Cambios hemodinámicos en la exploración mediante eco-doppler tras angioplastia con stent de arteria renal nativa / Haemodynamic changes in duplex ultrasound after native renal artery stenting

OBJETIVOS: Describir los cambios hemodinámicos que se producen en el ecodoppler tras una angioplastia con stent de arteria renal (AR) nativa. PACIENTES Y MÉTODOS: Se analizaron retrospectivamente todas las angioplastias sobre AR nativa realizadas entre los años 2000 y 2013, seleccionando aquellos casos con: 1) ecodoppler durante los 6 meses previos y posteriores al procedimiento, 2) angioplastia con stent de una AR con permeabilidad de la contralateral. Se compararon mediante el test de Wilcoxon las velocidades en el origen de ambas AR y la ratio renoaórtica (RAR), antes y después del procedimiento. RESULTADOS: Setenta y un casos (40%) cumplieron los criterios de inclusión. En las arterias tratadas, la velocidad media disminuyó significativamente un 56% tras el procedimiento (341 vs. 164 cm/s; p < 0,00). En un 73% de estas AR, las velocidades postangioplastia disminuyeron al rango de la normalidad (<200 cm/s). En las AR contralaterales (no tratadas), la velocidad media también disminuyó significativamente un 13% (199 vs. 175 cm/s; p = 0,029). Tras la angioplastia disminuyó de 41 a 33% el porcentaje de AR contralaterales con velocidad por encima del valor normal (>200 cm/s). La RAR también mostró una disminución estadísticamente significativa en la AR tratada (4,13 vs. 1,87; p < 0,000) como en la no tratada (2,71 vs. 2,28; p < 0,026). CONCLUSIONES: En la exploración ecodoppler tras una angioplastia con stent renal se produce una disminución significativa de las velocidades en el origen de ambas AR, la tratada y la no tratada. Este último hallazgo indica la existencia de una aceleración vicariante en la arteria no tratada, que disminuye cuando se corrige la lesión

OBJECTIVES: To describe the haemodynamic changes in duplex ultrasound after angioplasty and stenting of the native renal artery (RA). PATIENTS AND METHODS: All native RA angioplasties performed between 2000 and 2013 were retrospectively analysed, selecting those cases: 1) Duplex ultrasound within 6 months before and after the procedure, 2) unilateral renal artery angioplasty and stenting with patency of the contralateral RA. The flow velocities at the origin of the treated and untreated RA, and the renal aortic ratio (RAR), were compared using the Wilcoxon test before and after the procedure. RESULTS: Seventy-one cases (40%) satisfied the inclusion criteria, all of them without significant residual stenosis after the procedure. In the treated arteries, the mean velocity decreased significantly by 56% after the procedure (341 vs. 164 cm/s; P<.00). The post-angioplasty flow velocity in 73% of these RAs decreased to within the normal range (<200 cm/s). The mean velocity in contralateral RAs (untreated) also significantly decreased by 13% (199 vs. 175 cm/s; P<.029). After angioplasty, the percentage of contralateral RAs with velocity above normal (>200 cm/s) fell from 41 to 33%. The RAR also showed a statistically significant decrease in the treated RA (413 vs. 1.87; P<.000) and untreated RA (2.71 vs. 2.28; P<.026). CONCLUSIONS: Duplex ultrasound after renal angioplasty and stenting produced a significant decrease in the flow velocity at the origin of both the treated and untreated RAs. The latter finding suggests the existence of a vicarious acceleration in the untreated renal artery, which decreases when correcting the lesion

Roles of sensory nerves in the regulation of radiation-induced structural and functional changes in the heart.

