Gualtiero Pelosi

In vivo quantitative ultrasonic evaluation of myocardial fibrosis in humans.

The aim of this study was to assess in vivo whether the regional ultrasonic reflectivity, evaluated by a real-time integrated backscatter analysis, was related to the local content of connective tissue in human myocardium as estimated by quantitative histology of endomyocardial biopsies. Sixteen patients with presumptive diagnosis of cardiomyopathy were ultrasonically studied by means of an M-mode-based echocardiographic system with quantitative integrated backscatter analysis capabilities. A 2.25-MHz transducer was used. The integrated value of the rectified radiofrequency signal of the interventricular septum was taken as integrated backscatter index and expressed in percent normalized for the pericardial interface (assumed to be 100%). All patients also underwent multiple left ventricular endomyocardial biopsies, which were stained with Massons trichrome and studied with the use of a computer-assisted image analysis system. The percent integrated backscatter index was significantly higher in the presence of connective tissue area greater than 20% (eight patients) versus less than 20% (eight patients): 51 +/- 25% versus 26 +/- 11%, p less than 0.05. A significant correlation (p less than 0.05, R = 0.55) was found between percent integrated backscatter index and percent connective tissue area. In vivo on-line quantitative ultrasound analysis is feasible in man and reliably identifies variations in the regional extent of fibrosis in human myocardium.

Myocardial Blood Flow Response to Pacing Tachycardia and to Dipyridamole Infusion in Patients With Dilated Cardiomyopathy Without Overt Heart Failure A Quantitative Assessment by Positron Emission Tomography

BACKGROUND Myocardial blood flow (MBF) impairment has been documented in advanced dilated cardiomyopathy (DCM) in which hemodynamic factors, secondary to severe ventricular dysfunction, may limit myocardial perfusion. To assess whether MBF impairment in DCM may also be present independent of hemodynamic factors, the present study was designed to quantify myocardial perfusion in patients with mild disease without overt heart failure. METHODS AND RESULTS Absolute regional MBF (milliliters per minute per gram) was measured by positron emission tomography and 13N-ammonia in resting conditions, during pacing-induced tachycardia, and after dipyridamole infusion (0.56 mg/kg over 4 minutes) in 22 DCM patients and in 13 healthy subjects. Patients were in New York Heart Association functional class I-II and showed depressed left ventricular (LV) ejection fraction by radionuclide angiography (35 +/- 8%; range, 21% to 48%), normal coronary angiography, and normal or moderately increased LV end-diastolic pressure (9.2 +/- 5.5 mm Hg; range, 2 to 20 mm Hg). There were no differences in arterial blood pressure, heart rate, and rate-pressure product between patients and control subjects in the three study conditions. Compared with control subjects, DCM patients had lower mean MBF at rest (0.80 +/- 0.25 versus 1.08 +/- 0.20 mL.min-1.g-1, P < .01), during atrial pacing tachycardia (1.21 +/- 0.59 versus 2.03 +/- 0.64 mL.min-1.g-1, P < .01), and after dipyridamole infusion (1.91 +/- 0.76 versus 3.78 +/- 0.86 mL.min-1.g-1, P < .01). LV MBF values were related to baseline LV end-diastolic pressure at rest (r = -.57, P < .01) and during pacing (r = -.67, P < .01) but not after dipyridamole infusion (r = .19, P = .40). Five patients had LV end-diastolic pressure > 12 mm Hg; in 4, myocardial perfusion was severely depressed both at baseline and in response to stress. CONCLUSIONS In patients with DCM without overt heart failure, myocardial perfusion is impaired both at rest and in response to vasodilating stimuli. The abnormalities in vasodilating capability can be present despite normal hemodynamics; progression of the disease is associated with more depressed myocardial perfusion.

In vivo radiofrequency-based ultrasonic tissue characterization of the atherosclerotic plaque.

