First-pass radionuclide ventriculography followed by myocardial single photon emission computed tomography (SPECT) with 99Tcm-methoxyisobutyl isonitrile (sestamibi) was performed at rest and during dipyridamole infusion in 42 patients with suspected coronary artery disease. The presence of coronary stenoses of > or = 50% diameter was compared with the presence of rest or dipyridamole-induced abnormalities in perfusion or left ventricular function. Radionuclide-determined left ventricular ejection fraction (LVEF) was highly reproducible and correlated well with LVEF derived from contrast left ventriculography. Left ventricular ejection fraction decreased significantly after dipyridamole infusion in patients with multivessel disease (58 +/- 10% versus 52 +/- 11%, P < 0.01). The sensitivity and specificity for the detection of patients with coronary artery disease were 85 and 75% by myocardial SPECT, and 47 (P < 0.01 versus SPECT) and 75% by LVEF, respectively. However, in patients with multivessel disease, the sensitivity of LVEF was not different from that of SPECT (72% versus 89%, P = ns). The sensitivity of LVEF was higher in patients with multivessel disease than in those with single-vessel disease (19% versus 72%, P < 0.01). Radionuclide ventriculography followed by myocardial SPECT with 99Tcm-sestamibi allows simultaneous evaluation of ventricular contractile function associated with perfusion abnormality during dipyridamole infusion and may enhance the functional description of myocardial ischaemia.

Adult↗

PubMed1994

[Detection of Aspergillus fumigatus DNA by polymerase chain reaction in the clinical samples from individuals with pulmonary aspergillosis].

Aspergillosis is a disastrous cause of mortality and morbidity in patients in an immunocompromised state and old lung tuberculosis. However, the diagnosis of aspergillosis remains unsettled. In the present study, we developed a test to detect the Aspergillus fumigatus DNA using polymerase chain reaction (PCR) in clinical samples including sputum and bronchial aspirations from the patients with aspergillosis. We selected 2 pairs of oligonucleotide primers and the DNA for the small subunit ribosomal RNA of aspergillus fumigatus and they were significantly amplified. Although isolation of Aspergillus DNA may reflect contamination and colonization without infection, no aspergillus DNA was found in sputum or bronchial aspirations from the patients with lung cancer or interstitial lung diseases except a case of pulmonary fibrosis associated with rheumatoid arthritis chronically received 20 mg of corticosteroid. There was a 100% correlation between the culture results and the nested PCR results in the patients with pulmonary aspergillosis. These findings indicate that PCR detection of aspergillus fumigatus might be valuable for the diagnosis of aspergillosis.

Aged↗

PubMed1993

Inhibitory effects of heparin, aspirin and ketanserin on coronary artery vasoconstriction after arterial balloon injury in hypercholesterolemic miniature pigs.

OBJECTIVES: The present study aimed to clarify the effects of heparin, aspirin and ketanserin on coronary artery vasoconstriction after arterial balloon injury. BACKGROUND: The mechanisms of coronary artery vasoconstriction after coronary angioplasty are not well understood. METHODS: After being fed a cholesterol-rich diet for 1 month, 71 Göttingen miniature pigs were randomly allotted to five groups: 16 pigs with no pretreatment (group A); 21 pigs pretreated with heparin, 3,000 U (group B); 13 pigs pretreated with aspirin, 50 mg/day orally for 2 days (group C); 11 pigs pretreated with ketanserin, 1 mg/kg body weight (group D); 10 pigs pretreated with aspirin, 50 mg/day for 2 days, heparin, 6,000 U and ketanserin, 1 mg/kg (group E). After this pretreatment, the left anterior descending or the left circumflex coronary artery, or both, was denuded by a 2F balloon catheter. RESULTS: The coronary vasoconstriction at the injured sites reached a peak level 6 min after the arterial injury and subsided within 30 min. The coronary vasoconstriction at the injured site 6 min after arterial injury was 56 +/- 5% in group A, which was significantly greater than that in group B (28 +/- 6%, p < 0.01), group C (25 +/- 5%, p < 0.01), group D (26 +/- 7%, p < 0.01) or group E (24 +/- 5%, p < 0.01), whereas there was no significant difference in the coronary vasoconstriction among the latter four groups. CONCLUSION: These results suggest that serotonin released from aggregating platelets plays a major part in the platelet-dependent coronary artery vasoconstriction after arterial injury.

