PubMed Health⌕ Search

Biomedical subjects

P A Mullins

Publications and source records attributed to P A Mullins.

At least 19 recordsLinked to original sources
PubMed1997

Subchronic inhalation studies of styrene in CD rats and CD-1 mice.

Groups of 10 male and 10 female Charles River (CRL) CD (Sprague-Dawley-derived) rats were exposed to styrene vapor at 0, 200, 500, 1000, or 1500 ppm 6 hr per day 5 days per week for 13 weeks. Styrene had no effect on survival, hematology, or clinical chemistry. Males at 1500 ppm weighed 10% less after 13 weeks and males and females at 1000 and 1500 ppm consumed more water than controls. Histopathologic changes were confined to the olfactory epithelium of the nasal mucosa. Groups of 20 male and 20 female CRL CD-1 and B6C3F1 mice were exposed to styrene vapor at 0, 15, 60, 250, or 500 ppm 6 hr per day 5 days per week for 2 weeks. Mortality was observed in both CD-1 and B6C3F1 mice exposed to 250 or 500 ppm; more female mice, but not males, died from exposure to 250 ppm than from 500 ppm. Groups of 10 male and 10 female CRL CD-1 mice were exposed to styrene vapors at 0, 50, 100, 150, or 200 ppm 6 hr per day 5 days per week for 13 weeks. Two females exposed to 200 ppm died during the first week. Liver toxicity was evident in the decedents and in some female survivors at 200 ppm. Changes were observed in the lungs of mice exposed to 100, 150, or 200 ppm and in the nasal passages of all treatment groups, those exposed to 50 ppm being less affected. Satellite groups of 15 male rats and 30 male mice were exposed as described above for 2, 5, or 13 weeks for measurement of cell proliferation (BrdU labeling). No increase in cell proliferation was found in liver of rats or mice or in cells of the bronchiolar or alveolar region of the lung of rats. No increase in labeling index of type II pneumocytes was seen in mouse lungs, while at 150 and 200 ppm, an increased labeling index of Clara cells was seen after 2 weeks and in occasional mice after 5 weeks. Large variations in the labeling index among animals emphasize the need for large group sizes. For nasal tract effects, a NOAEL was not found in CD-1 mice, but in CD rats, the NOAEL was 200 ppm. For other effects, the NOAEL was 500 ppm in rats and 50 ppm in mice.

Administration, Inhalation↗
PubMed1997

Both endothelium-dependent and endothelium-independent function is impaired in patients with angina pectoris and normal coronary angiograms.

BACKGROUND: The aim of this study was to investigate both endothelium-dependent and endothelium-independent vasodilatation in syndrome X patients. Recently selective impairment of endothelium-dependent function has been reported in a small number of syndrome X patients. However, other investigators have reported impaired endothelium-independent function. METHODS: We infused the endothelium-independent vasodilators papaverine and glyceryl trinitrate, and endothelium-dependent vasodilator acetylcholine in the left coronary artery of 35 patients with syndrome X and in 17 control subjects (atypical chest pain, negative exercise test, and normal coronary angiograms). Coronary blood flow was measured with an intracoronary Doppler catheter positioned in the proximal left anterior descending coronary artery, and the artery diameter was assessed using quantitative coronary angiography. RESULTS: The mean increase in coronary blood flow in response to a 12 mg dose of papaverine was significantly less in the syndrome X group (185 +/- 74% vs 411 +/- 59%, P < 0.001). The increase in coronary blood flow in response to acetylcholine, at doses of 1, 3, 10, and 30 micrograms.min-1, was also significantly lower in the syndrome X group (12 +/- 13 (P < 0.05), 41 +/- 33, 57 +/- 68, and 124 +/- 87% (P < 0.001)) as compared to the control group (76 +/- 49, 214 +/- 116, 355 +/- 115, and 361 +/- 74%). CONCLUSION: These findings demonstrate that both endothelium-dependent and endothelium-independent dilatation of the coronary microvasculature is impaired in syndrome X.

Acetylcholine↗
PubMed1996

Cardioesophageal reflex: a mechanism for "linked angina" in patients with angiographically proven coronary artery disease.

