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Biomedical subjects

B Healy

Publications and source records attributed to B Healy.

At least 73 records · Page 4Linked to original sources
PubMed1989

Propranolol-induced changes in the catecholamine-containing cells and vesicles of SHR sympathetic ganglia.

The ultrastructural effects of long-term propranolol administration on the catecholamine-containing (CC) cells of cervical sympathetic ganglia were studied in spontaneously hypertensive rats. After 2 months of propranolol administration, there were hydrops of mitochondria, together with swelling and vesiculation of Golgi complex and rough endoplasmic reticulum. Such swollen organelles seemed to coalesce with each other, resulting in transformation of major parts of the cytoplasm into large membrane bound saccules. In that group of animals, the number of CC vesicles showed a significant decrease (P less than 0.025) compared to the control. Moreover, such vesicles looked more electron dense, with decreased electron-lucent haloes compared to the control. Blood pressure recording via rat tail cuff showed a significant drop (P less than 0.0001) of the mean systolic blood pressure in the treated animals. One month after stopping propranolol administration, resorption of the cytoplasmic saccules occurred, but the cytoplasm looked lighter and lost its granular appearance. The mitochondria regained their normal shape, though they appeared fewer in number. The CC vesicles were significantly reduced in number (P less than 0.001) and were less electron dense compared to the control. The possible implications of these findings on the mechanism of action of propranolol as an antihypertensive agent are discussed.

Animals↗
PubMed1989

Coronary artery bypass surgery vs coronary angioplasty: from antithesis to synthesis.

Over the last two decades, revascularization therapy has greatly improved the management of patients with coronary artery disease. Coronary artery bypass graft (CABG) surgery has been proven by several randomized trials to alleviate symptoms, prevent myocardial infarction, and prolong survival in patients with moderately severe disease. Percutaneous transluminal coronary angioplasty (PTCA) has emerged as an alternative treatment for an increasing number of these patients. The use of coronary angioplasty has been expanding rapidly to include single-vessel and multivessel disease and acute ischaemic syndromes. Although the angiographic success rate in properly selected cases exceeds 90%, there are limited data regarding the long-term results with angioplasty in the treatment of patients with multivessel disease. Procedure-related mortality and restenosis rate remain major areas of concern. Several randomized clinical trials (CABRI, RITA, GABI, EAST, BARI) currently in progress are comparing PTCA and CABG in the management of patients with multivessel coronary artery disease. It is anticipated that these studies will provide a wealth of information, enabling physicians to construct a revascularization strategy that will maximally benefit their patients.

Angioplasty, Balloon, Coronary↗
PubMed1989

Angiotensin II receptors in normal and failing human hearts.

To demonstrate the existence and help clarify the function of angiotensin II (Ang II) receptors in the human heart, we characterized the cardiac Ang II receptor and examined the levels and distribution of ventricular Ang II receptors in normal (n = 6) and failing (n = 14) hearts. Ang II receptors were characterized using the Ang II receptor agonist [125I]Ang II. Cardiac [125I]Ang II-binding sites were of high affinity (Kd, approximately 1 nmol/L) and low capacity (Bmax, approximately 3 fmol/mg membrane protein) and were pharmacologically specific [IC50 values for Ang II, [Sar1,Ile8]Ang II, and Ang III were 1.2, 3.0, and 400 nmol/L, respectively; the inactive Ang II metabolite Ang-(1-5), at a concentration of 1 mumol/L, inhibited [125I]Ang II binding by less than 10%]. These characteristics of cardiac [125I]Ang II-binding sites are similar to those of previously characterized mammalian heart Ang II receptors. In normal adult donor hearts (n = 5), Ang II receptor density in the left ventricle [LV, 2.90 +/- 1.40 (+/- SE) fmol/mg] was similar to that in the right ventricle (RV, 3.82 +/- 1.10 fmol/mg). The ventricular Ang II receptor density in adult patients with idiopathic (LV, 1.77 +/- 0.35 fmol/mg; RV, 1.58 +/- 0.29 fmol/mg; n = 8) or dilated cardiomyopathy (LV, 2.00 +/- 0.58 fmol/mg; RV, 2.56 +/- 0.52 fmol/mg n = 5) was similar to that in the normal heart. Ventricular Ang II receptors, localized by autoradiography using the Ang II receptor antagonist [125I]-[Sar1,Ile8]Ang II, were consistently found in the myocardium, cardiac adrenergic nerves, and coronary vessels of normal and failing ventricles. In human ventricles Ang II receptor levels were not correlated with age. Because ventricular Ang II receptor density in a normal neonatal human heart and that in a heart from an adolescent patient with idiopathic cardiomyopathy were more than 10-fold and more than 5-fold higher, respectively, than in normal adult ventricles, we investigated whether postnatal changes occur in ventricular Ang II receptors in rats. In male and female rats ventricular Ang II receptor density was about 2-fold higher in 1-day-old rats compared to that in 10-day-old or peripubertal rats. These data suggest developmental regulation of ventricular Ang II receptors. Our findings suggest that direct and neural angiotensinergic inputs to the myocardium play a role in the regulation of cardiac function in man and that these inputs are preserved in the failing heart.

