Biomedical subjects

C M Bloor

Publications and source records attributed to C M Bloor.

At least 19 recordsLinked to original sources

PubMed1995

Gene expression in a swine model of right ventricular hypertrophy: intercellular adhesion molecule, vascular endothelial growth factor and plasminogen activators are upregulated during pressure overload.

We have investigated the molecular changes which occur during pressure overload hypertrophy of the RV in swine. Animals were banded on the pulmonary artery so that right ventricular pressure was increased two-fold. The heart was harvested at 3, 7, 24 and 72 h after surgery. Between 7 and 72 h there was evidence of muscle damage and inflammation. Northern blot experiments showed that pressure overload induced a transient increase in the expression of the immediate early genes and in the developmentally regulated atrial natriuretic factor and skeletal muscle alpha actin genes. Consistent with the histological observations of inflammation, increases in the expression of the gene for intercellular adhesion molecule, which encodes a protein involved in the binding of leukocytes by endothelial cells and myocytes, was observed between 3 and 24 h. In addition, the expression of vascular endothelial growth factor, a growth and permeability factor specific for endothelial cells was increased at 3 and 7 h of pressure overload. An increase in the expression of urokinase plasminogen activator and its inhibitors, plasminogen activator inhibitors I and II, was also observed between 3 and 24 h. This was associated with an increase in urokinase activity in the myocardial tissue. These results indicate that hypertrophy in a large mammal such as swine induces a program of gene expression similar to that previously described in rodents and suggests that up-regulation of a variety of other genes is an early response to pressure overload.

Animals↗

PubMed1995

Urokinase plasminogen activator activity is increased in the myocardium during coronary artery occlusion.

We have previously demonstrated that collateral development takes place in a swine model of coronary artery occlusion. In this report we have examined the effect of coronary artery occlusion on urokinase and tissue plasminogen activator activity in the myocardium. Urokinase activity was increased four-fold in the ischemic heart compared to sham and unoperated controls. In contrast, the level of tissue plasminogen activator activity remained relatively constant. The increase in urokinase activity was associated with an upregulation of urokinase RNA levels and of the RNAs corresponding to the plasminogen activator inhibitors, PAI I and II. Urokinase has been shown to be an important angiogenic protease both in vivo and in cultured cells. Its increase during collateral development suggests that urokinase may play a role in angiogenesis in the ischemic heart.

Animals↗

PubMed1995

Nontraumatic sports death in high school and college athletes.

Nontraumatic deaths occur each year in organized high school and college athletics, resulting in considerable public concern. We conducted a study of the frequency and causes of nontraumatic sports deaths in high school and college athletes in the USA through the National Center for Catastrophic Sports Injury Research to define the magnitude of this problem and its causes. Over a 10-yr period, July 1983-June 1993, nontraumatic sports deaths were reported in 126 high school athletes (115 males and 11 females) and 34 college athletes (31 males and 3 females). Estimated death rates in male athletes were fivefold higher than in female athletes (7.47 vs 1.33 per million athletes per year, P < 0.0001), and twofold higher in male college athletes than in male high school athletes (14.50 vs 6.60 per million athletes per year, P < 0.0001). Cardiovascular conditions were more common causes of death than noncardiovascular conditions. Hypertrophic cardiomyopathy and congenital coronary artery anomalies were the most common causes of death. In high school and college athletes, males are at increased risk for nontraumatic sports deaths compared with females even after adjustment for participation frequency; college males are at greater risk than high school males. In all groups the deaths were primarily due to cardiovascular conditions.

Adolescent↗

PubMed1994

Clinical significance of coronary vascular adaptations to exercise training.

Coronary vascular adaptations to exercise training have been extensively studied at the microscopic level in animals and correlated with direct and indirect measurements of myocardial blood flow in patients with coronary artery disease. Animals have permitted more extensive study. These findings have generally supported an increased blood flow to the myocardium with exercise training. However, consistent positive structural and functional adaptations to training have not been observed in large animals. Clinical studies have been limited by methodological problems related to techniques for detecting ischemia and measuring myocardial blood flow and the variability in exercise stimulus. Well-established ischemia and high-intensity, long-duration training were the factors that promoted vascular growth in exercising patients with coronary artery disease. Animals studies also have demonstrated the necessity for myocardial ischemia to be present to induce coronary collateral development with exercise training. Optimal promoters of vascular growth in patients with coronary disease may consist of pharmacological interventions combined with exercise training.

