p less than 0.001) in those receiving transplants, suggesting preferential flow through the lung isograft. The results suggest that, in the early phase of pulmonary hypertension, single lung transplantation shifts pulmonary perfusion to the grafted lung, avoiding right ventricular pressure overload and thereby preserving exercise tolerance at a nearly normal level in rats with monocrotaline-induced pulmonary hypertension.     

Gene transfer of hepatocyte growth factor with prostacyclin synthase in severe pulmonary hypertension of rats

Objective: Hepatocyte growth factor (HGF) is a multi-potent growth factor, which has anti-fibrotic effects for lung injuries. In this study, we investigated whether human HGF gene transfer may attenuate the medial hypertrophy of pulmonary arteries and enhance the ameliorating effect of prostacyclin in monocrotaline (MCT)-induced pulmonary hypertension in rats. Methods and results: The day before MCT injection, HVJ-liposome complex with the cDNA encoding HGF gene (H group), PGIS gene (P group), and both HGF and PGIS gene (HP group) were transfected to the liver of rats as drug delivery system for the lung. Rats transfected with control vector served as controls (C group). Twenty-eight days after MCT injection, histological examination showed marked thickening of medial wall of pulmonary arteries and right ventricular hypertrophy. Percent medial wall thickness (%WT) of peripheral pulmonary arteries, pressure ratio of the right ventricle (RV) to the left ventricle (LV), and weight ratio of the RV to the LV plus septum were significantly increased in the control. Percent medial wall thickness was significantly ameliorated in H group and HP group in comparison with C group. Pressure and weight ratio of RV to LV was significantly ameliorated in P group and HP group in comparison with C group, and was significantly ameliorated in HP group than P group. Conclusions: In vivo gene transfection with HGF gene attenuated the medial hypertrophy of pulmonary arteries and enhanced the ameliorating effect of prostacyclin for pulmonary hypertension in MCT rats. Thus, gene therapy with HGF and PGIS may be a promising strategy for severe pulmonary hypertension.     

Failure to show decrease in small pulmonary blood vessels in rats with experimental pulmonary hypertension.

We induced chronic pulmonary hypertension in one group of rats by exposing them to chronic hypobaric hypoxia (380 mm Hg for three weeks) and in another group by administering a single subcutaneous dose of monocrotaline (60 mg/kg body weight). Both groups of rats showed increase of the right ventricular mean systolic blood pressure and right ventricular hypertrophy. We measured the surface area of histological sections of the left or right lungs and counted all small blood vessels with an external diameter of less than 50 microns and with a definite elastic coat lying distal to respiratory bronchioles. In the 10 rats with chronic hypoxic pulmonary hypertension the mean total number of small pulmonary blood vessels was 428.8 +/- 96.9 (SD) compared with 337.8 +/- 91.9 in 10 untreated control rats. The number of small pulmonary blood vessels per mm2 of lung tissue was 4.0 +/- 1.3 in the chronically hypoxic rats compared with 3.8 +/- 1.2 in the controls. The mean total number of small pulmonary blood vessels in nine rats with monocrotaline-induced pulmonary hypertension was 396.8 +/- 61.7 compared with 384 +/- 55.4 in three control rats. The number of small pulmonary blood vessels per mm2 lung tissue was 3.3 +/- 0.6 in the rats treated with monocrotaline compared with 3.6 +/- 0.6 in the control group. We conclude that the number of small pulmonary blood vessels is not reduced in rats with pulmonary hypertension induced by chronic hypoxia or monocrotaline.     

Lung angiotensin converting enzyme activity in rats with differing susceptibilities to chronic hypoxia.

The decrease in lung angiotensin converting enzyme (ACE) activity occurring in rats during chronic hypoxia might be related to the pulmonary haemodynamic response or to the hypoxia. A study in rats was carried out to investigate this question. Rats from the Hilltop (H) strain are known to develop more severe pulmonary hypertension as a result of chronic hypoxia than rats from the Madison (M) strain despite having virtually identical arterial and mixed venous oxygen tensions. Rats from H and M strains were exposed to hypoxia (0.5 atm) for 3-21 days and lung and serum ACE activities were determined. After three days' hypobaria lung ACE activity was significantly lower and serum ACE significantly higher in H than in M rats. Linear regressions for lung ACE activity and right ventricular:body weight ratios showed significant inverse correlations and were similar in the two strains. The results suggest that pulmonary hypertension and not hypoxia determines the reduction in lung ACE activity, possibly by releasing ACE into the blood stream.     