Adolescent↗
PubMed1988

Disproportionate epicardial dilation after transmural infarction of the canine left ventricle: acute and chronic differences.

The relation between acute disproportionate infarct dilation and late postinfarct left ventricular remodeling was examined by implanting multiple radiopaque epicardial markers in the left ventricle of eight dogs and determining regional surface deformation after acute and chronic transmural infarction. Transmural injury was produced by combining coronary ligation with distal embolization of a rubber polymer. Dogs were anesthetized and studied before and 1 h, 24 h and 1 week after infarction. Marker positions were recorded by rapid biplane cineradiography, and three-dimensional coordinates were reconstructed by a computer-assisted tracking system. Regional deformation was expressed by a local surface area equal to the sum of multiple (three to four) triangles generated by marker triplets. As early as 1 h after infarction, end-diastolic area in the infarct region increased by 20.3 +/- 3.1%, while that in the remote region increased by only 7.9 +/- 3.5%. Both changes and the difference between them were significant. At 24 h after infarction, both territories continued to undergo dilation, this time to a similar extent (additional +10.3% in the remote region and +10.1% in the infarct region), thus maintaining the significant disproportionate infarct dilation. At 1 week, however, the infarct territory remained dilated with a mean end-diastolic area 31.4 +/- 3.1% above control, while that in the remote region returned to a net mean 8.5 +/- 4.7% increase. Thus, the major extent of disproportionate infarct dilation occurs within 1 h after transmural injury and is accompanied by remote dilation as a compensatory response. The extent of further infarct dilation achieved by 24 h is maintained in the chronic infarct, and compensatory mechanisms enable noninjured myocardium to become less dilated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Increased afterload aggravates infarct expansion after acute myocardial infarction.

After acute transmural myocardial infarction, the heart may undergo major remodeling characterized by thinning and dilation of the infarct zone and overall enlargement of the heart. The effect of increased left ventricular pressure on infarct expansion and the extent to which it alters postinfarction remodeling were studied in a rat model. Rats with either aortic banding or a sham operation and a survival period of 3 weeks were further randomized to sham thoracotomy or left coronary ligation. Surviving rats were killed 7 days later and the hearts were fixed in diastole for morphologic analysis. Hearts with aortic banding had a mean peak to peak gradient of 20.7 +/- 4.9 mm Hg across the aortic band at death and a significantly thicker heart than that of the comparison group without an aortic band. Infarct size, as a percent of total left ventricular mass, at the time of death was less in the group with aortic banding, yet infarct expansion was more marked. However, when original infarct size was estimated taking into account the effects of aortic banding, scar formation, infarct expansion and infarct-induced hypertrophy, it was found to be similar in both infarct groups (45.50 +/- 4.2 versus 47.90 +/- 3.1%). Infarct expansion, as measured by cavity dilation and infarct thinning, occurred in both infarct groups but was greater in the group with aortic banding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Infants of depressed mothers show "depressed" behavior even with nondepressed adults.

To determine whether the "depressed" behavior (e.g., less positive affect and lower activity level) of infants noted during interactions with their "depressed" mothers generalizes to their interactions with nondepressed adults, 74 3-6-month-old infants of "depressed" and nondepressed mothers were videotaped in face-to-face interactions with their mothers and with nondepressed female strangers. "Depressed" mothers and their infants received lower ratings on all behaviors than nondepressed mothers and infants. Although the infants of "depressed" versus nondepressed mothers also received lower ratings with the stranger adult, very few differences were noted between those infants' ratings when interacting with their mother versus the stranger, suggesting that their "depressed" style of interacting is not specific to their interactions with depressed mothers but generalizes to their interactions with nondepressed adults as early as 3 months of age.

Adolescent↗
PubMed1988

Cellular mechanisms of myocardial infarct expansion.

