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Biomedical subjects

B H Bulkley

Publications and source records attributed to B H Bulkley.

At least 19 recordsLinked to original sources
PubMed1985

Effects of repeated brief coronary occlusion on regional left ventricular function and dimension in dogs.

The cumulative effects of repeated, brief episodes of regional ischemia on myocardial function and dimension were examined in 14 open-chest dogs. The left anterior descending coronary artery was occluded for 5 minutes, followed by 10 minutes of reflow, repeated 16 times, and then 1 hour recovery. Systolic function decreased progressively in segments made repetitively ischemic and remained depressed even after 1 hour of recovery. Average systolic shortening decreased 20% from baseline after recovery from the first occlusion, 82% after the 8th, 91% after the 16th, and 104% after the 1 hour recovery (p less than 0.015, analysis of variance). End-diastolic segment length progressively increased in regions made repetitively ischemic, lengthening 4% after the first occlusion, 10% after the third occlusion, 19% after the sixteenth occlusion, and 16% after 1 hour of recovery (p less than 0.02). Nonischemic end-diastolic segment length also showed a smaller but parallel increase, while non-ischemic systolic function showed compensatory improvement. After the dogs were killed, myocardial staining with triphenyl tetrazolium chloride revealed no necrosis. Electron microscopy, performed in 5 dogs, showed scattered mitochondrial swelling in both postischemic and nonischemic regions, but no evidence of irreversible injury. The ratio of myocardial blood flow in the region made repetitively ischemic to nonischemic flow, as measured with microspheres, was 1.00 +/- 0.02 before the occlusions and 0.90 +/- 0.03 just before death (difference not significant). Thus, in the dog progressively abnormal regional systolic function and regional and global diastolic dilatation can be produced by repetitive, brief, coronary occlusions, which are not associated with histochemical or ultrastructural evidence of myocardial necrosis.

Animals↗
PubMed1985

Intracoronary thrombolysis 3 to 13 days after acute myocardial infarction for postinfarction angina pectoris.

The restoration of anterograde coronary flow long after coronary thrombosis may be of benefit to patients with continuing ischemia. To determine whether "old" intracoronary thrombi are susceptible to lysis with thrombolytic agents, 18 patients with angina at rest during evolving acute myocardial infarction (AMI) and total occlusion of the infarct vessel were treated with intracoronary streptokinase 3 to 13 days after onset of AMI. In 12 of the 18 patients (67%), successful recanalization of the artery was achieved 6.9 +/- 2.7 days after AMI. Thrombolysis was followed by coronary angioplasty in 2 patients. To evaluate the efficacy of this approach in reducing post-AMI ischemia, the number of episodes of angina at rest was compared in patients with successful and unsuccessful attempts at recanalization. Even in patients without angioplasty, the mean number of daily episodes decreased from 1.02 +/- 0.6 to 0.09 +/- 0.2 in patients in whom reperfusion was achieved, and from 1.07 +/- 0.8 to 0.88 +/- 0.8 in those in whom it was not (p = 0.027 for the difference between the groups). Thus, in patients with early post-AMI angina, intracoronary streptokinase can restore flow in the occluded artery, may decrease the frequency of angina, and allows angioplasty to be performed.

Adult↗
PubMed1985

Thrombolysis with recombinant tissue plasminogen activator in atherosclerotic thrombotic occlusion.