Angiotensin converting enzyme activity and evolution of pulmonary vascular disease in rats with monocrotaline pulmonary hypertension.

We have investigated the role of angiotensin converting enzyme (ACE) in the development of pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular disease in rats given a single subcutaneous injection of the pyrrolizidine alkaloid monocrotaline. Thirty-six young female Wistar rats were divided into a test group of 27 animals and a control group of nine animals. Each test rat was given a single subcutaneous injection of monocrotaline (60 mg/kg body weight). On the first, third, fifth, seventh, tenth, twelfth, fourteenth, seventeenth, and twenty-second days after the injection of monocrotaline the mean right ventricular systolic blood pressure was measured in one control and three test rats. The animals were then killed and we measured the specific activity of ACE in serum and lung homogenate. We also evaluated muscularisation of pulmonary arterioles, medial hypertrophy of muscular pulmonary arteries, and right ventricular hypertrophy. The sequence of changes was as follows: muscularisation of pulmonary arterioles and medial hypertrophy of muscular pulmonary arteries were apparent seven days after administration of monocrotaline; pulmonary hypertension and reduced lung ACE activity occurred after 10 days; right ventricular hypertrophy was detected after 12 days. Serum ACE activity was unchanged. It is concluded that the reduction in lung ACE activity is a result rather than a cause of the pulmonary hypertension. This reduction in lung ACE activity may be a protective mechanism designed to limit the elevation of the pulmonary arterial pressure.     

Changes in cardiac dynamics by opening an interventricular shunt in dogs

Changes in right and left ventricular (RV, LV) dynamics caused by an interventricular shunt were examined in open-chest dogs. At a pulmonary to systemic blood flow ratio of 1.7 +/- 0.2 pulmonary flow increased by 53 +/- 13%, whereas aortic flow decreased by 9 +/- 2%. Shunt flow was continuous from the left to the right ventricle throughout the cardiac cycle, but 72 +/- 4% took place during the LV ejection phase. Peak systolic LV pressure declined by 6 +/- 3 mm Hg, LV end-diastolic segment length (SL) rose, and systolic shortening of the SL increased. Peak systolic RV pressure rose from 28 +/- 3 to 36 +/- 3 mm Hg and RV end-diastolic and end-systolic SL rose almost equally. Accordingly, RV systolic SL shortening did not rise despite the substantial augmentation in RV outflow. The transseptal end-diastolic pressure gradient did not rise, while the transseptal peak systolic gradient decreased when the shunt was opened. Similarly directed alterations were observed when the shunt was opened at different preloads and when the shunt flow was varied. Local work in the anterior wall of the right ventricle (calculated from the RV pressure SL loop) rose by 26 +/- 4%, whereas RV stroke work (product of mean systolic right ventricular pressure and pulmonary flow) rose by 57 +/- 12%; difference, P less than 0.05. LV stroke work and local work in anterior LV free wall rose in proportion when the shunt was opened.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of pulmonary regurgitation on left ventricular function after repair of tetralogy of Fallot

The influence of right ventricular (RV) volume overload by pulmonary regurgitation (PR) on left ventricular (LV) function was evaluated postoperatively in 23 patients with tetralogy of Fallot (TF). The age at operation was 3.1 +/- 1.7 (mean +/- SD) years. The age at postoperative study was 5.9 +/- 2.0 years. We determined RV end-diastolic volume (%RVEDV), RV ejection fraction (EF), %LVEDV, LV end-systolic volume (%LVESV), LVEF, and LV end-systolic stress (ESS)/%LVESV. Patients were divided into 2 groups on the basis of presence or absence of RV volume overload by PR as follows: The %RVEDV (175 +/- 23%) of group 1 (n = 10) was 150% greater than normal RVEDV. Group 2 (n = 13) had normal %RVEDV (108 +/- 23%). Preoperatively, there had been no differences in hemoglobin, %RVEDV, RVEF, %LVEDV, LVEF, and in the ratio of average cross-sectional area of the left and right pulmonary arteries to cross-sectional area of the normal right pulmonary artery between the 2 groups. Moreover, there were no differences in age at repair, or during postoperative study, nor in the postoperative ratio of RV to LV systolic pressure between the 2 groups. RVEF was significantly less in group 1 than in group 2 (0.53 +/- 0.05 vs 0.58 +/- 0.05, p less than 0.05). %LVEDV and %LVESV in group 1, 138 +/- 10% and 171 +/- 30% respectively, were significantly greater than those in group 2, 116 +/- 11% and 133 +/- 20% respectively (p less than 0.001 in %LVEDV and p less than 0.01 in %LVESV).(ABSTRACT TRUNCATED AT 250 WORDS)     

