Biomedical subjects

Marek A Deja

Publications and source records attributed to Marek A Deja.

12 recordsLinked to original sources

PubMed2006

Diazoxide provides maximal KATP channels independent protection if present throughout hypoxia.

BACKGROUND: It is not clear what the optimal timing of diazoxide administration for cardioprotection in human myocardium is. We aimed to establish it. We next checked whether protection depended on adenosine triphosphate (ATP)-inhibited potassium (KATP) channels. METHODS: Isolated human right atrial trabeculae were subjected to 90-minute hypoxia and 120-minute reoxygenation in vitro, followed by adding 10(-4) M norepinephrine. Diazoxide (100 microM) was added (1) as a 10-minute preconditioning signal with 10-minute washout before hypoxia or (2) 10-minute pretreatment without washout before hypoxia or (3) throughout hypoxia or (4) 10 minutes before and throughout hypoxia or (5) during the first 20 minutes of reoxygenation only. In the control, no diazoxide was added. In another set of experiments, diazoxide (100 microM) was present throughout hypoxia in control, while we tried to inhibit its protective effect with glibenclamide (1, 10, 100 microM) or 5-hydroxydecanoate (100 microM). RESULTS: The presence of diazoxide throughout hypoxia improved recovery of contractility during reoxygenation, allowed for significant response to norepinephrine at the end of reoxygenation, prevented "ischemic contracture" development, and reduced release of troponin I to tissue bath during hypoxia. Adding diazoxide 10 minutes before hypoxia conferred significantly weaker protective effects in all the above respects. We failed to show a protective effect of diazoxide used as a preconditioning signal or during reoxygenation. Neither 5-hydroxydecanoate nor glibenclamide significantly influenced protective effects of diazoxide added during hypoxia. CONCLUSIONS: Administration of diazoxide throughout hypoxia provided maximal protective effect, suggesting that diazoxide may be an important adjunct to cardioplegic solution. The protection offered by diazoxide used during hypoxia appears independent of its influence on KATP channels.

Cardiotonic Agents↗

PubMed2006

Left internal mammary artery improves 5-year survival in patients under 40 subjected to surgical revascularization.

BACKGROUND: The population of young patients under 40 requiring coronary bypass surgery is characterized by an extremely and unusually rapid progression of coronary heart disease. The aim of the present study was to assess the clinical status and quality of life in these patients after surgery in relation to the type of conduit used to revascularize the left anterior descending artery (LAD). METHODS: One hundred seventeen patients under 40 (range, 30-40 years) underwent coronary artery bypass grafting (CABG) at our institution between 1991 and 1999. Ninety-one patients received LIMA to LAD graft (group A), and in 26 patients the saphenous vein was used to graft this vessel (group B). Seventy-eight patients (63 in group A and 15 in group B) were assessed after a mean time of 71 +/- 26 months. They were asked to fill out a questionnaire aimed at their subjective assessment of their quality of life as compared with their preoperative status. RESULTS: Five-year actuarial survival was higher in patients with LIMA to LAD graft (log rank test: P < .004). The functional status of patients in group B was significantly worse in comparison to group A: respectively, CCS 2.2 +/- 1.1 versus 1.5 +/- 0.7; (P = .02), NYHA 2.2 +/- 1.1 versus 1.3 +/- 0.5; (P = .002). Patients in group B more frequently required reinstitution of nitroglycerine treatment (93% versus 56%; P = .025). We failed to show differences between the 2 groups as far as subjective quality of life is concerned. In summary, 63% of patients perceived it to be worse, 29% to be better, and 8% felt it had not changed. CONCLUSION: The use of LIMA is crucial in patients undergoing CABG under the age of 40 in order to achieve the best possible surgical results. Quicker recurrence of coronary disease symptoms is observed when a vein is used to graft the LAD. It may reflect an earlier progress of atherosclerosis in venous grafts.

Adult↗

PubMed2005

Angiotensin-converting enzyme inhibitors reveal non-NO-, non-prostacycline-mediated endothelium-dependent relaxation in internal thoracic artery of hypertensive patients.