Infarct expansion is acute regional dilatation and thinning of the infarct zone. There are several possibilities for the mechanism of this alteration in cardiac shape: thinning could be caused by 1) cell rupture, 2) a reduction in the intercellular space, or 3) stretching of myocytes or 4) slippage of groups of myocytes so that less cells are distributed across the wall. To determine the relative contributions of these cellular mechanisms of wall thinning and dilatation, detailed study of transverse histological sections of rat hearts with infarct expansion was performed 1, 2, and 3 days after coronary ligation. The number of cells across the wall was determined in six regions within, adjacent to, and remote from the infarct. Cell counting was performed so that the total number of cells across the wall and the number of cells per unit length (cell density) across the wall were determined. The transmural cell count and the cell density were correlated with the wall thickness in each region. Myocyte cross-sectional areas and sarcomere lengths were also measured. The results from the infarct expansion hearts were compared with those of sham-operated control hearts that had been similarly analyzed. To ensure that mechanisms identified in the rat were applicable to human infarct expansion, five hearts from patients who died within 3 days of infarction and two hearts from patients without coronary disease were studied histologically in a similar fashion. Wall thinning occurred in all regions of the rat infarct expansion hearts compared with controls (p less than 0.0001) but, as expected, was most pronounced in the infarct zone. A decrease in the number of cells across the wall accompanied the wall thinning at each site (p less than 0.0001), and this change in cell number was highly correlated with the changes in wall thickness (r = 0.915, p less than 0.001). Cell density increased from controls only within the infarct zone (p less than 0.001) and accounted for at most 20% of the thinning in that region. The change in cell density was attributable to both cell stretch (measured by increased sarcomere length and decreased myocyte cross-sectional area) and a decrease in the intercellular space. A similar strong correlation between wall thinning and decreased number of cells across the wall was identified in the human hearts (r = 0.94, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effects of chronic exercise on the coronary circulation in conscious rats with renovascular hypertension.

Since various studies suggest that chronic physical conditioning promotes myocardial vascularity, we investigated whether it could prevent the coronary reserve abnormalities of hypertensive cardiac hypertrophy. One week after operation, female Sprague-Dawley rats with two-kidney, one clip Goldblatt hypertension were either subjected to a moderate exercise program by swimming (n = 21) or kept sedentary (n = 16) for 9 weeks. Sedentary (n = 16) and exercised (n = 15) sham-operated rats served as controls. Maximal coronary blood flow and minimal coronary resistance, either per unit mass or for the entire left ventricle, an index of the functional cross-sectional area of the coronary resistance vessels, were determined in conscious, unrestrained rats by left atrial microsphere injection following maximal vasodilation with carbochrome (12 mg/kg). Following exercise, left ventricular mass was moderately (+5-10%) but significantly increased in normotensive rats, whereas left ventricular hypertrophy was significantly accentuated in the hypertensive rats. Minimal coronary resistance for the entire left ventricle was significantly decreased (-24%) in normotensive rats but did not change significantly in hypertensive rats. Minimal coronary resistance per unit mass (the coronary vasodilator reserve) tended to decrease in normotensive rats (-17%), whereas it tended to be further augmented in hypertensive rats (+13%). However, these differences were marginally significant and were not associated with any changes in maximal coronary blood flow per unit mass (the coronary flow reserve). Thus, in normal rats, exercise promoted myocardial arterial vascularity in parallel with the development of cardiac hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Failure of swimming exercise to improve capillarization in cardiac hypertrophy of renal hypertensive rats.

Female Sprague-Dawley rats were made hypertensive by the two kidney/one clip Goldblatt procedure, while control animals were sham-operated. One week later, half of the animals were subjected to a moderate swimming exercise and the other half remained sedentary. Thus, four experimental groups, each consisting of 14 rats, were formed: control animals that were exercised or kept sedentary and corresponding renal hypertensive animals either exercised or sedentary. In hypertensive rats, a significantly increased left ventricular weight and reduced coronary reserve were found. Cardiac hypertrophy in hypertensive rats was characterized by a lower number of capillaries on a tissue cross-section, larger heterogeneity of the capillary net, and a less uniform orientation of capillaries in space. Total length of capillaries in the hypertrophic hearts increased significantly, but less than the increase in cardiac weight, resulting in reduced capillary length density. Chronic swimming for 2 hr/day for a period of 6 weeks, subsequent to a 4-week acclimation period, did not significantly influence any of the investigated indexes of capillaries from hypertrophic hearts. In the normotensive rats, chronic swimming resulted only in a moderate increase in total capillary length associated with a small increase in the left ventricular weight of similar degree. Thus, chronic exercise in normotensive rats induced a moderate increase in total capillary length per left ventricle, while it did not alleviate impaired capillarization of hypertrophic hearts from hypertensive rats.

