Search PubMed⌕ Search

Biomedical subjects

G H Mudge

Publications and source records attributed to G H Mudge.

At least 37 records · Page 2Linked to original sources
PubMed1990

Endothelium-dependent dilation of the coronary microvasculature is impaired in dilated cardiomyopathy.

Dilator reserve of the coronary microvasculature is diminished in patients with dilated cardiomyopathy. Although increased extravascular compressive forces, tachycardia, and increased myocardial mass can explain some impairment, recent evidence suggests the possibility of intrinsic microvascular disease. We tested the hypothesis that impairment of endothelium-dependent dilation of the microvasculature could be a contributing mechanism. We infused the endothelium-dependent dilator acetylcholine (Ach) (10(-8) to 10(-6) M) and the smooth muscle vasodilator adenosine (AD) (10(-6) to 10(-4) M) into the left anterior descending coronary artery in eight patients with dilated cardiomyopathy (mean ejection fraction, 28%) and seven controls (atypical chest pain). Small vessel resistance was assessed by measuring coronary blood flow (CBF) at constant arterial pressure with a Doppler velocity catheter (corrected for cross-sectional area by angiography). With Ach, control patients increased CBF 232 +/- 40% (mean +/- SEM), whereas CBF did not significantly change in cardiomyopathy patients (41 +/- 24%) (p less than 0.0001, control vs. cardiomyopathy). With AD, control patients increased CBF 422 +/- 56% and cardiomyopathy patients increased CBF 268 +/- 43% (p = 0.13). An index of the proportion of coronary flow reserve attributable to endothelium-dependent vasodilation was obtained by standardizing each patient's Ach dose response to his maximal AD flow response. In seven control patients receiving both Ach and AD, 56 +/- 9% of the maximal AD flow response was attained with the endothelium-dependent vasodilator Ach, whereas in seven cardiomyopathy patients receiving both Ach and AD, only 23 +/- 14% of the maximal AD response was attained (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1989

Lovastatin therapy for hypercholesterolemia in cardiac transplant recipients.

Hypercholesterolemia (type II hyperlipidemia) after cardiac transplantation is common and may play a role in the accelerated rate of coronary atherosclerosis seen following the procedure. However, conventional cholesterol-lowering drugs are either ineffective or contraindicated for use in transplant recipients. The presence of type II hyperlipidemia was identified in 11 cardiac transplant recipients during a mean follow-up period of 15 months (range 3 to 41) after transplantation. Lovastatin, at an initial dosage of 20 mg/day, was administered for a period of 1 year. The maximal dosage of lovastatin was 60 mg/day. All patients received maintenance dosages of immunosuppressive agents, including cyclosporine-A, prednisone and, in some instances, azathioprine. Lipid profiles, hepatic transaminases, serum creatinine, creatine kinase and cyclosporine-A serum trough levels were measured quarterly. Total cholesterol decreased by 27% (354 +/- 50 vs 258 +/- 36 mg/dl, p less than 0.01) after 3 months and remained stable thereafter. Similarly, low density lipoprotein cholesterol decreased by 34% (221 +/- 51 vs 146 +/- 40 mg/dl, p less than 0.01) after 3 months and remained constant. Triglycerides, high density lipoprotein, hepatic transaminases, creatinine, creatine kinase and trough cyclosporine-A levels remained stable during the 1-year follow-up period. Lovastatin was uniformly well tolerated in this study group. When given in modest dosages, lovastatin appears to be a safe, effective and well-tolerated therapy for hypercholesterolemia in cardiac transplant recipients.

Adult↗
PubMed1989

Effect of smoking on the activity of ischemic heart disease.

