Miodrag Peric

Steroids and statins: an old and a new anti-inflammatory strategy compared

Objectives: This study compared the anti-inflammatory effects of methylprednisolone (MP) and atorvastatin and analysed their influences on clinical variables in patients undergoing coronary revascularization. Methods: Ninety patients with compromised left ventricular ejection fraction (≤30%) undergoing elective coronary surgery were equally randomized to one of three groups: statin group, treatment with atorvastatin (20 mg/day) 3 weeks before surgery; methylprednisolone group, a single shot of methylpredniosolone (10mg/kg); and control group. Results: Postoperative IL-6 was higher in the control group when compared to the methylprednisolone and statin groups (p<0.01). IL-6 was higher in the statin-treated patients (p<0.05 versus methylprednisolone). Administration of methylprednisolone as well as statin treatment increased postoperative cardiac index, left ventricular stroke work index, decreased postoperative atrial fibrilation rate and reduced ICU stay (p<0.05 versus control). The number of patients requiring inotropic support was lower in the methylprednisolone group when compared with the other two groups (p<0.01). Tracheal intubation time was reduced in patients who received methylprednisolone (p<0.01 versus control). Conclusions: Preoperative administration of either methylprednisolone or atorvastatin reduced pro-inflammatory cytokine release, improved haemodynamics, decreased postoperative atrial fibrilation rate and reduced ICU stay in patients with significantly impaired cardiac function undergoing coronary revascularization. Treatment with methylprednisolone was associated with less inotropic support requirements and reduced mechanical ventilation time.

Active infective endocarditis: low mortality associated with early surgical treatment.

BACKGROUND Early surgical treatment is important for successful outcome in selected cases of active, either native (NVE) or prosthetic valve endocarditis (PVE). The aim of this study was to evaluate the early results of the surgical treatment of active NVE and PVE. METHODS During a 3-yr period (January 1 1996-December 31 1998), 57 out of 60 patients (pts) with active, either NVE (46 pts) or PVE (11 pts) underwent surgical treatment. There were 11 women (23.9%), average age of the group being 43.3+/-9.1yr (18-73). They were operated on 12-35days, mean 17.7+/-7.5days (for NVE) and 5-33days, mean 13.2+/-10.1days (for PVE) after the diagnosis of endocarditis was first suspected. All pts had at least one absolute indication for early surgical treatment, the most frequent being (in NVE) worsening heart failure (19 cases) and inability to control the infection (10 cases), while in PVE it was valve dehiscence (8 cases). In 8 cases of NVE and 2 cases of PVE fresh, antibiotic sterilized aortic homograft was used to replace the aortic valve. RESULTS Operative mortality was 1.8% (1/57) and hospital mortality 5.2% (3/57). Three pts with PVE died before they were operated on, giving an overall mortality of 10% (6/60). Postoperative morbidity included valve dehiscence in two pts (probable late onset recurrent endocarditis - 3.5%), three episodes of acute renal failure (5.3%), four cases of respiratory insufficiency (7.0%) and one chronic pleural effusion (1.8%). All pts that were discharged from the hospital (54/60), are still alive and well 1-35months postoperatively (mean 20.3+/-9.6months), including pts with recurrent endocarditis and valve dehiscence, after they were successfully reoperated. CONCLUSIONS Along with early diagnosis and appropriate antibiotic treatment, aggressive surgical attitude is of importance for the successful outcome in this group of seriously ill patients. Our data indicate that early surgical treatment in cases of active endocarditis may be associated with low mortality and morbidity.