PURPOSE: Radiation-induced heart disease (RIHD) is a chronic severe side effect of radiation therapy of intrathoracic and chest wall tumors. The heart contains a dense network of sensory neurons that not only are involved in monitoring of cardiac events such as ischemia and reperfusion but also play a role in cardiac tissue homeostasis, preconditioning, and repair. The purpose of this study was to examine the role of sensory nerves in RIHD. METHODS AND MATERIALS: Male Sprague-Dawley rats were administered capsaicin to permanently ablate sensory nerves, 2 weeks before local image-guided heart x-ray irradiation with a single dose of 21 Gy. During the 6 months of follow-up, heart function was assessed with high-resolution echocardiography. At 6 months after irradiation, cardiac structural and molecular changes were examined with histology, immunohistochemistry, and Western blot analysis. RESULTS: Capsaicin pretreatment blunted the effects of radiation on myocardial fibrosis and mast cell infiltration and activity. By contrast, capsaicin pretreatment caused a small but significant reduction in cardiac output 6 months after irradiation. Capsaicin did not alter the effects of radiation on cardiac macrophage number or indicators of autophagy and apoptosis. CONCLUSIONS: These results suggest that sensory nerves, although they play a predominantly protective role in radiation-induced cardiac function changes, may eventually enhance radiation-induced myocardial fibrosis and mast cell activity.

Transthoracic cardiac ultrasonic stimulation induces a negative chronotropic effect.

The objective of this study is to investigate cardiac bioeffects resulting from ultrasonic stimulation using a specific set of acoustical parameters. Ten Sprague-Dawley rats were anesthetized and exposed to 1-MHz ultrasound pulses of 3-MPa peak rarefactional pressure and approximately 1% duty factor. The pulse repetition frequency started slightly above the heart rate and was decreased by 1 Hz every 10 s, for a total exposure duration of 30 s. The control group was composed of five rats. Two-way analysis of variance for repeated measures and Bonferroni post hoc tests were used to compare heart rate and ejection fraction, which was used as an index of myocardial contractility. It was demonstrated for the first time that transthoracic ultrasound has the potential to decrease the heart rate by ~20%. The negative chronotropic effect lasted for at least 15 min after ultrasound exposure and there was no apparent gross damage to the cardiac tissue.

Leg heating using far infra-red radiation in patients with chronic heart failure acutely improves the hemodynamics, vascular endothelial function, and oxidative stress.

BACKGROUND: Systemic thermal therapy (STT) has been associated with beneficial effects in patients with chronic heart failure (CHF). The fact, however, that it requires a dedicated as well as spacious facility and trained personnel makes it difficult to practice in the daily care of patients with CHF. OBJECTIVE: The aim of this study was to determine whether the leg thermal therapy (LTT) has a positive impact similar to that of STT in patients with CHF. Methods and Results Twenty patients with CHF (57 ± 17 years old, left ventricular ejection fraction=30 ± 10%) received LTT (45°C) for 20 minutes. Immediately after the treatment, the core temperature had increased (+0.3 ± 0.3°C) (p<0.01). While the LTT had no significant effects on the heart rate, systolic arterial pressure, and diastolic blood pressure, it increased the cardiac output (mixed venous oxygen saturation; +2 ± 3%) and decrease the pulmonary capillary wedge pressure (-2 ± 2 mmHg). The LTT significantly improved the flow-mediated vasodilatation (FMD) from 4.8 ± 2.6 to 7.1 ± 3.6%, the antioxidative markers, thiol from 4.0 ± 0.7 to 4.5 ± 0.9 µmoL/g, and the marker of oxidative deoxyribonucleic acid (DNA) damage, urine 8-hydroxy-2'deoxyguanosine (8OHdG) from 100 to 82 ± 3%, respectively (p<0.05). No patient had any adverse effects associated with LTT. Conclusion LTT acutely improved FMD, and oxidative stress in patients with CHF. Although the long-term effect of LTT remains to be investigated, its practicality which is comparable to that of STT would make it an attractive therapeutic strategy for patients with CHF.

