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Biomedical subjects

J J Morris

Publications and source records attributed to J J Morris.

At least 37 records · Page 2Linked to original sources

Operation for ventricular tachyarrhythmias: refining current treatment strategies.

For many patients with ventricular tachyarrhythmias, the optimal choice of palliative or curative therapies is not yet well established. To refine optimal current treatment strategies, baseline patient characteristics were studied in relation to likelihood of successful outcome in 240 consecutive patients undergoing operation for treatment of ventricular tachyarrhythmias from 1981 to 1991. Indications for operation were sudden cardiac death or inducible ventricular tachyarrhythmias refractory to medical therapy (or both). Treatment was directed endocardial procedures in 77 patients (32%), other cardiac procedures in 57 patients (24%) (coronary artery bypass grafting in 94% and valve procedure in 14%, either with [35%] or without [65%] concomitant implantable cardioverter-defibrillator), and implantable cardioverter-defibrillator alone in 106 patients (44%). Overall 30-day operative mortality was 5% (70% confidence interval, 4%-7%) and 2-year survival was 74% (70% confidence interval, 71%-77%). Overall 2-year freedom from sudden cardiac death was 97% (70% confidence interval, 96%-98%) and was similar (p = not significant) for all treatment modalities. For each treatment modality, multivariate analysis identified independent risk factors for operative mortality and 2-year tachyarrhythmia recurrence, advanced angina and congestive heart failure New York Heart Association classes, and overall mortality. To characterize better the use and benefit of coronary artery bypass grafting, risk factors related to outcome also were identified for patients stratified according to absence (44 patients) or presence (119 patients) of coronary artery disease excluding patients treated by directed endocardial procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Autotransfusion: is there a benefit in a current practice of aggressive blood conservation?

Findings from early studies suggested that the autotransfusion of shed mediastinal blood (ATS) after cardiac surgical procedures led to a reduction in the postoperative banked blood requirements. However, changes in baseline patient characteristics and other blood conservation methods may now negate the benefits of ATS. To determine whether the routine use of ATS is effective in the context of current surgical practice, risk factors related to postoperative banked blood requirements were analyzed in a prospective series of 155 consecutive patients undergoing cardiac operations: 71 patients before and 84 patients after the addition of ATS to an already aggressive standardized blood conservation protocol. The overall mean patient age was 66 +/- 11 years; the mean preoperative patient hemoglobin level was 11.8 +/- 1.8 g/dL; 48% of the procedures were elective and 12% were reoperations; coronary artery bypass grafting was performed in 73% of the patients and valve repair or replacement in 34%, with no differences between the non-ATS and ATS groups (all, p = not significant). The mean 24-hour postoperative blood loss was 1,278 +/- 814 mL in the non-ATS group and 1,721 +/- 1,510 mL in the ATS group (p < 0.03). The mean volume autotransfused in the ATS group was 1,122 +/- 97 mL. The overall reoperation rate for bleeding was 0.6% (70% confidence interval, 0 to 1.3%) and the hospital mortality was 1.9% (70% confidence interval, 0.8% to 3.1%), which did not differ between the non-ATS and ATS groups (both, p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Gender differences in left ventricular functional response to aortic valve replacement.

