Effects of dimethylthiourea on the cardiac function and oxyradical status in ischemia-reperfusion injury.
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We studied the effects of a nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME), on cardiac depression and bronchospasm provoked by systemic anaphylaxis in vivo in rabbits. Animals pretreated with L-NAME showed lower survival rates than control animals pretreated with normal saline. The survival rate in L-NAME-pretreated animals was increased by the administration of L-arginine after initiation of anaphylaxis. Cardiac output fell significantly in animals pretreated with L-NAME compared with controls, although venous return was increased. In animals pretreated with L-NAME, pulmonary resistance was significantly increased, and administration of arginine attenuated the bronchospasm. In conclusion, these results, along with the low survival rates in the L-NAME-treated animals, suggest that NO production may be beneficial to cardiac depression and bronchospasm in anaphylaxis in vivo.
This study examined the physiological effects of reducing training mileage in a veteran long distance runner while increasing exercise intensity. Variables measured included stroke volume, cardiac output, maximum oxygen uptake, ventilation threshold and performance time in a 10,000 m run. For 8 weeks, training mileage was reduced from 75.8 miles per week to 42.5 miles per week including interval training twice weekly. Following the specialized training, performance time was 10 seconds faster although VO2max and heart contractility had decreased. It was concluded that distance running performance can be maintained while considerably reducing training mileage and increasing exercise intensity twice a week.
During growth, central venous, right ventricular, pulmonary arterial, pulmonary capillary wedge, and systemic arterial pressures, heart rate, and cardiac output were repeatedly measured in 41 Friesian calves, considered as having conventional muscular conformation, and in 19 Belgian White and Blue double-muscled calves. A total of 123 and 70 recordings were collected in conventional and double-muscled calves, respectively. These circulatory indices were calculated: stroke volume, cardiac and stroke indices, pulmonary and systemic pulse pressures, pulmonary and systemic vascular resistance indices, and right and left ventricular work indices. Results indicated that systemic arterial and pulse pressures, as well as cardiac output, stroke volume, cardiac and stroke indices, and right and left ventricular work indices were significantly (P < or = 0.05 to 0.001) lower but, in contrast, pulmonary and systemic vascular resistance indices were significantly (P < or = 0.001) higher in double-muscled than in conventional calves. Right-sided vascular pressures and heart rate were similar in the 2 groups. These results indicated that global cardiac performance may be considerably poorer in double-muscled calves. Diminished cardiac performance of double-muscled calves appears to be related neither to relative bradycardia nor to reduced ventricular preload. The potential role of increased ventricular afterload or of reduced myocardial contractility in double-muscled cattle should be determined by direct measurements.
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During radiotherapy of thoracic tumors, the heart is often included in the primary treatment volume, and chronic impairment of myocardial function occurs. The cellular biomolecules are altered directly by radiation or damaged indirectly by free radical production. The purpose of this investigation was to evaluate the biochemical and functional responses of the rat heart to a single high dose of radiation. The effect of 20 Gy local X irradiation was determined in the heart of Wistar rats under general anesthesia. Mechanical performances were measured in vitro using an isolated perfused working heart model, and cardiac antioxidant defenses were also evaluated. Hearts were studied at 1 and 4 months after irradiation. This single dose of radiation induced a marked drop in the mechanical activity of the rat heart: aortic output was significantly reduced (18% less than control values) at 1 month postirradiation and remained depressed for the rest of the experimental period (21% less than control 4 months after treatment). This suggests the development of myocardial failure after irradiation. The decline of functional parameters was associated with changes in antioxidant defenses. The decrease in cardiac levels of vitamin E (-30%) was associated with an increase in the levels of Mn-SOD and glutathione peroxidase (+45.5% and +32%, respectively, at 4 months postirradiation). However, cardiac vitamin C and catalase levels remained constant. Since these antioxidant defenses were activated relatively long after irradiation, it is suggested that this was probably due to the production of free radical species associated with the development of inflammation.