Resonancia magnética del ventrículo izquierdo en sujetos sanos: valores normales de morfología, función, perfusión y viabilidad / Magnetic resonance Imaging of the left ventricle in healthy subjects: normal values for morphology, function, perfusion, and viability

Objetivos: Definir unos patrones de normalidad en la cuantificación de la función, la perfusión y la viabilidad cardíaca del ventrículo izquierdo (VI) mediante resonancia magnética (RM), analizando las diferencias relevantes por edad y sexo. Material y métodos: Se analizaron 18 sujetos sanos con edad comprendida entre los 15 y los 77 años. Las adquisiciones se realizaron utilizando 2 equipos de RM de 1,5 y 3 teslas. Mediante una herramienta informática para el procesado de las imágenes (Cardio-RM, View Forum, Philips Sistemas Médicos) se evaluaron parámetros morfofuncionales (volumen telediastólico y telesistólico, volumen latido, fracción de eyección, gasto cardíaco, masa miocárdica, espesor miocárdico, engrosamiento y movimiento miocárdico), de perfusión (pendiente ascendente máxima relativa, realce máximo relativo) y de realce tardío (porcentaje de hiperrealce tardío). Para el análisis estadístico se utilizó la prueba de la t de Student. Resultados: Se observaron diferencias entre sexos, con un aumento estadísticamente significativo de los volúmenes telediastólico y telesistólico, del volumen latido y de la masa miocárdica en los varones. Las mujeres presentaron un aumento estadísticamente significativo de la fracción de eyección. Los sujetos sanos mayores de 45 años presentan diferencias estadísticamente significativas en el espesor del miocardio. Conclusión: Se describen los valores de referencia de los parámetros morfofuncionales, de perfusión y de realce tardío para los estudio de RM del corazón. El sexo y la edad tienen que tenerse en cuenta como covariables relacionadas con algunos de estos parámetros (AU)

Objective: To define normal values of MRI parameters related to cardiac morphology, function, perfusion, and delayed enhancement of the left ventricle and to analyze differences based on age and sex. Material and methods: We used 1.5T and 3T MRI scanners to analyze 18 healthy subjects ranging in age from 15 to 77 years old. Dedicated image processing software (Cardio-MR, View Forum, Philips Medical Systems) was used to evaluate morphological and functional parameters (end-diastolic and end-systolic volume, stroke volume, ejection fraction, cardiac output, wall mass, wall thickness, wall thickening, wall motion), perfusion parameters (relative maximum upslope, relative maximum enhancement), and delayed enhancement (percentage of late hyperenhancement). Student's t-test was used for statistical analyses. Results: Sex differences were observed: end-diastolic and end-systolic volumes, stroke volume, and wall mass were significantly higher in men and the ejection fraction was significantly larger in women. Healthy subjects over 45 years of age had significantly greater wall thickness. Conclusion: We report cardiac MRI reference values for morphological, functional, perfusion, and delayed enhancement parameters. Sex and age should be taken into account as important variables related to some of these parameters (AU)

Fetal and neonatal responses following maternal exposure to mobile phones.

OBJECTIVE: To study fetal and neonatal heart rate (HR) and cardiac output (COP), following acute maternal exposure to electromagnetic fields (EMF) emitted by mobile phones. METHODS: The present study was carried out at Benha University Hospital and El-Shorouq Hospital, Cairo, Egypt, from October 2003 to March 2004. Ninety women with uncomplicated pregnancies aged 18-33 years, and 30 full term healthy newborn infants were included. The pregnant mothers were exposed to EMF emitted by mobile telephones while on telephone-dialing mode for 10 minutes during pregnancy and after birth. The main outcome were measurements of fetal and neonatal HR and COP. RESULTS: A statistical significant increase in fetal and neonatal HR, and statistical significant decrease in stroke volume and COP before and after use of mobile phone were noted. All these changes are attenuated with increase in gestational age. CONCLUSION: Exposure of pregnant women to mobile phone significantly increase fetal and neonatal HR, and significantly decreased the COP.

Effect of deep brain stimulation of the posterior hypothalamic area on the cardiovascular system in chronic cluster headache patients.

