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Biomedical subjects

D R Alonso

Publications and source records attributed to D R Alonso.

At least 37 records · Page 2Linked to original sources

Effects of nutrition on disease and life span. I. Immune responses, cardiovascular pathology, and life span in MRL mice.

Mice of the autoimmune, lymphoproliferative strain MRL/lpr and the congenic, nonlymphoproliferative strain MRL/n were fed one of six diets from weaning on-ward. These mice were sacrificed at 3 or 5 months of age. Low fat diets resulted in lower cholesterol and higher triglyceride levels than did cholesterol-containing high-fat diets. Caloric restriction of MRL/lpr mice was associated with an increased plaque-forming cell response to trinitrophenylated polyacrylamide beads, less lymphoproliferation, and less severe glomerulonephritis. Diet did not affect the incidence of autoimmune vasculitis in MRL/lpr mice sacrificed at 5 months. MRL/lpr mice fed a low-fat, calorically restricted diet from 5 months of age to death lived longer than mice which were fed ad libitum a cholesterol-containing, high-fat diet. At death, MRL/lpr mice fed the former diet had the autoimmune vasculitis which had been evident in mice killed at 5 months, whereas mice fed the latter diet, in addition to the vasculitis, had a high incidence of atherosclerotic lesions of intrarenal and aortic branch arteries.

Animal Nutritional Physiological Phenomena↗

Effects of nutrition of disease and life span. II. Vascular disease, serum cholesterol, serum thromboxane, and heart-produced prostacyclin in MRL mice.

Mice of the autoimmune strain MRL/1, the congenic strain MRL/n, and two control strains, Balb/c and C57BL/6 mice, were fed diets which varied in the content of lipid and cholesterol. Serum cholesterol levels were highest in mice fed diets containing cholesterol and lowest in mice fed laboratory "chow." Animals fed diets that increased serum cholesterol had decreased production of prostacyclin by vascular tissue and increased production of thromboxane A2 by platelets. Prostacyclin production by heart tissue in response to arachidonic acid showed a negative correlation (r = -0.86) with serum cholesterol. In contrast, serum thromboxane demonstrated a positive correlation (r = 0.70) with serum cholesterol. The prevalence of autoimmune vasculitis seen in MRL/lpr mice was not affected by diet. However, MRL/lpr mice fed a high-fat, cholesterol-containing diet had intimal vascular lesions containing foam cells typical of arteriosclerosis. It is suggested that diets that raise serum cholesterol may influence the nature of autoimmune-mediated vascular disease by altering the balance between thromboxane and prostacyclin.

Animal Nutritional Physiological Phenomena↗

Evaluation of a QRS scoring system for estimating myocardial infarct size. III. Correlation with quantitative anatomic findings for inferior infarcts.

This study evaluated by quantitative autopsy correlation a previously developed scoring system for estimating the size of myocardial infarcts based on the QRS complex of the electrocardiogram. This system was tested using electrocardiograms from patients with infarcts shown by autopsy to predominate in the inferior third of the left ventricle. The study was limited to patients whose electrocardiogram did not indicate left or right ventricular hypertrophy, left or right bundle branch block, or left anterior or posterior fascicular block. Thirty-one patients from 6 medical centers met these criteria. In the electrocardiogram of 28 of the 31 patients (90%), lead a VF exhibited a Q wave of at least 30 ms. The correlation coefficient between the total QRS score and the percent infarction of the left ventricle was 0.74. In patients without confounding factors in the electrocardiogram and with single infarcts, the electrocardiogram provides a marker for infarcts in the inferior third of the left ventricle and a quantitative QRS scoring system provides an estimate of infarct size.

Aged↗

Influence of diet on vascular lesions in autoimmune-prone B/W mice.

Autoimmune-prone B/W mice, which are known to develop severe glomerulonephritis and vasculitis, also are found to develop arteritis and proliferative and fatty-proliferative lesions of the aorta and its branches as well as renal inflammatory lesions. High intake of saturated fat in the diet enhances the development of these atherosclerotic and autoimmune lesions significantly in female mice, whereas restriction of dietary calories and fat inhibits their development. Ad lib feeding of laboratory chow, high in fiber and low in fat, does not foster development of vascular lesions but does permit the development of autoimmune renal disease.