The effects of levcromakalim and pinacidil on the human internal mammary artery

Summary— The present study was undertaken to examine the effects of pinacidil and levcromakalim, two potassium channel openers, on human internal mammary artery (HIMA) obtained from patients undergoing coronary artery bypass surgery, and to clarify the contribution of different K+ channel subtypes in pinacidil and levcromakalim action in this blood vessel. Pinacidil and levcromakalim induced a concentration‐dependent relaxation of the precontracted arterial segments (pEC50 = 5.77 ± 0.05 and 6.89 ± 0.03, respectively). 4‐Aminopyridine (3 mM), a non‐selective blocker of K+ channels, induced significant shifts to the right of the concentration‐response curves for pinacidil and levcromakalim. Tetraethylammonium (6 mM), charybdotoxin (0.4 μM) and apamin (0.1 μM), blockers of Ca2+‐sensitive K+ channels, had no effect on the pinacidil‐ and levcromakalim‐evoked relaxation. Glibenclamide (0.1–10 μM), a selective blocker of adenosine triphosphate (ATP)‐sensitive K+ channels, competitively antagonized the response to levcromakalim (pKB = 7.92 ± 0.07). In contrast, glibenclamide, in significantly higher concentrations (3–30 μM), non‐competitively antagonized the response to pinacidil. High concentrations of pinacidil (> 10 μM) relaxed arterial rings bathed by a medium containing 100 mM K+ with maximum response 83 ± 6%. Under the same conditions, the maximum levcromakalim‐induced relaxation on HIMA was almost abolished (15 ± 2%). It is concluded that pinacidil and levcromakalim do not relax the HIMA through the same subtype of K+ channel. ATP‐sensitive K+ channels are probably involved in levcromakalim‐ but not in a pinacidil‐induced relaxation in the HIMA. In addition, in pinacidil‐induced relaxation of the HIMA, K+ channel‐independent mechanisms seem to be involved.

Cardiac events after combined surgery for coronary and carotid artery disease.

OBJECTIVE To evaluate serious cardiac events after combined (either single or two stage) coronary artery surgery (CAS) and carotid endarterectomy (CEA) for concomitant coronary and carotid artery disease. METHODS We have analyzed our 15 year experience (January 1981-September 1996) with 201 consecutive patients operated on using both approaches. Group A consisted of 48 patients with the single-stage procedure, while in group B (153 patients), two stage procedure was carried out, either as carotid endarterectomy (CEA), followed by coronary artery bypass surgery (CAS) (group B1- 103 patients), or as CAS followed by CEA (group B2- 50 patients). Five patients from B1 group died after the CEA procedure, but were included, despite the fact they never reached the second stage. Left main coronary artery disease was found in 41 patients (20.4%), poor left ventricular function in 49 (24.4%) previous MI in 133 (66.2%), while 136 (67.7%) were in NYHA functional class III or IV. Bilateral carotid involvement was present in 61 patients (30.3%). Unstable angina was more prevalent in groups A and B2 (P < 0.0001). NYHA class III/IV in group A (versus B1, P = 0.001 and versus B2, P = 0.02), low ejection fraction in groups A and B2 (P < 0.0001), bilateral carotid stenosis in group B1 (versus A, P = 0.003 and versus B2, P < 0.0001), and ulcerated plaque in group B1 (P < 0.0001). These differences dictated the surgical strategy, which resulted in different protocols for clinical and operative management. RESULTS Early mortality for the entire group was 5.5% (11/201) 6.2% in group A, 7.8% in group B1 and 0% in group B2, respectively; (P > 0.05). Serious morbidity occurred in 7.5% of patients (8.3% in group A, 7.8% in group B1 and 6% in group B2, respectively; P > 0.05). Univariate analysis revealed only bilateral carotid stenosis to influence early outcome (P = 0.04). CONCLUSION Patients with concomitant coronary and carotid artery disease have relatively good immediate operative results, providing all existing lesions are corrected. Despite it did not reach the statistical significance, cardiac events were less frequent in groups A and B2 indicating possible protective effect of prior CAS in patients with concomitant disease.

Combined carotid and coronary artery surgery: what have we learned after 15 years?

UNLABELLED Optimal surgical strategy in patients with concomitant coronary and carotid artery disease is debatable. We have analysed 15-years of experience (January 1981-August 1996) with 195 consecutive patients in whom we have used two different surgical approaches. Group A consisted of 48 patients who underwent a single-stage surgical procedure, and group B (147 patents) underwent a two-stage procedure, either as carotid endarterectomy followed by coronary artery bypass surgery (group B1, 97 patients), or as coronary artery bypass surgery followed by carotid endarterectomy (group B2, 50 patients). Overall, there were 40 (20.5%) patients with left main coronary artery disease, 49 (25.1%) with poor left ventricular function, 128 (65.6%) with previous myocardial infarction, 134 (68.7%) were in New York Health Authority (NYHA) functional class III or IV, and bilateral carotid involvement was present in 57 patients (29.2%). Unstable angina was more frequent in groups A and B2 (P < 0.0001), NYHA class III-IV was more frequent in group A (versus B1, P = 0.001 and versus B2, P = 0.02), low ejection fraction (EF) was more frequent in groups A and B2 (P < 0.0001 for both), bilateral carotid stenosis in groups A and B1 (P = 0.02 and P = 0.0001, respectively) and ulcerated plaque in group B1 (versus A, P = 0.0001). These differences dictated the surgical strategy, which resulted in different protocols for clinical and operative management. RESULTS Early mortality for the entire group was 4.6% (9/195-6.2% in group A, 6.2% in group B1 and 0% in group B2, respectively P > 0.05). Serious morbidity occurred in 7.3% of patients (14/195-8.3% in group A, 7.2% in group B1 and 6% in group B, respectively P > 0.05). Univariate analysis revealed only bilateral carotid stenosis as a predictor of outcome (P = 0.04). Follow-up was completed for 156 patients (80.0%) and averaged 84.1 +/- 13.3 months (range 1-180 months). Kaplan-Meier survival estimate for the entire group was 81% and event-free survival was 76% at 5 years. Actuarial and event-free survivals were similar for all groups. Early and late outcome in these patients were influenced more by their preoperative clinical status than by the surgical strategy itself. It is therefore concluded that surgical approach should be individualized for the majority of patients.