Cigarette smoking has been causally linked to coronary heart disease. To investigate the effect of smoking on the activity of ischemic heart disease, 65 patients with chronic stable manifestations of coronary disease and a positive exercise tolerance test underwent continuous ambulatory monitoring to quantify the amount of ischemic ST segment depression during daily life. Twenty-four smokers were compared with 41 nonsmokers for frequency and duration of electrocardiographic signs of ischemia during 24 hours. A total of 4,968 hours of ambulatory monitoring were analyzed. The frequency of episodes was three times as often (median) and the duration of ischemia was 12 times longer (median duration, 24 vs 2 min/24 h) in smokers than nonsmokers. This finding remained statistically significant when a number of potentially confounding factors were controlled by means of logistic regression. This study shows that patients with coronary artery disease who smoke have significantly and substantially more active myocardial ischemia during daily life than patients who do not.

Activities of Daily Living↗
PubMed1989

Management of general surgical complications following cardiac transplantation.

Between February 1984 and May 1988, 55 patients underwent orthotopic cardiac transplantation at the Brigham and Women's Hospital, Boston, Mass. Basic immunosuppression was accomplished with steroid and cyclosporine therapies. Twelve patients suffered 14 major complications, including perforated ulcer in 3 patients; pancreatitis in 3 patients; pneumatosis coli in 2 patients; and cholecystitis, colonic necrosis, appendicitis, incarcerated umbilical hernia, pancreatic abscess, and toxic epidermal necrolysis in 1 patient each. Aggressive management of the patients included laparotomy in all but 2 patients with mild pancreatitis and the patient with toxic epidermal necrolysis, who was treated as a patient with a severe burn. In all of the patients, there was a resolution of these complications, except in one 59-year-old man with fatal hemorrhagic pancreatitis. Eleven of the 14 complications occurred during the initial hospitalization. The fatal case of pancreatitis was 1 of 5 (9%) operative mortalities in the entire series. Fifty operative survivors have been followed up for an average of 19 months, with four late deaths (8%) related to rejection. The actuarial probability of survival in patients discharged from the hospital was 90% at 12, 24, and 48 months.

Adolescent↗
PubMed1989

Power spectrum analysis of heart rate variability in human cardiac transplant recipients.

Beat-to-beat heart rate variability was studied by power spectral analysis in 17 orthotopic cardiac transplant patients. Heart rate power spectra were calculated from eighty-four 256-second recordings and compared with those taken from six normal subjects. The power spectra from the control subjects resolved into discrete peaks at 0.04-0.12 Hz and 0.2-0.3 Hz, whereas those of heart transplant recipients resembled broad-band noise without peaks. Log total power in the 0.02-1.0 Hz range was greater in the control subjects (0.982 +/- 0.084 [0.206], mean +/- SEM [SD]) than in the transplanted subjects (-0.766 +/- 0.059 [0.541]), (p less than 0.0001). Fifty-five electrocardiographic recordings from transplant patients were done within 48 hours of an endomyocardial biopsy. When the power spectra of those patients whose endomyocardial biopsies showed evidence of myocardial rejection were compared with those from patients who were found to be free of rejection, a significant difference was found in log total power (-0.602 +/- 0.090 [0.525] vs. -0.909 +/- 0.136 [0.577], p less than 0.02). We conclude that denervation of the heart significantly reduces heart rate variability and abolishes the discrete spectral peaks seen in untransplanted control subjects and that the development of allograft rejection may significantly increase heart rate variability.

Adult↗
PubMed1989

Atherosclerosis influences the vasomotor response of epicardial coronary arteries to exercise.

