Evidence of a correlation between pulmonary hypertension and collagen content in chronically overloaded human right atria.
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Publications and source records attributed to A M Calafiore.
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An imbalance between pro-oxidants and antioxidants is operative in atherosclerosis. Cigarette smoke is a major risk factor of atherosclerosis and has been reported to contain large amounts of oxidants. We assessed arterial (internal mammary artery) and plasma levels of vitamins E and C and lipid peroxides in 48 male patients, 24 smokers and 24 non-smokers, undergoing coronary bypass surgery. Lipid peroxidation was studied using fluorescent products of lipid peroxidation (FPLs). Tissue vitamins E and C levels were significantly lower and FPLs significantly higher in smokers than in non-smokers (P < 0.0006, 0.0005 and 0.0005, respectively). This pattern was associated with lower vitamin C and higher lipid peroxide plasma levels in smokers than in non-smokers (P < 0.0002 and 0.0005, respectively). Vitamins E and C plasma levels were strongly related to their tissue content both in smokers (r = 0.60, P < 0.005 and r = 0.57, P < 0.01) and in non-smokers (r = 0.42, P < 0.05 and r = 0.46, P < 0.05). Moreover, vitamin E content was significantly related to that of vitamin C only in the arterial tissue of both groups, pointing to the existence of a functional interaction between these antioxidants. In both groups, FPLs were significantly and inversely related to vitamin C in plasma and to vitamin E in tissue, suggesting the antioxidant primary of vitamin C and vitamin E in the plasma and arterial tissue compartments, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Intermittent antegrade warm blood cardioplegia has been used routinely at our institution over the last 3 years. We report here a comparison between the first 250 consecutive patients undergoing elective coronary artery bypass grafting in which intermittent antegrade warm blood cardioplegia was used (group A) and the last 250 consecutive patients who received intermittent antegrade cold blood cardioplegia, during bypass grafting (group B). There were no differences in sex, age, number of grafts, and functional status between the two groups; left ventricular ejection fraction was lower in group A. The overall mortality rate in group A was 0.8% versus 3.6% in group B (p < 0.05). There was no in-hospital mortality among high-risk patients (ejection fraction < or = 0.35) in group A (0/53) versus two deaths in group B (2/28) (p < 0.05). No patient in group A needed circulatory assistance; 4 patients in group B received intraaortic balloon pumping. Only 1 patient in group A required inotropic support versus 20 patients in group B (p < 0.0005), and 5 patients in group A received lidocaine hydrochloride for ventricular arrhythmias versus 18 in group B (p < 0.01). The rates of myocardial infarction and stroke were not different between the two groups. The peak concentration of the myocardial-specific isoenzyme of creatine kinase were higher in group B in absolute value (51 +/- 30 IU/L) than in Group A (38 +/- 38 IU/L) (p < 0.0005) and in percent of total creatine kinase (8.2% +/- 4.1% versus 6.2% +/- 2.9%, respectively).