Human tissue plasminogen activator holds promise for the dissolution of coronary thrombi by intravenous administration and without systemic anticoagulation. Prior animal experiments have been conducted only in vessels without disease. To test the thrombolytic efficacy of recombinant tissue plasminogen activator in the presence of diseased intima, an established model of atherosclerosis was utilized. The aorta of 16 New Zealand white rabbits (2 to 3 kg) was made atherosclerotic by balloon endothelial denudation and concurrent 1% cholesterol feeding for 8 weeks. An aged (24 hour) heterologous (human) clot, labeled with I-125 fibrinogen was injected into the distal aorta and produced thrombotic occlusion. After 1 hour of thrombosis (control period), recombinant tissue plasminogen activator (100,000 IU approximately equal to 1 mg protein, n = 6) or streptokinase (100,000 IU, n = 5) or saline solution (n = 5) was systemically infused over 30 minutes. Serial blood samples, obtained to determine fractional change in blood radioactivity over time, showed a fourfold increase of blood radioactivity after tissue plasminogen activator and streptokinase infusion compared with the control period (47,400 +/- 3,300 [mean +/- standard error] versus 11,800 +/- 300 counts/min, p less than 0.001). Time to 50% of maximal thrombolysis was 41 +/- 14 minutes (+/- standard deviation) for tissue plasminogen activator versus 63 +/- 16 minutes for streptokinase (p less than 0.01). In six of six rabbits receiving tissue plasminogen activator and four of five rabbits receiving streptokinase, reestablishment of distal aortic flow was detected via the indwelling catheter within 25 minutes of drug infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Regional wall motion improvement after coronary thrombolysis with recombinant tissue plasminogen activator: importance of coronary angioplasty.

To evaluate functional recovery in 20 consecutive patients with acute myocardial infarction who received recombinant tissue-type plasminogen activator, serial two-dimensional echocardiograms were performed before and immediately after tissue plasminogen activator administration and at 1 and 10 days postinfarction. Tissue plasminogen activator was administered intravenously (17 patients) or by intracoronary infusion (3 patients) after angiographic confirmation of total occlusion. Reperfusion, documented by angiography, occurred in 13 of the 20 patients. The mean time from onset of chest pain to thrombolysis was 5.1 +/- 1.1 hours. Echocardiograms were evaluated for regional function with a visual semiquantitative scoring system by two independent observers who had no knowledge of patient identity, temporal sequence, therapy or effect of therapy. There was no immediate or 24 hour improvement in wall motion. At day 10 compared with pretreatment, 28 of 33 reperfused infarct zone segments versus 6 of 20 nonreperfused infarct segments demonstrated improved wall motion (p = 0.01). This improvement did not relate to time from onset of chest pain to successful thrombolysis. Of reperfused infarct zone segments in the distribution of coronary artery balloon dilation, 19 of 23 segments exhibited improvement versus 7 of 17 (reperfused, no angioplasty) and 6 of 20 (nonreperfused, no angioplasty) segments (p = 0.001). Infarct zone segments reperfused at the time of ongoing chest pain demonstrated functional recovery compared with segments reperfused in the absence of chest pain (18 of 23 versus 10 of 20, respectively; p = 0.05). Thus, in this uncontrolled series, there was echocardiographically detectable improvement in function of reperfused infarct segments 10 days after coronary thrombolysis with recombinant tissue plasminogen activator.

Adult↗
PubMed1985

Results of a randomized prospective trial of intraaortic balloon counterpulsation and intravenous nitroglycerin in patients with acute myocardial infarction.

A randomized prospective clinical trial compared combined treatment with intraaortic balloon pumping and intravenous nitroglycerin for 4 to 5 days with routine clinical management in 20 patients with extensive myocardium at risk for infarction as evidenced by a thallium defect score of 7.0 units or greater. No significant differences in mortality or clinical outcome were observed between the 10 patients receiving the combined treatment and the 10 receiving routine management. In 14 patients two-dimensional echocardiograms obtained 6 to 24 hours after the onset of symptoms and at follow-up 6 to 16 days later (after completion of combined intraaortic balloon pumping plus nitroglycerin therapy) were analyzed to determine whether infarct segment or noninfarct segment lengths were affected by therapy. Among these 14 patients, 5 (3 receiving the combined therapy and 2 receiving routine management) demonstrated an increase in infarct segment length of greater than 1.0 cm. Mean infarct segment length increased 0.30 +/- 0.44 cm in patients receiving the combined therapy and 0.29 +/- 0.36 cm in patients on routine management (p = NS). In contrast, noninfarct segment length increased greater than 1.0 cm (mean increase 1.20 +/- 0.39) in five of seven patients on routine management but in none of 7 patients receiving intraaortic balloon pumping plus nitroglycerin therapy (mean decrease 0.22 +/- 0.20 cm) (p less than 0.05). No significant differences were noted in left ventricular ejection fraction, as measured by gated blood pool scintigraphy, or thallium perfusion defect score in a comparison of day 1 (pretreatment) with day 4 thallium or day 7 to 14 gated blood pool scintigrams. Thus, in patients with extensive myocardium at risk, it is unlikely that a reduction in mortality or a significant improvement in myocardial perfusion or ventricular function can be obtained by early intervention with intraaortic balloon pumping in combination with nitroglycerin. Although this combined therapy failed to prevent infarct segment lengthening (infarct expansion), the combined afterload-lowering effects of intraaortic balloon pumping and nitroglycerin did appear to prevent dilation or remodeling of noninfarcted segments during the first 2 weeks after acute myocardial infarction.