Trained, chronically instrumented, conscious dogs were used to evaluate the effect of propranolol (PRO), ethanol (ETH) or their combination (P + E) on the left ventricular (LV) function by first-pass radionuclide ventriculography (RNV). Six dogs were trained prior to a sterile left thoracotomy, where a left atrial catheter was implanted. After recovery of four days RNV was carried out by injecting a bolus of technetium-99m diethylenetriamine pentaacetic acid via the catheter to the left atrium. The data was collected for 12 sec. to a computer by frame rate of 20 frames/sec. from left lateral view of the dog. The experiments were performed both in four-leg standing and in 60-degree head-up tilted positions. After control measurements the data were obtained with 0.5 mg/kg of PRO, 0.45 g/kg of ETH and their combination. The P + E combination increased significantly LV end-diastolic and end-systolic volumes, whereas LV peak ejection rate and ejection fraction were decreased. Upright position diminished the LV volume and increased heart rate, while ejection fraction and cardiac output remained unchanged. The first-pass RNV method proved to be promising for measuring the cardiac pharmacological effects in conscious dogs. The combination of propranolol and ethanol in low doses induced an unexpectedly strong depression of LV function, which is supposed to be followed of latent cardiac depressing effect of ETH revealed by blockade of compensatory adrenergic mechanisms with PRO.
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In summary, newer imaging technologies yield three-dimensional pictures of the left ventricle. Detailed information is provided on regional wall motion, wall thickening, and ventricular volumes, which can be helpful in managing patients with cardiac disease. MR imaging gives the highest resolution images, and MR angiography can be invaluable in assessing the anatomy of an aortic dissection. Gated tomography with a technetium-based myocardial perfusion tracer can be thought of as a low-resolution cine MR imaging study. Combined function and perfusion nuclear studies performed at rest in an ICU can give information on myocardial perfusion and stunning, which is helpful in managing patients with acute ischemic syndromes. First pass RNA is probably the most accurate method for measuring RVEF and can be performed at the bedside using a portable multicrystal camera. Serial measurements of RVEF may be helpful in managing patients with pulmonary hypertension of various causes. For patients with documented acute myocardial infarction or chest pain and no acute myocardial necrosis or for patients undergoing preoperative risk assessment, combined perfusion and function using nuclear techniques yields both stress-induced ischemia and resting ventricular function in a single procedure and is timely and cost effective.
To investigate the possibility that prolonged carbon monoxide (CO) exposure would depress myocardial function, six chronically instrumented, unsedated goats were exposed to 160--200 ppm CO for 2 wk, resulting in a mean carboxyhemoglobin saturation of 20%. Cardiac index and stroke volume remained unchanged during and after exposure. Hematocrit and hemoglobin concentration started increasing on the 10th day of exposure, this increase reached statistical significance (P less than 0.05) on the 6th postexposure day. Contractility (Vmax) of the left ventricular myocardium and heart rate were unchanged during exposure to CO, but both were significantly (P less than 0.05) decreased at some time during the 1st wk after removal from CO. If there was a decrease in intrinsic myocardial function during CO exposure, it may have been masked by increased sympathetic activity. The mechanism(s) that might produce the decrease in heart rate and contractility after removal from CO are not obvious. Possible explanations are discussed.
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Golden Retriever dogs manifest an X-linked, Duchenne-like, muscular dystrophy with a characteristic lack of dystrophin. Histologic findings have demonstrated the cardiac involvement in these dogs to be a model for the cardiac insufficiency in human Duchenne muscular dystrophy (DMD). The goal of this study was to assess the capability of radionuclide angiography (RNA) as an assessment tool to measure the ventricular dysfunction in these dogs. Three dogs, one normal and two with muscular dystrophy (MD), were studied by equilibrium gated blood pool. Red blood cells were labelled with 420 MBq of 99mTc. The three dogs lying on their left sides on the table, received no drugs and were not restrained in any manner. RNA left ejection fraction (EF) and echographic measurements of left ventricular fractional shortening (FS) were performed during the same session. EF values were 61%, 48%, 36% and FS values were 47%, 32%, 26%, respectively, for the control dog, the 6 month old MD dog and the 12 month old MD dog. This preliminary study demonstrates the potential usefulness of RNA for the non-invasive follow-up exams of specific therapy in a canine model of muscular dystrophy.
Cardiovascular disease is one of the main causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). The observation that the disease may affect all cardiac tissues, although frequently in a subclinical fashion, has come to attention only recently after the introduction of non-invasive sensitive cardiac imaging technology in clinical practice. We review the current perspective of this topic, placing special emphasis on what is known and what is not known regarding cardiac disease in the pediatric population with SLE. Our current lack of information calls for the initiation of collaborative research in this area.