Angioplasty, Balloon, Coronary↗

PubMed1993

Hyperreactivity of aortic smooth muscle to serotonin is related to the presence of atheroma in Watanabe heritable hyperlipidaemic rabbits.

OBJECTIVE: The aim was to elucidate the contribution of atheromatous plaque to alterations of smooth muscle contraction to vasoconstrictive agents, by examining vasoreactivity of vascular smooth muscle from the thoracic aorta of 10-13 month old Watanabe heritable hyperlipidaemic rabbits. METHODS: From the same vascular ring of the lower thoracic aorta, a pair of small medial smooth muscle strips was prepared from the sites beneath the atheroma (atherosclerotic medial muscle strip) and from those beneath the plaque-free intima (normal medial muscle strip), and isometric tension was measured. RESULTS: Contractions to 118 mM KCl, histamine (30 nM to 10 microM), and noradrenaline (3 nM to 0.3 microM) were similar between atherosclerotic and the normal medial muscle strip. The ED50 to serotonin was 49(SD 28) and 116(66) nM (p < 0.05, n = 7) and the maximum tension to serotonin was 125(29)% and 82(29)% of that induced by 118 mM KCl (p < 0.01, n = 7) in atherosclerotic and normal medial muscle strip, respectively. Serotonin specific hyperreactivity of the atherosclerotic strip disappeared in Ca(2+)-free solution or in the presence of 10 microM H-7, an inhibitor of protein kinase C. After incubation with 0.1 microM phorbol 12,13-dibutyrate, an activator of protein kinase C, the isometric contractions induced by Ca2+ were significantly greater in atherosclerotic than in normal medial muscle strip. CONCLUSIONS: These results indicate that medial smooth muscle located beneath the atheroma is specifically hyperreactive to serotonin and that altered protein kinase C activity may explain in part the augmented response to serotonin.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1993

Resetting of regional preload due to ventricular shape change alters diastolic and systolic performance.

The diastolic and systolic pressure of one ventricle is increased by an increase in volume and/or pressure of the opposite ventricle; however, a mechanism for the ventricular interaction remains unclear. We hypothesized that the shape change of one ventricle elicited by the opposite ventricle would lead to resetting of the regional length, which may explain the ventricular interaction. We used 15 cross-circulated isovolumically contracting canine hearts in which both ventricular volumes were independently controlled. Diastolic regional segment area was calculated by multiplying circumferential and longitudinal lengths on right ventricular free wall (RVFW; n = 6), interventricular septum (IVS; n = 11), and left ventricular (LV) FW (n = 12). The regional area at relatively small volumes of both ventricles were expressed as 100%. With constant RV volume, increasing LV from 7 to 19 ml increased RV diastolic and systolic pressures by 2.7 and 5.5 mmHg, respectively. Conversely, increasing RV volume increased LV diastolic and systolic pressures by 2.3 and 7.5 mmHg, respectively. Increasing LV volume increased RVFW regional area from 121.0 to 124.6% (P < 0.01) and increased IVS regional area from 103.3 to 108.7% (P < 0.01), whereas the RV volume was held constant. Increasing RV volume also increased LVFW and IVS regional areas from 109.9 to 111.6% (P < 0.01) and from 106.8 to 108.9% (P < 0.05), respectively. Ventricular shape change elicited by ventricular interaction will increase the regional wall area, even though the volume of the chamber is unchanged. The increase in the regional area alters the position of the tissue on its resting and active length-tension relations and, thus, leads to enhancement of the chamber pressure.

