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The effects of bopindolol, a new beta-adrenoceptor blocker, on the exercise tolerance of 12 in-patients, mean age 57 (5 years), with stable angina pectoris and documented coronary artery disease were evaluated. All patients received on 4 different days a single oral dose of bopindolol 0.5 mg, bopindolol 1.0 mg, bopindolol 2.0 mg and placebo according to a double-blind latin square design. Treadmill symptoms- limited exercise tests were performed using a Bruce protocol, 3, 12 and 24 h after dosing. Bipindolol improved (P less than 0.05) exercise tolerance in comparison with placebo (by a maximum of 33%, 52% and 26% after the 2.0 mg dose) with no adverse effect on ischaemia. The primary action of bopindolol appeared to be to reduce myocardial oxygen consumption (mainly by its negative chronotropic effect) for up to the 24th hour after oral administration. Eight (66%) patients were angina free at the 3rd, 12th and 24th h exercise test. The effects of bopindolol were not dose-related. A short period of inactivity due to hospitalization may have influenced the exercise performance and led us to underestimate the presence of a dose-response. The results of this report suggest that bopindolol has a long lasting effect in the treatment of patients with chronic stable angina pectoris. [ABSTRACT FROM AUTHOR]

During the 1854 cholera outbreak in Florence, Italy, Filippo Pacini documented that the cause of the infection was a bacterium. This conclusion was also independently reached by John Snow during the 1854 cholera outbreak in London. By using an epidemiological method, Snow found that the infection spread through a polluted water network. Snow identified a water pump as the source of the disease. After removing the infected handle of this pump, the cases of cholera rapidly began to decrease. A microscopic examination of the water showed organic impurities but no bacteria. This discovery was ignored during Snow's lifetime. In contrast, through microscopy during the autopsies of cholera victims, Pacini observed that the disruption of their intestinal mucosa was closely associated with millions of the bacteria that he called Vibrio cholerae . Via histological techniques, Pacini detected that intestinal mucosa reabsorption dysfunction was the cause of debilitating diarrhoea, vomiting, severe dehydration and death. Nevertheless, his discovery of Vibrio cholerae was ignored during Pacini's lifetime. A survey of Pacini's autographic manuscripts suggests that Pacini and Snow may have shared mutual knowledge within their respective seminal papers. This survey also facilitates, for the first time, the creation of maps that illustrate the worldwide distribution of Pacini's cholera papers from 1854 to 1881. The consistent neglect of Pacini's discovery remains a true enigma.

Background: It is well known that nitrates can induce paradoxical myocardial ischemia., Methods and Results: Fifty patients (median age 73 years; range 67 to 78 years; 80% male) with healed myocardial infarcts were selected. All patients underwent resting single-photon emission computed tomography (SPECT) and resting baseline gated-SPECT using sestamibi or thallium-201 after the sublingual administration of 5 mg isosorbide dinitrate (ISD). Forty-eight per cent (24 of 50) of the patients demonstrated ISD-induced peri-infarct ischemia as observed by SPECT. Compared with patients without ISD-induced ischemia, patients with ISD-induced ischemia presented larger infarcts as determined by the extent of perfusion defects (mean [± SD] 27±12 pixels versus 11±9 pixels; P<0.0001), lower ejection fractions (39±17% versus 50±15%; P<0.02) and a higher incidence of severe coronary artery disease (P<0.04). At five years, the survival probability on Kaplan-Meier analysis was 42% and 96% for patients with and without ISD-induced ischemia, respectively (HR 5.6 [95% CI 1.6 to 20]; P=0.009)., Conclusions: Nitrates may have low efficacy in improving blood flow through the coronary vessels that supply large myocardial infarcts with high-resistance microvascular damage. At the same time, nitrates induce dilation and blood pressure decrease in remotely patent or mildly stenotic vessels. The blood pressure gradient elicited between the high- and low-resistance coronary vessels may provide the force for a blood flow steal from the viable zones of the infarct toward the healthy myocardium. The resultant nitrate-induced paradoxical ischemia could be a silent marker of myocardial instability and adverse outcomes in elderly patients with healed myocardial infarcts.