Background and Purpose The ultrasonic image can offer unique information on the composition of atherosclerotic plaque, ie, the relative content of lipids, fibrous tissue, and calcific deposits. To date, however, the echographic assessment of plaque structure is based on a subjective, qualitative evaluation of the bidimensional images. We evaluated the feasibility and accuracy of assessing, in vivo, the acoustic properties of arterial carotid plaques by means of a suitably modified echographic apparatus allowing direct access to the radiofrequency signal. Methods In 15 patients undergoing carotid thromboendarterectomy, the ultrasonic findings in 70 discrete sites (within the plaque, n=54; normal sites, n=11; or intraluminal thrombi, n=5) were correlated with the histological analysis (hematoxylin-eosin and Mallory trichrome stains) independently performed on the arterial samples. The pathological examination was carried out at a similar level of the insonation; the sites analyzed within the plaque were chosen because of their uniform echoic characteristics. In each ultrasonic region of interest selected from the echographic image, the integrated amplitude of the rectified radiofrequency signal was measured as the integrated backscatter index. Results The intimal-medial layer of normal carotid wall (n=11) exhibited values of −32.5 ± 9.4 dB. The integrated backscatter index in fatty sites (n=11, −40.3 ± 5.4 dB) differed from that of fibrous (n=12, −23.8 ± 5.0 dB) and calcified (n=26, −11.5 ± 5.2 dB, P < .01 for all intergroup differences) sites. Intraluminal thrombotic sites (n=5, −42 ± 5.1 dB, P < .01) differed from fibrous and calcified subsets (P < .01) but overlapped (P=NS) with fatty sites. Histological sampling also showed two sites of intraplaque hemorrhage that exhibited very low backscatter values (−53 and −58 dB) and three fibrofatty sites showing backscatter values (−28, −28, and −32 dB) intermediate between the fibrous and the fatty subsets. Conclusions Quantitative analysis of integrated backscatter of the arterial wall is feasible in humans and provides an operator-independent assessment of plaque echoic structure. In particular, integrated backscatter is effective in distinguishing lipidic, fibrotic, and calcific components in human atherosclerotic plaques.

Myocardial vitamin E is consumed during cardiopulmonary bypass: indirect evidence of free radical generation in human ischemic heart

Although a role for free radicals in myocardial damage during cardiopulmonary bypass for open heart surgery has been postulated, direct evidence of free radical production as well as consumption of tissue antioxidants such as vitamin E is still lacking. Twenty patients (age 26-66 yr, mean 48) undergoing elective open heart surgery with moderate hypothermia, and cold crystalloid cardioplegia, were studied. Cardiopulmonary bypass time was 61.4 +/- 31.2 min. The specimens of atrial tissue collection before and after cardiopulmonary bypass, were immediately frozen in liquid nitrogen. Mean vitamin E atrial content, measured by reverse phase HPLC, was 355 +/- 249 pmol/mg of dry weight basally, 135 +/- 85 pmol/mg (p < 0.05) at the end of the ischemic period and 405 +/- 288 pmol/mg after the reperfusion period (p < 0.01). Microscopic examination of right atrial biopsies ruled out differences in fibrosis or cellular damage as the cause of vitamin E changes. Although a great basal variability in atrial vitamin E content was observed, which was independent of age, sex and clinical status, a reproducible and substantial decrease in atrial vitamin E content after cardiopulmonary bypass occurred (mean reduction 45 +/- 17% and 55 +/- 22%, respectively, after ischemia and after reperfusion). This was directly related to the aorta cross-clamping duration and partially to the minimum temperature achieved. In conclusion, apart from the great variability observed in basal vitamin E tissue content, vitamin E was always reduced during cardiopulmonary bypass, suggesting an oxidative stress on the myocardium during open heart surgery.

Thermal balance and dialysis hypotension.