OBJECTIVES: The purpose of this study was to investigate the presence of a cardioesophageal reflex in patients with coronary artery disease that may explain the mechanism of "linked angina." BACKGROUND: It has been previously shown that esophageal acid stimulation can reduce coronary blood flow in patients with syndrome X, suggesting the presence of a cardioesophageal reflex in humans. METHODS: We studied the effect of esophageal acid stimulation on coronary blood flow in 14 patients with angiographically documented significant coronary artery disease and in 18 heart transplant recipients. Hydrochloric acid (0.1 mol/liter) and 0.9% saline solution were infused in random, double-blind manner (60 ml over 5 min) through a fine-bore tube positioned in the patient's distal esophagus, and coronary blood flow measurements were obtained after each infusion by use of a 3.6F intracoronary Doppler catheter positioned in the proximal left anterior descending coronary artery. RESULTS: Coronary blood flow was reduced significantly by esophageal acid stimulation in the coronary artery disease group (before acid 70.4 +/- 14.3 ml/min, after acid stimulation 46.4 +/- 19.1 ml/min [mean +/- SD], p < 0.01). However, there was no significant difference in coronary blood flow during saline infusion (73.5 +/- 15.3 vs. 72.5 +/- 14 ml/min). Coronary blood flow in the heart transplant group was not affected by acid or saline infusion. CONCLUSIONS: Esophageal acid stimulation can cause animal attacks and significantly reduce coronary blood flow in patients with coronary artery disease. The lack of any significant effect in heart transplant recipients with heart denervation suggests a neural reflex.

Aged↗
PubMed1996

Aging-associated endothelial dysfunction in humans is reversed by L-arginine.

OBJECTIVES: This study investigated the hypothesis that aging selectively impairs endothelium-dependent function, which may be reversible by administration of L-arginine. BACKGROUND: An impaired response to acetylcholine with aging has been demonstrated in humans. However, the mechanisms underlying this impaired response of the coronary microvasculature remain to be determined. METHODS: We infused the endothelium-independent vasodilators papaverine and glyceryl trinitrate (GTN) and the endothelium-dependent vasodilator acetylcholine (1,3,10 and 30 micrograms/min) into the left coronary artery of 34 patients (27 to 73 years old) with atypical chest pain, negative exercise test results, completely normal findings on coronary angiography and no coronary risk factors. Coronary blood flow was measured with an intracoronary Doppler catheter. The papaverine and acetylcholine infusions were repeated in 14 patients (27 to 73 years old) after an intracoronary infusion of L-arginine (160 mumol/min for 20 min). RESULTS: There was a significant negative correlation between aging and the peak coronary blood flow response evoked by acetylcholine (r = -0.73, p < 0.0001). However, there was no correlation to papaverine (r = -0.04, p = 0.82) and GTN (r = -0.24, p = 0.17). The peak coronary blood flow response evoked by acetylcholine correlated significantly with aging before L-arginine infusion (r = -0.87, p < 0.0001), but this negative correlation was lost after L-arginine infusion (r = -0.37, p = 0.19). CONCLUSIONS: The results suggest that aging selectively impairs endothelium-dependent coronary microvascular function and that this impairment can be restored by administration of L-arginine, a precursor of nitric oxide.

Acetylcholine↗
PubMed1996

Coronary flow reserve and oesophageal dysfunction in syndrome X.

The relative prevalence of abnormalities of coronary flow reserve and oesophageal function was ascertained in 32 syndrome X patients with typical angina chest pain, a positive exercise test, and normal coronary arteries. Coronary flow reserve in response to a hyperaemic dose of papaverine was measured using an intracoronary Doppler catheter positioned in the left anterior descending coronary artery. An abnormal coronary flow reserve was defined as being < 3.0. Patients were investigated for oesophageal dysfunction by manometry and 24-hour pH monitoring. Thirteen patients had an impaired coronary flow reserve (group 1) and 19 patients had a normal flow reserve (group 2). Eight of the 13 group 1 patients (62%) and 13 of the 19 group 2 patients (68%, p = NS) had evidence of oesophageal dysfunction on either manometry or pH studies. Therefore, a total of 26 (81%) syndrome X patients had either an abnormality of coronary flow reserve or oesophageal dysfunction suggesting that chest pain in these patients may be due to myocardial ischaemia or oesophageal dysfunction, thus confirming the heterogeneous nature of this syndrome. The prevalence of oesophageal abnormalities was independent of any abnormalities of coronary flow reserve.