Transmural coronary vasodilator reserve and flow distribution in unanesthetized calves sojourning at 3500 m

Regional myocardial blood flow (MBF; 15-micron-diam radionuclide-labeled microspheres) was studied in six unanesthetized calves sojourning at 3500 m (PB = 500 mm Hg) for 53 +/- 2 days. These high-altitude (HA)-exposed calves were studied during chronic hypoxemia (PaO2 = 48 +/- 1 mm Hg), maximal coronary vasodilation, and during acute normoxemia (PaO2 = 91 +/- 1 mm Hg). Nine calves born and raised at sea level (SL) were also studied at matched PaO2 during chronic normoxemia, maximal coronary vasodilation, and acute hypoxemia to serve as control. Marked pulmonary hypertension and right ventricular (RV) hypertrophy were present in HA calves. Left ventricular (LV) MBF of HA calves during chronic hypoxemia (1.05 +/- 0.11 ml X min-1 X g-1) was similar to that of normoxemic SL calves (1.11 +/- 0.06 ml X min-1 X g-1) but MBF in their hypertrophied RV (1.65 +/- 0.21 ml X min-1 X g-1) exceeded that in normoxemic SL calves (0.47 +/- 0.06 ml X min-1 X g-1). More interesting was the finding that RV and LV MBF of HA calves did not change between chronic hypoxemia and acute normoxemia. By contrast, acute hypoxemia of a similar degree caused a dramatic increase in RV as well as LV MBF of SL calves. Minimal LV coronary vascular resistance was similar in the two groups of calves. This meant that functional cross-sectional area of LV coronary vascular bed was not altered in response to sojourn at HA. Minimal RV coronary vascular resistance of HA calves was also not different from that of SL calves. This means that functional cross-sectional area of the RV coronary vascular bed in HA calves increased proportionately with the increase in their RV mass.     

Pulmonary complications of a roller pump right ventricular assist device

The pulmonary effects of a right ventricular assist device (RVAD) were evaluated in a model of ischemic right ventricular (RV) failure. The right coronary artery (RCA) was ligated for 240 min in 12 mongrel dogs. Group 1 (n = 5) was supported medically (iv fluids, epinephrine); Group 2 (n = 7) had an RVAD instituted 30 mins after RCA ligation, but no inotropic support was given. The RVAD was a standard roller pump providing right atrial to pulmonary artery flow which unloaded the RV. The ratio of area of infarction (AI) to area at risk (AR) of the RV was determined by vital dye staining. Total lung water (TLW) was determined by gravimetric analysis and expressed as milliliters per kilogram body weight. Throughout the experiment animals in Group 1 had significantly higher RV systolic pressures. Pulmonary vascular resistance was increased significantly in Group 2 at 4 hr (318% of baseline vs 33%). Mean pulmonary artery pressure increased significantly in Group 2 from 9.4 +/- 0.9 mm Hg at baseline to 21.0 +/- 5.0 mm Hg at 4 hr. Group 2 animals had a decreased AI/AR ratio (19 +/- 3 vs 57 +/- 9) and increased TLW (20 +/- 3 vs 9 +/- 1). Lung biopsies in Group 2 revealed perivascular, peribronchial, and intraalveolar hemorrhages that were not present in Group 1. In conclusion, a roller pump RVAD limits RV infarction but produces pulmonary hypertension, increases pulmonary vascular resistance, and creates pulmonary edema and hemorrhage in the process.     