Adaptation, Physiological↗

PubMed1993

Endothelial cell gene expression in response to injury.

Endothelial cells respond to injury with acute alterations in mediator generation and surface molecule expression. Endothelial cells may respond, depending on the stimulus, by altering the expression of various genes whose products are central to endothelial cell matrix remodeling, coagulation, and fibrinolysis, as well as interactions with polymorphonuclear leukocytes, platelets, and lymphocytes and in angiogenesis. These responses comprise endothelial activation or differentiation. The molecular events involved in endothelial perception of injury and in regulation of gene expression by cytokines, reactive oxygen intermediates, and mechanical forces are discussed. In addition, because endothelial cells from different sites exhibit heterogeneity regarding their injury responses, where possible this heterogeneity in endothelial gene expression is highlighted.

Animals↗

PubMed1993

Coronary arterial tree remodeling in right ventricular hypertrophy.

We investigated coronary vascular adaptations occurring in right ventricular hypertrophy (RVH). Six pigs had RVH induced by pulmonary artery stenosis for 5 wk. Three pigs served as controls. At autopsy we made silicone elastomer casts of the right coronary arteries (RCA) and collected morphometric data. We organized the segments and their diameters and lengths into a framework of a modified Strahler's ordering scheme in which the order number of an offspring is increased only if its diameter is greater than the diameters of its parents by a specific amount. The segments of the same order arranged in series are combined into elements. In RVH the total number of orders of vessels was larger than the control by 1; the total number of elements in each order increased greatly, whereas the diameters and lengths of each order decreased somewhat. The total RCA resistance decreased in RVH mainly because the total cross-sectional area (CSA) of every order was increased. Because the diameters of the resistance vessels decreased, this decrease in total RCA resistance was due to a numerical increase in resistance vessels. These findings indicate that new flow channels have been established. In contrast, the RCA was remodeled in that the lumen diameter increased. Pressure-flow curves showed a decrease of coronary resistance in RVH, in agreement with the morphometric findings. We conclude that there is significant remodeling of the coronary arterial vasculature in RVH, and any future analysis of coronary hemodynamics of the right ventricle in hypertrophy must take the morphometric remodeling into account.

Adaptation, Physiological↗

PubMed1993

Heparin accelerates coronary collateral development in a porcine model of coronary artery occlusion.

BACKGROUND: Coronary collaterals develop in response to an ischemic stimulus. However, collateral growth is not sufficient to result in the complete recovery of coronary reserves. Using a porcine model of gradual coronary artery occlusion, we investigated the effect of continuous heparin infusion on coronary collateral development. METHODS AND RESULTS: We placed ameroid constrictors on the left circumflex coronary artery of 16 minipigs; the ameroid constrictors completely occluded the left circumflex coronary artery at 10 +/- 1 days. Half of the animals also were instrumented with subcutaneously placed osmotic pumps and catheters that delivered heparin (300 units/h) into the external jugular vein. At 2, 3, and 4 weeks, we assessed blood flow at rest and during vasodilation using radioactive microspheres. Our results indicate that the animals receiving heparin restored resting myocardial blood flow to normal levels at or before 2 weeks; in contrast, we did not see normal resting myocardial blood flow levels in the untreated-ameroid animals until 3 weeks. Under vasodilated conditions, untreated-ameroid animals experienced a severe loss of coronary reserves at 2 weeks. Although this improved with time, these animals still were significantly underperfused at 4 weeks. In contrast, in the heparin-treated animals, coronary reserves returned to near-normal levels between 3 and 4 weeks. In addition, infarct size was significantly smaller in the heparin-treated animals. CONCLUSIONS: These experiments suggest that the administration of heparin in the early phases of gradual coronary occlusion accelerates the rate of return of normal blood flow under resting conditions, substantially increases the recovery of coronary reserve, and reduces the risk of infarction.

Animals↗

PubMed1993

Pulmonary vascular lesions occurring in patients with chronic major vessel thromboembolic pulmonary hypertension.

