Gianluca Polvani

Protectant activity of hexarelin or growth hormone against postischemic ventricular dysfunction in hearts from aged rats.

The ability of hexarelin, a recently synthesized hexapeptide with a strong growth hormone (GH)-releasing activity, or of GH itself to display a protectant activity against postischemic ventricular dysfunction in senescent hearts was studied in 24-month-old male rats. Heart preparations from control (saline-treated) senescent rats, subjected to moderate ischemia, showed at reperfusion: (a) a low recovery of postischemic left ventricular developed pressure (LVDP; 37% of the preischemic values; from 90 +/- 5.7 to 33.5 +/- 3.8 mm Hg; p < 0.01; n = 10) coupled to a substantial increase in coronary perfusion pressure (CPP; 71% over baseline; from 68.3 +/- 5.2 to 116.8 +/- 4.6 mm Hg; p < 0.01; n = 10); (b) a marked increase of creatine kinase (CK) released in the perfusates (6.6-fold increase over preischemic values; from 45 +/- 4 to 298 +/- 25 mU/min/g wet tissue; p < 0.001; n = 10). In vivo administration of hexarelin (80 microg/kg, b.i.d., s.c.) for 21 days resulted in a striking heart protection against reperfusion stunning. In fact, the recovery of LVDP at reperfusion was almost complete (90% of the preischemic values; from 93 +/- 5.8 to 83.7 +/- 5.9 mm Hg; p > 0.05; n = 9), and the increase in coronary resistance was minimal (from 67 +/- 5.8 to 79.7 +/- 6.9 mm Hg; p > 0.05; n = 9). Furthermore, the concentration of CK in the perfusates was increased only twofold (from 45.8 +/- 5.5 to 90 +/- 7.2 mU/min/g wet tissue; p < 0.05; n = 9), with a gradual return toward basal values at the end of reperfusion. The protectant activity of hexarelin was divorced from any detectable alteration of the somatotropic function, as assessed by pituitary GH messenger RNA (mRNA) and plasma insulin-like growth factor I levels. In vivo administration of GH (400 microg/kg b.i.d., s.c.) for the same time lapse resulted in only a partial protectant activity: 55% of LVDP recovery (from 91.5 +/- 6.2 to 50 +/- 3.5 mm Hg; p < 0.01; n = 6); 65% increase of coronary resistance (from 68 +/- 4.3 to 112.2 +/- 5.2 mm Hg; p < 0.01; n = 6); 5.3-fold increase of CK concentrations in heart perfusates on reperfusion (from 43.8 +/- 3.8 to 232 +/- 16 mU/min/g wet tissue; p < 0.001; n = 6). Evaluation of the rate of release of 6-keto-prostaglandin F1alpha (PGF1alpha), the stable metabolite of prostacyclin, in heart perfusates, and assessment of the vasopressor activity of angiotensin II on the coronary vasculature, did not show any change in these parameters among the three experimental groups. Collectively these data indicate that hexarelin displays a strong heart-protectant activity against myocardial stunning in senescent rats. The protection afforded by the peptide is likely due to a direct cardiotropic action and is far greater than that of GH. Neither compound appears able to interfere with the endothelium-dependent relaxant mechanism.

The radial artery: which place in coronary operation?

Previous long-term studies have shown unsatisfactory patency of saphenous vein grafts, compared with internal mammary artery grafts. Recently, the use of the radial artery as a coronary artery bypass graft has enjoyed a revival, on the basis of the belief that it will help improving long-term results of coronary operations. The recent report of encouraging 5-year patency rates, supports its continued use as a bypass graft. In this paper, we review the current knowledge about the radial artery as a bypass graft, with special emphasis on the clinical results.

