Heart failure in patients is associated with downregulation of mitochondrial quality control genes.

BACKGROUND: Mitochondrial dysfunction is one of key factors causing heart failure. We performed a comprehensive analysis of expression of mitochondrial quality control (MQC) genes in heart failure. METHODS: Myocardial samples were obtained from patients with ischemic and dilated cardiomyopathy in a terminal stage of heart failure and donors without heart disease. Using quantitative real-time PCR, we analysed a total of 45 MQC genes belonging to mitochondrial biogenesis, fusion-fission balance, mitochondrial unfolded protein response (UPRmt), translocase of the inner membrane (TIM) and mitophagy. Protein expression was analysed by ELISA and immunohistochemistry. RESULTS: The following genes were downregulated in ischemic and dilated cardiomyopathy: COX1, NRF1, TFAM, SIRT1, MTOR, MFF, DNM1L, DDIT3, UBL5, HSPA9, HSPE1, YME1L, LONP1, SPG7, HTRA2, OMA1, TIMM23, TIMM17A, TIMM17B, TIMM44, PAM16, TIMM22, TIMM9, TIMM10, PINK1, PARK2, ROTH1, PARL, FUNDC1, BNIP3, BNIP3L, TPCN2, LAMP2, MAP1LC3A and BECN1. Moreover, MT-ATP8, MFN2, EIF2AK4 and ULK1 were downregulated in heart failure from dilated, but not ischemic cardiomyopathy. VDAC1 and JUN were only genes that exhibited significantly different expression between ischemic and dilated cardiomyopathy. Expression of PPARGC1, OPA1, JUN, CEBPB, EIF2A, HSPD1, TIMM50 and TPCN1 was not significantly different between control and any form of heart failure. TOMM20 and COX proteins were downregulated in ICM and DCM. CONCLUSIONS: Heart failure in patients with ischemic and dilated cardiomyopathy is associated with downregulation of large number of UPRmt, mitophagy, TIM and fusion-fission balance genes. This indicates multiple defects in MQC and represents one of potential mechanisms underlying mitochondrial dysfunction in patients with heart failure.

Repair of flail anterior leaflets of tricuspid and mitral valves by cusp remodeling.

We present an alternative approach to extensive rupture of the chordae tendineae leading to flail anterior leaflets. Resection of the affected cusp segment, suture of the cut edges, and extensive plication of the segment of annulus devoid of leaflets abolished massive regurgitation while maintaining an adequate valve orifice.

Penetrating cardiothoracic war wounds.

OBJECTIVE: Penetrating cardiothoracic war wounds are very common among war casualties. Those injuries require prompt and specific treatment in an aim to decrease mortality and late morbidity. There are a few controversies about the best modality of treatment for such injuries, and there are not many large series of such patients in recent literature. METHODS: We analysed a group of 259 patients with penetrating cardiothoracic war wounds admitted to our institutions between May 1991 and October 1992. RESULTS: There were 235 (90.7%) patients with thoracic wounds, 14 (5.4%) patients with cardiac, wounds and in 10 (3.7%) patients both heart and lungs were injured. The cause of injury was shrapnel in 174 patients (67%), bullets in 25 patients (9.7%), cluster bomb particles in 45 patients (17.3%) and other (blast etc.) in 15 patients (6%). Patients, 69, had concomitant injuries of various organs. The initial treatment in 164 operated patients was chest drainage in 76 (46.3%) patients, thoracotomy and suture of the lung in 71 (43.2%) patients, lobectomy in 12 (7.3%) patients and pneumonectomy in 5 (3%) patients. Complications include pleural empyema and/or lung abscess in 20 patients (8.4%), incomplete reexpansion of the lung in 10 patients (4.2%), osteomyelitis of the rib in 5 patients (2.1%) and bronchopleural fistula in 1 patient (0.4%). Secondary procedures were decortication in 12 patients, rib resection in 5 patients, lobectomy in 2 patients, pneumonectomy in 4 patients, reconstruction of the chest wall in 2 patients and closure of the bronchopleural fistula in 1 patient. The cardiac chamber involved was right ventricle in 12 patients, left ventricular in 6 patients, right atrium in 7 patients, left atrium in 3 patients, ascending aorta in 2 patients and 1 patient which involved descending aorta, right ventricle and coronary artery (left anterior descending) and inferior vena cava, respectively. The primary procedure was suture in 17 patients (in 10 patients with the additional suture of the lung), suture + extraction of the foreign body in 4 patients, 2 of them with cardiopulmonary bypass. Complications were pericardial effusion in 6 patients, arrhythmia in 2 patients, myocardial infraction in 1 patient and migration of the foreign body in 1 patient. Patients, 7, died, five of the group with concomitant injuries, two of thoracic and one of cardiac injuries (5, 1.2 and 4.2%, respectively). CONCLUSIONS: Penetrating cardiothoracic wounds are among the most serious injuries in war, either in combat or among civilians. In spite of their nature, they can be treated successfully with relatively low mortality and morbidity.