BACKGROUND: The improving results with use of the radial artery and the inferior epigastric artery as coronary bypass conduits were analyzed to assess the suitability of these arteries for myocardial revascularization. METHODS: Both arteries were used in composite arterial conduits with an internal mammary artery as the blood source. The proximal anastomosis was always constructed before the initiation of cardiopulmonary bypass. From October 1991 to January 1995, 240 patients underwent myocardial revascularization using 163 radial arteries and 124 inferior epigastric arteries with one (224 instances) or both (two instances) internal mammary arteries as inflow conduits. Twenty-five saphenous veins were concomitantly used. There were 208 men and 32 women with a mean age of 60.8 +/- 8.6 years (range, 28 to 80 years). In 73 patients (30.4%), the operation was performed on an urgent basis, and in 11 (4.6%), it was a repeat operation. The mean left ventricular ejection fraction was 0.55 +/- 0.12, and in 21 patients (8.8%), it was less than 0.35. Of 681 distal anastomoses, 188 were constructed using the radial artery (35 double and one triple sequential anastomosis) and 125, using the inferior epigastric artery (one double sequential anastomosis). A mean of 3.0 arterial anastomoses per patient were constructed (3.1 anastomoses/patient including saphenous veins). Six patients (2.5%) underwent associated procedures: aortic valve replacement (2), carotid endarterectomy (2), mitral valve replacement (1), and aortic valve and ascending aorta replacement (1). Most of the inferior epigastric arteries were grafted on diagonal branches and most of the radial arteries, the circumflex territory. RESULTS: No deaths occurred in the operating room. Three patients (1.3%) died postoperatively, and 2 patients (0.8%) died 6 months after operation. At a mean follow-up of 18.5 +/- 10.4 months (range, 1 to 39 months), 227 patients (96.6%) were asymptomatic. The cumulative patency rate of the radial artery grafts was 93.1% and of the inferior epigastric artery grafts, 95.7%. CONCLUSIONS: Our data suggest that use of the RA and the IEA in composite conduits for myocardial revascularization is feasible. These arteries can be safely used when bilateral internal mammary artery or sequential internal mammary artery grafting is not advisable.
This study was designed to assess the effects of intermittent warm blood cardioplegia on myocardial energy metabolites, intracellular pH, and contractile function. The isolated blood-perfused pig hearts were divided into three groups. After 30 minutes of control perfusion, the hearts in group 1 (n = 10) received 90 minutes of continuous warm (37 degrees C) blood cardioplegia; the hearts in group 2 (n = 9) received six 5-minute periods of warm blood cardioplegia, interrupted by six 10-minute episodes of ischemia (37 degrees C). The hearts were then reperfused for 30 minutes. The hearts in group 3 underwent 150 minutes of control perfusion without cardioplegia or ischemic episodes. Phosphorus 31-nuclear magnetic resonance spectra showed that a 10-minute interruption of warm blood cardioplegia decreased phosphocreatine levels and intracellular pH by approximately 47% (p < 0.01) and 0.12 unit (p < 0.05), respectively, and increased inorganic phosphate levels by approximately 87%, whereas resumption of cardioplegia for 5 minutes resulted in almost 100% recovery of phosphocreatine and inorganic phosphate levels and intracellular pH. More important, subsequent interruptions did not result in any cumulative changes in phosphocreatine level, inorganic phosphate level, or intracellular pH beyond those changes observed after the initial cardioplegic interruption. Moreover, during reperfusion there were no significant differences in adenosine triphosphate and phosphocreatine levels among the three groups of hearts. Furthermore, hearts from groups 1 and 2 showed comparable recovery of contractile function. These results indicate that six 10-minute interruptions and six 5-minute restorations of warm blood cardioplegia caused only mild and reversible changes in myocardial energy metabolites and intracellular pH and these changes were not cumulative. This study suggests that antegrade intermittent warm blood cardioplegia may provide as much myocardial protection as does antegrade continuous warm blood cardioplegia in the normal heart.
