Enhanced sensitivity for detection of coronary artery disease by addition of atropine to dipyridamole echocardiography

Dipyridamole echocardiography test (DET) has gained acceptancedue to its safety, feasibility, diagnostic accuracy and prognosticpower. The main limitation of the test is a less than idealsensitivity in some patient subsets, such as those with limitedcoronary artery disease. Atropine with dipyridamole might theoreticallycombine to become a synergistic ischaemic stress test, by increasingmyocardial oxygen demand through chronotropic stress and byreducing flow supply through a shortening of the diastolic intervalunder maximal coronary vasodilation. The aim of this study wasto assess the effects of the addition of atropine to DET. Threehundred and twenty-one patients (age=58±9 years), referredfor testing in the echo lab, were initially studied by DET.Of these, 151 were stopped during or within the 2 min followingdipyridamole infusion because of achievement of a predeterminedend-point: obvious echocardiographic positivity (n = 137), severechest pain (n = 3), diagnostic ST segment changes (n = 7) orlimited side effects (n = 4). In another three cases, atropinewas not given due to a history of glaucoma or severe prostatichypertrophy. In the remaining 167 patients with a negative DETtest, atropine (0.25 mg intravenously, repeated every min upto a maximum of 1 mg, if necessary) was added, starting 3 minafter the end of the dipyridamole infusion. The dipyridamole-atropineecho test (DETA) was positive in 32 and negative in 135 patients,and no major side effects occurred in any patient. The peakheart rate was significantly higher during DETA than with DETalone (108±16 vs 86±14 beats . min^–1; P<0.0001).In the subset of 178 patients who were studied while not takingantianginal therapy, who had no prior myocardial infarctionor revascularization procedure and who underwent coronary catheterization,independently of the test results, coronary angiography showednormal coronary arteries in 48 patients and significant coronaryartery disease (CAD) ( 50% luminal reduction in at least onemajor coronary vessel by quantitative coronary arteriography)in 130 patients—with single-, double- and triple-vesseldisease in 56, 47 and 27 patients, respectively. The sensitivitywas 96/130 for DET and 110/130 for DETA (72 vs 85%, P<0.01)while the specflcity was 96% and 92% (P=ns), respectively. Theaddition of atropine to dipyridamole, which causes further chronotropicstress to the myocardium already challenged by flow maldistribution,is well tolerated and safe, and increases the sensitivity ofthe test for the detection of coronary artery disease with noloss in specificity.     

Dipyridamole-echocardiography test as a clue for assessing the organic 'ceiling' of individual coronary reserve

Twenty-four patients with a history of effort angina, a positiveexercise stress test (EST) and coronary artery disease wereenrolled in the study; 12 patientshada positive dipyridamole-echocardiographytest (DET) and 12 had a negative DET. Each patient performeda total of 4 ESTs in the absence of therapy on two successivedays; for each test the rate-pressure product (RPP), an establishedindex of my ocardial oxygen demand, was measured at the onsetof ischaemia (ST depression >0–15mV) or at the peakof maximal exercise (if a repeated EST was negative). Taking into account the lowest of the 4 RPP values ( x 1/100)in each patient, there was no significant difference betweenDET-negatives and DET-positives (185.2±49.3 vs 157.4±32.4).Conversely, when considering the highest of the 4 RPP valuesin each patient, there was a significant difference betweenDET-negatives and DET-positives (280.3 ± 63.9 vs 183.3± 37.0; p < 0.01). Thus, DET may provide a clinically useful tool for assessingin the individual the organic ’ceiling‘ of coronaryreserve, by eliminating the variability in coronary tone, whichmay affect EST reproducibility and the correct evaluation ofthe impairment of organic coronary reserve.     

Anomalous "VVI" Pacing of a Dual Chamber Pacemaker When Programmed in DDI(R) Mode

We describe the case of a dual chamber rate responsive pacemaker (Relay, model 294-03, Intermedics, Angleton, TX, USA) implanted in a 68-year-old male for sick sinus syndrome, which was not working properly when programmed in the DDIR mode, thus determining occasionally a sort of "VVI" pacing. However, the pacemaker performed well when programmed in the DDDR mode. We discovered that this was not a malfunction of a single device but rather a general behavior of this family of Intermedics dual chamber pacemakers (also not rate responsive), caused by a software problem.     

A short protocol for muscle MRI in children with muscular dystrophies

The use of muscle magnetic resonance imaging in patients with muscular dystrophies or congenital myopathies has been limited. We describe the development of a short protocol to be used in young patients with neuromuscular disorders. The protocol includes transverse T1-weighted spin echo sequence images of thighs and calves. The total scanning time is less than 30 minutes, and can be easily applied to patients over the age of 4 years without any need for sedation. Although only the leg muscles are imaged, the images obtained can still help to identify specific patterns of muscle involvement and provide additional help in the differential diagnosis of muscle disorders with overlapping clinical features.     

The Effects of Two Alkaloids Derived from Vinca Rosea on the Malignant Cells of Hodgkin's Disease, Lymphosarcoma and Acute Leukemia in Vivo

Hodgkin’s disease, lymphosarcoma, and acute leukemia have been studiedafter treatment with the Vinca rosea alkaloids (vinblastine and vincristine), inorder to demonstrate and evaluate the mitosis-arresting effects of the twodrugs on the malignant cells. Histologic sections, lymph node and bone marrow aspirations were performed immediately before and 24 hours after theintravenous administration of the drugs in 15 cases of Hodgkin’s disease, 12 oflymphoblastic lymphosarcoma, and 12 of acute leukemia, besides other miscellaneous cases.