Adult↗
PubMed1985

Global cardiac remodeling after acute myocardial infarction: a study in the rat model.

Infarct expansion, regional dilation and thinning of the infarct zone, occurs within 1 day after myocardial infarction. Whether the early change in regional shape of infarct expansion affects the architecture of remote normal regions is unknown. To study this question, 45 rats with a transmural infarct were killed at 1, 2 and 3 days after infarction and their hearts were examined for infarct size and extent of expansion. Wall thickness and radius of curvature were measured within, adjacent to and remote from the infarct zone. Equivalent regions were analyzed in eight control hearts. The extent of disproportionate wall thinning and increased radius of curvature within the infarct zone of hearts with expansion was not dependent on infarct size. Significant wall thinning and increased regional radius of curvature were also seen in adjacent and remote regions of the hearts with expansion (p less than 0.001). These structural changes outside of the infarct occurred independent of infarct age and size, and were not seen in hearts without infarct expansion. Thus, when disproportionate thinning and dilation occur in the infarct region, they are accompanied by a distortion in shape of the entire heart including remote normal myocardium. This remote remodeling of noninfarcted myocardium correlates with extent of expansion, but not with age or size of the infarct.

Animals↗
PubMed1985

Animal models for protecting ischemic myocardium: results of the NHLBI Cooperative Study. Comparison of unconscious and conscious dog models.

The Animal Models for Protecting Ischemic Myocardium Study was undertaken for the purpose of developing reproducible animal models that could be used to assess interventions designed to limit infarct size. This paper describes the results obtained in an unconscious dog model and in a conscious dog model, developed in three participating laboratories. The unconscious dog model, involving reperfusion after 3 hours of ischemia in open-chest dogs, was intended to determine whether therapy followed by early reperfusion would limit infarct size more than reperfusion alone. The conscious dog model used chronically instrumented dogs and permanent coronary occlusion to better mimic myocardial infarction in man. In both models, the proximal circumflex artery was occluded, and the primary experimental endpoint was infarct size, as measured by histological techniques 3 days after the initial occlusion. Infarct size was analyzed in relation to baseline variables including the anatomic area at risk, collateral blood flow to the subepicardial zone of ischemia and hemodynamic determinants of myocardial metabolic demand. Most of the variation in infarct size in control dogs could be related to variation in the area at risk, collateral blood flow, and rate pressure product. Using multivariate analysis and groups of 15 dogs, an intervention that limited infarct size by 10-13% of the area at risk would have been detected 50% of the time. Larger treatment effects would be detected more readily, and smaller effects often would be missed, unless group sizes were larger. Two drugs, verapamil and ibuprofen, were evaluated in both models, with experimental group sizes averaging 13 and 20 dogs, in the unconscious and conscious models, respectively. Three of 15 verapamil-treated dogs in the unconscious model study had much smaller infarcts than expected from baseline parameters. With these exceptions, neither drug limited infarct size in either model.

Anesthesia↗
PubMed1985

Testicular lesions in Whipple's disease.

In two patients with Whipple's disease a variety of abnormalities were found in the testis. In both there was a thickened tunica albuginea containing macrophages filled with Schiff-positive bacilli, and both exhibited Whipple bacilli alone or in small clumps within the tunica media of the testicular arteries. One patient had focal inflammatory lesions among the Leydig cells. The most prominent abnormality in each was the abundance of Whipple bacilli within the epithelium of the seminiferous tubules. Some of these bacilli (which were free rather than within macrophages) appeared to be being shed into the tubular lumen; there was no associated inflammation. In some areas macrophages filled with bacilli appeared to migrate from the arterial adventitia toward the seminiferous tubules. Potential significance of these findings is discussed relative to a variety of testicular and prostatic diseases, as well as the possible (and arguable) relationship to the acquired immune deficiency syndrome.