The status of small pulmonary arteries may influence diagnosis, surgical selection and postoperative outcome of patients with chronic major vessel thromboembolic pulmonary hypertension (CTEPH). Therefore, in patients with the established diagnosis of CTEPH, lung tissue was obtained by biopsy (15 patients) or at autopsy (16 patients) to assess the histopathologic composition of small pulmonary arteries. Pathologic examination disclosed the full range of pulmonary hypertensive lesions in the small arteries, including plexogenic lesions. The type and extent of hypertensive lesions did not relate to preoperative hemodynamic values, to patient age, or to symptom duration. The findings indicate that primary pulmonary hypertension cannot be differentiated from potentially correctable CTEPH on the basis of histopathologic findings in small pulmonary arteries. Furthermore, none of the histologic findings preclude a positive hemodynamic and clinical result from pulmonary thromboendarterectomy. However, development of these hypertensive changes may explain the deterioration which these patients experience preoperatively over time.

Adolescent↗

PubMed1993

UCSD's MedPics: implementation and impact on the curriculum.

MedPics is a computer-based image delivery system with supporting text fields and on-screen graphics to assist in key feature identification. It has been used by the University of California, San Diego as an integral part of the Human Disease course since 1992. Initially created to support pathology and histology, the program has now expanded to include hematology. MedPics has had a positive impact on the second year curriculum for which it was created. Moreover, use of this program has improved student attitudes toward computer-based resources and increased faculty interest in instructional development.

California↗

PubMed1992

Hypoxia induces endothelial cells to increase their adherence for neutrophils: role of PAF.

We investigated the interactions of polymorphonuclear neutrophils (PMN) and endothelial cells in myocardial ischemia using a hypoxia model. We exposed porcine aortic (PAEC) and porcine coronary microvessel (PCMEC) endothelial cells to 2% O2 for 2 h (PO2 = 53 mmHg) and measured the adherence of unstimulated neutrophils (PMN) to both control and hypoxia-conditioned endothelial cell monolayers. Hypoxia conditioning increased PMN adherence to PAEC and PCMEC by 51 and 101%, respectively, above control levels. The increase in PMN adhesion to PAEC was associated with a threefold increase in endothelial cell-associated platelet-activating factor (PAF) compared with control PAEC. The conditioned media from PAEC exposed to hypoxia also contained sixfold more PAF than control conditioned media, and it activated PMN to become adherent to untreated PAEC. The hypoxia-induced PAEC adhesion response was inhibited by preincubating PMN with the specific PAF receptor antagonist, L-659,989. We conclude that PAF is produced by cultured endothelial cells in response to hypoxia and that PAF generation is chiefly responsible for the increased adherence properties of hypoxia-conditioned endothelial cells. This response may play a major role in regulating PMN margination during myocardial ischemia.

Animals↗

PubMed1992

Myocardial beta-adrenergic receptor expression and signal transduction after chronic volume-overload hypertrophy and circulatory congestion.