BACKGROUND: To characterize gender differences in recovery of ventricular function and survival after aortic valve replacement (AVR), baseline characteristics related to outcome were analyzed in 1012 consecutive patients (329 women and 683 men) undergoing AVR in 1983 through 1990. METHODS AND RESULTS: Seventy-seven percent of patients had aortic stenosis (AS), 11% insufficiency (AI), and 12% mixed AS/AI; 42% underwent concomitant coronary artery bypass. Women as a group had a greater mean age (P < .0001), had AS more frequently than AI or AS/AI (P < .01), had coronary disease less frequently (P < .01), and had a higher preoperative left ventricular ejection fraction (EF) (P < .0001), although preoperative New York Heart Association (NYHA) functional class was similar (P = NS) compared with men. Male sex (P < .0001), advanced age (P < .0003), AI rather than AS (P < .01), and greater extent of coronary disease (P < .04) were independently associated with lower preoperative EF. Women with coronary disease were as likely as men (P = NS) to undergo concomitant coronary bypass, and completeness of revascularization did not differ (P = NS) by gender. Observed survival probabilities after AVR (expressed as 30-day/5-year) were .97/.81 overall, .94/.77 for women, and .98/.83 for men (P < .02). Cox model analysis showed advanced age, decreased preoperative EF, greater extent of coronary disease, requirement for annular enlargement, smaller prosthetic valve size, and advanced NYHA class (all P < .04) but neither female sex nor smaller body surface area (both P = NS) as multivariate risk factors for overall mortality. In 664 patients (66%), postoperative EF was measured a mean 1.4 years after AVR. In patients with preoperative EF < or = 45% (n = 167), the change in EF after AVR was greater (P < .02) in women (from 33 +/- 8% to 48 +/- 15%, P < .001) than in men (from 32 +/- 9% to 42 +/- 15%, P < .001). By multivariate regression analysis, female sex (P < .02) and lesser extent of coronary disease (P < .05) were independent predictors of early improvement in EF. Improvement in EF conveyed an independent subsequent survival benefit to both women (P < .03) and men (P < .001), and the magnitude of benefit did not differ (P = .4) between the two groups. CONCLUSIONS: These data suggest that gender-related factors importantly influence the adaptive and recovery response of the left ventricle to pressure and volume overload. However, gender differences in LV adaptation do not influence survival after AVR.

Aged↗

The effects of left heart assist on right ventricular muscle mechanics and ventricular coupling in the injured heart.

So that we could better characterize the effects of left heart assist on right ventricular myocardial muscle mechanics and ventricular mechanical coupling in the injured heart, nine dogs underwent 30 minutes of global cardiac ischemia supported by cardiopulmonary bypass followed by randomly varied levels of left heart assist at 0, 1.0, and 2.0 L/min (0, 37 +/- 4, and 74 +/- 7 ml/kg per minute). A centrifugal pump with left ventricle-to-aorta bypass was used with the intent to cause left ventricular volume unloading but without complete left ventricular pressure unloading. Right ventricular regional free wall and septal-free wall dimensions were measured by a sonomicrometer and right ventricular pressure by a micromanometer. Pressure and dimension data were acquired over a range of preloads produced by transient vena caval occlusion and at steady state at an initial control point and after ischemia at each level of left heart assist. Right ventricular regional early diastolic function was assessed by percent segmental relaxation during the first third of diastole, end-diastolic compliance by the end-diastolic pressure-dimension relationship, systolic contractile performance by the slope (Mw) and dimension axis intercept (Lw) of the linear preload recruitable stroke work relationship, and right ventricular isovolumic relaxation by the pressure decay time constant. Ischemia reduced Mw of both the free wall (38.3 +/- 16.1 to 16.4 +/- 4.2 erg.cm-3 x 10(3), p < 0.01) and septal free wall (30.2 +/- 12.7 to 13.4 +/- 4.9 erg.cm-3 x 10(3), p < 0.01) and shifted Lw rightward (1.3 +/- 0.3 to 1.4 +/- 0.3 mm, p < 0.01, and 2.8 +/- 0.8 to 3.0 +/- 0.9 mm, p < 0.01), which confirmed myocardial ischemic injury. There were no effects of left heart assist on free wall or septal-free wall systolic contractile performance assessed by Mw and Lw or on early diastolic relaxation assessed by percent segmental relaxation during the first third of diastole in either right ventricular region (all p = not significant). There were also no observed characteristic alterations of free wall or septal-free wall end-diastolic pressure-dimension relationships with left heart assist. The pressure decay time constant decreased with increasing levels of left heart assist (51 +/- 14, 49 +/- 16, and 43 +/- 11 msec, p < 0.05), which indicated an improvement in right ventricular isovolumic relaxation attributable to left heart assist. These data demonstrate that mechanical ventricular interactive effects during left heart assist are beneficial, but limited to isovolumic relaxation in the injured heart.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Outcome of mitral valve repair in patients with preoperative atrial fibrillation. Should the maze procedure be combined with mitral valvuloplasty?