Arteries↗
PubMed1984

Management of patients with hypertension and angina pectoris.

Management of patients with concomitant hypertension and angina pectoris mandates that the physician pay attention to the underlying pathophysiology. The heart, when exposed to years of hypertension, becomes "remodeled." Overall mass is enlarged, the walls are thickened, and initial cavity volume remains normal or relatively small. Left ventricular end-diastolic pressure rises in the setting of a hypertrophic noncompliant ventricle; coronary resistance and coronary perfusion pressure are increased; and coronary vascular reserve, even with widely patent coronary arteries, is decreased. Long-standing hypertension--a risk factor for coronary atherosclerosis--is often accompanied by epicardial coronary stenoses that aggravate these coronary abnormalities. In managing the patient with hypertension and angina pectoris, it is important to determine whether the angina occurs in the setting of hypertensive hypertrophic disease alone or coexists with coronary arterial stenoses. Also important to therapy is whether the ventricle is of normal size with good function or decompensated with dilatation and diminished function. The latter two anatomic considerations, namely, epicardial coronary patency and left ventricular cavity size, will influence the choice of an anti-ischemic regimen. For example, diuretic and nitrate therapy can be hazardous, and digitalis unnecessary, in the setting of a nondilated hypertrophic ventricle with hyperdynamic function. On the other hand, the combined use of beta blocking agents plus calcium antagonists is particularly effective in lowering blood pressure and in improving coronary blood flow. Finally, this combination has been shown to be rapidly effective and to have prolonged benefit in this setting. The choice of these latter agents is also affected by the underlying state of the ventricle. Calcium channel blocking agents without significant negative inotropic effect, such as nifedipine and nitrendipine, would be suitable in patients with decompensated ventricular function and dilated left ventricular cavities. Both of these drugs have been shown to increase cardiac output and contractility via a reflex effect and to have little or no direct negative inotropic effect. In contrast, verapamil has a direct negative inotropic effect. The final choice of agents must be tailored to the needs of the individual patient, and the physician also has to determine the role of specific agents in the natural history of hypertensive heart disease.

Adrenergic beta-Antagonists↗
PubMed1984

Acute anthracycline cardiotoxicity. Comparative morphologic study of three analogues.

Chemotherapeutic use of anthracycline antibiotics is limited by their cardiotoxic effects. A potential solution to this problem is the development of anthracycline analogues retaining antitumor efficacy but without cardiac toxicity. An isolated perfused rabbit heart model was used to compare the nature and extent of early ultrastructural effects on the myocyte of three anthracycline analogues purported to have lesser cardiotoxicity than Adriamycin (doxorubicin). Seventeen rabbit hearts were perfused with oxygenated Krebs-Ringer bicarbonate buffer at 39 degrees C containing either Adriamycin (4 mg/L), daunomycin (10.6 mg/L), aclacinomycin (8 mg/L), or rubidazone (17.6 mg/L). For comparison, three hearts each were exposed to phosphoramide mustard (14.7 mg or 25 mg/L) or 4-hydroperoxy cyclophosphamide (24 mg or 17 mg/L), two active congeners of cyclophosphamide, an agent interacting with DNA differently than the anthracyclines and which is known to be cardiotoxic in high dose. Two hearts were exposed to dactinomycin (0.1 mg or 0.2 mg/L) which intercalates with DNA in a manner similar to the anthracyclines but which is not cardiotoxic. Ten control hearts were perfused with oxygenated buffer solution only. Light microscopic study disclosed no differences between treated and control hearts. Electron microscopic examination showed a striking and distinctive clumping of nuclear chromatin with clearing of chromatin from the nuclear membrane in all anthracycline treated hearts but in no hearts treated with 4-hydroperoxy cyclophosphamide, phosphoramide Mustard, dactinomycin, or control hearts. The nuclear effects of the four anthracycline analogues were indistinguishable. Thus, all anthracycline analogues studied produced acute nuclear alterations which were distinctive from the changes produced by other DNA interactive chemotherapeutic agents. The relationship of the distinctive anthracycline nuclear changes to the late cardiomyopathy requires further definition.