Many Studies Have Confirmed Our Original Observation That Dialysate T Set At About 35° C Affords A Better Hemodynamic Protection Than The Standard Dialysate T Of 37-38° C. In This Review We Present Some New Data On The Hemodynamic Mechanism Of The Protective Effect Of Cold Dialysis On Blood Pressure. The Study Was Based On Serial Assessment Of The Percent Changes Occurring During Dialysis Treatment In Estimated Stroke Volume (Aortic Blood Flow Determined By Doppler Echocardiography), Blood Volume (Hemoglobinometry), Arterial Pressure (Dynamap), And Heart Rate (Ecg), From Which Cardiac Output (Co) Indexes And Total Peripheral Vascular Resistances (Tpvr) Were Derived. Of The 14 Pts Studied, 7 Showed A Drop In Mean Arterial Pressure (Map) Of 25° Or Greater During Standard Dialysis (Unstable Patients). Compared With The 7 Patients Having More Stable Intradialysis Map, Unstable Pts Showed Greater Reduction In Co Which Was Disproportionately Greater Than The Reduction In Blood Volume, And A Paradoxical Decrease In Tpvr, The Difference Being Highly Significant (P ≤ 0.01 For Both Changes). When Crossed-Over To Cold Dialysis, Along With A Significantly Lower Reduction In Map (P ≤ 0.01) The Unstable Pts Showed A Lower Decrease In Co Which Paralleled The Reduction In Blood Volume, And An Increase In Tpvr. These Changes Were Highly Significant (P ≤ 0.01). Data Suggest That Dialysis Hypotension Is Characterized By An Impaired Venous Return, Probably Due To The Peripheral Blood Pooling (Increased Ratio Between The ‘Unstressed’ And ‘Stressed’ Blood Volume) Associated With The Decrease In Tpvr. Exposure Of Extracorporeal Blood To Cold Dialysate Favours The Venous Return To The Heart By Increasing Tpvr And The ‘Stressed’ Blood Volume.

Glutathione depletion increases chemiluminescence emission and lipid peroxidation in the heart

Diamide, CDNB and phorone were used to deplete glutathione in retrogradely perfused rat hearts. Following glutathione depletion the spontaneous chemiluminescence increased by 70%, irrespective of the agent used. The glutathione depletion and the chemiluminescence emission were associated to an increase of malondialdehyde content in the heart, as determined by HPLC. Under these conditions the heart function was impaired and histological examination showed a coagulative myocytolysis, a pattern already described in human and experimental pathology, where a key role is attributed to a Ca2+ homeostasis impairment.

Increased ultra weak chemiluminescence emission from rat heart at postischemic reoxygenation: protective role of vitamin E

Aim of this study was to confirm an increased free radical generation rate during ischemia-reoxygenation, by ultra-weak chemiluminescence detection at the surface of perfused rat heart. We observed that reoxygenation following 30 min global ischemia, induces an increase of ultraweak chemiluminescence emission in isolated perfused heart only if partial depletion of vitamin E is induced by dietary manipulation. Moreover, in normal diet fed rats, vitamin E is partially consumed during global ischemia, but not during reoxygenation. Since chemiluminescence increases during post-ischemic reperfusion, when vitamin E myocardial content is lowered, the most probable free radicals involved are the hydroperoxyl radical derivatives of lipids. These radicals, indeed, are known both to produce photoemission by disproportion and to react with vitamin E. On the other hand, the nature of the reaction that consumes vitamin E during ischemia is still obscure. Accordingly, the basal level of vitamin E myocardial content seems to be a key factor for protecting the heart against reoxygenation injury and its consumption during ischemia could be a determinant of myocardial sensitivity to oxidative stress during reperfusion.

111In Platelet Scintigraphy for the Noninvasive Detection of Carotid Plaque Thrombosis

Background and Purpose— Thrombosis on atherosclerotic lesions in the large extracranial arteries is the main cause of embolization in the distal cerebral circulation and thus is involved in the pathogenesis of ischemic stroke. The assessment of biological characteristics of lesions that are predictive of thrombotic complications might help in stratification of the risk for stroke but is currently imperfect. Methods— We compared the performance of 111In-platelet scintigraphy with blood pool subtraction, ultrasound-based tissue texture analyses, and transcranial Doppler techniques in their ability to predict the occurrence of superficial thrombosis or the presence of a lipid pool in carotid artery plaque specimens removed at the time of carotid endarterectomy in 22 patients with unilateral carotid artery stenosis of >70%. Results— Positivity at 111In-platelet scintigraphy was present in 8 patients and correctly identified the presence of thrombosis superimposed on a complicated plaque. Neither tissue texture analysis nor emboli detection by transcranial Doppler, performed in 12 patients, significantly identified plaque thrombosis. None of the techniques used were able to detect the presence of a significant lipid pool inside the plaque. Conclusions— Indium-platelet scintigraphy is an accurate noninvasive diagnostic tool to detect thrombotic complications in carotid plaques. Prospective studies should assess its ultimate value in risk stratification, possibly to guide the decision of whether to perform endarterectomy in selected patient categories.