盐酸戊乙奎醚对野百合碱致大鼠肺动脉高压的抑制作用

目的探讨盐酸戊乙奎醚是否能够减缓野百合碱导致的大鼠肺动脉高压及是否能够预防或缓解肺血管重构。方法 3~4周龄健康雄性SD大鼠30只,体重90~100g,随机均分为正常对照组(C组)、野百合碱肺高压组(M组)、盐酸戊乙奎醚组(P组),每组10只。M组和P组腹腔注射野百合碱60mg/kg建造大鼠肺动脉高压模型,C组腹腔注射等容量生理盐水。P组大鼠于建模前15min时腹腔注射盐酸戊乙奎醚2mg/kg,建模第2天腹腔注射盐酸戊乙奎醚1mg/kg,C组和M组在相应时点腹腔注射等容量生理盐水,连续使用3周。在建模后第21天,三组大鼠检测血流动力学(肺动脉压、右心室压);处死大鼠前采集静脉血以备血液生化检测:ELISA法检测一氧化氮(NO)含量、内皮素-1(ET-1)含量。处死大鼠后留取左肺组织行病理切片以观察肺组织病理形态学变化,取右肺组织于-80℃冻存以备后续检测。结果 M组和P组右心室SBP、平均肺动脉压、肺动脉SBP和肺动脉DBP明显高于C组(P0.05);P组右心室SBP、平均肺动脉压、肺动脉SBP和肺动脉DBP明显低于M组(P0.05)。M组肺小动脉明显增厚,肺小动脉管腔狭窄甚至闭塞,肺组织炎性细胞浸润非常明显。P组肺小动脉壁增厚减轻,肺组织炎性细胞浸润减轻。M组大鼠血清中NO含量明显低于,ET-1的含量明显高于C组(P0.05);P组大鼠血清中NO含量明显高于M组和C组(P0.05),ET-1含量明显高于C组,但明显低于M组(P0.05)。结论使用野百合碱成功建造了大鼠肺动脉高压模型,NO含量降低、ET-1含量增加可能与野百合碱致大鼠肺动脉高压的形成有关;盐酸戊乙奎醚减缓野百合碱致大鼠肺动脉高压模型的肺动脉压力的升高、改善肺小动脉壁增厚可能与增加NO含量、降低ET-1含量有关。     

法舒地尔对肺血管重构的肺动脉高压大鼠的影响

目的 观察法舒地尔对发生肺血管重构的肺动脉高压(PAH)大鼠的影响.方法 将32只雄性Wistar大鼠随机均分为4组:对照3周组,模型3、6周组及治疗组;予野百合碱建模;治疗组于3周后予法舒地尔腹腔内注射.于3、6周末测定各组大鼠右心室收缩压(RVSP)、内皮素-1(ET-1)、N端脑钠素前体(NT-proBNP)、肺小动脉病理等.结果 (1)造模后RVSP随时间升高(31.2±7.6)、(43.3±8.3)、(56.9±6.9)mm Hg(1 mm Hg=0.133 kPa),治疗组(47.3±6.3)mmHg较模型6周组明显降低.(2)ET-1、NT-proBNP与RVSP呈正相关(r=0.721、0.454).(3)病理:造模后肺动脉平滑肌增生,管壁狭窄,至6周时近于闭塞,治疗组则明显好转.结论 对于已发生肺血管重构的PAH大鼠,法舒地尔能阻止肺动脉高压进展,ET-1、NT-proBNP可成为较理想的评估指标.

Abstract：

Objective To investigate the effects of Rho kinase inhibitor fasudil on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) with vascular remodeling in rats. Methods Thirty-two male Wistar rats were randomly and equally divided into control group ( C3 ), MCT-PAH 3- and 6-week model groups (H3, H6 ) and fasudil-treated group (F6). The right ventricle systolic pressure( RVSP), right ventricle/left ventricle and septum[RV/( LV + S)], plasma endothelin-1 and NT-proBNP were measured; small pulmonary arterial morphometry, ratio of vascular wall thickness to vascular external diameter (WT) and ratio of vascular wall area to the total area (WA) were also observed. Results ( 1 )The RVSP was highest in H6 group, followed by F6 group, H3 group, and C3 group[(56. 9 ±6. 9), (47. 3±6.3), (43.3±8.3) and (31.2±7.6) mm Hg (1 mm Hg=0. 133 kPa)]. But no significant difference was found between H3 and F6 groups; (2) The levels of plasma ET-1 and NT-proBNP were positively associated with RVSP, RV/(LV +S), WT and WA (r for ET-1 was 0.721, 0.607, 0.652, 0.707,P＜0.01; r for NT-proBNP was 0. 454, 0. 330, 0. 365, 0. 398,P ＜0. 05); (3) Pathematological assessment showed that the thickness and muscularization of small pulmonary artery were increased in H3 group as compared with C3 group, most significantly in H6 group, and those were significantly decreased in F6 group as compared with H6 group. Conclusion Fasudil can improve the MCT-induced PAH with vascular remodeling in rats. The plasma ET-1 and NT-proBNP could be used as good makers to evaluate the severity of PAH.     