Aclarubicin↗
PubMed1984

Progression and resolution of myocardial reflow injury.

The development of and recovery from a severe yet nonlethal myocardial injury following hyperkalemic cardioplegia and prolonged hypothermic global ischemia was examined over 14 days in a rat model of heterotopic intraabdominal cardiac isograft transplantation. Mitochondrial enzymatic markers of myocardial ischemic injury and light microscopic signs of damage were examined. Eighteen hearts were arrested in situ using hyperkalemic cardioplegia and subjected to a mean of 38 min of ischemia at 20 degrees C as transplantation was achieved. No changes in mitochondrial creatine kinase (CKm) activity, mitochondrial malate dehydrogenase (MDHm) activity, their ratio, or morphologic evidence of injury were found during 8 days of reperfusion. In a second group of 66 hearts, the duration of hypothermic cardioplegic ischemia was extended by 120 min before transplantation. Neither unreperfused hearts nor hearts reperfused for only 1 hr demonstrated significant depression of enzyme activities or microscopic evidence of injury. However, after 1 day of reperfusion, CKm and MDHm activities were depressed to 36 and 44% of control levels (P less than 0.05). These activities had returned to control levels by 2 days of reperfusion and remained stable for 12 days thereafter. Light microscopic analysis revealed cellular injury to be maximal at 1 to 2 days of reperfusion with gradual improvement noted over the following 12 days. These observations suggest the existence of a mitochondrial injury following prolonged cardioplegic arrest and hypothermic global ischemia that is maximal after 24 hr of reperfusion but shows evidence of improvement thereafter. These findings justify aggressive support of the poorly functioning heart for the first few days after prolonged global ischemia.

Animals↗
PubMed1984

Operative intervention for postinfarction angina.

Thirty-four patients (26 men and 8 women) underwent myocardial revascularization following myocardial infarction (MI) at the Johns Hopkins Hospital during 1980 through 1982. Average age was 59 years. Of the 33 patients with unstable angina, 61% had ischemia in the infarct zone and 39% had "ischemia at a distance." Mean time from MI to operation was 16 days. The MIs were equally divided between a transmural and a subendocardial location. Eleven patients had a history of congestive heart failure. Intraaortic balloon pumping was used preoperatively for anginal stabilization in 14 patients. Mean ejection fraction for the group was 52%. There were 3 operative deaths, all 3 due to myocardial failure. Late follow-up (mean, 13.7 months; range, 6 to 35 months) is complete for 28 patients. There was 1 late death, secondary to cardiac failure. There were no late MIs. Angina had recurred in 5 patients, but only 2 were taking antianginal medication. At the time of follow-up, 52% of patients were in New York Heart Association Functional Class I. This experience suggests that operative intervention for postinfarction angina can be accomplished with an acceptable mortality and thereby increase survival, reduce the later occurrence of MI, and relieve angina in this high-risk group.

Aged↗
PubMed1984

Early dilation of the infarcted segment in acute transmural myocardial infarction: role of infarct expansion in acute left ventricular enlargement.

Left ventricular enlargement after myocardial infarction is a poor prognostic sign, the mechanism of which has not been well defined. Early left ventricular dilation may be due to the Frank-Starling effect, which results in an increase in the length of uninfarcted segments in response to a reduction in contractile muscle mass. In contrast to this adaptive physiologic mechanism, left ventricular dilation may alternatively be caused by a pathologic process that stretches and thins the infarcted myocardial segment (that is, infarct expansion). To determine the relative contributions of these two mechanisms to left ventricular dilation after an initial transmural anterior myocardial infarction, two-dimensional echocardiograms were obtained from 27 patients within 72 hours of the onset of symptoms of myocardial infarction and from 13 healthy control subjects. In the minor-axis echocardiographic view at the level of the papillary muscles, anterior and posterior endocardial segment lengths at end-diastole were measured with a microprocessor-based graphic system. The papillary muscles were used as internal landmarks to demarcate the anterior and posterior segments. Anterior (infarcted) segment length in patients with myocardial infarction was 11.6 +/- 2.2 cm (mean +/- SD), whereas in control subjects, anterior segment length was 8.6 +/- 1.2 cm (p less than 0.001). Posterior (uninfarcted) segment length in the patients was not significantly different from posterior segment length in the control subjects (5.4 +/- 1.2 versus 5.3 +/- 1.0 cm, respectively). Measurable left ventricular dilation during the first 3 days after transmural anterior myocardial infarction is due to dilation of the infarcted segment and not of the normal uninfarcted segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