To examine late outcome of mitral valve repair in patients with preoperative atrial fibrillation, we reviewed the cases of 323 consecutive patients who underwent mitral valvuloplasty for mitral regurgitation from 1980 to 1991; average age of 215 men and 108 women was 64 years (range 14 to 88 years), and 224 patients (70%) were in New York Heart Association class III or IV before operation. The main indications for operation were severe mitral regurgitation (76%), coronary artery disease with associated mitral regurgitation (15%), and aortic valve disease (6%). At the time of mitral valve repair, coronary artery bypass grafting was done in 35% of patients, aortic valve replacement was done in 7%, and multiple other procedures were done in 10%. For all patients, the 30-day mortality rate was 2.5% (70% confidence limits 1.6% to 3.4%) and survivorships at 3 and 5 years were 81% and 76%, respectively. Before operation, 216 patients were in sinus rhythm and 97 patients had atrial fibrillation; in the latter group, 11 had recent onset of atrial fibrillation within 3 months preceding mitral valve repair. Comparing patients with preoperative atrial fibrillation to those with sinus rhythm, we found no significant difference in operative mortality (3% versus 1.9%) or 5-year survivorship (74.3% +/- 6.3% versus 76.9% +/- 4.0%). At late follow-up, atrial fibrillation was present in 5% of patients with preoperative sinus rhythm, 80% of patients with preoperative chronic atrial fibrillation, and 0% of patients with preoperative recent onset atrial fibrillation (p < 0.01). The left atrial size by echocardiography was larger in patients with preoperative atrial fibrillation compared with that in those with sinus rhythm (59 +/- 1.4 mm versus 50.9 +/- 0.7 mm; p < 0.05). There was, however, only a weak correlation between preoperative left atrial size and late atrial fibrillation. Further, age, gender, and associated coronary artery disease did not correlate with presence of atrial fibrillation at late follow-up. Prevalence of late thromboembolic events was similar in patients with preoperative sinus rhythm compared with that in those with atrial fibrillation. These data suggest that mitral valve repair should be done before or soon after the onset of atrial fibrillation to maximize the chance of postoperative sinus rhythm and avoid long-term anticoagulation with warfarin. However, the early and late results of mitral valve repair in patients with chronic atrial fibrillation are good, and concomitant operation for supraventricular arrhythmia must have negligible morbidity and no adverse effect on operative mortality.

Adolescent↗

Determinants of survival and recovery of left ventricular function after aortic valve replacement.

To determine factors that influence survival and recovery of ventricular function in patients undergoing aortic valve replacement in the current surgical era, baseline risk factors related to outcome were analyzed in 1,012 consecutive patients undergoing aortic valve replacement between 1983 and 1990. Forty-two percent of patients underwent concomitant coronary bypass. Observed survival probabilities (expressed as 30-day/5-year) were 0.97/0.81 overall, 0.99/0.89 for patients aged less than 70 years, and 0.95/0.74 for patients aged 70 years or greater. Advanced age (p < 0.0001), decreased ejection fraction (p < 0.0001), extent of coronary disease (p < 0.006), smaller prosthetic valve (p < 0.03), and advanced New York Heart Association class (p < 0.04) were incremental risk factors for mortality. In patients with preoperative ventricular dysfunction (ejection fraction < or = 0.45), ejection fraction measured 1.4 years after aortic valve replacement improved in 72% and the mean increment in ejection fraction was 0.175 (95% confidence interval, 0.154 to 0.195). The increment in ejection fraction was greater in female patients than in male patients (p < 0.02) and greater in patients without than with coronary disease (p < 0.02). Female sex (p < 0.02) and lesser extent of coronary disease (p < 0.05) were independent predictors of change in ejection fraction. In all patients, early improvement in ejection fraction conveyed an independent subsequent survival benefit (p < 0.0001). The results of aortic valve replacement in the current era are excellent, and the majority of patients with ventricular dysfunction demonstrate significant improvement. Early improvement in ejection fraction, influenced by coexistent coronary artery disease and sex-associated factors, importantly affects subsequent survival.