Adult↗
PubMed1994

Abnormal cardiac pain perception in syndrome X.

OBJECTIVES: The purpose of this study was to determine whether a diminished cardiac pain threshold contributes to chest pain in patients with syndrome X. BACKGROUND: There have been some reports of an altered pain perception in syndrome X. METHODS: Intracardiac catheter manipulation was performed in four groups of patients (syndrome X [group 1, 36 patients]; mitral valve disease and normal coronary arteries [group 2, 36 patients]; mitral valve disease and coronary artery disease [group 3, 36 patients]; and heart transplant recipients with normal coronary arteries [group 4, 36 patients]). Coronary flow velocity was measured in patients with syndrome X and in transplant recipients by use of an intracoronary Doppler catheter positioned in the left anterior descending coronary artery at intracardiac catheter manipulation. Coronary flow reserve in response to papaverine was also measured in patients with syndrome X and in transplant recipients. RESULTS: Intracardiac stimulation produced typical anginal chest pain in 34 group 1 (syndrome X) patients (94%). However, chest pain was produced only in five patients (14%) in group 2, seven patients (19%) in group 3 and no patients in group 4. There were no significant changes in coronary blood flow velocity associated with chest pain in group 1 patients. Coronary flow reserve in response to a hyperemic dose of intracoronary papaverine was significantly lower in the syndrome X group. There was no significant difference in the prevalence with which the stimulation tests produced chest pain in patients with syndrome X with an impaired coronary flow reserve or a positive radionuclide scan. CONCLUSIONS: The results of our study suggest that abnormal cardiac pain perception is a fundamental abnormality in syndrome X.

Adult↗
PubMed1994

Effect of transcutaneous electrical nerve stimulation on coronary blood flow.

BACKGROUND: Although neurostimulation has been shown to be of benefit in angina pectoris, the exact mechanism of its action is not clear. This study was performed to examine the effect of transcutaneous electrical nerve stimulation on coronary blood flow. METHODS AND RESULTS: The effect of transcutaneous electrical nerve stimulation was studied in 34 syndrome X patients (group 1), 15 coronary artery disease patients (group 2), and 16 heart transplant patients (group 3). Coronary blood flow velocity (CBFV) in the left coronary system was measured at rest and after a 5-minute stimulation period with a Judkins Doppler. There was a significant increase in the resting CBFV in group 1 (from 6.8 +/- 4.1 to 10.5 +/- 5.7 cm/s, P < .001) and group 2 (from 6.8 +/- 4.1 to 10.5 +/- 5.7 cm/s, P < .001). However, there was no significant change in the resting CBFV in group 3. There were no significant changes in the coronary arterial diameters as a result of neurostimulation. There was a significant decrease in the epinephrine levels in group 1 (from 79.6 +/- 17.8 to 58.5 +/- 17.5 ng/L, P = .01) and group 2 (from 102.2 +/- 27.2 to 64.1 +/- 19.1 ng/L, P = .01). CONCLUSIONS: Transcutaneous electrical nerve stimulation can increase resting coronary blood flow velocity. The findings suggest that the site of action is at the microcirculatory level and that the effects may be mediated by neural mechanisms.

Aged↗
PubMed1994

Is coronary flow reserve in response to papaverine really normal in syndrome X?

