PROGRESSIVE AXONOPATHY: AN INHERITED NEUROPATHY OF BOXER DOGS. AN IMMUNOCYTOCHEMICAL STUDY OF THE AXONAL CYTOSKELETON

The distribution of the major axonal cytoskeletal proteins has been determined in lumbar ventral roots and spinal cord of dogs with progressive axonopathy, an inherited neuropathy of boxer dogs. The three neurofilament proteins, and beta-tubulin, actin and fodrin were localized using immunocytochemistry. The majority of swollen axons in the nerve roots contained excessive, disorientated neurofilaments. In about 5% of such fibres the peripheral filaments in the axoplasm were orientated circumferentially and such zones were deficient in tubulin. Many, but not all, spheroids contained increased amounts of actin, often with internal areas of more intense staining. Similar findings were present in axonal swellings in the CNS, although their contents were more variable. The distribution of axonal fodrin in CNS and PNS appeared unaltered. The perikarya of many motor neurons in the spinal cord and brain stem contained phosphorylated neurofilaments. The results support previous suggestions that defects in slow axonal transport are involved in the pathogenesis of this disease.     

Effects of ketanserin on epicardial coronary arteries after coronary angioplasty in patients with stable angina

Previous studies have demonstrated the development of vasoconstrictionimmediately after percutanous coronary angioplasty (PTCA), distalto the dilated stenosis, presumably resulting from endothelialinjury. We have investigated the role of 5-HT₂ receptors inmediating vasomotor changes in proximal and distal coronarysegments and coronary stenoses, immediately after successfulPTCA in patients with chronic stable angina. We compared theeffects of the intracoronary infusion of 1 mg ketanserin (5-HT₂receptor antagonist) on proximal and distal coronary arterialsegments immediately after PTCA in both vessels subjected toPTCA and control vessels. Coronary diameters, before and afterangioplasty and after ketanserin administration, of proximaland distal segments and coronary stenoses were measured by computerizedquantitative coronary angiography (CAAS system) in 12 patients(10 male, two female; mean age 54 ±6 years) with stableangina subjected to PTCA. After coronary angioplasty, vasoconstrictionwas observed in the segment distal to the dilated stenosis butnot in the distal segments of control vessels ( – 0.12± 0.04 and – 0.02 ± 0.02 mm respectively,P<0.05). After ketanserin infusion significant dilatationwas found in the distal segments of both PTCA vessels and controlvessels, but the dilatation was greater in the PTCA vessels(P<0.05). No significant changes were found in the proximalsegments of either PTCA or control vessels, or at the PTCA site.In conclusion, the vasoconstriction distal to the site of PTCAis mediated, at least in part, via 5-HT₂ receptors.     

Vein plasma endothelin-1 and cyclic GMP increase during coronary angioplasty is related to myocardial ischaemia

Endothelin-1 and cyclic guanosine monophosphate (c-GMP) peripheralvein plasma levels increase during coronary angioplasty, butthe reason for this increase has not been elucidated. The purposeof this study was to investigate whether these changes are relatedto myocardial ischaemia, or to mechanical artery injury inducedduring the procedure. Thirty-two patients with stable anginapectoris and a single lesion were studied. They were aged 56±8 and were undergoing balloon angioplasty. Eight arterieswere totally occluded and 24 were partially occluded. Bloodsamples were drawn from a peripheral vein after coronary arteryengagement with the guiding catheter (baseline), after the firstballoon inflation, immediately after the end of the procedure,and 4 h later.In the total occlusion group endothelin-1 increasedby 7% (P ns), whereas in the partial occlusion group it increasedby 45% after the procedure (P<0.001). c-GMP in the partialocclusion group increased by 41% (P<0.001) after the procedurewhereas in the total occlusion group it increased by 5% (P ns).Thus, the increase in endothelin-1 and c-GMP peripheral veinplasma levels after coronary angioplasty is related to myocardialischaemia rather than to mechanical artery injury.     