We studied the vasomotion of epicardial coronary arteries during exercise and tested the hypotheses that abnormal vasoconstriction is related to the presence of atherosclerosis and may be related to endothelial dilator dysfunction. During cardiac catheterization quantitative coronary angiography was performed in 21 patients during supine bicycle exercise. 21 of 28 smooth, angiographically normal vessel segments dilated (14.0 +/- 1.8%) during exercise; four smooth segments did not change whereas only three constricted. In contrast, 15 of 16 vessel segments with irregularities constricted in response to exercise (17.0 +/- 0.1%) with only one segment dilating. All 10 stenotic segments constricted to exercise (23 +/- 4%). Six patients also received intracoronary acetylcholine before exercise to test endothelium-dependent dilator function. In five of six patients all nine vessel segments showed the same directional response to acetylcholine and exercise. Three irregular and two stenotic segments constricted with acetylcholine (51 +/- 21%) and exercise (9.0 +/- 0.6%). In contrast, four smooth segments dilated to acetylcholine (19 +/- 6%) and exercise (9 +/- 1%). Both exercise and acetylcholine generally dilated smooth but constricted irregular and stenosed coronary segments. It appears likely that atherosclerosis plays an important role in the abnormal vasomotion of diseased coronary arteries during exercise and the pattern of abnormality suggests impairment of vasodilator function.

Acetylcholine↗
PubMed1988

Frequency of hypercholesterolemia after cardiac transplantation.

Cardiac transplant patients are prone to accelerated coronary atherosclerosis. The mechanism by which this process occurs is not yet known, although immunologically mediated arterial injury is thought to play a primary role in its pathogenesis. Despite immunosuppressive potency, patients treated with cyclosporin A remain at significant risk for the development of accelerated atherosclerosis. It is hypothesized that cyclosporin A's hepatotoxic effects might contribute to the atherosclerotic process by impairing low density lipoprotein hepatic clearance in transplant patients, which would be reflected in a more atherogenic lipoprotein profile. To test this hypothesis, serum cholesterol levels were analyzed after transplantation. Significant and progressive increases in total cholesterol and in the total-to-high density lipoprotein cholesterol ratio were found. This atherogenic lipoprotein profile may contribute to accelerated atherosclerosis in cardiac transplant patients treated with cyclosporin A.

Adult↗
PubMed1988

Responses of coronary arteries of cardiac transplant patients to acetylcholine.

Accelerated coronary atherosclerosis is a major cause of graft failure after heart transplantation. Graft atherosclerosis is typically diffuse and difficult to detect even with coronary arteriography. Recently, acetylcholine was shown to dilate blood vessels by releasing a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). We have demonstrated paradoxical vasoconstriction induced by acetylcholine both early and late in the course of coronary atherosclerosis in patients, suggesting an association of endothelial dysfunction and atherosclerosis. In this report, we tested the hypothesis that coronary arteries of heart transplant patients can show endothelial dysfunction before or in the early stages of angiographically evident coronary atherosclerosis. Acetylcholine was infused into the left anterior descending artery of 13 heart transplant patients at 12 (n = 9) and 24 (n = 4) mo after transplantation. Vascular responses were evaluated by quantitative angiography. Among patients with angiographically smooth coronary arteries, relatively few (6/25) arterial segments had preserved vasodilator responses, while the majority failed to dilate (10/25) or paradoxically constricted (9/25). Angiographically irregular coronary arteries were present in three patients, in whom 8/10 segments showed marked paradoxical constriction and the remaining 2/10 failed to dilate. Only 1 of 13 patients retained appropriate dilation to acetylcholine in all segments. Nitroglycerin, which acts directly on vascular smooth muscle, dilated nearly all segments. No clinical features of the patients, including myocardial rejection appeared to correlate with the impaired functional response of vessels. Thus impaired response to acetylcholine is a common early finding in heart transplant patients and emphasizes the potential importance of endothelial dysfunction in the development of atherosclerosis.

Acetylcholine↗
PubMed1987

Time course of resolution of pulmonary hypertension and right ventricular remodeling after orthotopic cardiac transplantation.