BACKGROUND: An impaired coronary flow reserve in syndrome X has been demonstrated by many studies. Recently, however, a normal coronary flow reserve in response to papaverine was reported, but the number of patients in these studies was small. The aim of this study was to investigate whether coronary flow reserve in response to intracoronary papaverine is really impaired in syndrome X. METHODS AND RESULTS: We investigated 53 syndrome X patients (typical angina, a positive exercise test, and completely normal coronary arteries on angiography) and 26 heart transplant patients with normal coronary arteries (control group). All antianginal medications were stopped 48 hours before the study. A 3.6F intracoronary Doppler catheter was positioned in the proximal left anterior descending coronary artery and was connected to a Millar velocimeter. The coronary blood flow velocity at rest and in response to a hyperemic dose of papaverine was measured. Coronary flow reserve was defined as the ratio of hyperemic coronary blood flow velocity in response to papaverine and resting coronary blood flow velocity. The coronary flow reserve (mean +/- SD) in the syndrome X group was 2.72 +/- 1.39. The coronary flow reserve in the control group was significantly higher at 5.22 +/- 1.26 (P < .01). In both groups there was no significant difference in the heart rate or the mean arterial pressure during the study. CONCLUSIONS: Our study shows that coronary flow reserve in response to intracoronary papaverine is impaired in syndrome X patients.

Adult↗
PubMed1994

Measurements of human coronary vascular impedance.

The aim of this study was to develop a method of measuring human coronary circulation impedance in a clinical setting. The authors measured coronary flow reserve (CFR) in 27 patients with chest pain and normal coronary arteries. A Judkins-style, 8F Doppler-tipped angiographic catheter was positioned in the left coronary ostium. Resting coronary flow velocity (RFV) and response to a hyperemic 12 mg intracoronary dose of papaverine (PFV) were measured. The signals were recorded by a recorder connected to a microprocessor with analogue-to-digital converter and a maths coprocessor. Using this the authors could obtain values for impedance at RFV (IR) and at PFV (IP). The CFR was defined as the ratio: PFV/RFV. An impedance index (II) was obtained as the ratio of coronary vascular impedance at peak hyperemia to the impedance at rest. The CFR was 3.2 +/- 1.2 and the II was 0.33 +/- 0.11. There was a strong inverse correlation between the CFR and the II (r = -0.9). The authors conclude that this new approach may allow a further insight into the coronary pathophysiology and may become useful in clinical cardiology, eg, in the assessment of heart transplant and Syndrome X patients.

Adult↗
PubMed1993

Effect of hyperventilation and mental stress on coronary blood flow in syndrome X.

OBJECTIVES: To assess the effect of hyperventilation and mental stress on coronary blood flow and symptom production in patients with syndrome X. DESIGN: A prospective study. Hyperventilation and mental stress tests were performed on the ward and were repeated in the cardiac catheter laboratory where coronary blood flow velocity was also measured with an intracoronary Doppler catheter in the left anterior descending coronary artery. Oesophageal manometry studies were also performed. PATIENTS: 29 patients with syndrome X (typical anginal chest pain, a positive exercise test, and normal coronary angiogram). SETTING: A regional cardiothoracic centre. RESULTS: Hyperventilation produced typical chest pain in 16 patients on the ward. 13 patients experienced their typical chest pain with mental stress test 5. Ten patients experienced chest pain with both hyperventilation and mental stress tests. This pattern was reproduced exactly when the tests were repeated in the cardiac catheter laboratory. Hyperventilation produced a significant increase in the rate-pressure product during ward and laboratory testing. There was, however, no significant change in the rate-pressure product on mental stress tests. The mean (SEM) coronary flow velocity decreased significantly on hyperventilation in the catheter laboratory from 10.0 (0.92) cm/s to 5.9 (0.72) cm/s (p < 0.001). There was also a significant reduction in the mean (SEM) coronary blood flow velocity on mental stress tests from 9.8 (0.86) cm/s to 7.4 (0.6) cm/s (p < 0.001). This reduction in flow velocity occurred in the absence of any changes in diameter of the left anterior descending artery. Further analysis showed that the coronary flow velocity was reduced significantly in only that group of patients in which hyperventilation and mental stress provoked chest pain. There was a significant increase in the arterial concentrations of noradrenaline on both hyperventilation and mental stress testing. Oesophageal manometry showed abnormalities in 17% of patients. CONCLUSIONS: Both hyperventilation and mental stress can produce chest pain in patients with syndrome X and this is associated with a reduction in coronary blood flow velocity. The results of this study suggests that this reduction in coronary flow occurs as a result of increased microvascular resistance.

