Twenty-four hour hyperinsulinemic-euglycemic clamp improves postoperative nitrogen balance only in low insulin sensitivity patients following cardiac surgery.

BACKGROUND: Critically ill patients often suffer from a protein catabolic state. The aim of this study was to demonstrate that nitrogen balance (NB) in cardiac patients admitted to the intensive care unit (ICU) is related to their insulin sensitivity level and that supraphysiologic doses of insulin can restore anabolism. MATERIALS AND METHODS: Twenty-eight patients that were admitted to ICU in enteral and/or parenteral nutrition have been enrolled in this study. All patients received a standard nutrition protocol for at least 3 days before starting the study. These patients received either enteral or parenteral nutrition based on 1.4 kcal/kg/h and 1.1 g/kg/24 h of proteins. Participants were studied for three 24 h periods (P1 , P2 , and P3 ). Twenty-four hour NB was calculated from urinary urea nitrogen excretion, fixed protein and energy intake during each of the three periods (P1 , P2 , and P3 ). Simultaneous to P2, a 24 h hyperinsulinemic-euglycemic clamp (HEC) was performed to determine patients' insulin sensitivity (IS) or insulin resistance (IR), as well as the impact of high doses of insulin on NB. RESULTS: Nitrogen balance remained consistently positive in the IS group regardless of the clamp. In IR patients, NB was negative before the clamp and became positive during P2 and P3 . Insulin sensitivity improved during the HEC in IR patients (P < 0.001). CONCLUSIONS: A negative NB was found only in insulin resistant patients admitted to the ICU for more than 7 days. A 24-h period HEC improved NB in these patients.

Cryoballoon ablation for atrial fibrillation guided by real-time three-dimensional transoesophageal echocardiography: a feasibility study.

AIMS: Cryoballoon ablation (CBA; Arctic Front, Medtronic) has proven very effective in achieving pulmonary vein isolation. Real-time three-dimensional transoesophageal echocardiography (RT 3D TEE) is a novel technology, which permits detailed visualization of cardiac structures in a 3D perspective. The aim of the present study was to assess the feasibility, advantages, and safety of RT 3D TEE in guiding CBA in a series of patients affected by paroxysmal atrial fibrillation. METHODS AND RESULTS: Forty-five patients (34 males, mean age: 63 ± 12 years) underwent CBA guided by 3D TEE. A total of 190 veins could be documented by TEE. Real-time three-dimensional transoesophageal echocardiography successfully guided the operator to position the CB in the pulmonary vein (PV) ostium and obtain complete occlusion in all 190 (100%) veins. Transoesophageal echocardiography identified leakages in 25 (13%) veins led to successful elimination of PV-left atrium (LA) backflow by guiding correct balloon repositioning. In four (2%) veins, this imaging tool led to perform successful pull-down manoeuvres. After a mean 2.6 ± 1.4 applications, isolation could be documented in 190 (100%) PVs. Median procedural and fluoroscopy times were 145 and 24 min. During a median follow-up of 278 days, 37 (82%) patients did not experience atrial fibrillation recurrence following a 3-month blanking period. CONCLUSION: Cryoballoon ablation is safe and feasible under RT 3D TEE guidance. This imaging tool permits perfect visualization of all PV ostia and neighbouring LA structures. Most importantly, it proved very efficient in guiding the operator to achieve complete occlusion and successful isolation in all veins.

Diet-derived phytochemicals: from cancer chemoprevention to cardio-oncological prevention.

Cardiovascular diseases and cancer are the leading causes of death in most countries. These diseases share many common risk factors as well as pathogenetic determinants, and their incidence is related to age in an exponential manner. Furthermore, it has become apparent that several treatments used in therapy or even in prevention of cancer can impair the structural and functional integrity of the cardiovascular system, giving rise to an interdisciplinary field: cardio-oncology. However, tumors and cardiovascular diseases also share common protective factors: they can be prevented either by avoiding exposure to recognized risk factors, and/or by favoring the intake of protective compounds and by modulating the host defense machinery. These latter approaches are generally known as chemoprevention. A great variety of dietary and pharmacological agents have been shown to be potentially capable of preventing cancer in preclinical models, most of which are of plant origin. Phytochemicals, in particular diet-derived compounds, have therefore been proposed and applied in clinical trials as cancer chemopreventive agents. There is now increasing evidence that some phytochemicals can be also protective for the heart, having the potential to reduce cancer, cardiovascular disease and even anticancer drug-induced cardiotoxicity. We introduce the concept that these compounds induce pre-conditioning, a low level cellular stress that induces strong protective mechanisms conferring resistance to toxins such as cancer chemotherapeutics. Cancer cells and cardiomyocytes have fundamental differences in their metabolism and sensitivity to preconditioning, autophagy and apoptosis, so that dosage of the prevention compounds is important. Here we discuss the mechanisms responsible for the cardiotoxicity of anticancer drugs, the possibility to prevent them and provide examples of diet-derived phytochemicals and other biological substances that could be exploited for protecting the cardiovascular system according to a joint cardio-oncological preventative approach.