Absence of Effects of Short-Term Estrogen Replacement Therapy on Resting and Exertional QT and QTc Dispersion in Postmenopausal Women with Coronary Artery Disease

Women, on average, have a longer QT interval on the electrocardiogram and are at higher risk of developing torsade de pointes from antiarrhythmic therapy than men. Although endogenous estrogen may play a role in these sex differences, the effect of estrogen replacement therapy has not been examined. Ten women, 65 ± 7 years of age, wit/i stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease (at least one ≥ 70%) stenosis were studied. All women had been postmenopausal for at least 1 year, and none had ever received hormone replacement therapy (HRT). The patients received standard dose HRT (0.625 mg/day oral conjugated estrogen) or matching placebo for 4 weeks in random order, with crossover after a 4-week washout period. Exercise testing using the standard Bruce protocol was performed at the end of the first and third months of the study. Antianginal medications remained unchanged throughout the study period. Compared to placebo, HRT caused a significant increase in plasma estradiol levels from 5.55 ± 1.66 to 31.11 ± 14.95 pg/mL (P = 0.001). QT and QTc, as well as QT and QTc dispersion, did not differ at rest and at peak exercise between the two exercise tests. Likewise, other test results, including angina score, exercise time, ST-T changes, blood pressure, heart rate, and double product were unchanged. Short-term HRT did not alter cardiac repolarization at rest and during exercise in postmenopausal women with known coronary disease.     

Short-term effects of atrial versus atrio-ventricular pacing on myocardial ischaemia in coronary artery disease patients

This investigation was undertaken to evaluate the effects ofshort-term atrial vs atrio-ventricular pacing on myocardialischaemia. The study was in two parts. In part one, 12 coronary arterydisease patients were studied to investigate the effects ofthe two pacing modes on angina pectoris, coronary sinus O₂ saturationand lactate. The two pacing modes were each applied for 5 minat 25 beats. min^–1 more than the maximum heart rate ofthe exercise test. Coronary sinus O₂ saturation and lactatewere estimated before and after pacing. In part two, 13 patientswith left anterior descending coronary artery disease were studiedto investigate the effects of the two pacing modes on coronaryflow reserve, using a Doppler catheter in the above mentionedbranch after the administration of 10 mg intracoronary papaverine.The pacing rate was 15 beats . min^–1 greater than theresting heart rate. Coronary sinus lactate and O₂ saturation changes were the sameand angina pectoris developed at about the same time from thebeginning of pacing under both modes. Coronary flow reservewas 2.1±0.7 during atrial pacing and 2.1±1.1 duringatrio-ventricular pacing (ns). It is concluded that short-term atrial and atrio-ventricularpacing have the same effects on myocardial ischaemia in coronaryartery disease patients.     

Left ventricular filling pattern in {beta}-thalassaemia major -- a Doppler echocardiographic study

The pattern of left ventricular filling was assessed by Dopplerechocardiography in 38 adult ß-thalassaemia majorpatients; 28 with normal (age 25.2±5.3 years) and 10with abnormal (age 24.5±8.8 years) left ventricular systolicfunction. The findings were compared with those obtained from38 age and sex matched normal individuals. In patients with normal left ventricular systolic function,peak flow velocity in early diastole was higher than in thecontrols (94±16 vs 79±12 cm. s^–1 P <0.001).The peak flow velocity in late diastole was also greater (60±18vs 46±9cm. s^–1 P <0.001) but the ratio betweenthe early and late (atrial) peaks was approximately the samein both groups (1.74±0.72 vs 1.70±0.30 There wasno difference in deceleration time and rate between the twogroups (152±32 vs 151±21 ms and 504±93vs 508±115 cm. s^–2 respectively). None of the patientshad atrial predominant left ventricular inflow pattern. In patients with congestive heart failure the peak flow velocityin early diastole was greater than in the controls (96±10vs 79±2 cm. s^–1 P < 0.001) while in late diastoleit was smaller (39±6 vs 44±2 cm. s^–1 P <0.05).The ratio between the early and late peaks was greater in thepatients than in the controls (2.5±0.35 vs 1.8±0.08,P <0.001). The deceleration time and rate were not significantlydifferent in the two groups (153±33 vs 152±17msand 617±219 vs 550±56 cm. s^–2 respectively),until the end stage of congestive heart failure. Thus, leftventricular filling pattern in ß-thalassaemia majorpatients with normal left ventricular systolic function, issimilar to that seen in conditions of an increased preload.Patterns compatible with abnormally prolonged relaxation orrestriction do not appear.     