Lack of Association Between Serum Immunoreactivity and Chlamydia pneumoniae Detection in the Human Aortic Wall

Background—Only a few studies have focused the attention on the relation between elevated anti–Chlamydia pneumoniae (CP) antibodies and the detection of CP in the arterial wall. The aim of our study is thus to investigate the relationship between immune response to CP and detection of CP in the aortic walls of patients with abdominal aortic aneurysm. Methods and Results—A specimen of aortic wall was obtained from 102 consecutive patients who underwent abdominal aneurysm repair. The possible presence of CP was studied by polymerase chain reaction and confirmed by nonradioactive DNA hybridization. Antibody response to CP was studied (IgG, IgA titers). We found 33 patients (32.4%) with CP DNA+. No correlation between CP DNA detection and antibody titers was found (IgG P =0.52, IgA P =0.66). High correlation between IgG and IgA titer was observed (P <0.01). Endovascular presence of CP and antibody titers was not related to the age of the patient. Conclusions—CP antibody titers are not associated with the presence of CP in the aortic wall of patients with abdominal aortic aneurysm.

Determinants of Early and Late Outcome after Surgery for Type A Aortic Dissection

AbstractThe aim of this study was to identify the most important variables associated with early and late mortality in patients operated on for type A aortic dissection over a 15-year period. From January 1984 to March 1999, 110 patients underwent surgery for type A aortic dissection. The 88.1% of patients had an acute type A dissection (AD) and 11.8% had a chronic dissection (CD). Cardiac tamponade and shock occurred in 21.8% and 14.5% of the patients, respectively. The location of the primary intimal tear was in the ascending aorta in 70.9% of cases, in the arch in 17.2%, and in the descending aorta in 7.2%. Univariate and multivariate analyses were conducted to identify non-embolic variables independently correlated to in-hospital death. Kaplan-Meier and Cox regression analyses and hazard function for death risk were used to analyze factors influencing overall and surgical survival. The overall in-hospital mortality rate was 20.9% (23/110 patients), being 9% for CD and 21.6% for AD. Emergent procedures had an in-hospital mortality rate of 47.6%, whereas nonemergent operations had an in-hospital mortality rate of 13.7% (p < 0.01). Univariate analysis revealed 41 preoperative and operative variables, including age (years), age >70 years, remote myocardial infarction, cerebrovascular dysfunction, diabetes, preoperative renal failure, shock, cardiopulmonary bypass time (minutes), emergency operation, as factors associated to in-hospital death (p < 0.05). Stepwise logistic regression analysis for in-hospital death selected as independent predicting variables (p < 0.05) remote myocardial infarction [p = 0.006, odds ratio (OR) = 1.9], preoperative renal failure (p = 0.031; OR = 0.8), shock (p = 0.001; OR = 3.1), and age >70 years (p = 0.007; OR = 1.7). Follow-up ranged from 9 to 172 months (median 78 months), with Kaplan-Meier survivals for all the patients and hospital survivors of 42% and 54% at 10 years, respectively. Cox regression analysis has identified postoperative stroke [relative risk (RR) = 3.7; p = 0.012), intimal tear in the aortic arch (RR = 2.3; p = 0.036), and postoperative renal failure (RR = 4.5; p = 0.007) as independent predictors of reduced survival at follow-up. When this kind of analysis was performed on hospital survivors only, preoperative renal dysfunction (RR = 1; p = 0.013), reoperation (RR = 1.7; p = 0.004) and intimal tear in the aortic arch (RR = 1.2; p = 0.002) emerged as risk factors. The actuarial freedom from reoperation was 85.4% at 5 years. Multiple factors still influence early and late survival after surgery for type A aortic dissection. Preoperative renal impairment both affects early and late outcome. Early postoperative course affects late outcome in hospital survivors. The presence of the intimal tear in the aortic arch has a negative impact on late survival.