Effect of potassium channel opener pinacidil on the contractions elicited electrically or by noradrenaline in the human radial artery.

In order to discover an agent that can prevent spasm of the human radial artery, the aim of our study was to evaluate the effect of the K(+) channel opener, pinacidil, on contractions in the radial artery. Contractions of the radial artery were evoked by exogenously applied noradrenaline or by electrical field stimulation (EFS, 20Hz, neurogenic). Pinacidil induced concentration-dependent inhibition of both EFS- and noradrenaline-evoked contractions of the radial artery. Glibenclamide, a selective blocker of ATP-sensitive K(+) channels (Kir6.x containing subunit) antagonized in the same manner the pinacidil-induced inhibition of neurogenic contractions and contractions evoked by exogenous noradrenaline. The inhibition of pinacidil relaxation by tetraethylammonium (TEA), a blocker of Ca-sensitive K(+) (K(Ca)) channels, was more pronounced in EFS-contracted preparations. A blocker of voltage-sensitive K(+) (K(V)) channels, 4-aminopyridine (4-AP), inhibited pinacidil relaxation only in EFS-contracted preparations. In order to test the presence of different K(+) channels, immunohistochemistry of K(+) channels expression in the radial artery was performed. The vascular wall of the human radial artery showed variable positivity with the following applied antibodies: Kv1.2, Kv1.3, Kir6.1, and K(Ca)1.1. The antibodies against Kv1.6, Kv2.1, and Kir6.2 channel subunits were completely negative. These results suggest that the inhibitory effect of pinacidil on contractions of the human radial artery might be postsynaptic and associated with opening of smooth muscle Kir6.1-containing K(ATP) channels. TEA- and 4-AP-sensitive K(+) channels may also contribute to pinacidil effect in the human radial artery.

The use of acute normovolemic hemodilution in patients undergoing cardiac surgery

Avoiding allogeneic blood transfusion during cardiac surgery and during the post-operative period is of great importance. Acute normovolemic hemodilution (ANH) is one of the options for blood salvage. We have prospectively analyzed 310 consecutive patients (pts) after different open heart procedures, operated on during April-May, 2000. ANH was possible in 226 pts (73%) with hemoglobin level over 125 g/l and hematocrit over 36%. Of those, one unit of blood was withdrawn in 128 pts (70%), while two to five units of blood were taken in 68 pts (30%). Total number of autologous blood units taken was 296, for the average of 1.31 units/pt. Predictors of increased intra- and post-operative blood loss were hematocrit (Hct) <39% (76% vs. 24%, p<0.001), age over 65 (p=0.028), female sex (p=0.006), CPB duration over 90 min (63% vs. 37%; p<0.001) and preoperative left ventricular ejection fraction (LVEF) <35% (63% vs. 37%; p<0.001). All pts with the above-mentioned characteristics were in need for allogeneic blood transfusion. During their hospital stay, 142 pts did not get allogeneic blood (142/310, 46%), and all were in the ANH group (142/226, 62%).

