Biomedical subjects

S Sack

Publications and source records attributed to S Sack.

62 records · Page 4Linked to original sources

PubMed1994

Effects of a new Na+/H+ antiporter inhibitor on postischemic reperfusion in pig heart.

We investigated the effects of a new compound (3-methylsulfonyl-4-piperidinobenzoyl) guanidine hydrochloride (HOE 694) known to inhibit the Na+/H+ exchanger in a porcine model of ischemia/reperfusion. Ischemia was induced by coronary occlusion (twice for 10 min, with a 30-min reperfusion interval) followed by a 4-h reperfusion period. Treated animals (n = 8) received HOE 694 as a bolus (7 mg/kg) 20 min before ischemia and subsequently as a continuous infusion (0.07 mg/kg) throughout the experiment. Control pigs (n = 11) received vehicle. Regional wall function (percentage of segment shortening, % SS) of the treated animals was significantly improved as compared with that of controls after the 4-h reperfusion period (74.1 +/- 2.5 vs. 50.9 +/- 5.4, p < 0.005). Ventricular fibrillation (VF) could be prevented completely in treated pigs but occurred in 9 of 11 control animals (p < 0.001). Ultrastructural changes after ischemia and reperfusion were moderate and slightly abnormal in controls but much milder and completely recovered in the treated group, respectively. The tissue content of high-energy phosphates did not show a significant difference between groups. Inhibition of the sarcolemmal Na+/H+ antiporter with HOC 694 is antiarrhythmic and diminishes myocardial ischemic cell injury by preventing Na+ overload.

Adenine Nucleotides↗

PubMed1994

[Therapy of cardiogenic shock in acute myocardial infarct].

Cardiogenic shock in acute myocardial infarction patients is the most common cause of in-hospital death. Various studies showed, that 60 to 100% of patients in cardiogenic shock will die, if no early reperfusion of their coronary artery could be established. The incidence of cardiogenic shock has decreased during the last years, most likely due to early thrombolytic therapy and administration of nitroglycerin. Reasons for cardiogenic shock are either necrosis of 40% or more of the left ventricular wall, right heart infarction, or complications which can be treated by the surgeon, like papillary muscle rupture, ventricular septal defect or rupture of the free ventricular wall. Diagnosis is based on clinical criteria, echocardiography, and on hemodynamic monitoring. The hemodynamic criteria for cardiogenic shock are a cardiac index of < 2.2/l, and an increased wedge pressure of > 18 mm Hg; additionally, diuresis is usually < 20 ml/h. Therapy can be divided into the following categories: a) pharmaceutical interventions to increase cardiac output like vasodilators or positive inotrope drugs; b) mechanical support systems; c) acute interventions with the aim of reperfusion; d) acute surgical interventions addressing complications like papillary muscle rupture, ventricular septal defect or rupture of the free ventricular wall. While steps a) and b) are able to stabilize the hemodynamical situation in patients with cardiogenic shock, they are rarely the definitive treatment. Point c), reperfusion of the coronary artery, can be divided in thrombolysis or acute PTCA. Thrombolysis failed to show a beneficial effect in most studies, either after intravenous or intracoronary application. On contrast, acute PTCA showed to be of great benefit in various studies with a technical success rate of 54 to 100% and a survival rate of patients from 58 to 100%. Thus, emergency PTCA is the treatment of choice in cardiogenic shock. Point d), surgical interventions can be divided in acute bypass grafting, which should be reserved for patients with severe multivessel disease, left main involvement, or failed PTCA. Furthermore, acute heart transplantation is effective, but will be possible in a minority of patients only. The last part of surgically manageable complications are surgery of papillary muscle rupture and ventricular septal defect. Results of early surgery in papillary muscle rupture or ventricular septal defects are much better than delayed interventions. Rupture of the free wall is usually a fatal event. In summary, the most successful therapy of cardiogenic shock is early emergency PTCA.(ABSTRACT TRUNCATED AT 400 WORDS)

Angioplasty, Balloon, Coronary↗

PubMed1993

Ischaemic preconditioning--time course of renewal in the pig.