Short-Term Atrioventricular Sequential Pacing Does Not Adversely Affect Collateral Blood Flow: A Study During Angioplasty

Altered sequence of ventricular activation sequence results in marked derangements in mechanical events. In the present study, we investigated the comparative effects of atrial and AV sequential pacing on collateral blood flow during angioplasty. Twenty-eight patients with stable angina and left anterior descending artery disease undergoing balloon angioplasty were studied. Collateral flow was determined during balloon inflation from the distal flow velocity of the ipsilateral artery (17 patients) or from the increase of the maximal diastolic blood flow velocity (Vc) of the contralateral artery (11 patients). Flow measurements were made using the Doppler flow guidewire. The relative resistance in the collateral vascular bed (RRj also was estimated in the latter group of patients. After the first balloon inflation, two similar consecutive balloon inflations were done under atrial and AV sequential pacing, at a rate of 15 beats/min higher than the sinus rate, in the absence ofvasoactive medication. One minute after the initiation of pacing, the second and third balloon inflations were begun and the pacing continued until the balloon inflations were completed. In the ipsilateral group, average peak velocity was 84.6 t 24.2 mm/s during atrial pacing and 82.7 ± 29.7 mm/s during AV sequential pacing (P = NS). In the contralateral group. Vc was l8%± 12% during atrial pacing and 17%± 14% during AV sequential pacing, and the RR was 4.5 ± 4.7 and 4.9 ± 6.4, respectively (both P = NS). The coronary wedge/mean blood pressure was similar during the two tested balloon inflations. Short-term AV sequential pacing at rest does not adversely affect collateral blood flow and resistance in patients with left anterior descending artery disease.     

A correlative study of Quantitative EMG and biopsy findings in 31 patients with myopathies

A direct correlation of QEMG with muscle biopsy findings might help delineate the sensitivity of QEMG in identifying muscle pathology as well as provide information on electrophysiological- histological correlations. In a study of 31 patients with a variety of myopathies we found that the sensitivity of QEMG was between 24 to 69% depending of the specific method of signal analysis. The positive predictive value of abnormal QEMG was more than 90% while its negative predictive value was only about 20%. Amplitude outlier analysis was superior especially in minimally weak muscles (MRC > 4) and was particularly sensitive at detecting increased variability in fiber size and more subtle myopathic changes.Key words: Quantitative electromyography, muscle biopsy, sensitivity     

The reactivity of the contralateral artery at the time of balloon dilation during coronary angioplasty

The response of the contralateral arteries was investigatedduring balloon angioplasty of the left anterior descending artery.Thirty patients were studied. Coronary arteriograms were obtainedat baseline, during maximal balloon inflation and at the endof the procedure. Luminal diameter was measured by a quantitativecoronary arteriography analysis system. During balloon inflationthe luminal diameter of the proximal segment of the right coronaryartery increased by 24 ± 6% (P<0·05), and thatof the left circumflex artery increased by 0·6 ±6% (P=ns). Both returned to near baseline values after angioplasty.in patients with increased collaterals during balloon inflationthe left circumflex proximal segment increased more significantlythan in patients with unchanged collaterals. The luminal diameterof the distal segment of the right coronary artery increasedby 9 ± 8% (P<0·001) and that of the left circumflexartery by 8 ± 11% (P<0·01) during balloon inflation,returning to near baseline values after angioplasty. Thus, vasodilation of the contralateral arteries during ballooninflation at the time of coronary angioplasty occurs mainlyin the distal segments and appears to be related to an increasein collateral filling.     

Importance of the Site of Ventricular Tachycardia Origin on Left Ventricular Hemodynamics in Humans

Experimental animal data have indicated that the site of ventricular tachycardia origin and, hence, the degree of asynchronous contraction, may influence the hemodynamic tolerance during sustained ventricular tachycardia. However, data in man are scarce. We studied patients with preserved left ventricular function and absence of significant coronary artery disease. Ventricular tachycardia was simulated with rapid pacing (at 120 and 150 beats/min), performed randomly, from the right ventricular apex or the right ventricular outflow tract. Following pacing from one site, it was repeated from the alternate site. Compared to outflow tract pacing, QRS duration was significantly longer during rapid pacing from the apex. Left ventricular pressure was recorded using a micromanometer-tipped catheter. During sinus rhythm, peak systolic pressure was 142 ± 14 mmHg: at 120 beats/min, it decreased to 109 ± 12 mmHg during pacing from the apex and to 127 ± 21 mmHg during pacing from the outflow tract (P = 0.008). This difference diminished at 150 beats/min (101 ± 16 mmHg vs 112 ± 16 mmHg, respectively, P = 0.21). During sinus rhythm end-diastolic pressure was 13 ± 1 mmHg, which did not change significantly during pacing at 120 beats/min. During pacing at 150 beats/min, end-diastolic pressure increased to 21 ± 3 mmHg during pacing from the apex and to 16 ± 2 mmHg during pacing from the outflow tract (P = 0.005). Changes in first derivative of pressure and in isovolumic relaxation time constant were comparable during pacing from the two sites. Thus, it seems that tachycardias originating from the right ventricular outflow tract result in more favorable left ventricular hemodynamics, compared to those from the right ventricular apex