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.

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.

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.

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 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.

[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.

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.

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.

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.