In 81 patients with an ischaemic heart disease and myocardial infarction the evidence of the presphygmic index PI (non-invasive index) was tested concerning a beginning myocardial functional disturbance and a latent heart insufficiency, respectively, with the help of an invasive cardiopulmonary functional diagnostics which was performed under dosed bicycle ergometer load in the steady state. The presphygmic index PI correlates in significantly positive way with the end-diastolic pressure of the heart and the quotient from minute volume of the heart and the end-diastolic pressure of the pulmonary arteries (VM/PAEDP). The presphygmic index is on the basis of this correlation of the left-ventricular function suitable to establish disturbances of the myocardial functions and to give the possibility of a separation of the patients in cardially sufficient and cardially insufficient ones. Here the evidence of the presphygmic index might be larger concerning the recognition of a latent heart insufficiency than concerning the recognition of beginning myocardial functional disturbances. The presphygmic index apparantly possesses a high degree of sensibility then, when the myocardial functional disturbances coincide with a beginning reduction of the pumping action of the heart.
Transapical left ventricular bypass which withdraws blood directly from the left ventricular apex through a roller pump and outflow filter with return to the femoral artery has been applied in 6 patients with cardiac failure. All patients required total TALVB (with the aortic valve closed) for periods of one to 144 hrs, and 2 patients had recovery of life-sustaining myocardial function, allowing removal of the TALVB system. One patient had complete recovery without other organ dysfunction. Total TALVB continuously decompresses and unloads the left ventricle throughout systole and diastole, and maintains the circulation in otherwise terminal circumstances.
BACKGROUND: Because systolic and diastolic dysfunction frequently coexist, it is hypothesized that a combined measure of left ventricular chamber performance may be more reflective of overall cardiac dysfunction than systolic or diastolic measures alone. METHODS Study patients consisted of 170 subjects: 70 normals, 47 patients with severe dilated cardiomyopathy in NYHA class III-IV awaiting cardiac transplantation and 53 patients with idiopathic dilated cardiomyopathy of intermediate severity [NYHA class II, ejection fractions (EF) 30-50%]. EF, stroke volume and cardiac indexes were measured using conventional echo-Doppler methods. Pre-ejection period/ejection time (PEP/ET), isovolumetric relaxation time (IRT), isovolumetric contraction time/ET (ICT/ET) were also measured. A new derived index of myocardial performance: (ICT+IRT)/ET, was obtained by subtracting ET from the interval between cessation and onset of the mitral inflow velocity to give the sum of ICT and IRT. RESULTS The index was easily measured, reproducible, and had a narrow range in normals. The mean value of the index was significantly different between normal, intermediate and pre-transplant subjects (0.39 +/- 0.05, 0.59 +/- 0.10 and 1.06 +/- 0.24, respectively, p < 0.001 for all comparisons). The degree of inter-group overlap was smaller for the index compared to PEP/ET, ICT/ET and other parameters. Within functional groups, the value of the index did not appear to be related to heart rate, mean arterial pressure and the degree of mitral regurgitation. CONCLUSION (ICT+IRT)/ET is a conceptually new, simple and reproducible Doppler index of combined systolic and diastolic myocardial performance in patients with primary myocardial systolic dysfunction.
BACKGROUND: Left ventricular or biventricular pacing/stimulation can acutely improve systolic function in patients with dilated cardiomyopathy (DCM) and intraventricular conduction delay by resynchronizing contraction. Most heart failure therapies directly enhancing systolic function do so while concomitantly increasing myocardial oxygen consumption (MVO(2)). We hypothesized that pacing/stimulation, in contrast, incurs systolic benefits without raising energy demand. METHODS AND RESULTS: Ten DCM patients with left bundle-branch block (ejection fraction 20+/-3%, QRS duration 179+/-3 ms, mean+/-SEM) underwent cardiac catheterization to measure ventricular and aortic pressure, coronary blood flow, arterial-coronary sinus oxygen difference (DeltaAVO(2)), and MVO(2). Data were measured under sinus rhythm or with left ventricular or biventricular pacing/stimulation at the same heart rate. These results were then contrasted to intravenous dobutamine (n=7) titrated to match systolic changes during LV pacing. Systolic function rose quickly and substantially from LV pacing (18+/-4% rise in arterial pulse pressure, which correlates with cardiac output, and 43+/-6% increase in dP/dt(max); both P<0.01). However, DeltaAVO(2) and MVO(2) declined -4+/-2% and -8+/-6.5%, respectively (both P<0.05). Similar results were obtained with biventricular activation. In contrast, dobutamine raised dP/dt(max) 37+/-6%, accompanied by a 22+/-11% rise in per-beat MVO(2) (P<0.05 versus pacing). CONCLUSIONS: Ventricular resynchronization by left ventricular or biventricular pacing/stimulation in DCM patients with left bundle-branch block acutely enhances systolic function while modestly lowering energy cost. This should prove valuable for treating DCM patients with basal dyssynchrony.