Correlation between pre-operative metabolic syndrome and persistent blood glucose elevation during cardiac surgery in non-diabetic patients.

BACKGROUND: Cardiopulmonary-bypass (CPB) induces hyperglycemia. There is growing evidence that perioperative maintenance of blood glucose within the physiological range improves patients' outcome. Nevertheless, perioperative normoglycemia is often difficult to achieve during surgery with CPB and the response to insulin infusion is characterized by a considerable variability. The aim of this study was to determine to what extent the presence of pre-operative metabolic syndrome (MS) influences the blood glucose and insulin response during cardiac surgery. METHODS: Forty-five patients scheduled for elective cardiac surgery were screened for the presence of MS according to the International Diabetes Federation definition. Patients were then assigned to two groups: those with metabolic syndrome (MSP) and those without (control). During surgery, blood glucose levels were measured in all patients and hyperglycemia was treated with a standard protocol of continuous insulin infusion. RESULTS: The mean blood glucose levels during CPB increased only in the MSP group (P<0.001). Mean blood glucose in control patients did not increase during CPB (P=0.4). Patients with MS received 13.3+/-8.4 IU of insulin during CPB, while the control group did not require insulin treatment (P<0.001). Forty percent of patients in the control group and 100% of those in the MSP group developed post-operative insulin resistance. C-reactive protein was higher in the MSP group before, during and at 48 h after surgery. CONCLUSIONS: The mean blood glucose levels during CPB increased only in patients with MS, while they remained unchanged in patients in the control group.

[Clinical use of spinal or epidural steroids]. / Uso degli steroidi per via spinale ed epidurale.

Steroids, drugs with potent antiinflammatory properties on the damaged nervous roots, have been especially used as adjuvants of local anesthetics, by spinal route, in the treatments of low-back pain. Spinal route was chosen to obtain a higher local concentration of drug, with few systemic side effects and to improve drug's action mechanism. Steroids seem to interact with GABA receptors and thus control neural excitability through a stabilising effect on membranes, modification of nervous conduction and membrane hyperpolarization, in supraspinal and spinal site. Epidural steroids are especially used in the treatment of low back pain due to irritation of nervous roots. They have been administered alone or in association with local anesthetics and/or saline solution. Slow release formulations have been generally used (methylprednisolone acetate, and triamcinolone diacetate). Other indications of epidural steroids are: postoperative hemilaminectomy pain, prevention of post herpetic neuralgia, degenerative ostheoartrithis. Intra-thecal steroids have been frequently used in the treatment of lumbar radiculopathy due to discopathy, as an alternative treatment when epidural administration is ineffective. Positive results have been obtained with methylprednisolone acetate, alone or in association with local anesthetics. Complications related to intraspinal steroids injections are due to execution of the block and side effects of drugs. Complications associated with intrathecal steroids are more frequent and severe than epidural injections and include: adhesive arachnoiditis, aseptic meningitis, cauda equina syndrome. Steroidal toxicity seems to be related to the polyethylenic glycole vehicle. Anyway, slow release formulations contain less concentrated polyethylenic glycole. The epidural administration, a correct dilution of steroid with local anesthetics solution and/or saline solution, and a limited number of injections (no more than three) allows a significant reduction of steroid neurotoxicity.

Chordal plication and free edge remodeling for mitral anterior leaflet prolapse repair: 8-year follow-up.

BACKGROUND: Chordal suture plication and free edge remodeling represent a personal technique for the repair of anterior leaflet prolapse. We report the results of an 8-year experience. METHODS: Sixty-one patients with degenerative mitral regurgitation caused by prolapse of the anterior leaflet (11) or both leaflets (50) underwent anterior leaflet prolapse repair. Twenty patients who had associated cardiac procedures are included. RESULTS: There were two perioperative deaths. Postoperative mitral regurgitation fell to 0.4 +/- 0.7 versus 3.7 +/- 0.4 preoperative (p < 0.0001). Mean follow-up was 40.5 months. There were 3 late deaths and 3 mitral reoperations (1 of 3 repairs, 2 of 3 replacements). Thromboembolism and endocarditis occurred in 1 patient each. Actuarial overall survival, freedom from cardiac death, and freedom from mitral reoperation at 92 months were 85.1% +/- 7.9%, 88.9% +/- 7.7%, and 94.6% +/- 3.0%, respectively. CONCLUSIONS: Our technique of anterior leaflet prolapse repair appears effective, safe, and durable at mid- to long-term follow-up, and may be used in the presence of extensive disease of both leaflets.

