Massimo Porqueddu

Biological effects of off-pump vs. on-pump coronary artery surgery: focus on inflammation, hemostasis and oxidative stress

Cardiopulmonary bypass (CPB) has been recognized as a cause of complex systemic inflammatory response, which significantly contributes to several adverse postoperative complications. In the last few years, off-pump coronary artery bypass grafting has gained widespread diffusion as an alternative technique to conventional on-pump coronary artery bypass grafting. Surgeons supporting off-pump surgery state that the avoidance of the CPB and myocardial ischemia-reperfusion significantly reduces the postoperative systemic inflammatory response and other biological derangements and, possibly, may improve the clinical outcomes. We review, here, the available evidence concerning possible differences between off-pump and on-pump procedures in terms of inflammation, hemostasis and oxidative stress. Consistent differences in the involvement of these systems are observed, but they are limited to the final steps of the surgical procedures and the early hours after. These findings suggest that the global surgical trauma may be as important, or even more, as the CPB in terms of systemic inflammatory and coagulation-fibrinolytic pathway activation. Further studies are needed in order to confirm this hypothesis.

Quick, simple clamping technique in descending thoracic aortic aneurysm repair

BACKGROUND Although significant advances have been made in the surgical treatment of diseases affecting the descending thoracic aorta, paraplegia remains a devastating complication. We propose the quick, simple clamping technique to prevent spinal cord ischemic injury. METHODS From 1983 to 1998, 143 patients had descending thoracic aorta aneurysm repair. We divided the patients into the following three groups according to the surgical technique used: selective atriodistal bypass was used in group 1 (66 patients); simple clamping technique in group 2 (28 patients); and quick simple clamping technique in group 3 (49 patients). Mean aortic cross clamp time was 39+/-13 minutes in group 1, 37+/-11 minutes in group 2, and 17+/-6 minutes in group 3 (p<0.01 group 3 versus group 1 and group 2). RESULTS The overall incidence of paraplegia was 4.8% (7 patients), 4.5% (3 patients) in group 1, 14.3% (4 patients) in group 2, and 0 in group 3 (p<0.05 group 3 versus group 2). The overall in-hospital mortality rate was 5.5%. Multivariate logistic regression analysis showed a powerful effect of aortic cross-clamping time as risk factor for both paraplegia (p<0.008), with an odds ratio of 1.03 per minute, and in-hospital mortality (p<0.001), with an odds ratio of 2.5 per minute. The mean follow-up time was 65 months with a lower overall mortality rate in group 3 than in group 1 and group 2 (p<0.05). CONCLUSION In descending thoracic aortic aneurysm repair, spinal cord perfusion can be maintained adequately without reimplantation of segmental vessels or use of atriodistal bypass when the aortic cross-clamp time is short (<15 to 20 minutes).

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.

Cardiopulmonary bypass and oxygen consumption: oxygen delivery and hemodynamics

BACKGROUND This study was undertaken to investigate the relations between whole body oxygen consumption (VO2), oxygen delivery (DO2), and hemodynamic variables during cardiopulmonary bypass. METHODS One hundred one patients were studied during cooling, hypothermia, and rewarming. Oxygen consumption, DO2, hemodynamics, and DO2crit were measured at these times. RESULTS There was a direct linear relation between DO2 and VO2 during all three times. No relation between VO2 and hemodynamics was detected during cooling; during hypothermia, an inverse linear relation with peripheral arterial resistance was found. Finally, during rewarming, there was a direct relation with pump flow rate, and an inverse relation with arterial pressure and arterial resistance. The same relations among the variables were found at delivery levels above or below DO2crit. CONCLUSIONS During cardiopulmonary bypass there is a direct linear relation between DO2 and VO2; the relations with hemodynamic variables depend on the phases of cardiopulmonary bypass. This suggests that increasing delivery levels may recruit and perfuse more vascular beds, and higher delivery levels are advisable during perfusion. During rewarming and hypothermia, lower arterial resistances are also desirable to optimize VO2.

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.

Endothelial-Dependent Dynamic and Antithrombotic Properties of Porcine Aortic and Pulmonary Valves

BACKGROUND In the present study, the endothelium-dependent antithrombotic and dynamic properties of porcine aortic (AoV) and pulmonary valves (PuV) were investigated. METHODS Fifteen fresh AoV and 15 fresh PuV were obtained from 25 9-month-old swines. The valves were examined for endothelial function by pharmacologic evaluation (with and without endothelium) of both the endothelial-releasing capacity of prostacyclin and the endothelial-dependent dynamic response to relaxing (acetylcholine from 10[-10] mol/L to 10[-4] mol/L in AoV and PuV segments precontracted with norepinephrine [3 x 10(-6) mol/L]) and contracting (endothelin-1, from 10[-11] mol/L to 10[-5] mol/L; and NG-monomethyl-L-arginine, 10[-4] mol/L) drugs. The ultrastructural integrity of the endothelial valve layer was also examined with transmission electron microscopy. RESULTS Acetylcholine caused potent relaxation in both AoV and PuV specimens with, but not in those without, endothelium. Endothelin-1 produced a concentration-dependent tension increase in AoV and PuV with and without endothelium. However, the intrinsic activity of the peptide significantly increased in tissues without endothelium. NG-monomethyl-L-arginine evoked a progressive increase in resting tension of the preparations, but the AoV and PuV without endothelium were less sensitive to the inhibition of the nitric oxide generation. Aortic and pulmonary valves with an intact endothelium showed a spontaneous ability to release prostacyclin. The basal release of this lipidic autacoid significantly decreased in cardiac valves without endothelium. This phenomenon was observed in both basal conditions, and under stimulation with the aforementioned drugs. Transmission electron microscopy showed the perfect preservation of endothelial cells in all the preparations examined. CONCLUSIONS Valvular endothelium of AoV and PuV seems to have similar antithrombotic and dynamic functions of vascular endothelium, actively participating in valvular homeostasis.