Current approaches to pulmonary regurgitation

Objective: To evaluate the effects on ventricular function and volumes following right ventricular outflow tract reconstruction (RVOTR) with pulmonary homograft replacement (PVR) and percutaneous pulmonary valve implantation (PPVI) for predominant pulmonary regurgitation. This study was not intended to compare the two approaches. Methods: We prospectively examined 25 patients (mean age 21+/-13 years, 96% tetralogy of Fallot, 1/25 with conduit dysfunction) who had PVR with RVOTR for severe pulmonary regurgitation (PR), and 11 patients (mean age 20+/-9 years, 64% tetralogy of Fallot, 9/11 with conduit dysfunction) who underwent PPVI for predominant PR. Mean age at primary repair in both groups was 4.3+/-6.6 years. Magnetic resonance imaging was performed prior to, and 1 year following, interventions. Results: Before procedure, NYHA classification was similar in both groups 2.1+/-0.5. Following interventions, there was a significant reduction in RV volumes in both groups. In the surgical (PVR) group, RV end-diastolic volume (EDV) decreased from 151+/-49 to 97+/-32ml/m(2) (p<0.0001) whereas end-systolic volume (ESV) decreased from 80+/-43 to 46+/-23ml/m(2) (p<0.0001). In the PPVI group, RV EDV decreased from 106+/-27 to 89+/-25ml/m(2) (p=0.002) and RV ESV from 49+/-20 to 40+/-16ml/m(2) (p=0.034). Both groups had a significant improvement in RV (63+/-20 to 72+/-16ml/beat, p=0.003 (PVR group), 53+/-14 to 67+/-16ml/beat, p=0.030 (PPVI group)) and LV effective stroke volume (61+/-18 to 73+/-16ml/beat, p=0.001 (PVR group); 59+/-24 to 75+/-16ml/beat, p=0.009 (PPVI group)). Conclusions: Following either PVR with RVOTR or PPVI, there was a significant reduction in RV volumes and an improvement in RV function. Importantly, in both groups, LV effective SV increased, and this may be the parameter to judge the benefit of the procedure. These results also support PPVI as an extra dimension in complex RVOT management.     

Inhaled nitric oxide does not alter pulmonary or cardiac effects of fat embolism in dogs after cemented arthroplasty

PURPOSE: We examined the effect of inhaled nitric oxide (NO) on the acute pulmonary hypertension and right ventricular (RV) dilation after fat embolism. METHODS: A bilateral cemented arthroplasty (BCA), created fat embolism in 20 dogs. In Part A, 12 dogs were randomized to an NO group (n=6, inhaled NO 40 ppm before BCA and throughout the study) or a control group (n=6). In Part B, a third group of dogs (n=8) were given NO 20-40 ppm 2-3 min after BCA when pulmonary artery pressure (PAP) increased. Transesophageal echocardiography (TEE) and invasive hemodynamic monitoring evaluated the hemodynamic response to BCA. Postmortem, quantitative morphometry was used to estimate the number of fat emboli and diameter of lung vessel occluded by fat. RESULTS: Part A: The increase in PAP in the NO group (16 +/- 1 to 34 +/- 9 mmHg) within three minutes of BCA was not different from that in the control group (14 +/- 4 to 35 +/- 9 mmHg). Within three minutes of BCA, TEE demonstrated RV dilation in all groups (P < 0.05) but there was no difference in the change in RV area in the NO and control groups. When NO was given after BCA, no difference in PAP or RV dilation was noted from that in the control group. There were no differences, at post mortem, between the groups in the diameter of lung vessel occluded by fat CONCLUSION: Whether given before the embolic insult or two to three minutes after the onset of pulmonary hypertension, inhaled NO did not attenuate the acute pulmonary hypertension or RV dilation after cemented arthroplasty.     