Animals↗

PubMed1993

Role of coronary artery spasm in progression of organic coronary stenosis and acute myocardial infarction in a swine model. Importance of mode of onset and duration of coronary artery spasm.

BACKGROUND: Coronary spasm may play an important role in progression of organic coronary stenosis and myocardial infarction, but the mechanisms responsible for these complications are not known. This study aimed to examine whether the mode of onset and the duration of coronary spasm influenced progression of organic coronary stenosis and acute myocardial infarction in a swine model of coronary spasm. METHODS AND RESULTS: Göttingen miniature pigs were subjected to cholesterol feeding, balloon-induced coronary arterial denudation, and x-ray irradiation. Five months later, coronary spasm was induced by intracoronary injection of serotonin. In 10 pigs, coronary spasm was provoked abruptly and maintained for 25 minutes by five repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes (group A, abrupt onset and short duration). In group B, coronary spasm was provoked gradually by intracoronary injections of serotonin at graded doses of 0.1, 0.3, and 0.6 microgram/kg every 5 minutes and was then maintained for 25 minutes in four pigs (group B1, gradual onset and short duration) and for 120 minutes in six pigs (group B2, gradual onset and long duration) by repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes. Intramural hemorrhage was noted histologically at the spastic site more frequently in group A with abrupt onset (nine of 10 pigs) than in group B with gradual onset (two of 10 pigs) (p < 0.01). Progression of organic coronary stenosis due to intramural hemorrhage was noted in seven pigs (six pigs in group A and one pig in group B), including three cases of total coronary occlusion. Evidence for the evolution of acute myocardial infarction (serial ECG findings, left ventriculograms, and histological findings) was noted in one pig (7%) of group A or B1 with short duration and in five of six pigs (83%) in group B2 with long duration (p < 0.01 versus group A and B1). CONCLUSIONS: These results indicate that: 1) intramural hemorrhage was frequently induced by coronary spasm of abrupt but not of gradual onset, 2) intramural hemorrhage resulted in acute progression of coronary stenosis and sometimes resulted in persistent total coronary occlusion leading to acute myocardial infarction, and 3) prolonged coronary spasm resulted in acute myocardial infarction without progression of organic coronary stenosis.

Animals↗

PubMed1993

Role of ATP-sensitive K+ channel on ECG ST segment elevation during a bout of myocardial ischemia. A study on epicardial mapping in dogs.

BACKGROUND: ATP-sensitive K+ channels are activated when the myocardium becomes ischemic. However, the role of the ATP-sensitive K+ current in the emergence of ECG ST changes during ischemia remained unclarified. METHODS AND RESULTS: The left anterior descending coronary artery (LAD) was cannulated and perfused with arterial blood from the carotid artery through a bypass tube in 8 anesthetized, open-chest dogs. An array of 60 unipolar electrodes mounted on a sock was used to record epicardial electrograms of the whole heart. Pinacidil (10 micrograms.kg-1 x min-1), an ATP-sensitive K+ channel opener, was infused into the bypass tube for 2 minutes, and the electrograms were recorded before and after the infusion. The elevation of the ST segment and the increase of QRST area were observed spatially over the LAD-perfused region. At the electrode showing the largest ST segment elevation, the activation recovery interval, an index of action potential duration, was shortened from 202 +/- 9 to 111 +/- 18 milliseconds (P < .001). These electrographic changes were similar to those noted in 2-minute coronary occlusion (n = 8). The extent of ST segment elevation during coronary occlusion was attenuated after the intravenous pretreatment with glibenclamide (0.3 mg/kg), a blocker of the KATP channel (n = 5). CONCLUSIONS: The findings of this study suggest that the activation of ATP-sensitive K+ channels during a bout of acute myocardial ischemia plays an important role in the emergence of ECG ST elevation.