The objective of this study was to determine the cardiovascular effects of chronic stimulation of the posterior hypothalamic area (PHA) in cluster headache (CH) patients. Systolic and diastolic blood pressure (SBP, DBP), cardiac output, total peripheral resistance (TPR), heart rate (HR) and breathing were monitored at supine rest and during head-up tilt test (HUTT), Valsalva manoeuvre, deep breathing, cold face test and isometric handgrip in eight drug-resistant chronic CH patients who underwent monolateral electrode implantation in the PHA for therapeutic purposes. Autoregressive power spectral analysis (PSA) of HR variability (HRV) was calculated at rest and during HUTT. Each subject was studied before surgery (condition A) and after chronic deep brain stimulation (DBS) of PHA (condition B). Baseline SBP, DBP, HR and cardiovascular reflexes were normal and similar in both conditions. With respect to condition A, DBP, TPR and the LF/HF obtained from the PSA of HRV were significantly (P < 0.05) increased during HUTT in condition B. In conclusion, chronic DBS of the PHA in chronic CH patients is associated with an enhanced sympathoexcitatory drive on the cardiovascular system during HUTT.

Splanchnic blood flow and oxygen consumption: effects of enteral nutrition and dopexamine in the elderly cardiac surgery patient.

BACKGROUND: After cardiac surgery, patients are at risk of organ dysfunction because of decreased perfusion. Different measures have been used to increase the splanchnic blood flow. We compared the effects of enteral nutrition and dopexamine on the cardiac output, splanchnic blood flow and oxygen consumption. METHODS: Sixteen patients undergoing cardiac surgery were included. Indocyanine green extraction and thermodilution were used for repeated measurements of the splanchnic blood flow and cardiac output. On the first post-operative day, indocyanine green infusion was started. Patients were randomized to start with dopexamine (Dpx group) or enteral nutrition (EN group). After 180 min, both groups received a combination of dopexamine and enteral nutrition. Blood gases from the hepatic vein and pulmonary and radial arteries were analysed repeatedly. RESULTS: In the Dpx group, the cardiac index increased with dopexamine infusion, but not when enteral nutrition was added. In the EN group, enteral nutrition alone did not increase the cardiac index, but dopexamine addition increased the cardiac index in this group. The splanchnic blood flow increased initially in the Dpx group, but then returned to baseline and remained constant on addition of enteral nutrition. In the EN group, the splanchnic blood flow initially remained at baseline, but increased after dopexamine addition. There was no difference between the groups with regard to systemic or splanchnic oxygen consumption or the oxygen extraction ratio. In the Dpx group, lactate increased from baseline with no further increase on addition of enteral nutrition. Lactate was unchanged in the EN group. CONCLUSIONS: Dopexamine and enteral nutrition caused no adverse effects on oxygen consumption or the oxygen extraction ratio. Enteral nutrition did not increase the splanchnic blood flow or cardiac index. Dopexamine increased the systemic blood flow with only a transient effect on the splanchnic blood flow. Dopexamine increased the lactate concentration, possibly indicating a more ischaemic condition.

Far-infrared therapy: a novel treatment to improve access blood flow and unassisted patency of arteriovenous fistula in hemodialysis patients.