Background: Fifteen patients with ischaemic cardiomyopathy and inducible ischaemia were studied to determine the mechanisms of mortality. Failure of the contractile reserve during daily life activities may reflect a prognostic index., Methods: Single photon emission cardiac tomography and radionuclide ambulatory monitoring (Vest) data were analysed in all patients with a 7-year follow-up., Results: At peak exercise on Vest, the 7 non-survivors (N-SURV) showed worse peak ejection rates (PERs) and ejection fractions (EFs) compared with the 8 survivors (SURV), (2 ± 0.6 vs. 3.3 ± 0.7; end-diastolic volumes (EDVs), P < 0.003), and (34 ± 10% vs. 50 ± 13%; P < 0.02), respectively. However, exercise peak filling rates (PFRs) (1.9 ± 0.6 vs. 2.7 ± 0.9; EDVs/s) and exercise heart rates (HRs), (97 ± 17 vs. 106 ± 10), did not differ between the two groups (P > 0.05). In SURV, exercise PERs, which represented rapid left ventricular (LV) emptying, were significantly correlated with exercise PFRs, representing rapid LV filling, (r = 0.71, P < 0.04) but not in N-SURV (r = 0.66, P > 0.05). Among SURV, the Frank-Starling mechanism was thus preserved but not in N-SURV. Upon Cox analysis, overall LV function parameters, exercise PER was the only predictive measure associated with mortality (b = - 0.018, relative hazard ratio = 0.98, P = 0.02)., Conclusions: Exercise PER reduced values reflected failure of the Frank-Starling mechanism, the incapacity of the heart to perform rapid contractile adaptations to daily life activities and a poor prognosis.

The authors report the case of a 49-year-old man with episodes of chest discomfort. Exercise/rest single-photon emission tomography (SPECT) with technetium-99m sestamibi (MIBI) revealed inferior and septal myocardial ischaemia, and MIBI anterior reverse redistribution, representing damaged myocardium. Cardiac tomography documented anomalous origin of the right coronary artery (ARCA) arising from the left sinus of valsalva coursing between the aorta and pulmonary artery. Myocardial ischaemia and myocardial damage revealed by SPECT are related to the transient coronary flow reduction elicited by the compression of the ARCA that is produced by the great arteries during exercise. The ARCA is a rare condition, but may cause myocardial infarction and sudden death. β-blockers and dihydropyridine calcium-channel blockers may provide cardioprotection from inducible myocardial ischaemia. However, in case of failure of medical cardioprotection, relocation of the ARCA to the appropriate aortic sinus and coronary bypass grafting could be considered as the best options.

Background: Multiagent chemotherapy (MCT) has mitochondrial targets. Since technetium-99m-sestamibi (MIBI) is a marker of mitochondrial metabolism, cardiac MIBI uptake and MIBI washout rate (%WR) may detect MCT-induced cardiotoxicity., Methods: In 16 cancer patients on MCT for 10 months and in 14 non-cancer controls, cardiac MIBI uptake between early (30 min) and delayed (3 hours) post-injection planar images was measured as counts per pixel (cpp). The MIBI cardiac %WR was also measured., Results: When MCT patients and controls were compared, early and cardiac delayed MIBI uptake were greater in MCT patients (45 ± 12 cpp vs. 30 ± 4 cpp; p <0.04) and (30 ± 8 cpp vs. 25 ± 2 cpp; p < 0.02), but % WR did not change (12 ± 4% vs. 13 ± 3%; p = ns). However, in the MCT patients, the MIBI cardiac %WR was more rapid because it was obtained at the same time as in the control patients but from a greater amount of MIBI cardiac uptake. On 36-months follow-up, only MCT patients died of cardiac death. Overall survival risk parameters, only delayed cardiac MIBI uptake (Odds ratio = 1.7, p<0.001) and early cardiac MIBI uptake (Odds ratio = 1.2, p<0.02) were found to be significantly associated with cardiac mortality., Conclusions: In experimental studies, anticancer drugs elicit mitochondrial membrane hyperpolarization with passive cardiac MIBI uptake. In MCT patients, the increased cardiac MIBI uptake and rapid %WR compared with controls may reflect mitochondrial membrane dysfunction, pre-clinical cardiotoxicity and thus poor prognosis.