BACKGROUND: We have shown that treatment of hypertension with ACE inhibitors (ACE-I) enhances relaxation to acetylcholine in human internal thoracic artery (ITA) above this in nonhypertensive patients receiving no ACE-I. Present study assesses the endothelium-dependent responses mediated by neither NO nor prostacyclin in human ITA. METHODS: We compared isolated ITA rings from hypertensive patients treated with ACE-I (ACE-I group) with those from normotensive patients on no ACE-I (control group). Relaxation to acetylcholine was assessed before and after inhibition of NO synthase and cyclooxygenase with L-NMMA and indomethacin, respectively. RESULTS: The maximal relaxation in ACE-I group was 79+/-3.3% and was depressed by incubation with L-NMMA and indomethacin to 41+/-2.7% (p<0.001); pD(2)=7.7+/-0.1 vs. 7.4+/-0.8 (p=0.265). The maximal relaxation to acetylcholine was lower in the control group: 65+/-3.3% (p=0.01); pD(2)=7.5+/-0.1 (p=0.07). Incubation with L-NMMA and indomethacin produced contraction to acetylcholine with a maximum of 43+/-7% (p<0.001); pD(2)=5.3+/-0.3 (p<0.001). The area under the concentration-response curve for acetylcholine-induced relaxation in ACE-I group equaled [arbitrary units] 596+/-71 and after incubation with L-NMMA and indomethacin 281+/-40 (p=0.002). Estimated LNMMA- and indomethacin-resistant relaxation, absent in control group, accounted for 47+/-4% of relaxation to acetylcholine in ACE-I group. Estimated NO- and prostacyclin-mediated relaxation was higher in control group than ACE-I group: 628+/-74 vs. 315+/-47 (p=0.009). CONCLUSIONS: The results suggest that therapy with ACE-I improves endothelial function of hypertensive patients mainly by enhancing the endothelium-derived hyperpolarizing factor (EDHF) (and not NO)-mediated responses. It seems that it reveals measurable non-NO- non-PGI-mediated endothelium-dependent relaxation otherwise absent in conduit arteries.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2004

Diazoxide provides protection to human myocardium in vitro that is concentration dependent.

BACKGROUND: Diazoxide has been shown to confer significant myocardial protection in many experiments. This study was designed to assess its influence on the structural injury and functional recovery of human myocardium subjected to hypoxia/reoxygenation in vitro. METHODS: The isolated electrically driven human right atrial trabeculae, obtained during cardiac surgery, were studied. The tissue bath was oxygenated with 95% oxygen and 5% carbon dioxide, hypoxia being obtained by replacing oxygen with argon. The influence of diazoxide on atrial contractility was studied first. Next, the two trabeculae from one atrial appendage were studied simultaneously, adding diazoxide to the tissue bath 10 minutes before hypoxia in one, with another serving as a control. We tested 10(-4.5) mol/L and 10(-4) mol/L diazoxide in three sets of experiments testing 30, 60, and 90 minutes of hypoxia. We continued reoxygenation for 120 minutes (in 60-minute and 90-minute hypoxia experiments) and subsequently tested reaction to 10(-4) mol/L norepinephrine. Apart from continuous recording of the contraction force, we measured the troponin I release into the tissue bath after ischemia and reoxygenation. RESULTS: Diazoxide exerted a negative inotropic effect in human atrial muscle (pD(2)=3.96 +/- 0.18). Both concentrations of diazoxide studied resulted in better functional recovery of atrial trabeculae subjected to 30 minutes of hypoxia. With longer hypoxia, only the higher diazoxide concentration provided significant protection as assessed by contractility. After 120 minutes of reoxygenation, only diazoxide-treated muscle was viable enough to respond to norepinephrine. Only 10(-4) mol/L diazoxide resulted in lower troponin I release during hypoxia and reoxygenation. CONCLUSIONS: This study shows that diazoxide provides significant concentration-dependent protection against hypoxia/reoxygenation injury to human myocardium in vitro.

Cell Hypoxia↗

PubMed2004

Total arterial revascularization for multiple vessel coronary artery disease: with or without cardiopulmonary bypass.

BACKGROUND: To assess the usefulness of off-pump technique for more technically demanding coronary artery bypass procedures using exclusively arterial conduits. METHODS: Analysis of perioperative data of 324 consecutive patients in whom total arterial revascularization for multiple- vessel coronary artery disease was performed--181 cases on-pump and 143 cases off-pump. RESULTS: On average in the on-pump group 2.7 +/- 0.8 (range, 2-5) grafts per patient were constructed versus 2.4 +/- 0.7 (range, 2-4) grafts per patient in the off-pump group (P < .001). Of the total number of 490 anastomoses performed on-pump, 83 (17%) were side-to-side and of 349 anastomoses performed off-pump, 51(15%) were side-to-side, a nonsignificant difference (P = .4). The aorta was used as a site for proximal anastomosis of 1 or more arterial conduits in 105 patients (58%) who underwent on-pump surgery and in 57 patients (40%) who underwent off-pump surgery (P = .002). In the off-pump group, the right internal thoracic artery (RITA) was rarely (12%) routed through the transverse sinus to circumflex branches compared with the on-pump group (34%) (P = .017). RITA in off-pump patients was more often used to revascularize the anterior wall (47% versus 29%; P = .08). We observed no difference in mortality (1.7% versus 0%; P = .3), incidence of perioperative myocardial infarction (8.8% versus 7.7%; P = .8), stroke (1.7% versus 1.4%; P = .8), or atrial fibrillation (24% versus 19%; P = .3). We observed less inotropic support and less blood-product use in off-pump patients. CONCLUSION: Total arterial revascularization for multiple-vessel coronary artery disease may be safely performed off-pump. We observed tendency to somewhat smoother postoperative course in the off-pump group.

Adult↗

PubMed2004