Vascular access malfunction, usually presenting with an inadequate access flow (Qa), is the leading cause of morbidity and hospitalization in hemodialysis (HD) patients. Many methods of thermal therapy have been tried for improving Qa but with limited effects. This randomized trial was designed to evaluate the effect of far-infrared (FIR) therapy on access flow and patency of the native arteriovenous fistula (AVF). A total of 145 HD patients were enrolled with 73 in the control group and 72 in the FIR group. A WS TY101 FIR emitter was used for 40 min, and hemodynamic parameters were measured by the Transonic HD(02) monitor during HD. The Qa(1)/Qa(2) and Qa(3)/Qa(4) were defined as the Qa measured at the beginning/at 40 min later in the HD session before the initiation and at the end of the study, respectively. The incremental change of Qa in the single HD session with FIR therapy was significantly higher than that without FIR therapy (13.2 +/- 114.7 versus -33.4 +/- 132.3 ml/min; P = 0.021). In comparison with control subjects, patients who received FIR therapy for 1 yr had (1) a lower incidence (12.5 versus 30.1%; P < 0.01) and relative incidence (one episode per 67.7 versus one episode per 26.7 patient-months; P = 0.03) of AVF malfunction; (2) higher values of the following parameters, including Delta(Qa(4) - Qa(3)) (36.2 +/- 82.4 versus -12.7 +/- 153.6 ml/min; P = 0.027), Delta(Qa(3) - Qa(1)) (36.3 +/- 166.2 versus -51.7 +/- 283.1 ml/min; P = 0.035), Delta(Qa(4) - Qa(2)) (99.2 +/- 144.4 versus -47.5 +/- 244.5 ml/min; P < 0.001), and Delta(Qa(4) - Qa(2)) - Delta(Qa(3) - Qa(1)) (62.9 +/- 111.6 versus 4.1 +/- 184.5 ml/min; P = 0.032); and (3) a better unassisted patency of AVF (85.9 versus 67.6%; P < 0.01). In conclusion, FIR therapy, a noninvasive and convenient therapeutic modality, can improve Qa and survival of the AVF in HD patients through both its thermal and its nonthermal effects.

Sympathoimmune anomalies underlying the response to stressful challenge in human immunodeficiency virus spectrum disease.

OBJECTIVE: This study examined immune, endocrine, and cardiovascular reactivity during stressful behavioral challenge in human immunodeficiency virus (HIV) seropositive (HIV+) and seronegative (HIV-) men and women and assessed whether immunocellular reactivity was differentially associated with concomitant alterations in sympathetic response. METHODS: The 133 HIV+ [84 asymptomatic, 49 symptomatic] and 92 HIV- subjects completed a speech stress reactivity protocol. RESULTS: Immunocellular reactivity to the speech stressor did not differ among asymptomatic and symptomatic HIV+ groups; however, relative to seronegatives, reactivity differences were present. Specifically, HIV+ subjects exhibited greater increases in total number of T cells, as well as in cytotoxic/suppressor T cells, activated T cells, and activated cytotoxic/suppressor T cells, and less increase in natural killer (NK) cell numbers. In addition, less stress-induced increase in NK cell cytotoxicity was observed along with greater suppression of the lymphoproliferative response to mitogen stimulation in the HIV+ group. Although no group differences in catecholamine reactivity were observed, the association of immunoreactivity with catecholamine responsiveness differed between serostatus groups. Specifically, the HIV+ subjects compared with HIV- subjects displayed greater lymphocytosis per unit change in norepinephrine; whereas NK cell reactivity was positively related to epinephrine responsiveness, but only in the HIV- group. These findings were present even after controlling for age and body mass, as well as other potential influences on immunocellular migration, such as cortisol levels and prevailing cardiac output. CONCLUSION: Early in HIV spectrum disease, functional abnormalities in the stress-induced migratory ability of specific immunocellular subsets are present that may reflect an underlying pathophysiological alteration in sympathoimmune communication.

Effects of amifostine on radiation-induced cardiac damage.

The purpose of this study was to investigate whether administration of amifostine prior to irradiation could reduce radiation damage of the rat heart. Female Spraque-Dawley rats were randomized to receive single-dose irradiation (0-22.5 Gy) locally to the heart. Fifteen to twenty minutes before radiation exposure, the animals received either intraperitoneally administered amifostine (160 mg/kg) or buffered saline solution. At 6 months post-irradiation, cardiac function was assessed by the in vitro working rat heart preparation. The severity of interstitial and/or perivascular fibrosis in different anatomical regions of the rat heart was assessed using a semi-quantitative scoring system. Radiation exposure to doses > or = 20 Gy markedly reduced coronary flow, aortic flow and cardiac output. Administration of amifostine prior to radiotherapy afforded protection against these effects and normal cardiac output was maintained, even after 22.5 Gy. A small, non-significant, reduction in histological damage (i.e. perivascular fibrosis and interstitial fibrosis) was also apparent in animals treated with amifostine. There was a clear protective effect of amifostine on the severity and extent of macroscopic damage in lung tissue included in the cardiac irradiation field. The findings of this study suggest that a single dose of amifostine administered prior to irradiation is effective in reducing cardiac damage.