The authors report a case of a young male with median arcuate ligament syndrome (MALS). An abnormally low insertion of the median arcuate ligament fibres caused extrinsic compression and stenosis of the coeliac trunk. However, partial dissection of ligament fibres by laparoscopic surgery did not relieve abdominal angina. Multidetector CT confirmed that MALS did not differ from the preoperative scan. The arcuate ligament compressed the coeliac trunk on expiration, thereby eliciting occlusion of the coeliac trunk. Inspiration induced decompression of the ligament with partial release of occlusion of the coeliac trunk. This leads to hypo-perfusion of intestinal organs and abdominal angina. Considering the severe impairment of quality of life, open surgery for decompression of the coeliac trunk with vascular reconstruction is a reasonable option.

Background: The aim of this study was to validate a new diagnostic tool, nitrate echocardiography (NE), for the identification of viable noncontracting myocardium in patients with a history of prior myocardial infarction (MI). Nitroglycerin (NTG) may be useful for this purpose for its peculiar pharmacodynamic action and may represent an option other than dobutamine echocardiography for the detection of hibernating segments in the presence of severely reduced coronary reserve., Methods: Twenty selected patients (pts) with an old MI were studied with NE and planar thallium scintigraphy with reinjection. NE was performed by administering i.v. NTG starting at 0.4 mcg/kg/minute with equal increments every five minutes up to 2 mcg/kg/minute or to early interruption of the test (decrease of systolic blood pressure > or = 20% or improvement of previously akinetic segments). Left ventricular wall motion was analyzed by dividing the left ventricle (LV) into 16 segments, and a wall motion score index (WMSI) was calculated. Thallium images were obtained at peak exercise, at four hours, and after reinjection. Myocardial viability was defined as an improvement in thallium uptake after reinjection in fixed defects., Results: Basal echo demonstrated 74 akinetic segments; of these 21 (28%, 11 pts) showed improved contractility during NTG infusion at a mean dose of 0.87 +/-0.33 mcg/kg/minute. WMSI decreased from 1.69 +/- 0.29 to 1.46 +/- 0.31 (P = .001). The only hemodynamic response was a drop in systolic blood pressure (136 mmHg to 124; P = .02). Thallium studies showed 29 segments with a four-hour reversible defect and 79 segments with a four-hour fixed defect; of the latter, 14 regions demonstrated improvement in tracer uptake after reinjection (17.7%; 10 pts). Nine pts had a positive echo and thallium study, while 8 showed no improvement either during NE or after thallium reinjection. Two pts had a false-positive nitrate echocardiogram. Therefore, according to an echo/thallium study match, sensitivity, specificity, and accuracy are 90%, 80%, 85%, respectively., Conclusion: NE is a reliable and low-cost method for the detection of viable noncontracting myocardium in selected patients with CAD but needs further validation for widespread application.

Background: The aim of this study was to evaluate the ability of echocardiography, associated with nitroglycerin infusion, in the detection of myocardial viability in patients with recent infarction., Patients and Methods: Fourteen patients (11 male, 3 female, mean age 59 +/- 8 years) with first acute myocardial infarction (12 Q wave, 2 non-Q wave) underwent predischarge (18 +/- 3 days) nitrate echocardiography. All patients underwent delayed planar thallium scintigraphy within four weeks from AMI. Nitrate echocardiography was performed with a nitroglycerin infusion starting from 0.4 mcg/Kg/min every 5 minutes up to 2.0 mcg/Kg/min; the test was terminated with an improvement of wall motion abnormalities or with a drop of systolic blood pressure > or = 20%. Wall motion abnormalities were evaluated with a 16-segment wall motion score index (WMSI). Thallium was performed after a symptom-limited exercise test, after 3 and 24 hours. The left ventricle was divided in 15 regions. Thallium was considered the gold standard for myocardial viability., Results: Basal echo identified 59 dyssynergic segments: of these, 12 (20%-6 patients) showed improvement in contractility during nitrate echocardiography at a mean dose of 0.9 +/- 0.3 mcg/Kg/min. WMSI decreased from 1.42 +/- 0.22 to 1.27 +/- 0.13 (p = 0.022), with no significant change of haemodynamic data (mean systolic blood pressure from 125 to 112 mmHg; mean heart rate from 66 to 76 beats/min; mean rate/pressure product from 8415 to 8848; all p = ns). Thallium scintigraphy showed 40 fixed defects (19%-7 patients) and 10 (4.7%-7 patients) late reversible defects. 20% of the 3-hour fixed defects improved at 24-hour imaging. 5/7 patients with echo improvement had 24-hour reversible defects, while 6/7 with no WMSI improvement had 24-hour fixed defects. Therefore, nitrate echocardiography demonstrated 71% sensitivity, 86% specificity, 83% positive predictive value, 75% negative predictive value and 78% accuracy., Conclusions: Nitrate echocardiography may be a feasible and low cost method in the detection of myocardial viability after myocardial infarction, but awaits further validation.