Animals↗

Smoke inhalation: radiologic manifestations.

The medical records and radiographs of 62 patients admitted for smoke inhalation were reviewed to determine the value of the plain chest radiograph in the early detection of inhalation injury. Pulmonary edema resulting from the inhalation injury often leads to pulmonary insufficiency, and its early diagnosis is crucial to the management of patients with this condition. In addition to the usual presentation of pulmonary edema, subtle radiographic findings of interstitial edema such as perivascular fuzziness and peribronchial "cuffing" were observed. Of 56 patients with significant inhalation injury, 35 (62.5%) had radiographic findings attributed only to smoke inhalation. These abnormalities often had a characteristic distribution in the lungs, and in the majority of patients they appeared in the first 24 hours after the injury. The radiologic diagnosis of inhalation injury may be made at a time when findings of other diagnostic tests are still equivocal or mildly abnormal, thus alerting the clinician to impending pulmonary failure.

Adolescent↗

Effect of endothelium on glycosaminoglycan accumulation in injured rabbit aorta.

Previous studies have indicated that reendothelialized regions of injured rabbit aortas are more susceptible to diet-induced atherosclerosis than persistently deendothelialized regions or uninjured aortas. However, the mechanism responsible for this selective lipid deposition is not understood. One possibility is that these regions differ with respect to the quantity and type of glycosaminoglycan-containing proteoglycans which are known to interact with lipoproteins. To determine whether these regions differed with respect to their glycosaminoglycan composition, the authors divided 53 rabbits into four groups. Groups IA and IB were fed a regular diet beginning 5 weeks prior to aortic deendothelialization; Groups IIA and IIB were fed the same diet supplemented with 0.5% cholesterol. The rabbits were continued on these diets following aortic deendothelialization with a balloon catheter. Those in Groups IA and IIA were sacrificed either at 2-5 weeks or 6-8 weeks following deendothelialization; proteoglycans were assessed morphometrically following staining with alcian blue. Groups IB and IIB were sacrificed at 10 weeks following injury; glycosaminoglycans were extracted from deendothelialized and reendothelialized aortas, separated by electrophoresis, and quantitated by scanning densitometry. Morphometric analysis of stained aortic sections revealed significantly increased quantities of alcianophilic material in the neointima of reendothelialized aortas as compared with deendothelialized aortas in both diet groups. Chemical analysis revealed significantly more of each glycosaminoglycan in reendothelialized aortas when compared with deendothelialized or uninjured aortas. The major glycosaminoglycans present in all regions were heparan sulfate and chondroitin sulfate; and although absolute quantities of these particular glycosaminoglycans increased in the reendothelialized region, their relative percentages remained the same for each area analyzed. Cholesterol feeding did not appear to influence glycosaminoglycan concentration and composition in reendothelialized and deendothelialized regions when compared with normal diets, but cholesterol feeding alone did increase aortic glycosaminoglycans in uninjured aortas. The results suggest that the presence of endothelium influences the quantity and type of glycosaminoglycans accumulating in the neointima, and that the differences in proteoglycans in the reendothelialized artery may account at least in part for the propensity of this area to accumulate lipid and evolve as atherosclerosis.

Animals↗

Evaluation of a QRS scoring system for estimating myocardial infarct size. II. Correlation with quantitative anatomic findings for anterior infarcts.

The ability of an independently developed QRS point score to estimate the size of infarcts predominantly within the anterior third of the left ventricular was evaluated by quantitative pathologic-electrocardiographic correlation. The study was limited to 21 patients with a single infarct documented by postmortem examination, for whom an appropriately timed standard 12 lead electrocardiogram was available that did not exhibit signs of left or right ventricular hypertrophy, left or right bundle branch block or anterior or posterior fascicular block. At necropsy the heart was cut into five to seven slices. The location and size of the infarct was quantitated by computer-assisted planimetry of the slices. The electrocardiogram of 19 (90 percent) of the patients exhibited either a Q wave or an R wave of no more than 20 ms in lead V2. The infarct in the two patients without this electrocardiographic finding was small, occupying 2 and 3 percent of the left ventricle, respectively. The percent infarction of the left ventricle correlated with the QRS point score (r=0.80). Thus in patients without complicating factors in the electrocardiogram and with a single infarct, the electrocardiogram provides a marker for infarction in the anterior third of the left ventricle and permits estimation of infarct size.