Cytomegalovirus disease as a possible etiologic factor for early atherosclerosis.

A group of 284 patients who underwent orthotopic heart transplantation between April 1986 to June 1991 and who were followed up for at least five years was analyzed in this paper. Patients were divided into three groups according to the presence or absence of cytomegalovirus infection or disease: patients without infection, patients with serologycaly proven infection and patients with cytomegalovirus disease. The analysis of survival was performed with respect to all major factors that influence survival: age and sex of a donor and a recipient, number of rejection episodes, perioperative ischemic time and pulmonary vascular resistence. A recipient's age was shown to be a significant factor. Patients who experienced at least one episode of cytomegalovirus disease had significantly worse long-term survival compared to those with the infection only or without the infection. That difference was caused by the increased incidence of coronary atherosclerosis, which caused deaths in patients with a previous episode of cytomegalovirus disease. A possible mechanism responsible for this phenomenon is discussed.

Coronary vascularization in patient maintained on chronic hemodialysis.

A patient, maintained on hemodialysis for 16 years because of chronic renal failure caused by chronic glomerulonephritis, who underwent surgical coronary revascularization, is presented. The authors conclude that preoperative hemodialysis, careful hydration of the patient, right management of cardiopulmonary bypass, use of hemodilution and aprotinin can contribute to escivating of hemofiltration and heterologue blood transfusion in uremic patients who undergo well timed coronary revascularization.

Inotropic agents in the treatment of postoperative low cardiac output syndrome.

Two basic groups of inotropic drugs that are in the treatment of postcardiotomy low cardiac output syndrome (LCOS) are presented. The authors emphasize the advantages of phosphodiesterase inhibitors (PDE III) as compared to catecholamines.

Adult respiratory distress syndrome.

In this article the authors present a case of successful treatment of a 54-year old male patient with non-insulin dependent diabetes mellitus (NIDDM) and triple-vessel coronary artery disease who underwent surgical myocardial revascularization and was reoperated on the same day because of excessive bleeding. The patient was given cca 5000 mL of whole blood and cca 3000 mL of blood derivatives. The first postoperative chest X-ray showed radiological signs of ARDS. The therapy was based upon authors' experience and was consisted of controlled mechanical ventilation (respiratory volume 12-15 mL/kg, 10-14 cycles/min, I/E ratio 1:2, FIO2 0.6, PEEP 2-5 cm H2O), daily bronchoscopies with bronchoaspiration, aggressive diuresis, negative fluid balance, specific antibiotic therapy, and last but not least, of prostaglandin E1 (PGE1) 0.5-20 micrograms/kg/min combined with dopamine inotropic support (2-5 micrograms/kg/h). Simple but careful clinical observation still remains a milestone for all therapeutic measures taken in ARDS patients.

The patent ductus arteriosus as a source of recurrent peripheral embolisations.

A patient with a multiple peripheral embolisation of unknown origin is presented. Because of her extreme obesity, some diagnostic procedures could not be performed (CAT), and some were performed with great difficulty (conventional ECHO, DSA of the aorta). Transesophageal echocardiography was the key procedure in the diagnosis of the floating thrombotic mass in the descending aorta. A surgical operation was performed, and a thrombus was found in the aortic orifice of the hemodynamically insignificant patent ductus arteriosus. The patient has now been 18 months in good condition and free of thromboembolic events.