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.

Retention of endothelium-dependent properties in human mammary arteries after cryopreservation

BACKGROUND We investigated the effects of cryopreservation and antibiotic treatment on endothelium-dependent vasomotor properties of human internal mammary arteries (IMAs). METHODS Sixty IMA specimens from routine coronary artery bypass grafting procedures were randomly assigned to six groups. Group I (controls) were immediately tested after harvest. Remaining groups were prepared according to a stepwise design: group II, 6 hours of warm ischemia; group III, 6 hours of warm ischemia + 24 hours at 4 degrees C (without antibiotics); group IV, 6 hours of warm ischemia + 24 hours of 4 degrees C antibiotic disinfection; group V, 6 hours of warm ischemia + 24 hours at 4 degrees C (without antibiotics) + cryopreservation; and group VI, 6 hours of warm ischemia + 24 hours of 4 degrees C disinfection+cryopreservation. The IMA specimens were cut into rings and the tension of vascular smooth muscle was recorded. The IMA rings were contracted with norepinephrine (3 x 10(-6) mol/L) and tested with cumulative concentrations of acetylcholine (from 1 x 10(-9) to 1 x 10(-5) mol/L), contracted with endothelin-1 (from 1 x 10(-11) to 1 x 10(-6) mol/L), and contracted with the nitric oxide-synthase inhibitor NG-monomethyl-L-arginine (1 x 10(-4) mol/L). Rings were also tested for their capacity to generate 6-keto-prostaglandin F1 (the stable metabolite of prostacyclin), and endothelial cell viability rate was finally evaluated with the trypan blue dye exclusion method. RESULTS Our results show that a complete cryopreservation protocol does not significantly modify (p > 0.05) the relaxant activity to acetylcholine in norepinephrine-precontracted IMA rings (controls; 90.2% +/- 4.2% vs group VI, 77.1% +/- 6.2%) or the vasoconstrictor response induced by endothelin-1 (controls, 62.6% +/- 2.8% versus group VI, 73.7% +/- 4.8%) and NG-monomethyl-L-arginine (controls, 22.4% +/- 1.5% versus group VI, 18.9% +/- 1.9%). Furthermore, IMA cryopreservation does not significantly modify (p > 0.05) the endothelial release of prostacyclin either in basal conditions (-20% versus controls) or during pharmacologic intervention with acetylcholine (-18% versus controls), endothelin-1 (-17% versus controls), and NG-monomethyl-L-arginine (-18% versus controls). CONCLUSIONS We conclude that the IMA endothelial function does not seem significantly injured by any of the current steps of disinfection and cryopreservation.

Intracardiac ectopic thyroid : conservative surgical treatment

The case of a patient with an intracardiac ectopic thyroid is reported. A cardiac tumor was found in a 66-year-old woman and was diagnosed by two-dimensional echocardiography. An intraoperative biopsy was performed, and the mass was recognized as an ectopic thyroid and treated with a conservative surgical approach because of the size, location, and relationship to adjacent structures. The 60-month follow-up shows normal echocardiographic images and the good clinical status of the patient.

Effects of Warm Ischemia on Valve Endothelium

BACKGROUND This study investigates the time-dependent resistance of the endothelium of porcine aortic and pulmonary valves to different periods of warm ischemia (WIT). METHODS Twenty-five 9-month-old swine were divided after death into five groups of WIT (0, 6, 12, 24, and 36 hours). Aortic and pulmonary valves were removed and a total of 15 aortic and 15 pulmonary valve specimens were obtained for each WIT interval. Valves were then examined for (1) their viability rate by the trypan blue dye exclusion method at light microscopy (percent of viability compared with 0 hours of WIT); (2) ultrastructural signs of irreversible or reversible ischemic damage by transmission electron microscopy (cell disruption, dilation of endoplasmic reticulum, cytoplasmic edema, nuclear and mitochondrial changes); (3) endothelial function by pharmacologic evaluation of both the endothelial-releasing capacity of prostacyclin and the endothelial-dependent dynamic responses to relaxing (acetylcholine from 1 x 10(-10) mol/L to 1 x 10(-4) mol/L) in aortic and pulmonary valve segments precontracted with norepinephrine (1 x 10(-6) mol/L) and contracting (NG-monomethyl-L-arginine, 1 x 10(-4) mol/L) drugs. RESULTS Our results showed an endothelial progressive time-dependent ischemic injury, which reached significance after 12 hours of exposure. Viability and functional data indicated that 6 hours of WIT only provoked slight endothelial damage (p > 0.05 respect to time 0 hours), with signs at transmission electron microscopy consistent with a reversible injury. At 12 hours of exposure, we observed a significant reduction (p < 0.05) with respect to time 0 of the viability rate of prostacyclin production and of the endothelium-dependent dynamic responses to acetylcholine and NG-monomethyl-L-arginine. These functional impairments, although significant, were not consistent, however, with a complete loss of viability. Transmission electron microscopic observations confirmed the appearance of signs of irreversible injury; nevertheless, some elements were found to be well preserved or presented reversible damage. After 24 hours of WIT, ultrastructural and functional data were consistent with a dramatic decrease compared with controls in endothelial viability and functions (p < 0.01). Finally, after 36 hours of WIT, there was a subtotal loss of viability, of functions (p < 0.001) and, at transmission electron microscopic observations, of the endothelial layer of the valves. CONCLUSIONS Our data show that the endothelial cells are resistant to short periods of WIT (up to 6 hours), and suggest that these cells can endure longer exposures, up to 12 hours of warm ischemia. Periods of 24 and 36 hours of WIT provoke progressive irreversible damage.