Comparison of in vivo cardiac function with ex vivo cardiac performance of the rat heart after thoracic irradiation.

The aim of the study was to compare in vivo cardiac function with ex vivo cardiac performance after local heart irradiation in the same rat. Left ventricular ejection fraction (LVEF) was measured in vivo by radionuclide ventriculography in Sprague-Dawley rats up to 16 months after a single dose of 20 Gy. Four days after in vivo measurements, cardiac performance was determined ex vivo, using the isolated working rat heart preparation. After irradiation, cardiac performance measured ex vivo deteriorated more rapidly than the in vivo measured LVEF. Within 4 months post-treatment, ex vivo cardiac output and stroke volume started to decrease and declined continuously throughout the observation period of 16 months. The reduction in stroke volume was already significant (p < 0.04) at 4 months post-treatment, whereas the decline in cardiac output was significant (p < 0.05) at 12 months post-treatment. In vivo, no change in LVEF was observed during the first 12 months post-treatment. Thereafter, LVEF decreased rapidly from 65 +/- 2% to 46 +/- 8% (p < 0.01), at 16 months post-treatment. Up to 12 months post-irradiation, LVEF was not correlated to ex vivo cardiac output. At 16 months post-treatment, when clinical symptoms of heart failure become evident, a positive relation between both parameters was found. The lack of correlation between the in vivo and ex vivo measurements of cardiac function during the first 12 months post-treatment might be explained by the involvement of compensatory mechanisms being operative in vivo to maintain sufficient cardiac output.

Late effects of X irradiation on regulation of cerebral blood flow after whole-brain exposure in rats.

Hemodynamic parameters such as total cerebral blood volume (total CBV), cerebral parenchymal blood volume (CBV), cerebral blood flow (CBF) and cerebral blood velocity index were measured in rats 6, 12 and 18 months after single exposures of brain to 5, 10, 15 and 20 Gy X rays for total CBV, CBF and blood velocity index, and only 20 Gy for CBV. Total CBV and blood velocity index were determined by a noninvasive blood dilution method using [99mTc]pertechnetate and CBF by [131I]iodoantipyrine brain extraction. The CBV was obtained from both parenchymal plasma and erythrocyte volumes measured in isolated brain by 125I-labeled serum albumin and 51Cr-labeled erythrocytes, respectively. Neither the dose nor the time after irradiation influenced total CBV. Nevertheless, CBV decreased slightly while CBF decreased strongly at 12 and 18 months after 20 Gy. In contrast, the blood velocity index increased progressively at 12 and 18 months after 15 Gy and at all times after 20 Gy. According to the coexistence in irradiated brains of a remodeling with microvascular occlusions and dilated abnormal vessels, this lowered CBF can be explained by the smaller number of open capillaries and a "steal phenomenon" through low-resistance channels developed in the parenchymal and extraparenchymal vasculatures. Such a "steal phenomenon" is also supported by the response of the blood velocity index, which appears to be the earliest sensitive index for the detection of hemodynamic changes with respect to time (6 months) and dose of radiation (15 Gy).

Late response to whole-lung irradiation alone and with whole-body hyperthermia in dogs.