In Hodgkin’s disease aspirates and sections showed a clear-cut metaphasearrest in the post-VLB specimens, chiefly affecting the pre-Sternberg or Hodgkin cells. This effect, besides corroborating the fundamentally stathmokineticmechanism of VLB in Hodgkin’s disease, was considered an additional factorin confirming the widely proposed conception that these cells represent thefundamentally proliferating and malignant tissue of this disease.

In the acute leukemias and lymphoblastosarcomas, cytomorphologic andquantitative studies demonstrated that the oncolytic effects correlated wellwith the magnitude of metaphasic blockade. It is postulated that only activelyproliferating cells—the so-called "growth fraction"—are the target for thesealkaloids.

Submitted on January 30, 1966 Accepted on June 26, 1966     

Plasma membrane fluidity in isolated rat hepatocytes: A comparative study using DPH and TMA-DPH as fluorescent probes

The study of membrane fluidity is a rapidly expanding field of research and its interest in hepatology has been stressed recently. The present study is the first report concerned with the determination of membrane fluidity of isolated rat hepatocytes. The data have been compared with those obtained in plasma membrane fractions and subfractions (basolateral or canalicular) derived from homogenates. The fluorescent probes used to measure the fluidity were diphenylhexatriene (DPH) a 'classical' probe, and its derivative trimethylammoniodiphenylhexatriene (TMA-DPH) at 25 degrees C and at 37 degrees C. The values obtained with DPH were lower than those with TMA-DPH, probably due to the localization of the probes in different regions of the phospholipid bilayer. In addition, DPH revealed significant differences in the fluorescence polarization values obtained in isolated hepatocytes compared with membrane fractions, which was in contrast to TMA-DPH, where the respective values were of the same order of magnitude. This behaviour is probably due to the mobility of DPH in the membrane core and its rapid internalization into the cell, whereas TMA-DPH remains anchored for a long time on the cell surface. These findings suggest that TMA-DPH is a better probe than DPH for measuring the fluorescence polarization of whole isolated hepatocytes and that the use of different probes might be of help in exploring different zones of the membrane bilayer.     

Muscle MRI findings in a three-generation family affected by Bethlem myopathy

We report clinical and muscle magnetic resonance imaging (MRI) findings in three individuals (aged 6, 26 and 73 years) from a three-generation family with Bethlem myopathy, confirmed by molecular genetic analysis which showed an exon skipping mutation in the COL6A1 gene. The clinical severity ranged from mild proximal weakness and distal laxity in the younger patients, to inability to stand or walk and severe contractures in the 76-year-old grandmother. The pattern of muscle involvement showed variable severity in parallel with the severity of motor function impairment. Although there was a marked variability in the severity of the MRI findings, it was possible to recognize a specific pattern of muscle involvement in all three patients. This consisted of involvement of the peripheral region of the vastus lateralis and hamstrings muscles with relative sparing of their central part. This was best appreciated in the third decade of life, but could also be identified both in the younger patient with minimal MRI changes and in the oldest patient, despite her more severe and diffuse muscle involvement. This report suggests that muscle MRI could be used as an additional tool to establish the pattern and the degree of muscle involvement in patients with Bethlem myopathy. Further studies in a larger cohort are needed to evaluate the specificity of these findings.     

Transthoracic Sensor for Noninvasive Assessment of Left Ventricular Contractility: Validation in A Minipig Model of Chronic Heart Failure

Background: Invasively measured left ventricular (LV) dP/dt is the accepted standard for measuring acute and chronic directional changes in LV contractility. Recently, we developed a noninvasive force sensor based on an accelerometer positioned on the chest, which measures the vibrations generated by isovolumic myocardial contraction. The aim of this paper was to compare noninvasive (accelerometer) versus invasive (LV dP/dt) indices of myocardial contractility in a chronic minipig model of pacing‐induced heart failure (HF). Comparative assessment was performed both at rest and following dobutamine infusion. Methods: In adult male minipigs (n = 6), LV contractility was simultaneously assessed both invasively (LV dP/dt, Millar catheter) and noninvasively (accelerometer) at rest and following dobutamine (up to 7.5 mcg/kg/min), both before and after development of HF by pacing the LV at 180 beats/min for 3 weeks. Results: Invasive and noninvasive assessments were obtained in 24 conditions (12 at rest and 12 after dobutamine infusion). Sensor‐based cardiac force changes were significantly related to positive peak LV dP/dt_max changes following dobutamine infusion both in normal (r = 0.88, P < 0.001) and failing heart (r = 0.89, P < 0.001). The force‐frequency relation showed a tight correlation between invasive and noninvasive assessment (r = 0.68, P = 0.02). Conclusions: The force‐frequency relation can be assessed noninvasively by a transthoracic sensor based on an accelerometer. The method can efficiently detect the development of resting dysfunction and the contractile reserve at different HF steps, with potential for wearable HF monitoring. (PACE 2010; 795–803)