Aged↗

The role of aromatic hydrocarbons in the genesis of breast cancer.

The incidence of breast cancer in women has increased dramatically over the last decade. Epidemiological markers of this increased incidence include: endocrine related phenomena (early menarche, age of first parity and age of menopause); exposure of the breast to X-radiation; and a group of seemingly disparate factors--urban residence, dietary selection and alcohol consumption. Although experimental breast cancer may be induced by estrogenic hormones, X-radiation and aromatic hydrocarbons, only aromatic hydrocarbons have not been previously implicated in human mammary carcinogenesis. The seemingly unrelated human factors can best be understood by examining the role of breast tissue in aromatic hydrocarbon metabolism. Aromatic hydrocarbons are important environmental chemicals produced by the incomplete combustion of hydrocarbons for use in energy production. Benzene, benz(a)pyrene, dibenz(ah)anthracene and 1-nitropyrene, known experimental breast carcinogens, are produced in this way. Human exposure to aromatic hydrocarbon metabolites induces and promotes altered DNA by mechanisms described as increased intracellular pro-oxidant production as well as direct adduction to DNA. The breast is anatomically embedded in a major fat depot which stores and concentrates aromatic hydrocarbons and can metabolize these hydrocarbons to carcinogenic metabolites. Ductal cells concentrate these metabolites and themselves become target cells for carcinogenesis. Some lifestyle factors increase the amount of carcinogens produced or enhance their activity. A unitary model for mammary carcinogenesis in humans as well as in experimental carcinogenesis is hypothesized. If correct, the hypothesis would account for some of the increase in breast cancer incidence in industrial countries--and would suggest environmental and dietary modifications that would inhibit hydrocarbon induced mammary carcinogenesis.

Animals↗

Non-steroidal antiandrogens. Design of novel compounds based on an infrared study of the dominant conformation and hydrogen-bonding properties of a series of anilide antiandrogens.

Antiandrogenic activity is observed in anilides containing a tertiary hydroxyl group, and these compounds are used to define a pharmacophore in terms of their physicochemical properties. Infrared spectroscopy shows that these anilides exist in a single conformation, which exerts a powerful influence on the hydrogen-bond donor ability of the hydroxyl group in a model system. Arguments are presented which suggest that hydrogen-bonding ability is an important contributor to biological activity. Compounds were synthesized that reproduced these properties in series not containing an amide bond. Such compounds were found to exhibit good antiandrogen activity. We suggest that quantitative information on hydrogen bonding might also be useful in other systems.

Androgen Antagonists↗

Influence of diabetes and mammary artery grafting on survival after coronary bypass.