Action Potentials↗

PubMed1993

Serotonin-induced coronary spasm in a swine model. A minor role of defective endothelium-derived relaxing factor.

BACKGROUND: Coronary spasm may be caused by endothelial dysfunction, vascular smooth muscle hyperreactivity, or both. We aimed to determine the relative role of endothelial dysfunction and vascular smooth muscle hyperreactivity in the pathogenesis of coronary artery spasm in the swine model in vivo. METHODS AND RESULTS: In Göttingen miniature pigs given a high cholesterol diet, a segment of the left coronary artery was denuded and irradiated with x-ray (total, 30 Gy). Three months after endothelial denudation and irradiation, vasomotor responses of the denuded and control sites to agonists were assessed by quantitative arteriography. Serotonin (10 micrograms/kg) provoked coronary spasm at the denuded site (diameter reduction, 79 +/- 6%) associated with ST elevation but not at the nondenuded control site (21 +/- 6%). Intracoronary infusion of N omega-nitro-L-arginine methyl ester (LNNA, an inhibitor of endothelium-derived nitric oxide) of 1 and 3 mg/kg potentiated constriction evoked with serotonin (1, 3, 10 micrograms/kg) at the control site but did not alter it at the denuded site. However, serotonin-induced constriction after LNNA was still less at the control site (31 +/- 3%) than at the denuded site (80 +/- 5%). Endothelium-dependent vasodilation with substance P (0.1, 1, 10 ng/kg), which was inhibited by LNNA, was less (P < .01) at the denuded site than at the control site, whereas vasodilation with the nitrovasodilator SIN-1 (0.1, 1, 10 ng/kg) was comparable between the two sites. Histological study revealed regenerated endothelial cells and intimal thickening at the denuded site. CONCLUSIONS: The results suggest that the denuded segment of the coronary artery with regenerated endothelium was associated with defective endothelium-dependent vasodilation mediated by nitric oxide and vascular smooth muscle hyperreactivity to serotonin. However, provocation of coronary spasm with serotonin resulted primarily from vascular smooth muscle hyperreactivity but not by defective nitric oxide production in this swine model.

Animals↗

PubMed1993

Comparison of adenosine and treadmill exercise thallium-201 stress tests for the detection of coronary artery disease.

To determine the clinical usefulness of adenosine Tl-201 imaging for the evaluation of coronary artery disease, 22 patients with suspected coronary artery disease who underwent adenosine and exercise Tl-201 single photon emission computed tomography (SPECT) were studied. The peak levels of heart rate (83 vs 123 bpm, p < 0.001), systolic blood pressure (124 vs 164 mmHg, p < 0.001), diastolic blood pressure (70 vs 86 mmHg, p < 0.01) and rate pressure products (10220 vs 20410 bpm x mmHg, p < 0.001) were markedly smaller during adenosine infusion than during exercise. Segmental agreements between adenosine and exercise tests were 90% (218 of 242 segments) regarding the presence of perfusion defects and 89% (215 of 242 segments) regarding the presence of redistribution. Regional Tl-201 uptake (r = 0.85, p < 0.001) and the extent (r = 0.75, p < 0.001) and intensity (r = 0.83, p < 0.001) of Tl-201 defects during adenosine testing were closely correlated with those of exercise testing. Adenosine and exercise tests showed similar sensitivities for the identification of individual coronary stenosis (85% vs 78%). However, in patients who were unable to perform adequate exercise (maximal heart rate < 120 bpm), the sensitivity of adenosine imaging tended to be higher than that of exercise imaging (92% vs 69%, p = 0.07). Adenosine Tl-201 imaging is an alternative to the exercise test for assessing the severity and loci of coronary artery disease, especially in patients who are unable to perform adequate physical exercise.

Adenosine↗

PubMed1993

Assessment of preload reserve in myocardial ischemia--the relation between preload reserve and ischemic size differs between anterior descending and circumflex coronary artery occlusions in a canine model.