Diagnostic accuracy of transesophageal echocardiography for detection of atrial masses.

The aim of this study was to assess the diagnostic accuracy of transthoracic (TTE) and transesophageal echocardiography (TEE) for the detection of atrial masses. The authors' own experiences with the use of TTE and TEE images in the assessment of atrial masses are reported. These masses included tumors, thrombi, and valvular vegetations. The study groups consisted of 14 consecutive patients (7 women an 7 men), age range 24-72 (mean age 56.6 < +13.4) years. Eleven patients had left atrial tumor, two patients had atrial thrombi, and one patient had vegetation in left atrium detected with TEE. Eight patients had left atrial myoma, two patients had right atrial myxoma, and one patient had right atrial leiomyosarcoma. There was no false negative and no false positive TEE diagnosis, yielding a 100% sensitivity and specificity of TEE in detecting atrial masses. TEE detected atrial masses in six (43%) patients, provided poor images in five (36%) patients, and failed to reveal atrial masses in three (21%) patients. The TEE diagnosis was confirmed by surgery and pathohistology in all patients. The ability of TEE to visualize both atria with great diagnostic accuracy makes it a very valuable procedure in the assessment of atrial masses.

Treatment of adult respiratory distress syndrome--our way.

From July 1991 to September 1992 the authors treated twenty-eight patients with proven adult respiratory distress syndrome (ARDS). In this paper five patients with ARDS accompanying septicaemia are presented. In this group of patients, elevated pulmonary artery pressure or pulmonary hypertension (PAH) could not have been caused by LV failure, as it was possible in remaining twenty-three patients with ARDS after open heart surgery, so the effect of prostaglandin E1 (PGE1) on pulmonary hypertension could be followed accurately. Moreover, ARDS after septicaemia carries the worst prognosis. All patients were admitted from other hospitals, they were intubated and mechanically ventilated. ARDS was diagnosed 4 to 7 days after the primary injury.

Minimally invasive coronary surgery--our experience.

Minimally invasive coronary artery surgery (MICS) has been defined as proceeding myocardial revascularization without cardiopulmonary bypass. Between January 1996 and August 1997, 19 patients (18 males, 1 female), aged 47-67 years (mean age 57.2 +/- 5.1 years), were operated on. All patients had single vessel coronary disease. In 11 (57.9%) patients, the operation was performed through median sternotomy, in 5 (26.3%) through left anterior small thoracotomy (the LAST procedure). In two (10.5%) patients, the operation began as a LAST, but conversion to median sternotomy was required due to lateroposition of the left anterior descending artery (LAD). In one (5.3%) patient, a minimal procedure was converted in to conventional cardiosurgical procedure with thrombendarterectomy and anastomosis of the left internal mammary artery (LIMA) to LAD. Anastomosis of LIMA to LAD was performed in 9 (47.4%) cases and of right internal mammary artery (RIMA) to right coronary artery (RCA) in four (21.1%) cases. In two (10.5%) cases, saphenous vein was used as a graft to RCA, and in four (21.1%) cases, to LAD. One (5.3%) patient died on the fourth postoperative day. One patient developed perioperative myocardial infarction, and one patient was reoperated on due to postoperative bleeding. Permanent pacemaker was implanted in one (5.3%) patient because of slow atrial fibrillation. The ischemic time was 8 to 25 minutes, and the whole procedure was completed in 90-175 minutes. Intensive care unit stay was up to 18 hours in 12 (63.2%) patients. The whole duration of hospitalization took from 7 to 14 days (mean 10.6 +/- 2.4 days). Minimally invasive coronary surgery is a safe and effective method in the surgical treatment of one-vessel coronary artery disease.

[Direct communication of the pulmonary artery with the left atrium]. / Izravni spoj plucne arterije s lijevim atrijem.