Animals↗
PubMed1987

Steroid administration after myocardial infarction promotes early infarct expansion. A study in the rat.

Whether steroids lead to thinner scars and larger aneurysms by delaying collagen deposition or worsening infarct expansion before significant collagen deposition begins is unknown. Rats underwent either transmural infarction by left coronary ligation or sham operation. Both infarct and sham rats were randomized to methylprednisolone 50 mg/kg i.p. X 4 or saline treatment within 24 h after operation. Sacrifice occurred before (3 d) or after (7 d) collagen deposition typically begins. Despite similar infarct size, infarct wall thickness was 1.35 +/- 0.08 mm in the saline and 0.99 +/- 0.12 mm in the methylprednisolone group (P less than 0.001) at 3 d. This decrease in wall thickness was explained by a decrease in the number of myocytes across the infarct wall (r = 0.99; P less than 0.001), suggesting that steroids promote myocyte slippage. Furthermore, methylprednisolone caused no further infarct thinning or cavity dilatation beyond 3 d. Thus, high-dose methylprednisolone given within 24 h after transmural infarction worsens infarct expansion before collagen is laid down by promoting the slippage of necrotic myocytes.

Animals↗
PubMed1987

The rapid evolution of a myocardial infarction in an end-artery coronary preparation.

The potential for salvaging infarcting myocardium depends on the time course of the infarction process. To determine the rate of infarct evolution in an end-artery coronary preparation similar to the coronary arterial system of the human heart, each of 84 swine underwent a reversible occlusion of the left anterior descending coronary artery for varying lengths of time, after which flow was reestablished into the occluded region for either 2 or 48 hr. Infarct size was assessed by nitro blue tetrazolium (NBT) staining and confirmed by histologic examination in the 48 hr animals. The region at risk of ischemic injury was determined by injection of monastral blue dye. Infarction progressed rapidly, with a mean of 1.9 +/- 1.5% of the risk region infarcting after 15 min of occlusion, 20.3 +/- 5.7% at 30 min, 43.3 +/- 4.8% at 45 min, 59.9 +/- 2.4% at 60 min, 70.6 +/- 1.7% at 90 min, 84 +/- 2.0% at 180 min, and 88.6 +/- 2.0% after 48 hr. Although there was good correlation in infarct sizing between NBT and histologic techniques at 2 and 48 hr of reperfusion, NBT underestimated infarct size at 15 and 30 min. These data suggest that in the setting of an end-artery coronary anatomy, reperfusion must be carried out within 90 min of coronary occlusion to achieve significant salvage of infarcting myocardium, a period of time much shorter than previously suspected.

Animals↗
PubMed1986

Importance of risk factors in the angiographic progression of coronary artery disease.

Although specific risk factors correlate with the development of clinical coronary events, little is known about their importance in patients with established coronary artery disease (CAD). A numerical scoring system was used to assess serial coronary angiograms in subjects who had detailed risk factor determinations. Strong linear correlations were demonstrated between the extent of progression of CAD and diastolic blood pressure (BP) (p = 0.002), systolic BP (p = 0.094), the number of cigarette pack-years smoked among current smokers (p = 0.022), fasting blood glucose level (p = 0.017) and low levels of physical activity at leisure (p = 0.097). This analysis of sequential coronary angiograms identifies BP, cigarette smoking, diabetes mellitus and physical activity as important risk factors in the progression of CAD. These variables merit attention in the management of patients with symptomatic CAD and in secondary coronary prevention trials investigating risk factor modification.

Adult↗
PubMed1986

Effect of exercise on acute myocardial infarction in rats.

Infarct expansion, the time-related thinning and dilation of an acute transmural infarct, leads to aneurysm formation and cardiac rupture in humans. In this study, the effect of exercise on acute infarct expansion early after myocardial infarction was examined in 129 rats. Ninety rats were exercised on a treadmill for 1.5 hours daily for 1 week beginning on the day of coronary artery ligation; the remaining 39 rats remained in their cages. There was no effect on the prevalence or extent of expansion; specifically, infarct wall thickness, left ventricular diameter and expansion grade (0 to 4+) were similar in the exercise and control rats. There was no difference in infarct size or the number of animals with aneurysmal shape changes in the exercise and control groups. There was no significant difference between the two groups in the histologic finding of intramural hemorrhage, a feature that has been associated with cardiac rupture, and no complete rupture was seen. However, there was a nonsignificant trend toward higher mortality in the exercised group. Thus, the findings of this study suggest that moderate exercise early after myocardial infarction produces no significant detrimental effect on infarct size or left ventricular topography in the rat model.

Animals↗