BACKGROUND: The volume-overload, high-output state induced by aortocaval fistula is unique because it is not generally associated with marked abnormalities of contractile function. Thus, changes in beta-adrenergic receptor (beta AR) expression should reflect more directly the influence of neurohumoral adrenergic tone, clarifying the manner in which peripheral (neurohumoral) versus primary myocardial factors are operative in decreased beta AR-dependent signal transduction. METHODS AND RESULTS: We examined the beta-adrenergic receptor-responsive adenylyl cyclase pathway in hearts from pigs subjected to volume-overload hypertrophy with circulatory congestion. Nine pigs underwent initial pharmacological and hemodynamic studies, and, 5 weeks after aortocaval fistula placement, when signs of circulatory congestion were evident, these measurements were repeated. Biochemical analyses of plasma and myocardium from these animals and seven normal animals were compared. Experimental animals showed signs of circulatory congestion (tachypnea, weight gain, pulmonary rales) within 3-4 weeks of fistula placement. Necropsy showed ascites and biventricular cardiac hypertrophy, but no fibrosis or inflammation was present on histological inspection. Heart rate responsiveness to beta AR stimulation was blunted, with ED50, for isoproterenol increased 133% (p less than 0.001) after development of circulatory congestion. Biochemical analyses of the beta AR-responsive adenylyl cyclase pathway showed uniform decreases in beta AR number in right atrium, right ventricle, and left ventricle (36-41% decreases, p less than 0.005). Downregulation was selective for beta 1-receptors, and remaining receptors in the right and left ventricles showed low-affinity agonist binding, suggesting an uncoupling from Gs. All measures of adenylyl cyclase activity were diminished significantly in membrane homogenates from the right atrium (mean reduction, 50 +/- 10%) and left ventricle (mean reduction, 44 +/- 8%) after volume overload. Finally, we found that amounts of cardiac Gs, as measured in reconstitution assays, were decreased in both the right atrium (p less than 0.02) and the left ventricle (p less than 0.01) of volume-overloaded animals but that levels of pertussis toxin substrate were unchanged. CONCLUSIONS: Biochemical findings occurred in the absence of myocardial inflammation or fibrosis and without pharmacological interventions, suggesting that circulatory congestion, with attendant elevation in plasma norepinephrine, may be a sufficient stimulus to induce such changes. The data are compatible with a catecholamine-driven beta AR pathway desensitization. Thus, a primary defect in intrinsic contractile function is not a necessary component for abnormalities of the myocardial beta AR-responsive adenylyl cyclase pathway.

Adenylyl Cyclases↗

PubMed1992

Coronary collateral development in swine after coronary artery occlusion.

We have quantified the development of the coronary collateral circulation in the pig. The collateral circulation was induced to grow by placing an ameroid occluder on the left circumflex coronary artery. Two to 16 weeks after ameroid placement, the coronary collateral circulation was identified after the injection of several colors of a silicone polymer into the coronary arteries and the aorta. We identified intercoronary and extracardiac collaterals and quantified their number, location, size, and wall thickness. Intercoronary collaterals grew to a level that represents a 14-fold increase in normal collateral blood flow under resting conditions compared with the values in an animal not subjected to coronary artery occlusion. Extracardiac collaterals could potentially supply approximately 30% of resting flow. The sources of the extracardiac collaterals were the bronchial and internal mammary arteries. Coronary collateral morphometry and DNA synthesis in the pig heart also were examined. Coronary collaterals had significantly less smooth muscle than did normal arterioles. This may account, in part, for the reduced response of the coronary collaterals to vasodilators. We observed intense DNA synthesis in endothelial and smooth muscle cells in the first 2 or 3 weeks of ischemia. However, DNA synthesis rapidly ceased after this time, coincident with coronary collateral reserve values (ischemic/nonischemic regional blood flow ratios during maximal vasodilation) reaching their maximum level. This suggests that failure of the vessels to continue proliferating accounts for the occurrence of the plateau in blood flow levels.

Animals↗

PubMed1992

Coronary vascular remodeling and coronary resistance during chronic ischemia.

Our previous observations that minimal coronary resistance (MCR) decreases by 60% in a model of chronic ischemia suggest that angiogenesis and vascular remodeling occurred. To test this hypothesis we conducted quantitative morphometry on the arteriolar (ART) and capillary (CAP) beds of 14 pigs subjected to chronic ischemia. We induced chronic ischemia by ameroid occlusion of the left circumflex coronary artery for 2 to 8 weeks. We measured numerical densities (ND) and total cross sectional areas (CSA) of the ART and CAP in the ischemic regions. In the same pigs minimal coronary resistance (MCR) was measured during adenosine infusion, using a constant pressure coronary perfusion pump. In 8 other pigs we gave tritiated thymidine to determine the extent of DNA synthesis in smooth muscle and endothelial cells. At autopsy we injected colored silicone into the vessels of these pigs so we could evaluate the coronary collateral vessels as well as the other arterioles. After 3 weeks of ameroid occlusion, ART ND increased 45% above control, while ART CSA increased 21% above control. After 8 weeks of ameroid occlusion, there were further significant increases in ART CSA, but not in their ND. These changes corresponded to a decrease in MCR to 35% of control after 3 weeks of ameroid occlusion. After 8 weeks of ameroid occlusion, MCR had increased to 49% of control, however there was a further increase in ART CSA to 58% above control. DNA synthesis was occurring since endothelial and smooth muscle cells had total DNA labeling indexes of 1.2% (compared to 0.01% for controls) 2-5 days after ameroid occlusion, but were near control levels by 8 weeks. Many arterioles showed endothelial cell denuding and medial damage. Also capillaries showed degenerative changes and new sprouts. Silicone casts of the left circumflex bed vessels showed increased volumes averaging 55% more than controls. These data imply that angiogenesis is partly responsible for the decreased minimal coronary resistance seen in chronic ischemia. The loss of wall integrity in old arterioles and increased compliance in newly formed arterioles and capillaries also may contribute to the reduced resistance. Newly formed vessels are a significant portion of the total number of vessels. The combined effect of these changes is a reduced minimal coronary resistance that is modulated by 8 weeks. Measurements of coronary collateral growth paralleled the changes in the ischemic bed suggesting that angiogenesis factors controlling growth in both the bed at risk and its periphery are controlled by similar temporal events.