The aim of this study was to compare the effect of intermittent antegrade warm blood cardioplegia and intermittent antegrade cold blood cardioplegia on myocardial metabolism and free radical generation of the ischemic-reperfused human myocardium. Thirty patients undergoing mitral valve procedures were randomly allocated to two groups: group 1 (15 patients) received warm blood cardioplegia and group 2 (15 patients), cold blood cardioplegia. Myocardial metabolism was assessed before aortic clamping, 1 minute after crossclamp removal, and after 20 minutes of reperfusion, by collecting blood simultaneously from the radial artery and coronary sinus. All samples were analyzed for lactate, creatine kinase, reduced and oxidized glutathione, ascorbic acid, fluorescent products of lipid peroxidation, and leukocyte activation (elastase). In all patients, early reperfusion was associated with significant coronary sinus lactate release. In group 2, but not in group 1, significant coronary sinus release of reduced and oxidized glutathione, fluorescent products of lipid peroxidation, and creatine kinase was also found; moreover, arterial-coronary sinus difference of ascorbic acid content was increased only in group 2, suggesting a transmyocardial consumption of this antioxidant vitamin. After 20 minutes of reperfusion, coronary sinus lactate release was no longer present in group 1, whereas significant production was still evident in group 2. In this group, significant coronary sinus release of fluorescent products of lipoperoxidation and reduced and oxidized glutathione was also observed at this time. No significant release of elastase from the coronary sinus was noted in the two groups throughout the study. The left ventricular stroke work index measured at the end of the study indicated a better functional recovery in group 1 than in group 2. In conclusion, intermittent antegrade warm blood cardioplegia protects the myocardium from ischemia-reperfusion injury better than intermittent antegrade cold blood cardioplegia; this phenomenon may be partly due to the decreased tissue oxidant burden mediated by intermittent warm blood cardioplegia.
Between July 1992 and May 1994, 148 patients (18 females) underwent myocardial revascularization with a radial artery (RA) graft. The left RA was used in 97.3% of cases. All but two patients received at least one additional arterial conduit: 137 left and 59 right internal mammary arteries (IMA); 23 inferior epigastric arteries; and 21 right gastroepiploic arteries. Total arterial revascularization was achieved in 127 patients (85.8%). An average of 3.0 anastomoses/patient were constructed, 2.8 of which were arterial. RA proximal anastomoses were placed on the IMA in 75% of cases, while direct anastomosis to the aorta (23.7%) or to a saphenous vein (1.3%) was performed in the remainder. When anastomosed to an IMA, the RA was subsequently infused intraluminally with 10 mg of papaverine (1 mg/mL). The target artery was the left anterior descending or one of its branches in 14.7% of cases, the circumflex system in 76.3%, and the native right coronary or one of its branches in the remaining 9%. An infusion of diltiazem (4 mg/hour) was started once the aorta was unclamped, and patients were maintained on oral diltiazem for 6 months postoperatively. Operative mortality was 1.4% (2 patients), with the additional late deaths from noncardiac causes. In one patient there was a prolonged serous drainage from the RA donor site. Of the 144 survivors 140 are asymptomatic. Follow-up angiography demonstrated 100% early patency (< 30 days, 41 patients), and 94% late patency (6 to 20 months, mean 14 months, 30/32 patients). This study suggests the RA can be used safely as an alternative to saphenous vein in coronary bypass surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