The late effects of whole-lung irradiation with and without whole-body hyperthermia were studied in beagle dogs. The reference doses ranged from 18 to 49.5 Gy given in 1.5-Gy fractions over 6 weeks. Whole-body hyperthermia was given in three 2-h treatments to a deep rectal temperature of 42.0 degrees C. Radiation was given simultaneously with hyperthermia on those days. Physiological and histopathological responses were evaluated. Physiological changes included decreases in cardiac output, systemic blood pressure, dynamic compliance and serotonin uptake. Early changes included an increase in extravascular water and total protein in the lavage. These changes were considered mild, were compensated for and occurred only in dogs receiving doses of 40.5 Gy or greater given in 1.5-Gy fractions over 6 weeks. Histopathological changes were typical of irradiated lung and included pleural fibrosis, interstitial fibrosis, fibrotic foci, and peribronchial and perivascular fibrosis. There was no enhancement of late injury to lung by hyperthermia seen in this study.

Changes in cardiac performance and sympathetic stimulation during and after fractionated radiotherapy in a rat model.

The consequences of fractionated irradiation on the number of cardiac alpha- and beta-adrenergic receptors, myocardial norepinephrine concentration and in vitro assessed heart function were studied in Sprague-Dawley rats. Animals were locally irradiated on the thorax with a total dose of 50 Gy, in 5 weeks, using two different fractionation schemes (5 x 2.0 Gy/week and 3 x 3.3 Gy/week). Functional and biochemical assays were performed during treatment and at 6 months after initiation of treatment. During fractionated irradiation, the numbers of alpha- and beta-adrenergic receptors tended to rise. During this period, myocardial norepinephrine concentration remained fairly constant and no decrease in cardiac output was observed. At 6 months, a significant increase of the numbers of alpha- and beta-adrenergic receptors was observed in the 3.3 Gy/fraction group compared to age-matched controls, p = 0.012 and p = 0.02, respectively. At this time point, the myocardial norepinephrine concentration had decreased below control levels (p = 0.008 for the 3.3. Gy/fraction schedule, and p = 0.03 for the 2.0 Gy/fraction schedule). At 6 months, the cardiac output declined to 61% (p = 0.009) and 69% (p = 0.04) of control values for the 3.3 and 2.0 Gy/fraction schedules, respectively. The present data clearly show development of late cardiac sequelae caused by fractionated thorax irradiation with a total dose of 50 Gy. Moreover, this study lends support to the importance of fraction size with regard to the severity of the radiation-induced cardiac damage.

In vitro assessment of cardiac performance after irradiation using an isolated working rat heart preparation.

The effect of irradiation on cardiac function was assessed using an isolated working rat heart preparation. The animals were given single doses of X-rays in the range 15-30 Gy to their hearts. Cardiac output (CO = aortic flow + coronary flow), heart weight and body weight were followed for a period of 10 months after treatment. Irradiation led to a decrease in cardiac function. This reduction was dose-dependent and progressive with time after treatment. The shape of the Frank-Starling curves constructed for irradiated hearts suggests a loss of contractile function of the myocardium. Coronary flow rates measured in 'working' hearts and in 'Langendorff' hearts were not significantly changed by the irradiation treatment. The isolated working rat heart preparation proved to be a simple and suitable animal model for the investigation of irradiation-induced cardiotoxicity.

Morphological and functional changes in the rat heart after X irradiation: strain differences.