Animals↗

PubMed1992

Compensatory angiogenesis during progressive right ventricular hypertrophy.

We investigated vascular adaptations occurring in progressive right ventricular hypertrophy (RVH) in adult mini pigs. Fourteen mini pigs had progressive RVH induced by implanting an inflatable cuff on the main pulmonary artery for 1-5 months and were compared to a control group (N = 11). RVH animals were divided into two groups, a moderate RVH (MH) that had RV/BW ratio increases of 20%-70% above controls and a severe hypertrophy group (SH) that had RV/BW ratio increase of 70%-117%. We measured coronary blood flow reserve (CBFR) with radiolabelled microspheres at maximal exercise and during adenosine vasodilation. Adenosine vasodilation did not decrease CBFR either regionally or transmurally in both the MH and SH groups. During exercise CBFR showed a small but significant decrease in the SH group. No intervention changed the endo/epi flow ratios. Morphometric studies showed that myocytes increased in cross sectional areas (CSA) in these hypertrophied hearts. The CSA of capillaries and arterioles and their numerical densities increased significantly in the endocardial and epicardial regions in both MH and SH groups. Capillary density showed a small but significant decrease in both MH and SH groups. We measured DNA synthesis in these hearts using tritiated thymidine labelling. We found a high labelling index in endothelial cells and a moderate labelling index in smooth muscle cells in early stages of hypertrophy. These data show that angiogenesis, observed in the morphometric studies and by DNA labelling, prevents CBFR changes during progressive RVH in the pig. Furthermore, angiogenesis is not uniform at different stages of progressive RVH.

Adaptation, Physiological↗

PubMed1990

Aortic valve repair for aortic stenosis in adults.

The stenotic aortic valve was surgically repaired in 48 adults, 21 women and 27 men, aged 38 to 83 years. Five had congenital aortic stenosis (AS), with a mean aortic valve gradient and area of 58 +/- 23 mm Hg (standard deviation) and 0.54 +/- 0.13 cm2, respectively; 32 had senile AS with a mean aortic valve gradient and area of 43 +/- 20 mm Hg and 0.98 +/- 0.41 cm2; and 11 had rheumatic AS with a mean aortic valve gradient and area of 59 +/- 24 mm Hg and 0.47 +/- 0.15 cm2. Only 6 patients underwent isolated aortic valvoplasty, 11 underwent concomitant mitral valve procedure, and 34 underwent concomitant coronary revascularization. Repair consisted of decalcification in 33 patients and decalcification as well as commissurotomy in 15 patients. There were three hospital deaths, none related to the aortic valve. Only 2 patients (both rheumatic) did not improve clinically. During follow-up (mean, 64 +/- 41 months) aortic valve restenosis developed in 24% (10 patients, 3/5 congenital, 4/11 rheumatic, and 3/32 senile) at a mean of 64 +/- 28 months. Postoperative Doppler echocardiographic assessment of 21 patients with senile AS at 1.1 +/- 2.7 and 18.1 +/- 1.4 months showed significantly lower aortic valve gradient and improved area in comparison with preoperative values. At 36 +/- 2.7 months, aortic valve gradient and area were not significantly different than preoperative values, and at 58.5 +/- 2.6 months aortic valve gradient was 1.41 (p = 0.07) times the preoperative value. At 7 years, actuarial freedom from aortic valve-related symptoms of the patients with senile AS was 87%. We conclude that in select patients aortic valve repair results in excellent relief of AS. Late restenosis is expected and more likely to occur in the valves with congenital and rheumatic disease than in those with senile disease.