Partial Left Ventriculectomy and Limited Heart Transplantation Availability

Background and Aim: Partial left ventriculectomy, a novel cardiac volume reduction operation, is applied in countries without a developed heart transplantation program. We sought to determine its impact in our population of patients. Methods: Partial left ventriculectomy was performed in 38 patients during the last 4 years. Basic inclusion criteria were nonischemic dilated cardiomyopathy and poor response to medical therapy for heart failure. Hemodynamic evaluation was carried out before and after operation. A modified surgical technique of mitral valve repair and ventricle suturing was applied. Results: Thirty‐day, 6‐month, and 2‐year survival rates were 82%± 7%, 65%± 8%. and 61%± 9%, respectively. Duration of heart failure symptoms was the only predictor of survival (p = 0.042). A high proportion of noncardiac causes of death was noted. Functional capacity in surviving patients improved at every successive measurement up to 1 year postoperatively. Conclusions: The introduction of partial left ventriculectomy in a country with limited heart transplantation availability had a great impact on the management of end‐stage heart failure and may represent the only surgical option for some patients. The average cost per patient was substantially lower when compared to heart transplantation.

Radial Artery Harvesting for Coronary Artery Bypass Grafting: A Stepwise-Made Decision

BACKGROUND The purpose of this study was to propose a safe, stepwise, testing system to select radial arteries that are suitable for conduits on the basis of their morphologies and characteristics of the collateral circulation. METHODS Before operation, 113 patients underwent the modified Allen test, Doppler ultrasonography, and pulse oximetry testing. Morphologic criteria used for radial artery exclusion were small size of radial or ulnar artery (< 2 mm in inner diameter), diffuse calcifications, and congenital anomalies of forearm arteries. Collateral circulation was interpreted as insufficient if the reverse flow in the anatomic snuffbox was absent or if the increase of the ulnar peak systolic flow velocity was less than 20%. RESULTS A positive modified Allen test was found in 10.6% of patients. As assessed by Doppler ultrasonography, 27 patients (23.9%) were not candidates for radial artery harvesting according to morphologic and functional abnormalities of forearm and hand circulation. Pulse oximetry test results were abnormal in 6.2%. After a follow-up period of 8.9 +/- 1.8 months, 23 patients (29.1% of operated patients) were controlled for Doppler ultrasonographic changes in the ulnar artery. The mean peak systolic flow velocity was significantly higher than the preoperative value measured at rest (p < 0 .001). CONCLUSIONS After preoperative tests, including the modified Allen test, Doppler ultrasonography, and pulse oximetry, 30.1% of patients were not considered candidates for radial artery harvesting. This method provides preoperative radial artery selection according to its morphologies, compensatory capacity of collateral circulation, and anatomic properties of ulnar artery.

Simultaneous hybrid carotid stenting and coronary bypass surgery versus concomitant open carotid and coronary bypass surgery: a pilot, feasibility study

OBJECTIVES Concomitant carotid and cardiac surgery carries an increased perioperative morbidity and mortality risk. Whether the hybrid procedure of carotid artery stenting (CAS) and coronary bypass surgery decreases the risk of stroke and other complications is still unknown. The aim of this study was to assess early outcomes after simultaneous hybrid CAS and coronary bypass grafting versus open concomitant carotid and coronary bypass surgery. METHODS We included 20 patients in this study. According to the protocol, all the patients were divided into two groups: Group 1 (10 patients) with hybrid CAS and coronary bypass surgery and Group 2 (10 patients) with concomitant carotid and coronary surgery. Different preoperative, intraoperative and postoperative variables were compared. The primary end point was combined incidence of stroke and death 30 days after surgery or during initial hospitalization. The secondary end points were myocardial infarction, atrial fibrillation, blood loss and need for blood transfusion and duration of intensive care unit and hospital stay. RESULTS Groups 1 and 2 were similar in preoperative characteristics including age (65.3 ± 6.8 vs 70.7 ± 7.0, P = 0.191) New York Heart Association class (2.3 ± 0.5 vs 1.8 ± 0.7, P = 0.218), EuroSCORE (2.8 ± 2.0 vs 3.6 ± 2.3, P = 0.547), the degree of carotid stenosis (79 ± 12 vs 87 ± 13%, P = 0.224) and average left ventricular ejection fraction (44.3 ± 12.4 vs 43.4 ± 13.3%, P = 0.896). Also, the groups did not differ in intraoperative variables with an exception of extracorporeal circulation time (65.7 ± 14.1 vs 90.0 + 17.4 min, P = 0.023), which was significantly shorter in Group 1. Although rare, and without significant difference, primary end point occurred only in Group 2 (1 stroke and 1 death, 20%). There was no difference in the duration of mechanical ventilation, need for transfusion and duration of intensive care unit and hospital stay between the two groups. CONCLUSIONS Although limited by a small sample size, our results show that the hybrid procedure of carotid stenting and coronary surgery might be a good therapeutic option but further extended studies are needed to assess its real value.