Effect of aspirin and ticlopidine on plasma tissue factor levels in stable and unstable angina pectoris.

Patients with unstable angina have an increased activation of the coagulation system. Aspirin and ticlopidine given in combination may potentiate each other by the combination of different action mechanisms and may reduce the risk of coronary occlusion and clinical instability. Plasma tissue factor (TF) levels collected into the stenotic coronary artery may be an index of TF expression within the vasculature. In 160 patients undergoing angioplasty for a 81+/-5% coronary lesion, we measured TF in blood samples collected from a vein and from the coronary ostium. Immediately after and 10 minutes after the dilation procedures the samples were withdrawn also beyond the lesion. Heparin 150 U/kg was given as an anticoagulant. All patients were pretreated with 250 mg/day of aspirin. One hundred twenty patients were randomly assigned to receive 24, 48, or 72 hours of ticlopidine treatment (250 mg/twice daily). TF levels did not increase during angioplasty but there was a significantly higher TF expression in unstable than in stable patients, irrespective of the invasiveness of debulking procedures. When ticlopidine was given for 72 hours, TF levels were similar to normal laboratory values both in stable and unstable patients. This combined antiplatelet pretreatment may be of benefit in unstable angina patients, with a favorable cost/benefit ratio.

[Repair of anterior mitral leaflet prolapse: state of the art]. / La riparazione del prolasso del lembo anteriore mitralico: stato dell'arte.

Surgical repair of anterior leaflet prolapse has evolved and widely expanded over the past decade. A number of surgical techniques have been developed. In this study a review of all reparative techniques has been provided. A classification has been proposed according to the involvement of valve components and, eventually, to graft employment. For each technique the following points have been detailed: a) advantages and drawbacks; b) likelihood of effective valve repair based on morpho-pathologic variability of degenerative mitral disease; c) long-term outcome as freedom from reoperation. The authors provide indications for early surgical anterior leaflet prolapse repair and recommend that surgeons should be familiar with many reparative procedures to select the right option and improve their operative results.

Haemodynamic effects of intravenous clonidine on propofol or thiopental induction.

The study evaluated the effects of premedication with intravenous clonidine on thiopental or propofol requirements for induction and haemodynamic changes associated with both induction and endotracheal intubation. Clonidine administered intravenously before induction of anaesthesia reduced propofol or thiopental requirements. The association of clonidine and propofol caused, after injection of the induction drug, a decrease in mean arterial pressure which was significantly greater than with thiopental. Moreover, a major haemodynamic stability was registered before and after laryngoscopy in the clonidine-thiopental group. These findings might contraindicate the clonidine-propofol combination in patients with cardiovascular disease.

[High-risk pulmonary surgery in potential candidates for a heart transplant]. / Chirurgia polmonare ad alto rischio in potenziali candidati a trapianto cardiaco.

Severe ventricular dysfunction and concomitant infection are considered absolute contraindications for major thoracic operations and immunosuppressive therapy, respectively. However, cardiac transplantation represents the first-choice treatment in advanced heart failure. We report the case of a patient with dilated cardiomyopathy and severe left ventricular dysfunction (ejection fraction = 25%), initially not considered as a potential heart transplant candidate due to the presence of a lung abscess. The patient subsequently underwent atypical pulmonary resection with intraoperative and perioperative intraaortic balloon counter-pulsation for circulatory support and was then listed for cardiac transplant. Pitfalls and intra/postoperative strategy, all of which are potentially important aspects in minimizing operative risk, are discussed.

Combined carotid and cardiac procedures: improved results and surgical approach.

Severe cerebrovascular complications following cardiac surgical procedures remain a major concern, particularly in patients with significant carotid atherosclerotic involvement (14% of perioperative stroke). Operative mortality for carotid operations in patients with documented Coronary Artery Disease (CAD) may be as high as 20%. Seventy patients underwent combined operations (unilateral carotid stenosis > 70%, unilateral stenosis > 50% with ulcerated plaque or bilateral stenoses > 50%; and this also included patients with unilateral occlusion). Cardiac procedures were 69 coronary artery bypass grafts, four left ventricular aneurysmectomies, three aortic valve replacements and surgery on two mitral valves. Seven perioperative deaths occurred, which were all caused by cardiac events. There were no perioperative strokes. Carotid endarterectomy immediately before cardiopulmonary bypass is a safe and expeditious approach to coexisting significant cardiac and carotid disease. In our experience, technical details in monitoring and minimizing cerebral ischemia are possibly more crucial in these severe vasculopathic patients. Moreover, it is probably advantageous from an economic standpoint compared with other therapeutic treatments.