Adult↗

Anterior S-T segment depression in acute inferior myocardial infarction: indicator of posterolateral infarction.

Although patients with acute inferior myocardial infarction often manifest S-T segment depression in precordial electrocardiographic leads, the pathophysiologic abnormalities associated with this finding are poorly understood. To examine this problem, electrocardiographic findings on admission were compared with results of radionuclide cineangiography performed within 38 hours of the onset of symptoms in 25 patients with inferior infarction. Summation of S-T depression in leads V1 through V4 permitted the separation of patients into two groups: Group A (11 patients with 0.20 mV or less of S-T depression) and Group B (14 patients with 0.45 vM or more of S-T depression). The radionuclide cineangiogram revealed inferior wall dysfunction in all patients. Additional posterolateral dysfunction was seen in 13 patients, all in Group B. Patients in Group B had a relatively larger infarction (peak creatine kinase Units - 756 +2- 358 in Group A versus 1,566 +/- 983 units in Group B, p less than 0.01) and greater functional impairment (ejection fraction - 45 +/- 12 in Group A versus 33 +/- 12 in Group B, p less than 0.01). The relation between precordial S-T segment depression and posterolateral dysfunction appears to be largely independent of electrocardiographic evidence of "true posterior infarction." Thus moderate or severe anterior precordial S-T depression in patients with acute inferior infarction is a sensitive and specific indicator of relatively extensive myocardial damage, primarily involving the posterolateral region.

Adrenergic beta-Antagonists↗

Prostacyclin production by arterialized autogenous venous grafts in dogs.

Arteries are capable of producing significantly larger quantities of prostacyclin than are veins. To test the hypothesis, whether prostacyclin production by the vessel wall is related to blood pressure and flow, we measured the amounts of PGI2 released and synthesized by venous segments transplanted for 6 weeks into the arterial circulation. These results were compared with the production of prostacyclin by normal veins and arteries. In 20 dogs a segment of jugular vein was interposed into the carotid system; a sham dissection was done on the opposite side. "Arterialized" vein grafts showed prominent intima lined by endothelium, medial smooth muscle cell proliferation and fibrotic proliferation in adventitia. Spontaneous and arachidonic acid-stimulated prostacyclin production (measured by radioimmunoassay for 6-keto-PGF1 alpha) was not significantly different between arterialized venous autografts and jugular veins. Significantly larger amounts of prostacyclin were synthesized by the carotid artery. Thus, histologic changes and rheologic effects occurring in vein grafts transposed to the arterial site do not affect prostacyclin production.

Animals↗

Electrocardiographic poor R-wave progression. Correlation with postmortem findings.

Electrocardiographic criteria have been derived from vectorcardiographic and angiographic correlation which allow division of patients with electrocardiographic "poor R-wave progression" or "reversed R-wave progression" into the following four etiologic groups: (1) anterior myocardial infarction; (2) left ventricular hypertrophy; (3) type-C right ventricular hypertrophy; and (4) the normal variant. The sensitivity, specificity, and predictive value of this approach to the electrocardiogram with poor or reversed R-wave progression were studied in a series of 33 patients examined at autopsy. Using the scheme and criteria outlined, 85 percent (11/13) of the pathologic anterior myocardial infarctions were correctly diagnosed. The electrocardiographic criteria correctly identified 75 percent (15) of 20 patients with poor or reversed R-wave progression without postmortem evidence of myocardial infarction, with only 12 percent (2/17) predictive error. The relative risk of autopsy-documented anterior myocardial infarction in patients meeting the specified electrocardiographic criteria was six times that of other patients with poor or reversed R-wave progression.