A rare communication between the right pulmonary artery and the left atrium in a 3.5-year-old girl is described. Cyanosis of a central type and a continuous murmur over the heart were presenting symptoms. Echocardiography revealed only excessive pulsations of the pulmonary artery, while catheterization pointed to an abnormal aneurysmal communication between the right pulmonary artery and the left atrium. At this point the O2 saturation was at the level of the left atrium. The communication was clinically classified as a type IV according to Nelson. After an unsuccessful attempt through a right thoracotomy, the ligature of this fistula has been performed in the second attempt through a median sternotomy and under complete extracorporeal circulation. Clinical course and review of literature of this rare anomaly of the heart are being presented.

[Surgical treatment of congenital obstruction of the left ventricular outflow tract]. / Kirursko lijecenje prirodene opstrukcije izlaznog dijela lijevog ventrikula.

This report presents the classification and all types of left ventricular outflow tract obstructions. The possibilities of operative therapies are surveyed as well. Results of surgical treatment in 34 patients with obstruction to left ventricular outflow are shown. The majority of patients underwent operation under extracorporeal circulation (84.4%), while the rest were operated by means of the inflow occlusion technique (14.7%). The obtained results were compared with those from the literature. The importance of echocardiographic evaluation of location of the left ventricular outflow tract obstruction and the appropriate choice of a surgical technique according to the patient's age are emphasized.

The importance of glucose-insulin-potassium with cardiopulmonary bypass prior to cardioplegic arrest in open-heart surgery.

The benefit of a high dose glucose-insulin-potassium (33% glucose, 80 mmol KCl, 120 units of insulin - 1 mL/kg) (GIK) with cardiopulmonary bypass support (CPB) prior to cardioplegic arrest in open-heart surgery has been evaluated in this article. Twenty non-diabetic patients (PTS) were selected upon their preoperatively impaired left ventricular ejection fraction (LVEF < 45%) and were divided into two groups. Group 1 was given GIK and 20 minutes of CPB prior to cardioplegic arrest; Group 2 was the control group with no GIK and no CPB support. Hemodynamics was measured prior to surgery, 30 minutes after weaning from CPB, and 12 and 24 hours postoperatively. There were less rhythm disturbances and need for intraoperative defibrillation in Group 1 (2:10 pts VS 8:10 pts in the Group 2). There were significantly higher values of cardiac index (CI) in Group 1 30 minutes after weaning from CPB (2.5 +/- 0.28 VS 2.11 +/- 0.25: p < 0.01), while there was no significant difference in late postoperative course. Left ventricular stroke work index (LVSWI) in Group 2 was significantly higher 12 hours after the surgery (38.35 +/- 8.93 VS 29.76 +/- 8.17:p < 0.05). At 30 minutes and 24 hours postoperatively there was no significant difference, but clinical difference was observed, probably due to necessary inotropic stimulation in Group 2. There was neither clinical nor statistical difference in right ventricular stroke work index (RVSWI) throughout the whole measurement. The authors emphasise the importance of GIK with CPB in myocardial protection in patients undergoing open-heart surgery.

[War injuries of the thorax]. / Ratne ozljede prsnog kosa.

Chest injuries are very common in war circumstances. Chest injury is commonly associated with other injuries of intrathoracic organs and development of shock, which has to be treated immediately. Our patients with war chest injuries are presented, along with our approach to the treatment of these injuries. "The conservative treatment" is stressed, with particularly importance of proper chest drainage, as a corner stone of proper and successful therapy. Shock treatment and prevention of atelectasis does present an unavoidable procedure of this type of therapy.

[Acute renal failure in heart transplantation]. / Akutno zatajenje bubrega u transplantaciji srca.

In this study the incidence and the development of acute renal failure (ARF) in heart transplant recipients is presented. Among the thirteen heart transplant recipients eight of them developed oliguric or nonoliguric ARF. Besides the known factors such as actual condition of the patient, kidney function, peri and post-operative compromised circulation, our results demonstrate the significance of postoperative cyclosporin concentration in combination with the use of other drugs. The results also show the importance of the way cyclosporin has been administrated. The parenteral route of appliance is connected with the greater risk of higher drug concentration in the plasma than the peroral one. In connection with this is the higher incidence of adverse reactions to cyclosporin given parenterally. In addition to ranitidine and captopril, which have been mentioned earlier, the findings of our study indicate that greater attention has to be paid to the treatment with ketoconazol given in combination with cyclosporin, since it results in decreased cyclosporin clearance. Other nephrotoxic drugs like amphotericin also increase the possibility of renal lesions. The incidence of acute renal failure in this group of patients is high. Our data suggest that the reasons for the development of ARF are multifactorial. These data further suggest that a reasonable way to solve nonoliguric form of acute renal failure is to maintain the "internal balance" and that it is not necessary to perform extracorporeal elimination of nitrogen substances, if there are no additional complications (i.e. gastrointestinal bleeding).(ABSTRACT TRUNCATED AT 250 WORDS)