Degenerative aortic stenosis represents the most common form of aortic stenosis. The aim of this study was to evaluate the relationship between symptoms, valvular disease severity and prognosis. We studied the evolution of valvular aortic stenosis in 65 patients (39 males and 26 females, mean age 77.78 +/- 6.2 years) for a period of 7 years. All patients were submitted to accurate anamnestic examination, ECG, color Doppler echocardiography. Sixteen patients (26%) underwent cardiac catheterization. Associated diseases were: hypertension (45%), diabetes (40%), dyslipidemia (29%), chronic obstructive lung disease (6%). In 64% patients, the diagnosis of aortic stenosis was made after symptoms onset, and in 36% was occasional. Mean age at symptoms onset was 70 +/- 17 years: dispnoea was present in 81%, chest pain in 32%, and syncope in 8%. At the beginning of the follow-up, echocardiography showed, aortic stenosis to be mild in 21.73%, moderate in 60.8% and severe in 17.4%. At the end of the follow-up, mild stenosis was present in 9.5%, moderate in 38.7%, and severe in 51.8%. At entry, 56.6% had pure aortic stenosis, 34.78% had steno-insufficiency and 8.7 had an associated mitral valve insufficiency. At the end of the follow-up pure aortic stenosis was present in 17%, steno-insufficiency in 40%, and associated mitral valve insufficiency in 4.3%. Surgery was performed in 21% of the patients (77% valve replacement and 23% valve replacement and aortocoronary bypass). The mortality, at the end of the follow-up, was 31%. Causes of death were: heart failure (61%), arrhythmias (23%), and surgical complications (16%).(ABSTRACT TRUNCATED AT 250 WORDS)
In 20 patients receiving cold crystalloid cardioplegia (n = 10) or cold blood cardioplegia (n = 10) during elective coronary artery bypass grafting, the atrial myocardium was tested for glutathione-related antioxidant defenses and lipid peroxidation. In both groups, ischemia and reperfusion induced a significant increase in lipid peroxidation values (p < 0.05) that was associated with a depression of nonprotein thiol compound levels (p < 0.05). Compared with the cold crystalloid cardioplegia-treated patients, the cold blood cardioplegia-treated patients showed a lower lipid peroxidation (p < 0.05) and higher values of nonprotein thiol compounds (p < 0.05). Moreover, a significant ischemia and reperfusion-dependent activation of glutathione transferase was observed only in the cold crystalloid cardioplegia-treated patients. Selenium-dependent glutathione peroxidase and glutathione reductase activities did not change after release of the aortic cross-clamp and did not differ between the two groups. The highest postoperative plasma level of the myocardial-specific isoenzyme of creatine kinase was significantly more elevated in the cold crystalloid cardioplegia patients. Overall, these tissue biochemical features indicate a lower oxidant burden in the myocardium of cold blood cardioplegia-treated patients, a finding suggesting superior protection for the ischemic and reperfused human myocardium also through antioxidant-type mechanisms, apparently medicated by the antioxidant capacity of erythrocytes and specific plasma molecules.
From October 1991 to May 1993, 130 patients were submitted to myocardial revascularization using complex preformed arterial conduits. The age ranged from 29 to 75 years (mean age, 60.1 years); 121 patients were male. One hundred twenty-six patients had double- or triple-vessel disease. The mean ejection fraction was 0.53 (range, 0.22 to 0.79); only 6 patients had an ejection fraction less than 0.35. In 6 cases the procedure was a reoperation. We used 360 arterial conduits, 163 of which as free grafts (3 left internal mammary arteries, 16 right internal mammary arteries, 86 inferior epigastric arteries, 57 radial arteries, and 1 right gastroepiploic artery). One hundred fifty-four free grafts were anastomosed to one or both internal mammary arteries and one to a radial artery. We constructed 136 complex arterial conduits (branched, lengthened, or both). In 6 cases a double arterial system had to be used in a single patient. There was no operative mortality, and no inotropic or mechanical supports were used. The overall mortality rate was 1.5%. Early angiographic controls (between the 7th and 15th postoperative days) demonstrated 100% patency; late angiographic controls (at a mean interval of 9.5 months after operation) documented a mean patency rate ranging from 94.1% of the radial arteries to 100% of the left internal mammary arteries and right gastroepiploic arteries. At a mean follow-up of 7.2 months (range, 1 to 15 months) all patients are alive without recurrence of symptoms.