The role of changes in preload in maintaining stable hemodynamics during coronary obstruction was assessed in the presence of myocardial ischemia due to occlusions of the left anterior descending (LAD) and left circumflex (LCX) coronary arteries. Changes in preload (mean left atrial pressure) to maintain a constant stroke volume after coronary occlusion were examined in 18 anesthetized dogs (LAD occlusion in 9 dogs, LCX occlusion in 9 dogs). The level of ischemia was assessed sonomicrometrically. Ventricular function curves relating left atrial pressure to stroke volume were assessed during a control state and after 1 min of coronary occlusion. The extent of preload reserve after coronary occlusion was examined on the ventricular function curves and was defined as the change in mean left atrial pressure required to maintain stroke volume at the level of the control state under conditions of regional ischemia. Ischemic size was determined by a stereo-angiogram after the animals were sacrificed. The extent of preload reserve (X) was linearly related to the ischemic size (Y) in both LAD (Y = 0.90 + 0.16X, r = 0.76, p < 0.001) and LCX (Y = -1.79 + 0.19X, r = 0.79, p < 0.001) occlusions. The slopes of the regression lines in LAD and LCX occlusions were the same. The X intercepts of these lines were -5.6% and 9.4% of the left ventricular weight in LAD and LCX ischemia (p < 0.001), respectively. Thus, the presence of systolic wall motion abnormalities due to coronary occlusion can be compensated for hemodynamically by changes in the preload reserve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Ratio of lung to heart thallium-201 uptake on exercise and dipyridamole stress imaging in coronary artery disease--implication of SPECT.

To examine whether measurements of lung thallium-201 (Tl-201) uptake with single photon emission computed tomography (SPECT) following exercise or dipyridamole infusion provide complementary information as reported in planar imaging, we examined 140 patients undergoing exercise or dipyridamole Tl-201 SPECT and coronary arteriography for the diagnosis of coronary artery disease (CAD). On the reconstructed coronal tomographic image, regions of interest were placed over the left upper lung field and the left ventricular myocardium. Lung to heart ratio (L/H ratio) was calculated as a fraction of average Tl-201 counts per pixel in the lung divided by those in the myocardium. An L/H ratio of larger than a value of mean +2 standard deviation, derived from patients without significant coronary stenosis, was considered as abnormal. The patients with abnormal L/H ratio on exercise Tl-201 SPECT had larger extent and severity scores of Tl-201 defects on the initial image, lower left ventricular ejection fraction, higher end-diastolic pressure and higher incidence of multi-vessel CAD than those with the normal ratio. However, in dipyridamole studies, abnormal L/H ratio did not relate to scintigraphic or hemodynamic severity. These data confirmed that increased lung Tl-201 uptake after exercise suggested the presence of extensive CAD or left ventricular dysfunction. However, L/H ratio might be less useful in dipyridamole studies. Thus, quantitative measurements of L/H ratio with exercise but not dipyridamole SPECT could provide additional information related to the involved cardiac pump performance in CAD.

Adult↗

PubMed1993

Assessment of the variability in coupling intervals of ventricular premature contractions.