Objective: A recent prospective study in patients with dilated cardiomyopathy has reported that the disease is familial in at least 20% of cases, but the pattern of inheritance could not be ascertained. The presence of an autosomal dominant pattern, such as seen in hypertrophic cardiomyopathy, could make it possible to search for single gene defects with linkage analysis, whereas polygenic inheritance would be consistent with the autoimmune hypothesis. To assess the pattern of inheritance, we retrospectively identified patients with familial disease and assessed their first degree relatives (parents, siblings and children) for dilated cardiomyopathy., Design and Patients: The family history of 105 consecutive patients with dilated cardiomyopathy was reviewed and 14 who had at least one first degree relative with documented disease were identified as probands. Their healthy relatives (109) were studied by physical examination, electrocardiography, M mode and cross sectional echocardiography, and were classified as unequivocally normal or as potential carriers. The potential carriers had abnormal electrocardiography with either at least one echocardiographic measurement of left ventricular cavity dimension or percentage fractional shortening outside 2 SDs of normal values (based on age and body surface area). The potential carriers underwent 24 hour Holter monitoring and maximal treadmill exercise., Results and Conclusion: Twenty three relatives (21%) were classified as potential carriers: 12 had an increased left ventricular end diastolic dimension, with reduced percentage fractional shortening in three; 11 had an abnormal electrocardiogram and increased end diastolic dimension, with reduced percentage fractional shortening in five. Such abnormalities were very mild and follow up is necessary to find whether such changes represent early disease. Pedigree analysis was most consistent with polygenic inheritance.

The efficacy of combining gallopamil and isosorbide-5-mononitrate (IS-5-MN) was evaluated in 15 patients with "mixed" angina and documented coronary artery disease who participated in a 4-week, double-blind, double-dummy, crossover, placebo-controlled trial. After the first week of the placebo phase (single-blinded), all patients received in three different weeks IS-5-MN 20 mg three times daily, gallopamil 50 mg three times daily, and the same dosages of IS-5-MN and gallopamil three times daily. Exercise tolerance, and peak values of heart rate, systolic blood pressure, double product (DP/100), and ST-segment were evaluated with a treadmill test at the end of each phase. The improvement in exercise tolerance obtained by the combination of the two drugs was significantly greater (p < 0.01) than that achieved by IS-5-MN but not that by gallopamil monotherapy (NS). This effect was accompanied by significant (p < 0.05) reduction (-61%) in ST-segment and significant (p < 0.05) increment (+8%) in peak heart rate only after administration of the combination of the two drugs. The number of ST-depression (ST-) > 1 mm or ST-elevation (ST+) episodes on 24-h Holter monitoring lasting > or = 1 min were also noted in all patients at the end of each phase of the trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Patch tests were performed on 43 workers employed in an animal fodder plant, a typical dust-laden environment. The aim of the study was to establish and assess the incidence of preclinical sensitization to the substances used, some of which are well known allergens, and identify which of these were mostly responsible. On the whole, the tests did not reveal any major reaction to the allergens used, nor polysensitization. However, an unexpected number of cases was sensitized to phenothiazine, a substance that had not been use for the preceding two years. This observation is of interest since phenothiazine is scarcely allergenic and skin eruptions occur only after photosensitization.