The effect of diabetes on survival after coronary bypass surgery is uncertain. Also, although the overall clinical benefits of internal mammary artery (IMA) grafting are well established, the survival benefit attributable to IMA grafting in diabetics is not well characterized. To determine the influence of diabetes and IMA grafting on survival after bypass surgery in the current surgical era, characteristics related to subsequent outcome were analyzed in 5,654 consecutive patients undergoing surgery in the decade of the 1980s. The 1,132 diabetic patients (20%) had more extensive coronary disease, had more left ventricular dysfunction, were older, were more frequently female, received a greater number of grafts (mean, 3.5 versus 3.1), and received more IMA grafts (67% versus 58%) than the 4,522 nondiabetic patients (all p less than 0.001). Overall 5-year survival probability was 0.91 in nondiabetic and 0.80 in diabetic patients (p less than 0.0001). Nondiabetic survival exceeded diabetic survival even in high-risk subgroups such as ejection fraction less than or equal to 0.40 (0.80 versus 0.66, p less than 0.02), age greater than or equal to 65 years (0.85 versus 0.73, p less than 0.0003), and, urgent surgery (0.89 versus 0.76, p less than 0.0001). By multivariate analysis, impairment of left ventricular function, advanced age, failure to use an IMA graft, diabetes, female sex, urgent surgery, number of diseased vessels, and mitral insufficiency were incremental risk factors for cardiac mortality (all p less than 0.006). Failure to use an IMA graft and diabetes were equally strong predictors of outcome. Use of an IMA graft conveyed an independent survival benefit to both nondiabetic (p less than 0.0001) and diabetic (p less than 0.02) patients. The magnitude of the survival benefit attributable to IMA grafting in the two groups did not differ (p = 0.4). Diabetes is an important risk factor for late cardiac mortality after bypass surgery and should be included in analyses of the efficacy of therapies for coronary artery disease. IMA grafting conveys a similar benefit to diabetic and nondiabetic patients but does not negate the adverse effect of diabetes on survival.

Age Factors↗

Mechanisms of ischemia in coronary artery disease: spontaneous decrease in coronary blood supply.

Myocardial ischemia has traditionally been related to increased demand, but recent data suggest that intermittent episodes of decreased supply are also important. This article discusses the phenomena underlying the factors that produce spontaneous (non-effort-related) ischemia. These include local arterial phenomena, arterial plaques, endothelial phenomena, neural phenomena, and circadian patterns. The clinical spectrum of myocardial ischemia can be viewed as an interplay among supply, demand, local arterial reactivity, and acute plaque disruption. In addition, neural phenomena and circadian patterns of multiple cardiovascular phenomena combine to make the coronary circulation susceptible to an increased concentration of events in the morning hours, around the time of awakening. With this extension of our understanding of myocardial ischemia, we have reasonable assurance that methods of treatment will advance significantly in the near future.

Animals↗

Clinical evaluation of single versus multiple mammary artery bypass.

The superior patency and clinical advantages of internal mammary artery (IMA) grafting are well established. However, the relative benefits of routine multiple IMA grafting remain uncertain. To determine whether routine multiple compared with single IMA utilization improved survival of patients undergoing coronary bypass procedures, 1,063 patients were prospectively allocated, beginning in 1984, to divergent management strategies of single (group 1, n = 420) versus multiple IMA grafting (group 2, n = 643). Subsequent analysis of anatomical extent of disease and preoperative baseline risk factors showed no differences (p = NS) between the two groups. All variables reflecting operative technique were similar (p = NS) for the two groups, except 74% of group 1 patients with multivessel disease received a single IMA graft, whereas 71% of group 2 patients with multivessel disease received multiple IMAs (p less than 0.05). By multivariate analysis, impairment of left ventricular ejection fraction, acute evolving myocardial infarction, advanced age, and unstable angina were incremental risk factors for mortality (all p less than 0.03), but group assignment (p = 0.4) and ultimate therapy were not (p = 0.6). Survival probabilities (expressed as 30-day group 1/group 2; 4-year group 1/group 2) were overall (0.97/0.98; 0.93/0.90), elective (0.98/0.99; 0.97/0.92), acute (0.95/0.97; 0.89/0.88), age of less than 65 years (0.98/0.99; 0.97/0.93), age of 65 years or older (0.93/0.97; 0.84/0.89), ejection fraction of 0.40 or more (0.97/0.99; 0.95/0.94), ejection fraction of less than 0.40 (0.95/0.96; 0.87/0.82), nondiabetic (0.98/0.98; 0.94/0.91), and diabetic (0.92/0.97; 0.88/0.87). No differences in survival were significant (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

Painless exercise ST deviation on the treadmill: long-term prognosis.