The cardiomyopathies.

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Adrenergic beta-Antagonists↗
PubMed1984

Vascular lesions of the gastrointestinal system in Whipple's disease.

In five cases of Whipple's disease the vessels in several organs of the gastrointestinal system were carefully examined for PAS-positive bacilli. Bacilli were particularly abundant in the arteries of the small intestinal serosa and the liver, but they were also present in stomach, colon, gallbladder and mesenteric lymph nodes. The predominant site of involvement was the arterial tunica media. In addition to focal degeneration and fibrosis in the tunica media, other local reactions included arteritis and intimal proliferation. Within the tunica media and less often the endothelium the bacilli were found alone or in small clumps, but in the tunica adventitia they were usually present within macrophages. The possible significance of this Whipple's arteriopathy is considered relative to unexplained gastrointestinal bleeding, focal ischemia due to arterial narrowing, and some role in the further dissemination of bacilli being shed from the endothelium.

Adult↗
PubMed1984

Localization of regional myocardial ischemia by recording of monophasic action potentials.

Identification of regional myocardial ischemia by TQ-ST segment mapping, while commonly used, is relatively imprecise and nonspecific. In 41 open-chest dogs we examined whether monophasic action potentials (MAPs) recorded from the myocardial surface by means of a new contact-electrode technique could be used to more precisely and specifically index regional myocardial ischemia. After ligation of the left anterior descending coronary artery (LAD), epicardial and endocardial MAPs from the ischemic region demonstrated shortening of plateau duration followed by a progressive loss in amplitude to 48 +/- 8% and in maximum upstroke velocity (dV/dtmax) to 9 +/- 2% of control (n = 7). Regional hyperkalemia produced by intracoronary injection of potassium chloride also resulted in regional decreases in duration, amplitude, and dV/dtmax of the MAP. Similar to previously reported effects on transmembrane action potentials, ischemia- or hyperkalemia-induced loss in MAP amplitude was due to decreases in both diastolic (negative) and systolic (positive) potential and paralleled TQ segment depression and "true" ST segment elevation in unipolar direct current-coupled electrograms recorded from an adjacent site. In eight canine hearts we compared the abilities of MAP recordings and TQ-ST segment measurements in defining a region of myocardial ischemia. Transmural ischemia with a sharp flow border was produced by LAD ligation and distal embolization with dental rubber. One hour later simultaneous MAP and TQ-ST mapping was performed in each dog at 45 to 65 epicardial sites inside and outside the ischemic region. TQ-ST voltage was significantly increased 10 to 20 mm outside the visible cyanotic border, reaching a maximum just inside the border and decreasing progressively toward the center of the ischemic region to values not significantly different from those from sites 10 mm outside the ischemic border. In contrast, MAP amplitude and dV/dtmax were normal up to 5 to 10 mm outside the cyanotic border, decreased sharply across a lateral transition zone of only 8 mm to 8.7 +/- 2.3% and 4.3 +/- 0.9% of control, respectively, at sites 4 to 6 mm inside the border, and were uniformly abnormal across the entire ischemic region. Recordings made 3 hr after LAD ligation revealed an overall decline in the magnitude of TQ-ST, making definition of the ischemic border by TQ-ST even less precise, whereas the differences between MAPs from normal and ischemic myocardium had become even more pronounced than after 1 hr. Thus, unlike TQ-ST segment measurements, MAP recordings uniquely define ischemic and nonischemic sites and more precisely localize the border of an ischemic region.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