Intermittent antegrade warm blood cardioplegia (IAWBC) is a not usual technique of myocardial protection. We propose a delivery protocol that standardizes the length of ischemic intervals, duration of each cardioplegic dose and K+ amount. Cardioplegia is represented by blood, taken from the oxygenator and injected directly into the aortic root, and K+, added by means of a syringe pump. We reviewed the first 300 patients who underwent elective or urgent coronary artery by-pass procedures (group A) and compared them with the last 300 patients operated on with intermittent antegrade cold crystalloid cardioplegia (group B). The overall mortality in group A was lower than in group B (0.7 vs 3.0, p < 0.05); there was no in-hospital death in patients with poor left ventricle (LVEF < 35%) in group A (0/64 vs 3/39, p < 0.025). Reduction of mortality was due to a drastic fall of morbidity. In group A no patients needed circulatory assistance (13 in group B, p < 0.0005) or intraaortic balloon pumping (9 in group B, p < 0.005) in operating room or in intensive care unit (ICU); only 1 patient had inotropic drug (29 in group B, p < 0.0005) and only 6 needed lignocaine infusion (27 in group B, p < 0.0005). Incidence of postoperative myocardial infarction was lower in group A (4 vs 9 in group B) as well cerebrovascular accidents (4 vs 10 in group B), but difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
In 31 male patients undergoing coronary bypass surgery who underwent different periods of cardioplegic hypothermic arrest, the activities of glutathione peroxidase, glutathione reductase, glutathione transferase, copper/zinc-containing and manganese-containing superoxide dismutases, and catalase were studied in the right atrial myocardium, before and 5 minutes after aortic cross-clamping. The levels of thiobarbituric acid reactive substances (TBARS) and nonproteic thiol compounds (NP-SH) were also assessed. Prolonged ischemia followed by reperfusion induced activation of the major myocardial antioxidant enzymes with marked NP-SH depression and TBARS increase, despite cold crystalloid cardioplegic protection. These changes were significantly related to the duration of the ischemic arrest, suggesting: (1) that reperfusion free radical generation is dependent on the severity of the previous ischemic period; and (2) the occurrence of myocardial oxidative stress during cardiopulmonary bypass.
In the progression from myocardial hypertrophy to heart failure, abnormalities in the interstitial space of the heart seem to play a critical role. The formation of an extracellular oedema and the alterations in coronary subendocardial perfusion are associated with the development of interstitial fibrosis. Cardiac experimental studies documented the presence of augmented interstitial fluid volume and pressure and a subsequent remodelling of the fibrillar network of the extracellular space of the myocardium during the phases of the cardiovascular response to a sudden overload. Variations of the Starling's forces balance caused by enhanced endothelial permeability or due to an impairment of cardiac lymphatic drainage may contribute to the development of an acute heart failure. During stable hyperfunction, the organization of a chronic oedema should account for interstitial changes in the hypertrophic myocardium. Reactive fibrosis seems to be under hormonal control. The activation of the renin-angiotensin-aldosterone system is responsible for interfascicular and intercellular accumulation of fibrillar collagen within the cardiac interstitium. Perivascular fibrosis in the subendocardium may impair intramyocardial distribution of coronary flow. When an inadequate hypertrophy occurs, because of an elevation in ventricular wall stress, myocardial oxygen consumption rises and this may lead to the exhaustion of coronary blood flow reserve in the subendocardial layers. This underperfusion may be responsible for the development of myocardial ischemia. Coronary hemodynamic changes in the microcirculation as those prompted by interstitial alterations may contribute to the onset of myocyte necrosis and to the formation of restorative fibrosis. The progressive mechanical overload of the spared hypertrophied myocytes could explain the initiation of a positive feedback mechanism which perpetuates endomyocardial perfusion impairment, interstitial oedema and remodelling, finally, causing myocyte deaths and fibrous tissue proliferation. These structural alterations and their pathophysiological counterparts appear to be closely related to the evolution from compensatory hypertrophy to chronic myocardial failure in hypertrophic heart disease.