[Aortico-left ventricular tunnel]. / Aorto-lijevoventrikulski tunel.

The boy was first admitted to the Department of Pediatric Cardiology at the age of 4 1/2 because of cardiac murmur diagnosed on the third day of life. A diastolic murmur of a grade 4/6, left ventricular hypertrophy as well as left aortal and ventricular dilatation were discovered. The findings showed a tendency of increase with time, but the patient had no symptoms. X-ray in the long axis view revealed a defect within the upper part of the interventricular septum immediately below the aorta, and dilated right coronary sinus. An invasive diagnostic method was undertaken, as well. The operative procedure was done with a total cardio-pulmonary bypass and hypothermia (29 degrees C). A tunnel from the anterior aortal wall through the outflow tract of the right ventricle to the left side of the heart was established intraoperatively. The defect was solved by a "sandwich" technique (two patch technique). Postoperative period was uneventful. A Doppler echocardiogram demonstrated the normal hemodynamic status of the patient without the left-to-right or right-to-left shunt and aortal insufficiency.

[The effect of implementation of a unit dose drug distribution system on drug consumption]. / Utjecaj primjene sustava raspodjele jedinicne terapije na potrosnju lijekova.

As an important drug consumer in Dubrava University Hospital, Department of Cardiac Surgery has been chosen for testing a new model of drug distribution system known as unit dose drug distribution system. During the first 39 weeks in 1996--comparative period, drugs were delivered from the Pharmacy to the Department of Cardiac Surgery in traditional way, known as floor stock system. Next 65 weeks, until the end of 1997--pilot study period, drugs were delivered directly from the Pharmacy to the patients, using unit dose drug distribution system. Consumption of drugs was measured every week by statistical unit DDD/100 hospital days (Defined Daily Dose) according to Anatomic-Therapeutic-Chemistry (ATC) classification of drugs. For statistical measurements, beside common arithmetic means, geometric means were used which are less sensitive to extreme values of drug consumption. During comparative period drug consumption was chaotic with great oscillations around mean value, while in pilot study period that process was without great oscillations around lower mean value and did not exceed the limits of process. Drug consumption was completely under control, so it was a predictable process. In the pilot study period total drug consumption was 39% less, while consumption of drugs from group C was 30% less. During comparative period group C makes 34%, while in the pilot study period it makes 38% of the total drug consumption. This model of drug distribution in hospital leads to a rationalization of drug consumption and great savings. The pharmacist-physician interactive role began to emerge as a direct result of these changes in the drug distribution system. Hospital pharmacist has become a visible member of health care team who is responsible for Quality of all medication-related activities and thus has taken opportunity for clinical pharmacy practice.

[Hemodynamic effects of amrinone, dobutamine and dopamine in the cardiac low output syndrome following open-heart surgery]. / Hemodinamski ucinak amrinona, dobutamina i dopamina u sindromu niskog minutnog volumena srca nakon kirurskog zahvata na otvorenom srcu.

Low heart stroke volume syndrome is clinically manifested with hypoperfusion of all body systems. Inotropic or mechanical support is applied. Acute heart failure is one of the most important complications after open heart surgery. Catecholamines have been up to non considered as a therapy of choice for the acute heart failure. Effectiveness of catecholamines could be limited with some side effects. Phosphodiesterase inhibitors promise a new therapeutic approach. PDE III primary act through phosphodiesterase inhibition which leads to a rise of aAPM levels. Thus they show positive inotropic and lusitropic effects, which could be monitored by occlusive pulmonary capillary pressure values. Amrinone is obviously superior to inotropic catecholamines.