Cardiomegaly↗

Ultrastructural characterization of the border zone surrounding early experimental myocardial infarcts in dogs.

The existence of a border zone composed of reversibly injured myocardium surrounding an evolving infarct has been the subject of controversy. In experiments designed to search for such a border zone by electron microscopy, 12 mongrel dogs underwent permanent ligation of the left anterior descending coronary artery (LAD). Two to 6.5 (average = 4.2) hours later, the hearts were excised, the area at risk (myocardium perfused by the LAD) was outlined by injection of fluorescent microspheres, and the myocardial infarct was demonstrated by the nitro blue tetrazolium (NBT) gross histochemical method. Myocardial samples for electron-microscopic study were obtained from the periphery of the infarct (tissues unstained by NBT) and serially from the immediately adjacent myocardium, which was stained deep blue by NBT. Grossly, the infarcts always involved the subendocardial myocardium, extended for a variable distance in the epicardial direction, and closely approximated the lateral margins of the area at risk. When examined by electron microscopy, the infarct periphery showed evidence of irreversible damage, thus confirming the ability of NBT to detect early myocardial necrosis. Multiple samples of the NBT-stained myocardium immediately adjacent to the infarct showed varying degrees of reversible ischemia, thus demonstrating, at the ultrastructural level, the existence of a border zone of intermediate myocardial injury. This border zone was substantial (3--4 mm in width) along the subepicardial aspect of the infarct and very thin (1--2 mm) laterally. In conclusion, a significant border zone was demonstrable by electron microscopy in the subepicardial myocardium of 8 out or 12 canine hearts with recent coronary artery occlusion. In the remaining 4 hearts, the infarcts had already reached the epicardium at the time of study, and only a thin lateral border zone was present.

Animals↗

Chronic lability of arterial pressure in the rat does not evolve into hypertension.

1. In rats, electrolytic lesions of the A2 group of catecholamine neurons result in lability of arterial pressure without hypertension. 2. To establish whether labile arterial pressure, when chronic, will lead to fixed hypertension, we placed lesions in the A2 area of adult male Sprague-Dawley rats and measured mean arterial pressure, heart rate and their variability (expressed as the standard deviation) 11 months later. Controls were age-matched, unoperated or sham-operated rats. 3. In rats with A2 lesions: (a) the mean arterial pressure was lower (103 +/- 7.5 mmHg; n = 6; P < 0.05) than in sham-operated (123 +/- 4.7 mmHg; n = 4) or unoperated (120 +/- 3.1 mmHg; n = 9) controls; (b) the standard deviation of mean arterial pressure was higher (16 +/- 1.8 mmHg; P < 0.001) than in sham-operated (5 +/- 0.7 mmHg) or unoperated controls (7 +/- 0.6 mmHg); (c) the mean and standard deviation of heart rate did not differ between groups. No histopathological changes were detected in the A2 group. 4. Chronic lability of arterial pressure does not evolve into sustained hypertension nor does it induce systemic lesions.

Animals↗

Advantages of hypothermic potassium cardioplegia and superiority of continuous versus intermittent aortic cross-clamping.