Adult↗

PubMed1990

Effect of long-term exercise on regional myocardial function and coronary collateral development after gradual coronary artery occlusion in pigs.

The effect of myocardial ischemia, induced by long-term exercise, on regional myocardial function and coronary collateral development was examined in pigs after gradual occlusion of the left circumflex coronary artery (LCx) with an ameroid occluder. Thirty days after surgery, regional myocardial function and blood flow were assessed during exercise in 22 pigs separated into exercise (n = 12) and sedentary groups (n = 10). The exercise group trained on a treadmill for 25 +/- 1 days, 30-50 min/day, at heart rates of 210-220 beats/min. After 5 weeks, another exercise test was performed. In the exercise group, after training, we observed an improvement in systolic wall thickening, expressed as a percentage of rest, in the collateral-dependent LCx region from 64 +/- 8% to 87 +/- 6% (p less than 0.01) at moderate exercise levels (220 beats/min) and from 45 +/- 7% to 73 +/- 7% (p less than 0.01) at severe exercise levels (265 beats/min). Transmural myocardial blood flow in the LCx region expressed as a ratio of flow in the nonoccluded region of the left ventricle also increased significantly (p less than 0.01) during severe exercise after 5 weeks. The sedentary group showed an improvement in systolic wall thickening in the LCx region during moderate exercise compared with the initial exercise test (p less than 0.05) but no significant change in systolic wall thickening or myocardial blood flow ratios during severe exercise after 5 weeks. We conclude that long-term exercise after gradual LCx coronary artery occlusion in pigs improves myocardial function and coronary collateral reserve in collateral-dependent myocardium during exercise.

Animals↗

PubMed1990

Dissecting aneurysm of a coronary artery due to percutaneous transluminal balloon angioplasty.

Percutaneous transluminal balloon angioplasty (PTCA) is utilized successfully to dilate stenotic coronary arteries. The procedure is a frequent nonsurgical method to restore coronary artery blood flow to ischemic myocardium. In this paper, we report a case of intimal tear and medial dissection of the right coronary artery leading to a dissecting aneurysm and occlusion of the coronary artery. The patient died following coronary artery bypass grafts, and the autopsy demonstrated the dissecting aneurysm of the coronary artery.

Aortic Dissection↗

PubMed1988

Altered minimal coronary resistance to antegrade reflow after chronic coronary artery occlusion in swine.

We examined coronary pressure-flow relations after chronic coronary artery occlusion induced by placement of an ameroid occluder on the left circumflex coronary artery in swine. An acute open-chest procedure was performed in nine pigs 27 +/- 2 days (mean +/- SEM) after surgical placement of the ameroid occluder, and in eight nonoperated control pigs. Coronary vascular resistances were measured during maximal coronary vasodilation with adenosine. Minimal coronary resistance was assessed before and after cannulation and extracorporeal perfusion of the left circumflex coronary artery distal to the site of the ameroid occluder in pigs from the ameroid group and in a similar site in control pigs. Minimal coronary resistance to antegrade reflow in the left circumflex region was decreased significantly in ameroid pigs compared with control pigs (0.06 +/- 0.01 vs. 0.26 +/- 0.03 mm Hg.min.100 g/ml, p less than 0.001, respectively). Decreased minimal coronary vascular resistance was present transmurally in the left circumflex region of ameroid pigs. Altered vascular resistance occurred only in myocardium distal to the ameroid occluder since the nonoccluded left anterior descending region in ameroid pigs had minimal coronary resistance similar to that of the same region from control pigs (0.23 +/- 0.03 vs. 0.19 +/- 0.02 mm Hg.min.100 g/ml). Thus altered minimal coronary vascular resistance occurs and probably reflects vascular proliferation and/or vascular alterations which result in an increased total cross-sectional area of the vasculature in the myocardium distal to the occlusion.

Animals↗