To evaluate the clinical correlates and long-term prognostic significance of silent ischemia during exercise, 1,698 consecutive symptomatic patients with coronary artery disease who had both treadmill testing and cardiac catheterization were studied. These patients were classified into three groups: Group 1 = patients with no exercise ST deviation (n = 856), Group 2 = patients with painless exercise ST deviation (n = 242) and Group 3 = patients with both angina and ST segment deviation during exercise (n = 600). Patients with exercise angina had a history of a longer and more aggressive anginal course (with a greater frequency of angina, with nocturnal episodes and/or progressive symptom pattern) and more severe coronary artery disease (almost two-thirds had three vessel disease). The 5 year survival rate among the patients with painless ST deviation was similar to that of patients without ST deviation (86% and 88%, respectively) and was significantly better than that of patients with both symptoms and ST deviation (5 year survival rate 73% in patients with exercise-limiting angina). Similar trends were obtained in subgroups defined by the amount of coronary artery disease present. In the total study group of 1,698 patients, silent ischemia on the treadmill was not a benign finding (average annual mortality rate 2.8%) but, compared with symptomatic ischemia, did indicate a subgroup of patients with coronary artery disease who had a less aggressive anginal course, less coronary artery disease and a better prognosis. Thus, silent ischemia during exercise testing in patients with symptomatic coronary artery disease represents an intermediate risk response in the spectrum of exercise-induced ischemia.

Adult↗

Differential ventricular ischemic injury: an experimental model of right ventricular failure with a variable degree of left ventricular dysfunction.

The hemodynamic manifestations of right ventricular dysfunction after ischemic injury depend not only on the severity of injury but also on the degree of coexistent left ventricular dysfunction. A better understanding of right ventricular failure and of optimal therapies has been hindered in part by lack of suitable experimental models of selective and differential ventricular injury. Therefore, we developed a technique of differential ventricular myocardial protection during a period of global cardiac ischemia and examined the effect of such an injury on intrinsic right and left ventricular myocardial function, metabolism, and regional blood flow. Twenty-six dogs were subjected to 30 minutes of ischemia while being supported by cardiopulmonary bypass. During ischemia, right and left ventricular myocardial temperatures were independently varied by selective ventricular endomyocardial thermal regulation. Nine dogs underwent right and left ventricular normothermic ischemia, eight underwent right and left ventricular hypothermic ischemia, and nine underwent right ventricular normothermic and left ventricular hypothermic ischemia. In both ventricles, normothermic ischemia resulted in greater depression of ventricular ability to generate stroke work as a function of end-diastolic dimension (p less than 0.05), greater depletion of myocardial adenine nucleotide content (p less than 0.05), and greater subendocardial reperfusion hyperemia (p less than 0.05). Myocardial temperature of the contralateral ventricle during ischemia had no effect (p = not significant) on intrinsic ventricular functional, metabolic, or regional blood flow response to injury. For a given degree of right ventricular injury assessed by these parameters, the degree of left ventricular injury could be independently varied by as much as 50%. This is a particularly suitable model for the investigation of acute right ventricular failure.

Adenine Nucleotides↗

Silent myocardial ischemia: pathophysiology and clinical recognition.

Silent myocardial ischemia is reported to account for approximately one-fifth of all myocardial infarctions and to be very common in patients with a history of angina pectoris. It may also play an important role in sudden cardiac death. Detection of silent ischemia is best accomplished by treadmill testing, electrocardiogram, or Holter monitoring. When detected, it should be treated vigorously in high-risk patients and all postinfarction patients. Recommendations regarding to the ideal therapy still await the results of controlled clinical testing, although preliminary reports indicate that topical nitrates are effective.

Coronary Disease↗

Quantification of the contractile response to injury: assessment of the work-length relationship in the intact heart.