Single lung transplantation in rats with fatal pulmonary hypertension.

Effects of single lung transplantation on fatal pulmonary hypertension were evaluated in rats receiving a lethal dose of monocrotaline. Inbred rats treated with monocrotaline (80 mg/kg) received a left lung isograft at 4 weeks (n = 9) and at 6 weeks (n = 6), when moderate and severe pulmonary hypertension, respectively, had developed. Medicated (n = 12) and nonmedicated rats (n = 12) served as control animals. Each rat was tested weekly with treadmill for exercise tolerance and oxygen consumption during a 10-week period after medication and after they were killed. Medicated control rats lost exercise tolerance and highest oxygen consumption per unit time consistently to the range of resting value (or 45% of nonmedicated control rats), and all died from severe pulmonary vascular occlusive disease with right ventricular hypertrophy before 10 weeks (right ventricular/left ventricular weight ratio of 1.16). All rats receiving a left lung isograft at 4 weeks survived and regained highest oxygen consumption per unit time (87% of nonmedicated control rats), with the lung transplant receiving 65% (nonmedicated control rats, 39%) of cardiac output and milder right ventricular hypertrophy (right ventricular/left ventricular weight ratio of 0.46). Except for one, all rats that received a left lung isograft at 6 weeks tolerated single lung transplantation, but they died soon after reperfusion because of pulmonary edema in the graft that received 58% of cardiac output with right ventricular/left ventricular weight ratio of 0.79. Results of single lung transplantation in rats were dependent on severity of pulmonary hypertension. In rats with moderate pulmonary hypertension, single lung transplantation was successful in reversing exercise intolerance and right ventricular hypertrophy. Single lung transplantation was unsuccessful when pulmonary hypertension was severe in the rat model because increased flow toward the lung transplant resulted in graft pulmonary edema.     

Right ventricular function: a comparison between blood and crystalloid cardioplegia

Blood cardioplegia resulted in better left ventricular (LV) function than crystalloid cardioplegia after elective coronary artery bypass operations. However, most methods of cardioplegic delivery may not adequately cool and protect the right ventricle, and right ventricular (RV) dysfunction may limit hemodynamic recovery. Therefore, RV and LV temperatures were measured intraoperatively and RV and LV function were evaluated postoperatively in 80 patients with double-vessel or triple-vessel coronary artery disease who were randomized to receive either blood cardioplegia or crystalloid cardioplegia. Myocardial performance, systolic function, and diastolic function were assessed with nuclear ventriculography by evaluating the response to volume loading. Preoperatively the groups were similar. Intraoperatively, blood cardioplegia resulted in significantly warmer LV and RV temperatures (left ventricle: 15.5 degrees +/- 0.2 degrees C with blood cardioplegia and 12.6 degrees +/- 0.3 degrees C with crystalloid cardioplegia [p less than .0001]; right ventricle: 18.3 degrees +/- 0.3 degrees C with blood cardioplegia and 15.1 degrees +/- 0.3 degrees C with crystalloid cardioplegia [p less than .0001]). Postoperatively, blood cardioplegia resulted in better LV performance (higher LV stroke work index at a similar LV end-diastolic volume index [EDVI]) (p = .01), better LV systolic function (similar systolic blood pressures at smaller LV end-systolic volume indexes [ESVI]), (p = .04), and improved LV diastolic function (lower left atrial pressures at similar LVEDVIs) (p = .03).(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased susceptibility of the left compared to the right ventricle to remote ischemia/reperfusion injury in human C1-inhibitor-overexpressing transgene mice.