The relative effectivenss of hypothermic potassium (K) cardioplegia in conjunction with either continuous or intermittent aortic cross-clamping was evaluated in 20 mongrel dogs. Isovolumetric left ventricular (LV) contractions and myocardial biopsies were obtained before and after a total of 90 minutes of aortic cross-clamping. The dogs were randomly divided into four groups of five dogs each as follows: Group I, continuous 90 minute cross-clamping and multidose K at 4 degrees C (40 mEq/L); Group II, intermittent cross-clamping consisting of six 15 minute periods of cross-clamping separated by 5 minute reperfusion periods and K cardioplegia at 4 degrees C given at the start of each cross-clamping period; Group III, continuous 90 minute cross-clamping and multidose buffered saline at 4 degrees C; Group IV, intermittent cross-clamping, consisting of six 15 minute periods of cross-clamping separated by 5 minute reperfusion periods and buffered saline at 4 degrees C given at the initiation of each cross-clamp period. Group I dogs had the best myocardial performance, with no difference between control values of peak LV pressure and dP/dtmax and those recordings obtained 60 minutes after release of the aortic cross-clamp. Significant depression of LV function was noted in all other groups. Examination of force-velocity and length-tension relationships confirmed better myocardial performance in Groups I and II (multidose K at 4 degrees C) than in Groups III and IV (buffered saline at 4 degrees C). Groups I and III (continuous cross-clamping) had no de-rease in diastolic LV compliance after cross-clamping, whereas compliance was decreased in both Groups II and IV (intermittent cross-clamping) at higher preloads (p less than 0.05 and p less than 0.025, respectively). The wet weight/dry weight myocardial ratios were lower in Groups I and III (continuous cross-clamping) than in Groups II and IV (intermittent cross-clamping). Although creatine phosphate (CP) concentrations were rapidly restored by reperfusion in all groups, adenosine triphosphate (ATP) and glycogen myocardial stores were better preserved at the end of cross-clamping in Groups I and II (multidose K at 4 degrees C). Although LV diastolic compliance was decreased and myocardial water content was increased in Groups II and IV (intermittent cross-clamping), no differences in the minimal extent of subendocardial hemorrhage, edema, and contraction-band necrosis were observed among any of the groups examined electron microscopically. The present study identifies continuous aortic cross-clamping with multidose K at 4 degrees C as a superior method of myocardial protection.

Animals↗

Ischemia and infarction in the isolated rabbit heart: a model for the evaluation of myocardial imaging agents.

An isolated-heart preparation has been adapted to permit rapid evaluation of, and imaging by, myocardial tracers. The rabbit heart provided a mass large enough for imaging and serial biopsies. Coronary arteries could be selectively ligated and provided landmarks for epicardial ST segment mapping. Uptake ratios between a tissue sample and normal myocardium (T/N), obtained using Tc-99m glucoheptonate as an infarct-seeker, increased with duration of the ischemic period, which was followed by reflow. After 25 min of occlusion the T/N was 4.5; after 40 min T/N = 6; after 60 min T/N = 8; and after 120 min T/N = 19. This well-controlled adjunct to in vivo studies allows evaluation of myocardial imaging agents without interfering with systemic effects or blood and tissue background. Functional and structural changes can be sequentially measured and correlated with the localization of various radiopharmaceuticals.

Animals↗

Perioperative myocardial infarction associated with coronary artery bypass graft surgery: improved sensitivity in the diagnosis within 6 hours after operation with 99mTc-glucoheptonate myocardial imaging and myocardial-specific isoenzymes.

The present study was performed to evaluate scintigraphic imaging with technetium 99m-labeled glucoheptonate and serum enzyme levels of creatine phosphokinase isoenzyme (MB-CPK) in the early diagnosis of perioperative acute myocardial infarction associated with saphenous vein bypass graft operations. Myocardial imaging was done in 27 patients (50% of whom were considered high-risk) before operation and again 5 hours after operation. Four of these patients (15%) had both electrocardiographic and serum MB-CPK evidence of acute myocardial infarction, and all 4 had developed positive postoperative scintigrams. Four other patients had only elevated serum MB-CPK, and scintigrams became positive after operation in 3 of them. In addition, serum MB-CPK 6 hours after operation was 83 +/- 21 mIU/ml (mean +/- standard error of the mean) in patients with positive postoperative scans compared with 24 +/- 5 mIU/ml in those patients with negative postoperative scintigrams (p less than 0.001). Myocardial imaging with 99mTc-glucoheptonate in the perioperative period is rapid, safe, and atraumatic. Furthermore, our results suggest that it is a sensitive method for the early diagnosis of perioperative acute myocardial infarction, and, when imaging is combined with serum MB-CPK isoenzyme analysis, the reliability of the diagnosis of acute myocardial infarction is enhanced even further. Only 1 of the patients who showed perioperative myocardial damage had acute hemodynamic compromise or obvious impairment of recovery in the immediate postoperative period, and the 30-day mortality of the total group was 4% (1 of 27).

Acute Disease↗