Most patients with severe congestive heart failure have secondary pulmonary hypertension (PHT). Elevation of pulmonary vascular resistance (PVR) to greater than 480 dynes.sec.cm-5 (6 Wood units) is currently the principle hemodynamic contraindication to orthotopic cardiac transplantation. We performed serial two-dimensional Doppler echocardiographic examinations and right heart catheterizations in 24 recipients (21 men, 14-58 years old) of orthotopic cardiac transplants to determine the time course of resolution of PHT and the concomitant remodeling of the donor right ventricle. Right and left heart filling pressures declined in parallel and reached the upper normal range at 2 weeks after the transplant procedure and remained unchanged at 1 year follow-up. Mean pulmonary arterial pressure (mm Hg) decreased from 38 +/- 9 preoperatively to 22 +/- 5 at 2 weeks and was 19 +/- 5 at 1 year after the transplantation procedure. At 1 year after surgery, PVR had decreased from 202 +/- 89 dynes.sec.cm-5 preoperatively to 99 +/- 36 dynes.sec.cm-5 (p less than .001), while cardiac output increased from 3.7 +/- 1.2 to 6.3 +/- 1.5 liters/min (p less than .001). Echocardiographic analysis showed that transplant recipients had an enlarged right ventricle on day 1 after surgery, and a volume overload contraction pattern and tricuspid regurgitation was present in the majority. This increase in right ventricular size was maintained at 1 year follow-up while the incidence of tricuspid regurgitation decreased. We conclude that there is rapid resolution of moderately elevated pulmonary arterial pressures after cardiac transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Early and late results of coronary bypass surgery. Evolution and the influence of cardioplegia.

Comparison of 1085 patients having coronary bypass surgery without cardioplegia from Jan. 1970 to Aug. 8, 1977 with 1060 patients operated upon with cardioplegia from Aug. 9, 1977 to Dec. 31, 1980 suggests that improved myocardial protection afforded by cardioplegia combined with profound topical hypothermia has its principal impact in those patients requiring urgent or emergency operations by reducing the probability of intraoperative left ventricular failure after coronary bypass. The need for postoperative balloon pumping and the risk of intraoperative death were significantly lower in patients operated upon with hypothermia + cardioplegia myocardial protection. In patients who survived 30 days after operation there was no significant improvement in long-term survival, incidence of myocardial infarction, or recurrence of angina pectoris in the cardioplegia group despite a greater average number of grafts per patient and a smaller number of ungrafted but obstructed coronary arteries.

Adult↗
PubMed1986

Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries.

Acetylcholine is believed to dilate normal blood vessels by promoting the release of a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). By contrast, if the endothelium is removed experimentally, acetylcholine constricts blood vessels. We tested the hypothesis that muscarinic cholinergic vasodilation is impaired in coronary atherosclerosis. Graded concentrations of acetylcholine and, for comparison, the nonendothelial-dependent vasodilator nitroglycerin were infused into the left anterior descending artery of eight patients with advanced coronary stenoses (greater than 50 percent narrowing), four subjects with angiographically normal coronary arteries, and six patients with mild coronary atherosclerosis (less than 20 percent narrowing). Vascular responses were evaluated by quantitative angiography. In several segments each of four normal coronary arteries, acetylcholine caused a dose-dependent dilation from a control diameter of 1.94 +/- 0.16 mm to 2.16 +/- 0.15 mm with the maximal acetylcholine dose (P less than 0.01). In contrast, all eight of the arteries with advanced stenoses showed dose-dependent constriction, from 1.05 +/- 0.05 to 0.32 +/- 0.16 mm at the highest concentration of acetylcholine (P less than 0.01), with temporary occlusion in five. Five of six vessels with minimal disease also constricted in response to acetylcholine. All vessels dilated in response to nitroglycerin, however. We conclude that paradoxical vasoconstriction induced by acetylcholine occurs early as well as late in the course of coronary atherosclerosis. Our preliminary findings suggest that the abnormal vascular response to acetylcholine may represent a defect in endothelial vasodilator function, and may be important in the pathogenesis of coronary vasospasm.

Acetylcholine↗
PubMed1986

Long-term survival of more than 2,000 patients after coronary artery bypass grafting.