Acute myocardial injury has been demonstrated as a remote sequela of severe lower torso ischemia-reperfusion (I/R) due to proinflammatory events. In a model of I/R injury, administration of C1 esterase inhibitor (C1-Inh) reduces myocardial necrosis. We investigated the susceptibility of the left (LV) versus right ventricle (RV) and the protective effect of transgenic C1-Inh-overexpressing mice. Two groups of mice (n = 6) underwent a 2-h lower torso ischemia followed by 3 h of reperfusion: transgenic and wild type with sham-operated controls. Animals were then injected with (125)I bovine albumin. Heart was removed and samples from right and left ventricular free wall were harvested, weighted, and radioactivity was determined. Permeability index for wild-type animals in the RV was 0.22 +/- 0.04, compared to 0.17 +/- 0.07 in controls (NS), and in the LV 0.36 +/- 0.08, compared to 0.21 +/- 0.05 in controls (p <.01). The LV showed a significantly higher value compared to the right (0.22 +/- 0.04 vs. 0.36 +/- 0.08, p <.01). No difference was seen in the RV between transgenic and wild-type mice; however, in the LV the values decreased significantly in transgenic animals (p <.015). Thus, remote myocardial injury after lower torso I/R is present in both ventricles; however, the LV seems to be more susceptible as assessed by albumin permeability. Inhibition of the classic complement cascade may be a promising therapeutic approach for myocardial protection in reperfusion injury.     

Right ventricular dysfunction in acute thermal injury.

The elevated cardiac output (CO) and pulmonary artery hypertension (PAH) observed in thermal injury offers a unique opportunity to study the effects of a combined pressure-flow load on the right ventricle in previously healthy persons. Potential responses include a diminished right ventricular ejection fraction (RVEF), increased right ventricular end-diastolic volume index (RVEDVI), and augmented myocardial oxygen consumption because of increased systolic wall tension. We investigated these factors in 15 nonhypoxic patients without sepsis having 15--75% body surface area burns using flow directed catheters and the thermodilution technique. All patients increased their CO in response in fluid resuscitation, but six patients with an elevated mean pulmonary artery pressure (greater than 20 mmHG and increased pulmonary vascular resistance (greater than 1.2 mmHg/min/L) had right ventricular dysfunction as evidenced by an increase (188 +/- 15 ml/M2) in RVEDVI and a decreased (0.26 +/- 4 ml/M2) RVEF. Patients without PAH had a smaller RVEDVI (115 +/- 4 ML/M2) and larger RVEF (0.39 +/- 0.02). Patients with PAH and RV dysfunction were older, had larger body surface area burns, lower systemic diastolic artery pressures (63 +/- 4 mmHg) and higher heart rates (114 +/- 7 beats/min); RV end-diastolic pressures were minimally elevated (9.5 +/- 1.4 mmHg). The decrease in RVEF and increase in RVEDVI may limit the hemodynamic response to fluid volume replacement and survival.     

Right ventricular outflow tract reconstruction for pulmonary regurgitation after repair of tetralogy of Fallot. Preliminary results.

BACKGROUND: Pulmonary regurgitation after tetralogy of Fallot (ToF) repair is associated with right ventricular dilatation, failure and arrhythmia. Timing and technique for re-intervention remain controversial. METHODS: Our recent approach is to reconstruct the dilated right ventricle outflow tract (RVOT) as a fibro-muscular sleeve to support a pulmonary homograft valve conduit in orthotopic position. Indication is based on clinical and magnetic resonance (MR) criteria. We reviewed all patients who underwent RVOT reconstruction between January 2004 and February 2005. There were seven children (mean age 14+/-2 years) operated 13+/-2 years after ToF repair, and 12 adults (mean age 30+/-15 years) operated 23+/-10 years after ToF repair. Exercise testing and MR evaluation prior to surgery and at 1 year postoperative follow-up were compared. RESULTS: There was no operative mortality. At 1 year, pulmonary regurgitation was mild or less in 16/19 patients. Right ventricular (RV) end-diastolic (158+/-51 to 103+/-36ml/m(2), p<0.001) and end-systolic volumes (85+/-42 to 49+/-24ml/m(2), p=0.001) fell significantly. Importantly, effective RV stroke volume (43+/-10 to 48+/-7ml/m(2), p=0.019) and left ventricular (LV) stroke volume (43+/-7 to 47+/-7ml/m(2), p=0.009) increased significantly. The mean RV/LV end-diastolic volume ratio fell markedly in both children and adults (2.22+/-0.62 to 1.38+/-0.52). However, no improvement in maximal VO(2) on exercise was noted in either group. CONCLUSIONS: RVOT reconstruction restored valve function, improved RV dimensions and left and right stroke volumes. Maximal exercise capacity did not improve in either children or adults.