The appearance of impaired left ventricular diastolic function in chronic ischemic heart disease often precedes systolic dysfunction. Myocardial ischemia and increased calcium loading have been implicated in the genesis of increased left ventricular stiffness. We have assessed the effects of long-term therapy with different classes of calcium channel-blocking drugs on left ventricular peak filling rate in patients with chronic stable angina and congestive heart failure secondary to ischemic heart disease. Therapeutic effects of nicardipine (30 mg t.i.d.), nisoldipine (10 mg b.i.d.), and verapamil (120 mg t.i.d.) (4 weeks) have been assessed on radionuclide left ventricular diastolic filling parameters in patients with chronic stable angina using placebo-controlled studies. All three drugs significantly improved exercise capacity as compared with placebo. Verapamil produced significant improvements in peak filling rate (p less than 0.005), time to peak filling rate (p less than 0.01), and first one-third filling fraction (p less than 0.005), whereas nicardipine only improved peak filling rate (p less than 0.005); neither drug altered the mean ejection fraction (n = 20). Nisoldipine did not significantly alter diastolic filling parameters or ejection fraction (n = 10). Nisoldipine and digoxin were also assessed in congestive heart failure (New York Heart Association [NYHA] classes II and III) associated with ischemic heart disease (n = 26) (open parallel design). Neither produced significant alterations in peak filling rate and ejection fraction after 3 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise and redistribution thallium-201 imaging is commonly used for the detection and evaluation of left ventricular ischaemia and infarction. The right ventricle is frequently visualised after stress and sometimes on redistribution images. The visualisation of the right ventricle at rest is thought to be abnormal and is suggestive of pressure or volume overload of the right ventricle, either a result of pulmonary hypertension or secondary to left ventricular dysfunction. Using stress and delayed 201Tl imaging we have shown reversible left and right ventricular ischaemia and fixed left ventricular perfusion defects in two patients with multivessel coronary artery disease and left ventricular dyskinesia caused by prior myocardial infarction. Judging by the rarity of this finding as well as taking into consideration 201Tl kinetics, it is suggested that reversible right ventricular ischaemia after exercise may only be detected in patients with coronary artery disease who have severely compromised ventricular function. This finding may have therapeutic and prognostic significance.

The relation between heart rate and ischemic ST-segment depression was studied in 70 patients with documented obstructive coronary artery disease (CAD) and reproducible effort angina. Symptom-limited treadmill exercise testing was performed before and after a 2-week placebo period and 24-hour FM ambulatory electrocardiographic monitoring at the end of the placebo period. The means (+/- standard deviation) of the basal and placebo values for exercise time, heart rate and maximal ST-segment depression were: 6.4 +/- 2.6 minutes vs 6.9 +/- 2.8 minutes (difference not significant [NS]), 125 +/- 17 beats/min vs 125 +/- 19 beats/min (NS) and 2.3 +/- 0.8 mm vs 2.1 +/- 0.8 (NS), respectively. Ambulatory monitoring revealed 205 episodes of significant ST-segment depression (J + 80 ms; 49 episodes with more than 1 mm, 83 with more than 2 mm, 39 with more than 3 mm and 34 with more than 4 mm). Of all episodes of ST-segment depression, 130 (64%) were asymptomatic. The episodes lasted for 3 to 110 minutes. The maximal 24-hour ambulatory heart rate and ST-segment depression during ischemic episodes were expressed as a percentage of those seen during exercise-induced ischemia. When all ambulatory ischemic episodes (both symptomatic and asymptomatic) were compared with exercise-induced ischemic changes in the individual patient, there was little difference in heart rate (91 +/- 15% vs 90 +/- 18%, NS) but there was a greater magnitude of ST-segment depression (122 +/- 57% vs 104 +/- 52%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the role of collaterals in patients with effort angina we retrospectively compared the coronary cineangiograms of 14 subjects ("responders") who improved their exercise tolerance after acute nifedipine therapy with 14 subjects ("non-responders") with the same symptomatology who did not respond to the same treatment. The status of collaterals was graded with a score from a minimum of 0 to a maximum of 5. The responders showed a greater score than the non-responders (3 +/- 1 vs. 1 +/- 1, P less than 0.001), whereas there was no difference in the number of stenosed vessels between the two groups (1.8 +/- 0.9 vs. 2 +/- 0.8). Thus, in patients with effort angina and critical coronary stenosis, the presence of an efficient coronary collateral circulation can favour the increase in coronary flow reserve after vasodilator therapy. Our results suggest that the grading of collaterals may add useful information to the simple classification of one-, two- or three-vessel coronary artery disease.