Release of Contracting Autacoids by Aortae of Normal and Atherosclerotic Rabbits

Summary: The aim of our study was to examine the release of various lipid and peptide contracting autacoids by aortae of normal and atherosclerotic rabbits. Leukotriene (LT) E4, an enzymatic derivative of LTC4, thromboxane (Tx) B2, and endothelin‐1 (ET‐1) were measured by radioimmunoassay techniques in aortic preparations of normal and cholesterol‐fed rabbits. Intact aortae of normal rabbits incubated with the calcium ionophore A23187 for 1 h at 37°C released LTE4 and TxB2 (22 ± 3.5 and 14.8 ± 2 pg/mg of tissue, respectively, mean ± SEM, n = 33). Removal of aortic endothelium was associated with a significant reduction in LTE4 (44%) and TxB2 (58%) release. In aortic preparations from cholesterol‐fed rabbits, the release of LTE4 was significantly enhanced (41 ± 8 pg/mg of tissue, mean ± SEM, n = 27) whereas TxB2 was not significantly altered. No detectable amounts of ET‐1 were measured after 1 h of incubation. However, at 4 h, an endothelium‐dependent release of ET‐1 from normal aortae was demonstrated. In atherosclerotic aortae, ET‐1 release was significantly higher than in controls (10 ± 1.3 vs. 5 ± 0.5 pg/cm2, mean ± SEM, n = 16). We conclude that enhanced formation of vasoconstrictor autacoids may contribute to altered vasomotion of atherosclerotic blood vessels.

Regional myocardial glucose utilization assessed by (14C) deoxyglucose

T h e ava i l ab i l i t y of l abe l l ed d e o x y g l u c o s e , a de pos i t t r ace r of g lucose m e t a b o l i s m , has r e c e n t l y m a d e p o s s i b l e to s t u d y the r e g i o n a l c a rbohy d ra te c o n s u m p t i o n in d i f f e ren t t i s sues . A c c o r d i n g to the m e t h o d f i rs t d e v e l o p e d b y Sokolof f e t al. (1) for the cen t r a l n e r v o u s sys tem, we a i m e d to assess g l uc ose u p t a k e in d i f f e ren t r e g i o n s of the hea r t b y a u t o r a d i o g r a p h i c d e t e c t i o n of 14C-deoxyglucose m y o c a r d i a l c o n c e n t r a t i o n . I n th i s s t u d y we d id n o t a t t e m p t to m e a s u r e a b s o l u t e g l u c o s e c o n s u m p t ion, b u t we l im i t ed our o b s e r v a t i o n to re la t ive d i f f e r ences in m y o c a r d i a l t r ace r c o n t e n t , 2 hrs f o l l owing its p e r i p h e r a l i n j ec t i on , w h e n d i s t r i b u t i o n was c o n s i d e r e d n o t to be f l o w d e p e n d e n t a n d 14C-DG w i t h i n the cell is a l m o s t c o m p l e t e l y c o n v e r t e d to ~4C-deoxyglucose-6-phospha te . F u r t h e r m o r e , in 2 e x p e r i m e n t s , r e g i o n a l m y o c a r d i a l b l o o d f low dist r i b u t i o n , by l abe l l ed m i c r o s p h e r e s , was a s s e s s e d t o g e t h e r w i t h r eg iona l g l u c o s e u p t a k e in o rder to co r re la t e m e t a b o l i c s u p p l y (flow) to c o n s u m p t i o n (14C-DG up t ake ) in t he s a m e m y o c a r d i a l r eg ions .