Minimally invasive direct coronary artery bypass grafting: midterm results and quality of life

BACKGROUND There is increasing interest in minimally invasive direct coronary artery bypass grafting (MID-CABG); however, there is still little information about midterm results and postoperative quality of life. METHODS From March 1995 to March 1998, 64 patients underwent MIDCABG at our hospital. Their mean age was 60+/-9.5 years; 22 (34.4%) had unstable angina. All patients were followed-up by both direct visit and questionnaire to assess the postoperative quality of life. RESULTS There were no perioperative deaths nor conversions to sternotomy; the perioperative myocardial infarction rate was 1/64 (1.6%). Predischarge angiography showed overall and unobstructed patency rates of 96.8% (62 of 64) and 93.8% (60 of 64), respectively. At follow-up (25+/-11.4 months) actuarial survival was 100%, and survival free of myocardial infarction was 98.4%+/-1.6% at 3 years. Both the Physical Activity Score and the Psychological General Well-being Index improved significantly after the operation, with percentage improvements of 31% and 23%, respectively, at 12 months postoperatively. CONCLUSIONS In selected patients MIDCABG can be a reliable and safe option. Patients who undergo this procedure are free of major complications and enjoy a good quality of life after surgery.

Experimental Tracheal Transplantation Using a Cryopreserved Aortic Allograft

Background: The tracheal reconstruction after wide resections remains a critical surgical problem. Our aim was to replace trachea with a tissue easy to vascularize, which allows a simple reconstruction and does not require an immunosuppressive regimen. Materials and Methods: A segment of cryopreserved aorta was used in order to verify its adequacy as tracheal substitute. In phase 1, the thoracic aorta of 10 rabbits was excised, obtaining 20 segments that were cryopreserved. Ten segments were implanted in the omentum of 10 rabbits that were sacrificed on postoperative days 7, 14 and 21, and the grafts were examined histologically. In phase 2, a segment of cryopreserved aorta arranged with a silicone prosthesis was transplanted in 10 rabbits and wrapped with omentum. The animals were sacrificed on postoperative days 7, 14 and 21. Results: In phase 1, the neovascularization of the grafts was present after 7 days, and after 14 days the fibroblasts invaded the lumen of the aorta. In phase 2, 8 rabbits survived and the histologic examination after 7, 14 and 21 days showed neovascularization, the absence of rejection and the proliferation of fibroblasts inside the lumen of the aorta; this growth has been restrained by an endoluminal prosthesis. Conclusions: Our study demonstrated that replacing the trachea with cryopreserved aorta is technically feasible and does not evoke immunologic reactions. It requires, however, a silicone tube inside the allograft to limit the colonization of fibroblasts.

Ectopic Thyroid Tissue in the Ventricular Outflow Tract: Embryologic Implications

The case of a 66-year-old female patient with a tumor located in the right ventricular outflow tract is reported. Histologic examination of an intraoperative biopsy revealed that the tumor was an intracardiac ectopic thyroid. We performed conservative surgery with partial resection of the mass. After 5 years, the patient is asymptomatic and leading a normal life. The authors examine the relation between the embryologic development of the primitive heart and the thyroid primordium and suggest the hypothesis of ectopic thyroid location in the right- or left-ventricular outflow tract.

Oxygen metabolism during and after cardiac surgery: role of CPB

BACKGROUND Cardiopulmonary bypass (CPB) has been reported to increase oxygen metabolism and to influence the relation between oxygen consumption (VO(2)) and delivery (DO(2)) in the early hours after cardiac surgery. To investigate the role of CPB, we studied oxygen metabolism in coronary artery bypass procedures performed on-pump (CABG) and off-pump (OPCAB). METHODS Twenty-five patients were randomized to undergo CABG (n = 14) or OPCAB (n = 11). All patients received the same anesthetic management. Oxygen metabolism variables were assessed before induction of anesthesia and up to 18-hours after surgery. RESULTS At baseline, before induction of anesthesia, there were no differences between CABG and OPCAB in oxygen consumption (VO(2)), delivery (DO(2)), or extraction (ExO(2)). After surgery VO(2) and ExO(2) increased in both groups, while DO(2) decreased. No significant differences between CABG and OPCAB were detected in postoperative VO(2), DO(2), and ExO(2) levels. The relation between VO(2) and DO(2) was very similar in CABG and OPCAB patients throughout the study, and no significant differences were detected in slopes and intercepts of the regression lines between CABG and OPCAB at all time points. There was, however, a significant effect of time on the relation between VO(2) and DO(2): this relation was stronger in the postoperative period, and the slope of this relation increased over time as well. CONCLUSIONS A hypermetabolic state and progressive and significant increases in the strength of the relationship between VO(2) and DO(2) and in the slope of this relationship occur after both CABG and OPCAB. Cardiopulmonary bypass is not responsible for these changes in oxygen metabolism.