The relation among glutathione-related enzyme activities, thiobarbituric acid-reactive substances of the human aorta and internal mammary artery, and serum lipids was studied in 40 male patients undergoing coronary revascularization. Glutathione peroxidase and glutathione reductase activities were significantly higher in the internal mammary artery, whereas glutathione transferase activity was elevated in the aortic wall. Moreover, non-selenium-dependent glutathione peroxidase activity was detectable only in the aorta. The levels of thiobarbituric acid-reactive substances were significantly higher in the aorta. A positive correlation was found among the activity of glutathione peroxidase, glutathione reductase, and thiobarbituric acid-reactive substances in the internal mammary artery and total cholesterol, low density lipoprotein cholesterol, and triglycerides. In the aortic wall, a positive correlation among the activity of glutathione peroxidase, glutathione transferase, thiobarbituric acid-reactive substances, and the previously mentioned serum lipids was evident. In contrast, high density lipoprotein cholesterol was inversely related to enzymatic activities and thiobarbituric acid-reactive substances in both the internal mammary artery and aorta. In conclusion, significant differences in the levels of glutathione-related enzyme activities and thiobarbituric acid-reactive substances in the internal mammary artery and aorta were found, suggesting a different ability of the two tissues to counteract oxidative stress: the glutathione-related antioxidant properties and the level of lipid peroxidation in the arterial tissue seem to be specifically influenced by serum lipids.
The authors report a case of non traumatic dissection of the left extracranial internal carotid artery. Their main topics deal with the clinical-diagnostic aspects and the therapeutic approaches adopted, compared with the specific literature's most recent data. In addition they have discussed--some--investigations aimed at the best follow-up of those diseases.
The continuous exposure to blood components, including prooxidants, makes the blood vessel wall susceptible to oxidative stress and free radical mediated reactions (Henning and Chow, 1988; Stamm et al., 1989; Halliwell and Gutteridge, 1984). Free radicals can be produced extracellularly via the respiratory bursts of activated neutrophils, or intracellularly, via oxidation of hypoxanthine by xanthine oxidase (Henning and Chow, 1988; Stamm et al., 1989; Rubanyi, 1988). Microsomal enzymes such as lipoxygenase and cyclooxygenase may also be a source of reactive species of oxygen (Henning and Chow, 1988; Stamm et al., 1989; Rubanyi, 1988; Mason et al., 1980). It has been proposed that free radicals are involved in the initiation and progression of various cardiovascular diseases including arteriosclerosis (Henning and Chow, 1988; Stamm et al., 1989; Yagi, 1988; Jürgens et al., 1987). Thus the adequacy of the defence systems against free radicals is critical for the susceptibility of blood vessel wall to oxidative damage. Among the enzymatic systems capable of protecting the cell against oxidative injury, selenium dependent glutathione peroxidase (Se-GSH-px), glutatione reductase (GSSG-rx) and glutathione transferase (GST) play a crucial role (Flohe' et al., 1976; Mannervik and Danielson, 1988). Using glutathione (GSH) as a cofactor, Se-GSH-px reduces H2O2 to water and organic hydroperoxides to the corresponding alcohols (Flohe' et al., 1976). This reaction leads to conversion of GSH into its oxidized form (GSSG). In the presence of NADPH, GSSG-rx is able to reduce the oxidized glutathione.(ABSTRACT TRUNCATED AT 250 WORDS)
The activities of glutathione peroxidase (GSH-px), glutathione reductase (GSSG-rx) and glutathione transferase (GST) were measured in myocardial specimens obtained from right atria of patients subjected to different period of ischaemic arrest (aortic clamping ranging from 10 min to 90 min) followed by 60 min. of reperfusion, during open heart surgery 41-90 min. period of aortic clamping induced a significant increase of GSH-px activity with both H2O2 (p less than 0.05) and cumene hydroperoxide (p less than 0.025) as substrates when compared with baseline levels. Aortic clamping and reperfusion, however did not significantly change the myocardial activities of glutathione transferase and glutathione reductase. It is suggested that the increase of GSH-px in ischaemic-reperfused human hearts may render the myocardium less susceptible to oxidative attack particularly during the reoxygenation period when the level of active oxygen species is greatly elevated.
We report a case of a 49 year-old woman suffering from severe aortic regurgitation due to Takayasu's disease involving the ascending and abdominal aorta and the brachial arteries. The patient was managed successfully with aortic valve replacement. Considering the Literature data, the pathogenesis of the aortic insufficiency and the main surgical and anaesthesiologic problems related to the Takayasu's disease are discussed.