Inferior epigastric artery as a conduit for myocardial revascularization: a two-year clinical and angiographic follow-up.

The inferior epigastric artery has been proposed as a suitable conduit for myocardial revascularization but its mid-term patency rate has not been assessed. A prospective clinical and angiographic study on the use of the inferior epigastric artery as an additional arterial conduit together with bilateral internal thoracic artery grafting was conducted in 38 patients. No deaths or major postoperative complications occurred. Twenty-three patients underwent repeat angiography after an average of 21.2 months. The left and right internal thoracic artery grafts patency rate was 95.6% (44/46), while inferior epigastric artery patency rate was 52.2% (12/23). By relating patency to the grafted coronary branch, the following results were obtained: 100% for the left anterior descending (3/3), right coronary (1/1) and ramus medianus (1/1); 40% (4/10) and 37.5% (3/8) for diagonals and obtuse marginals respectively. The low patency rates observed when the inferior epigastric artery is used on diagonals and obtuse marginals indicate that this vessel cannot be considered a suitable conduit for extensive application of arterial revascularization. We suggest that the inferior epigastric artery should only be used in patients presenting with contraindications to bilateral internal thoracic artery or right gastroepiploic artery grafting, or exhibiting unsuitable saphenous veins.

Myocardial metabolism studied during warm blood antero-retrograde reperfusion in ischaemic human hearts.

We propose modified warm blood antegrade-retrograde reperfusion (WBARR) of arrested hearts as a metabolic model with which to study substrate exchange and energy metabolism during the recovery phase after 90 min of ischaemia in man. Eleven anaesthetized patients undergoing aorto-coronary bypass were studied during WBARR. The protocol was designed as follows: period 1, a warm blood reperfusion with potassium (3 min); period 2, a warm blood reperfusion without potassium (2 min). The perfusion flow rate averaged 250+/-2 ml/min at the beginning of period 1 and 218+/-19 ml/min at the beginning and at the end of period 2; the perfusion was performed antegradely and retrogradely in the arrested hearts. Samples were simultaneously taken from the coronary venous sinus (CVS) and from the aortic root needle (AR). At the beginning of WBARR lactate release was 85+/-44 micromol/min and at the end it had significantly decreased to 21+/-99 micromol/min (P<0.03). Simultaneously, non-esterified fatty acids (NEFA) and beta-hydroxy-butyrate were initially released (71+/-61 and 22+/-66 micromol/min, respectively), while at the end of the WBARR there was an uptake of both NEFA (20+/-22 micromol/min; P<0.01) and beta-hydroxy-butyrate (12+/-35 micromol/min; P=0.290). Alanine, glycerol and branched chain amino acid balance across the heart did not significantly change. In summary after 90 min of ischaemia the heart energy metabolism is mainly anaerobic and based on glucose consumption, with lactate, NEFA and amino acids, which are mainly released. After 5 min of WBARR (recovery from ischaemia), lactate release is significantly reduced and NEFA becomes the energy supply of the heart. In conclusion, (1) WBARR is a valuable method with which to study myocardial metabolism in anaesthetized humans and may be combined with the use of tracers; (2) the study of myocardial metabolism in arrested hearts eliminates the imprecisions arising from the noncontinuous coronary blood flow; (3) NEFA become an important source of energy utilized by human hearts in the recovery phase from ischaemia.

Surgery of cavo-atrial renal carcinoma employing circulatory arrest: immediate and mid-term results.

From 1990 to 1995, 12 patients with cavo-atrial renal cell carcinoma underwent resection of the tumor. Circulatory arrest was employed in 11/12 cases. The neoplasm extended to the inferior vena cava in two patients and to the intrahepatic veins or right atrium in five cases. Two severely cardiac compromised patients died perioperatively. Of five patients who showed preoperative suspicion of isolated metastases, 3 patients died postoperatively because of relapsing disease after a mean period of 10.8 months. Five patients are alive and doing well after a mean follow-up of 14.8 months. In our experience myocardial dysfunction determined poor immediate survival. Mid-term survival was influenced by preoperative metastases and lymph-node involvement, but not by intracaval extension. Circulatory arrest appears to be a relatively safe technique to remove renal carcinoma with cavo-atrial extension and should be indicated whenever there are no metastases.