Adventitial vessel growth and progenitor cells activation in an ex vivo culture system mimicking human saphenous vein wall strain after coronary artery bypass grafting

Saphenous vein graft disease is a timely problem in coronary artery bypass grafting. Indeed, after exposure of the vein to arterial blood flow, a progressive modification in the wall begins, due to proliferation of smooth muscle cells in the intima. As a consequence, the graft progressively occludes and this leads to recurrent ischemia. In the present study we employed a novel ex vivo culture system to assess the biological effects of arterial-like pressure on the human saphenous vein structure and physiology, and to compare the results to those achieved in the presence of a constant low pressure and flow mimicking the physiologic vein perfusion. While under both conditions we found an activation of Matrix Metallo-Proteases 2/9 and of microRNAs-21/146a/221, a specific effect of the arterial-like pressure was observed. This consisted in a marked geometrical remodeling, in the suppression of Tissue Inhibitor of Metallo-Protease-1, in the enhanced expression of TGF-β1 and BMP-2 mRNAs and, finally, in the upregulation of microRNAs-138/200b/200c. In addition, the veins exposed to arterial-like pressure showed an increase in the density of the adventitial vasa vasorum and of cells co-expressing NG2, CD44 and SM22α markers in the adventitia. Cells with nuclear expression of Sox-10, a transcription factor characterizing multipotent vascular stem cells, were finally found in adventitial vessels. Our findings suggest, for the first time, a role of arterial-like wall strain in the activation of pro-pathologic pathways resulting in adventitial vessels growth, activation of vasa vasorum cells, and upregulation of specific gene products associated to vascular remodeling and inflammation.

Do Women Currently Receive the Same Standard of Care in Coronary Artery Bypass Graft Procedures as Men? A Propensity Analysis

BACKGROUND The purpose of this study was to determine whether, in recent years, sex differences in the type of care during coronary artery bypass graft surgery procedures occurred. METHODS Between 1995 and 2004, 5,935 consecutive patients (4,867 men and 1,068 women) underwent isolated coronary artery bypass graft surgery; propensity score matching was used to investigate whether sex adversely impacts standard care and early outcomes of coronary revascularization. RESULTS Of the 1,068 women undergoing isolated coronary artery bypass graft surgery, only 280 (26.2%) were matched on propensity scores with men. Distribution of preoperative variables among matched pairs was, on average, equal. Propensity-matched women received similar number of distal anastomoses as men (2.70 +/- 0.89 versus 2.82 +/- 0.97; p = 0.13), had similar rates of complete revascularization (82.5% versus 81.6%; p = 0.78), and of off-pump procedures (24.3% versus 27.5%; p = 0.39); also, the rate of utilization of arterial grafts (left internal mammary artery 98.5% versus 98.2%; p = 0.73; right internal mammary artery 3.2% versus 3.2%; p > 0.99; radial artery 8.2% versus 9.6%; p = 0.55), as well as the number of distal anastomoses performed with arterial grafts (1.11 +/- 0.36 versus 1.13 +/- 0.39; p = 0.47), were similar in women and men. No differences were detected in major complications (in-hospital mortality, perioperative myocardial infarction, and stroke) in propensity-matched pairs, whereas women had lower reexploration for bleeding and blood transfusion rates. CONCLUSIONS The preoperative profiles of women and men were markedly different, as only one fourth of women could be matched. In the current era, after adjustment for preoperative variables, female patients received the same standard of care as men, with improved results in some minor early outcomes.