Among 2,004 patients who underwent their first coronary artery bypass graft operation between January 1970 and December 1980 without concomitant valve replacement or aneurysmectomy, life-table survival was 89% at 5 years and 80% at 8 years after surgery. In a multivariate Cox model analysis, the independent correlates of long-term survival were emergent operation with cardiogenic shock (multivariate mortality rate ratio [RR] = 14.0), use of a postoperative intraaortic balloon pump (RR = 3.9), ejection fraction less than 50% (RR = 2.4), preoperative history of congestive heart failure (RR = 2.2), cardiopulmonary bypass time (RR = 1.4 for each 30-minute increment), uncorrected mitral regurgitation (RR = 1.5 for each increment of angiographic gradation), left main coronary artery narrowing (RR = 1.7) and diabetes (RR = 1.6). After controlling for these factors, age, sex and the percentage of narrowings that were bypassed were not independent correlates of long-term survival.

Adult↗
PubMed1986

Clinical response to coronary artery reoperations.

Repeat coronary artery bypass operations were performed on 112 patients at a university hospital between 1971 and 1981. When compared with patients who did poorly after a first operation but did not have repeat surgery, patients undergoing repeat surgery tended to be younger, to have a higher smoking rate and to have fewer prior myocardial infarctions, fewer diseased vessels and fewer lesions in distal vessels. At least 1 graft was occluded in 83% of patients undergoing reoperation, and a mean of 1.7 grafts were placed at reoperation. The operative mortality rate was 4%, with a follow-up mortality rate of 6% at a mean of 3.8 years. After reoperation, patients initially showed improvement to a mean specific activity scale class of 1.6, compared with 2.4 before the first operation and 2.7 before the second operation. The principal correlate of a better long-term symptomatic response compared with that in the period before the first operation was a lower serum cholesterol level, whereas the principal correlate of a better symptomatic response compared with that in the period just before the reoperation was the left ventricular ejection fraction. As recurrent symptoms after a first coronary artery operation become more prevalent, consideration of the selection factors and prognostic correlates of reoperation will become increasingly important.

Coronary Angiography↗
PubMed1986

Benefits of experience. Treating coronary artery disease.

The authors examined the issue of learning by doing in terms of both the cost and outcome of treating coronary artery disease at one hospital between 1977 and 1981. Over time, the quality of outcome improved for both medical and surgical patients. During this time of cost-plus reimbursement, there was less conclusive evidence of concurrent technical efficiency gains. These findings are consistent with the hypothesis that the benefits of experience can be substantial but they do not just happen: they require proper provider motivation.

Boston↗
PubMed1986

Metabolism and excretion of a glutathione conjugate of acetaminophen in the isolated perfused rat kidney.

Acetaminophen-glutathione (APAP-GSH) is the initial sulfur-containing metabolite of APAP produced by the liver. However, little, if any, APAP-GSH is found in the urine of intact animals. Rather, the cysteine (APAP-CYS) and N-acetylcysteine (APAP-NAC) conjugates are the predominant sulfur-containing metabolites of APAP excreted in the urine. To define more precisely the role of the kidney in total body disposition of APAP, the metabolism and excretion of each of these metabolites was quantified in the isolated perfused rat kidney (IPK). With perfusate concentrations of 0.031, 0.125 and 0.250 mM APAP-GSH, the IPK metabolized APAP-GSH to APAP-CYS rapidly. Further metabolism of APAP-CYS to APAP-NAC proceeded at a much slower rate. Consequently, at 0.031 mM APAP-GSH, negligible amounts of APAP-CYS were found in the urine. However, as the concentration of APAP-GSH was increased so did the excretion of APAP-CYS. In contrast, the excretion of APAP-NAC did not exhibit dependence on APAP-GSH concentration. APAP-NAC was excreted by a probenecid sensitive transport mechanism whereas APAP-CYS excretion appeared to be related only to glomerular filtration. In addition, the disappearance of APAP-GSH was much greater than could be accounted for by glomerular filtration. These data indicate that the IPK is an effective model for the study of metabolism and excretion of xenobiotics that have undergone conjugation with GSH.

Acetaminophen↗