BACKGROUND: The coupling interval of ventricular premature contraction is relatively constant in some patients, while it varies in others. The clinical implications of this variability in the coupling intervals of ventricular premature contractions remains to be clarified. METHODS: Ambulatory electrocardiograms were recorded in 48 patients who had 2000 or more ventricular premature contractions per day. In each subject, 24 h ambulatory electrocardiograms were recorded in the absence of antiarrhythmic drug (control), and during treatment with various antiarrhythmic drugs. Data on R-R intervals were obtained using a Marquette 8000T, and transmitted to a personal computer. For each of the control recording, an R-R interval scatterplot was constructed by plotting the coupling intervals of ventricular premature contractions as a function of the preceding R-R intervals of normal sinus beats. The standard deviation of the coupling intervals (SDNV), that of the preceding R-R intervals (SDNN), and their ratio (SDNV/SDNN) were calculated. RESULTS: At control recording, two primary R-R scatterplot patterns were recognized; 1) Fixed, where the coupling intervals remained constant at various preceding R-R intervals (SDNV/SDNN < 0.5 and SDNV < 50 msec) (n = 29), and 2) Variable, where the coupling intervals showed a much greater (n = 19). The prevalence of organic heart disease was higher in the Variable group than in the Fixed group (47% vs 14%, p < 0.05). SDNV/SDNN was higher in patients with organic heart disease than in those without (0.62 +/- 0.34 vs 0.44 +/- 0.23, p < 0.05). The efficacy of antiarrhythmic drugs was compared between the two groups. A reduction of 80% or more in the total number of ventricular premature contractions was considered effective. Class Ia, Ib, and Ic drugs had almost the same efficacy in the Fixed and Variable groups (Ia, 43% and 41%; Ib, 36% and 22%; Ic, 64% and 63%, respectively). Class II drugs (beta-blockers) were more effective in the Fixed group than in the Variable group (50% vs 0%, p < 0.05). CONCLUSION: The R-R interval scatterplot of ambulatory electrocardiograms was useful in exploring the variability in the coupling intervals of ventricular premature contractions, and may help to predict the efficacy of antiarrhythmic drugs.

Adolescent↗

PubMed1993

Changes in pulmonary hemodynamics during normoxia and hypoxia in awake rats treated with intratracheal bleomycin.

Pulmonary hemodynamics of bleomycin-induced interstitial fibrosis model (group-BLM, n = 10) and saline-treated control (group-C, n = 12) were studied in awake rats. Four weeks before hemodynamic study, bleomycin sulfate and normal saline was intratracheally instilled to the group-BLM and the group-C, respectively. Pulmonary artery and abdominal aortic catheters were indwelled two days before the hemodynamic study. In room air, mean pulmonary artery pressure (Ppa) was significantly higher and systemic artery pressure was significantly lower in group-BLM than in group-C; Ppa = 21 +/- 1 cmH2O (mean +/- S.E.) for group-C and 38 +/- 4 cmH2O for group-BLM. Cardiac output did not differ among the groups. Mean pulmonary vascular resistance (PVR) of group-BLM was double that of group-C. Right ventricle was hypertrophic in group-BLM. When exposed to 10% O2, PVR of group-C significantly rose, whereas PVR of group-BLM showed very little increase, showing attenuation of the hypoxic pulmonary vasoconstriction (HPV). Magnitude of the HPV was inversely related to Ppa during air breathing. We conclude that notable pulmonary hypertension and right ventricular hypertrophy occur, and HPV is blunted four weeks after bleomycin instillation, at the most severe period of this lung fibrosis model. We speculate that the high intravascular pressure partly contributed to the blunted HPV in bleomycin-treated group.

Animals↗

PubMed1993

[Spontaneously healed P. carinii pneumonia in the course of steroid therapy for interstitial pneumonia--many trophozoites in bronchoalveolar lavage].

A case in which P. carinii was observed in bronchoalveolar lavage fluid during steroid therapy for interstitial pneumonia in a 63-year-old man is reported, he had received steroid therapy for interstitial pneumonia of unknown origin. Three weeks later, he developed acute pneumonia with Streptococcus pneumoniae, and simultaneously P. carinii was detected in the bronchoalveolar lavage fluid. Both the pneumonic shadows and P. carinii disappeared following intravenous infusion of penicillin and rapid reduction of steroid. Electron microscopic analysis of P. carinii demonstrated numerous tubular expansions and endogenies of P. carinii, suggesting that P. carinii was growing in the intra-alveolar spaces. Phospholipid analysis demonstrated a transient increase in total phospholipid content during P. carinii pneumonia, suggesting that P. carinii can affect surfactant metabolism.

Bronchoalveolar Lavage Fluid↗