The hearts of mature male rats of the Wistar and Sprague-Dawley strains were locally irradiated with single doses of 17.5 and 20.0 Gy of X rays, respectively. These two dose levels had previously been shown to result in a comparable latent period between irradiation and the death of rats of these two strains from cardiac failure. Morphological changes in the myocardium and modifications in cardiac function were assessed in the animals at 28, 70, and 100 days after irradiation. The first radiation-induced change which was observed in the myocardium was a rapid decline in capillary density and a loss of alkaline phosphatase activity by the capillary endothelial cells. The capillary density was reduced to approximately 50% of that of unirradiated control values at 28 days and to approximately 40% of the control values between 70 and 100 days after irradiation. The loss of enzyme activity was also detected at 28 days. Examination of histological sections showed an increase by 70 days in the areas with negative enzyme activity up to approximately 70% of the myocardium. The reduction in capillary density and the loss of enzyme activity occurred before any marked pathological changes were seen in the myocardium. The pathological lesions seen in the myocardium at 100 days after irradiation were qualitatively and quantitatively the same in the two strains of rat. Measurements of cardiac output in Sprague-Dawley rats showed a gradual decline in output after irradiation; however, measurements in Wistar rats showed a progressive increase in cardiac output over the same period of time. It was shown by rubidium extraction that there was an increase in the percentage of the total cardiac output distributed to the ventricular muscle of Sprague-Dawley rats, while similar measurements in Wistar rats showed no significant change. In spite of the marked strain differences observed in cardiac output and rubidium extraction, blood perfusion per gram of ventricular muscle was apparently not modified in both strains of rat after irradiation. These findings indicated that the correlation between morphological effects after irradiation and the functional expression of damage is highly complex.

Unilateral radiation pneumonitis in sheep: physiological changes and bronchoalveolar lavage.

Radiation pneumonitis is a life-threatening result of therapeutic thoracic irradiation, yet its mechanisms are poorly understood. We studied the effects of unilateral lung irradiation (3,000 rad) in sheep from the immediate response to the later development of radiation pneumonitis. We defined radiation pneumonitis by its diagnostic clinical feature, radiographic infiltration of the irradiated zone with a straight margin corresponding to the radiation port. The immediate response in the few hours after irradiation was characterized by cough, labored respiration, hypoxemia (arterial PO2 decreased 19 Torr), mild pulmonary hypertension (pulmonary arterial pressure increased 20%), and lymphopenia. Hemodynamics and gas exchange returned to normal by day 2 but became abnormal again before or during radiation pneumonitis at 32 +/- 2 days. Respiratory distress, hypoxemia, and pulmonary hypertension recurred during radiation pneumonitis. Bronchoalveolar lavage during radiation pneumonitis contained increased neutrophils (19 +/- 4%, control = 7%), increased protein (0.27 +/- 0.1 g/dl, control = 0.12 +/- 0.03), and severely impaired ability to lower surface tension. Alveolar macrophages from both lungs during unilateral radiation pneumonitis exhibited impaired generation of superoxide after phorbol myristate (only a 30% increase). Normal control alveolar macrophages increased superoxide production after stimulation greater than 400%. We conclude that unilateral lung irradiation in sheep causes a mild immediate response followed by radiation pneumonitis at 1 mo. Unilateral radiation pneumonitis in this model is associated with ipsilateral neutrophilic alveolitis, increased bronchoalveolar lavage protein, and impaired surfactant function, as well as bilateral functional abnormalities of alveolar macrophages.

Right heart catheterization in rats with pulmonary hypertension and right ventricular hypertrophy.

Using a special Millar ultraminiature catheter pressure transducer, right ventricular functional parameters were measured in anesthetized, closed-chest rats under control conditions, during acute pulmonary hypertension and after induction of right ventricular hypertrophy. Acute i.v. infusion of noradrenaline and a brief period of hypoxia in female Sprague-Dawley rats elicited a marked increase in right ventricular systolic pressure (RVSP) and in the maximal rate of rise in right ventricular pressure (RV dp/dtmax). After 3 and 16 days of daily administrations of triiodothyronine in female Sprague-Dawley rats, all right ventricular hemodynamic parameters were enhanced along with the increase in left ventricular function. The right and left ventricles were hypertrophied, and cardiac output was increased. After 40 and 45 days subsequent to bilateral thorax irradiation of male Brown-Norway rats, RVSP and RV dp/dtmax were increased, the right ventricle was hypertrophied, while the left ventricle did not exhibit appreciable hemodynamic or morphologic alterations. Cardiac output was depressed. Thus, these two experimental models differ considerably as to the mechanism and time course of the development of right ventricular hypertrophy as well as to the participation of the left ventricle and the involvement of volume overload.