To enhance diagnostic accuracy in coronary artery disease, cardiac cinefluoroscopy for the detection of coronary artery calcification was combined with exercise test and ambulatory ST-segment monitoring in 104 symptomatic patients before they underwent coronary angiography. In 44 patients with typical angina the combination of the three noninvasive tests and the exercise test alone both detected 92% of subjects with clinically important coronary artery disease. In 60 patients with atypical angina, the combination of the three noninvasive tests screened 77% of the subjects with clinically important coronary artery disease versus 43% after exercise test only (P less than 0.001). The exercise electrocardiogram was false negative in a substantial number of patients with atypical angina due to the presence of a good coronary reserve or to a daily circadian variation in the tone of the coronary arteries. Under these circumstances, cardiac cinefluoroscopy gave additional anatomic information to the physiological assessment of ischemia provided by the exercise test and ambulatory ST-segment monitoring. Our study suggests that the combination of cardiac cinefluoroscopy with other noninvasive tests may be particularly useful in screening atypically symptomatic populations.

In 15 patients with moderate congestive heart failure not completely controlled on digoxin (0.25 mg o.d.) and frusemide (25 mg o.d.), we compared the addition of captopril (12.5 to 50 mg b.i.d.) with increasing doses of frusemide (25 to 100 mg o.d.), in a randomized double-blind, double-dummy, comparative trial. Thirteen patients completed the 3 months study: two dropped-out in the frusemide group. Statistically significant clinical improvement occurred in both treatment groups. Exercise tolerance also significantly improved in both groups in a parallel fashion. Echocardiographic cardiac function data showed a significantly better pattern of changes in the captopril group. The addition of low doses of captopril to basal therapy seems to be as effective as the addition of high doses of frusemide in uncontrolled moderate congestive heart failure. This approach with captopril also appears to be more physiological and safe.

To investigate the mechanisms of ischemic arrhythmias during daily life, 32 patients with stable angina pectoris and documented ischemic episodes were studied by 24-hour ambulatory electrocardiographic monitoring. The severity of arrhythmias observed at or before peak ST-segment depression (early arrhythmias) and arrhythmias presenting during or after resolution of the ST-segment changes (late arrhythmias) was graded according to a modified Lown classification. Eleven patients (34%) had ischemic arrhythmias and had a greater number of ischemic episodes (6.0 +/- 5.4 vs 2.3 +/- 1.5, p less than 0.001) than patients without ischemic arrhythmias. Ischemic episodes accompanied by arrhythmias had a greater ST-segment depression (2.8 +/- 1.6 mm vs 1.9 +/- 0.6 mm, p less than 0.001), and duration (18.2 +/- 14.8 minutes vs 5.7 +/- 2.6 minutes, p less than 0.001) than those without arrhythmias. Ventricular tachycardia was observed in 3 patients during the early phase of ischemia and in 2 during or after recovery. Early but not late ventricular tachycardias were preceded by prodromal ventricular ectopic activity. Late arrhythmias were more frequent and severe than early arrhythmias, with an increased incidence of R-on-T ectopic complexes. In patients with stable angina, potentially life-threatening arrhythmias are closely associated with severe repetitive episodes of ischemia, and different mechanisms produce early and late arrhythmias. Prevention or reduction of the severity of ischemic episodes occurring during daily life in patients with stable angina may be more effective than prophylactic antiarrhythmic therapy.