Adult↗
PubMed1993

Clinical presentation and functional prognosis in syndrome X.

OBJECTIVES: To assess the effect of clinical presentation on functional prognosis in patients with syndrome X. DESIGN: A prospective study. Patients with syndrome X presenting with unstable angina and stable angina were followed up with a questionnaire to examine their functional state. PATIENTS: 41 patients with syndrome X and unstable angina and 41 patients with syndrome X and stable angina. Syndrome X was defined as typical anginal chest pain, a positive exercise test, and normal coronary angiogram. SETTING: Regional cardiothoracic centre. RESULTS: The mean follow up time was 36 (range 20-51) months for the unstable angina group and 35 (range 19-51) months for the stable angina group. No patient was lost to follow up in either group. At follow up 28 patients in the unstable angina group were pain free compared with 15 patients in the stable angina group (p = 0.008). Seven patients in the unstable angina group had further hospital admission with chest pain after the cardiac catheterisation compared wtih 12 patients in the stable angina group (NS). Seven patients in the unstable angina group believed that they had heart disease compared with 27 in the stable angina group (p < 0.001). 26 patients in the unstable angina group but only eight patients in the stable angina group were unlimited in their physical activity (p < 0.001). 12 patients in the unstable angina group compared with 27 patients in the stable angina group were unable to work normally because of chest pain (p < 0.001). The mean (SD) duration of symptoms before cardiac catheterisation was 7.9 (4.7) months in the unstable angina group and 13.4 (5.6) months in the stable angina group (p < 0.001). 10 patients in the unstable angina group and 24 patients in the stable angina group still attended hospital outpatient clinics because of chest pain (p = 0.004). 16 patients in the unstable angina group and 29 patients in the stable angina group were still taking regular antianginal medication (p < 0.001). CONCLUSIONS: Patients with syndrome X who present with unstable angina have a significantly better functional prognosis than those presenting with symptoms of stable angina. This may reflect differences in underlying pathophysiological mechanisms.

Adult↗
PubMed1993

Coronary flow reserve measurements with a new Judkins-style Doppler angiographic catheter.

The authors assessed whether measurements obtained by Judkins-style Doppler catheters are comparable to those achieved with the intracoronary Doppler technique in 42 patients with normal coronary arteries on angiography (19 syndrome X and 23 heart transplant patients). Resting coronary flow velocity and response to a hyperemic intracoronary dose of papaverine was measured with a Judkins-style, 8F Doppler-tipped catheter positioned in the left coronary ostium and a 3.6F intracoronary Doppler catheter positioned in the proximal left anterior descending artery. Mean coronary flow velocity at rest was significantly higher with the Judkins Doppler (10.1 +/- 4.6 vs 6.3 +/- 4.5 cm/sec, p < 0.01). The mean coronary flow velocity at peak hyperemia was also significantly higher with the Judkins Doppler (33.7 +/- 14.1 vs 19.7 +/- 11.5 cm/sec, p < 0.01). Coronary flow reserve was 3.57 +/- 1.3 with the Judkins Doppler and 3.47 +/- 1.2 with the intracoronary Doppler (r = 0.85). A second study was performed in 14 heart transplant patients with the intracoronary Doppler positioned in the left main coronary artery. The resting and hyperemic flow velocities were again higher with the Judkins Doppler but the differences were not statistically significant. There was again a strong correlation between the Doppler catheters for coronary flow reserve measurements. The Judkins-style Doppler technique appears to be a quick, safe, and accurate alternative to the intracoronary Doppler technique.

Cardiac Catheterization↗
PubMed1992

Coronary artery bypass grafting nine years after cardiac transplantation.

Angina and increasing exertional dyspnea developed in a 53-year-old man 9 years after cardiac transplantation. Left heart catheterization revealed severe proximal triple coronary artery disease, and he underwent surgical revascularization. Now 18 months after the operation he continues to be free of symptoms.

Coronary Angiography↗