We used a sonomicrometric determination of ventricular dimension to examine the effect of ischemia and reperfusion on the work-length relationship in the intact heart to develop a useful and precise variable of ventricular contractile response to injury. Twenty anesthetized dogs were instrumented with epicardial ultrasonic dimension transducers to record right ventricular free wall chord length and left ventricular minor-axis length, micromanometers to record ventricular pressures, and an electromagnetic probe to record pulmonary arterial (n = 8) or aortic (n = 7) flow. Dogs were subjected to either 20 min (n = 7) or 30 min (n = 13) of global cardiac ischemia supported by cardiopulmonary bypass. Data were acquired over a range of end-diastolic volumes produced by transient (5 to 10 sec) vena caval occlusion before and after ischemia. In both ventricles, systolic epicardial dimensional shortening correlated with flow probe-measured stroke volume (mean r = .969) and regional stroke work calculated as the integral of instantaneous ventricular pressure and epicardial dimension correlated with measured global stroke work (mean r = .960), confirming the validity of dimensional measurements. Regression analysis demonstrated a highly linear relationship between calculated regional stroke work and end-diastolic length in the right ventricle (mean r = .973) and left ventricle (mean r = .967), quantifiable by a slope (Mw) and x intercept (Lw). Change in afterload produced by pulmonary arterial or aortic constriction resulted in no significant changes in Mw or Lw in either ventricle. Ischemia and reperfusion decreased Mw and shifted Lw to the right in both ventricles. The decrease in Mw with 30 min ischemia exceeded the decrease with 20 min ischemia by 29% in the right ventricle and by 32% in the left (p less than .04) with up to 1 hr of reperfusion. Changes in Lw were not related to severity of injury. After ischemia, infusion of calcium increased Mw by 177% in the right ventricle and by 67% in the left (p less than .03) without significant changes in Lw. Independent of load conditions, the slope Mw, of the linear stroke work vs end-diastolic length relationship is a valid and precise index of right and left ventricular contractile response to global ischemia in the intact circulation. This variable may be useful in evaluating therapies designed to limit myocardial injury and enhance ventricular functional performance.

Animals↗

Norepinephrine-induced vasoconstriction is increased in intimal hyperplastic arteries of the dog.

Norepinephrine-induced arterial contraction in vitro is known to be increased after endothelial denudation and during the subsequent development of intimal hyperplasia. We now report the response to norepinephrine in intimal-thickened iliac vessels in conscious dogs. Seven dogs underwent balloon catheter deendothelialization of the right iliac artery. Three weeks later, ultrasonic transducers were implanted on both iliac arteries to record dynamic vessel dimension. A catheter was inserted into the terminal abdominal aorta for drug infusion and blood pressure monitoring. The dogs were studied unsedated 2 days after instrumentation. Norepinephrine was infused at doses that did not affect blood pressure (0.01 to 0.05 micrograms/kg/min). Control vessel diameter decreased from 5.2 mm +/- 0.3 to 5.1 mm +/- 0.3 (2.4% +/- 1.0% when standardized to baseline diameter) and intimal hyperplastic vessels from 6.2 mm +/- 0.4 to 5.7 mm +/- 0.4 (7.6% +/- 1.7%). The difference between control and intimal hyperplastic vessel vasoconstriction was significant at p less than 0.0025. The calculated reduction in total vessel cross-section area for control vessels was 4.5% +/- 1.9%. In intimal hyperplastic vessels total cross-sectional area was reduced by 14.5% +/- 3.3% by vasoconstriction and the luminal cross-sectional area was reduced by 17.9% +/- 0.7% by the intimal hyperplasia. These data suggest that luminal compromise due to intimal hyperplasia is compounded by increased sensitivity to norepinephrine. This effect, demonstrated in a large elastic artery shortly after endothelial denudation, may be of even greater significance in a smaller vessel with advanced intimal hyperplasia.

Animals↗