OBJECTIVE: The aim was to examine whether ischaemic preconditioning can be renewed by a second cycle of brief coronary occlusions in pigs subjected to two different reperfusion intervals (1 h or 4 d). METHODS: Ischaemic preconditioning was induced by a cycle of two 10 min occlusions of the left anterior descending coronary artery separated by 30 min of reperfusion. Infarction was induced with a subsequent 1 h occlusion and a 2 h reperfusion period. There were four experimental groups: in group I (n = 5), a 30 min reperfusion was interposed after the preconditioning cycle prior to the sustained occlusion; in group II (n = 5), this time frame was extended to 1 h; in group III (n = 5), the preconditioning cycle was renewed 1 h after the first cycle; in group IV (n = 5), the second cycle was performed 4 d later. Control pigs (n = 5) were subjected to 1 h coronary occlusion and 2 h reperfusion without previous short occlusions. Infarct size was measured with p-nitro blue tetrazolium and was expressed as a percent of area at risk. RESULTS: The percent of the risk region infarcted was 69.9 (SEM 3.8)% for controls, 22.9 (3.5)% in group I (p < 0.001 v controls), 67.3 (5.2)% in group II, 66.3 (4.2)% in group III, and 17.9 (3.9)% in group IV (p < 0.001 v controls). Regional wall function measured with ultrasonic crystals deteriorated through the reperfusion intervals, indicating different underlying mechanisms for ischaemic preconditioning and myocardial stunning. CONCLUSIONS: Ischaemic preconditioning with two 10 min occlusions reduced infarct size resulting from a 60 min coronary occlusion when that was performed 30 min after the last short occlusion. This effect was lost after 1 h. Preconditioning could be renewed by a second cycle of brief coronary occlusion and reperfusion 4 d but not 1 h after the first cycle. These results suggest the release of a mediator from an exhaustible pool.

Animals↗

PubMed1992

Echocardiographic and angiographic evaluation of left ventricular function during percutaneous transluminal aortic valvuloplasty.

Transesophageal echocardiography was used to study the effect of the balloon inflation on left ventricular function in 20 patients with critical aortic stenosis undergoing balloon valvuloplasty. Balloon inflation caused an increase of end-diastolic (15% to 34%) and end-systolic (57% to 72%) left ventricular volume. Left ventricular wall stress increased from 30 +/- 10 x 10(3) dyn/cm2 at diastole and 121 +/- 40 x 10(3) dyn/cm2 at systole to 44 +/- 11 x 10(3) dyn/cm2 and 191 +/- 55 x 10(3) dyn/cm2, respectively, when the balloon was inflated (P less than 0.05). Turbulent regurgitant jet across the mitral valve increased from 15 +/- 2% to 25 +/- 3% during balloon inflation (P less than 0.01). Continued monitoring of left ventricular function after balloon deflation demonstrated prolonged enlargement of left ventricular volumes. Our data show that balloon inflation causes an increase of left ventricular volume and impairment of contraction. Increase of left ventricular wall stress--associated with a reduction of coronary blood flow, due to lower aortic pressure--could result in ischemic myocardial injury.

Aged↗

PubMed1976

Emotional adjustment of adolescents and young adults with cystic fibrosis.

Twenty-seven adolescents and young adults with cystic fibrosis were studied to evaluate the phychological impact of this chronic illness. At first glance, most patients appeared to function adequately on a daily basis. However, four sources of psychological stress, leading to emotional disturbance, were identified: altered physical appearance causing distorted body images and denial of sexuality, strained interpersonal relationships resulting in isolation and mental strain, conflicts in upbringing, and increased awareness of the future and of death. Guidelines for the physician treating these young adults and their families include: (1) encouragement for greater involvement by the patient's father; (2) assisting the mother to find outside interests and to allow more independence to the patient; (3) stressing communication about cystic fibrosis within the home; (4) emphasizing outside activity for each patient; (5) repeated discussions of the patient's concerns while emphasizing his strengths; (6) anticipation of problems, specific to cystic fibrosis, such as sterility in males; and (7) encouragement of interpatient communication.

Activities of Daily Living↗

PubMed1975

The two-professional marriage: a new conflict syndrome.

The two-professional marriage that begins during the period of preprofessional or professional training is apt to break down during the immediate postraining period. Reasons for this occurrence are discussed in the light of marital dynamics and adult developmental issues, with special emphasis on female professional role development.

Divorce↗

PubMedDate not supplied

Crystallization and preliminary X-ray diffraction analysis of UDP-N-acetylglucosamine enolpyruvyltransferase of Enterobacter cloacae.

Single crystals of UDP-N-acetylglucosamine enolpyruvyltransferase of Enterobacter cloacae have been grown by vapor diffusion using phosphate buffer as the precipitant. The crystals belong to the monoclinic space group C2 with a = 86.9 A, b = 155.9 A, c = 83.8 A, beta = 91.6 degrees. Assuming two monomers per asymmetric unit, the solvent content of these crystals is 63%. Flash-frozen crystals diffract to beyond 2 A resolution.

Alkyl and Aryl Transferases↗

PubMedDate not supplied

The structure of the nucleotide-binding site of kinesin.

Kinesin is a microtubule-based motor protein responsible for anterograde transport of vesicles and organelles in nerve axons and other cell types. The energy necessary for this transport is derived from the hydrolysis of ATP which is thought to induce conformational changes in the protein. We have solved the X-ray crystal structures of rat brain kinesin in three conditions intended to mimic different nucleotide states: (1) with ADP bound to the nucleotide-binding site, (2) with bound ADP in the presence of AIF(-)4, and (3) with ADP hydrolyzed to AMP by apyrase. In contrast to analogous cases observed in GTP-binding proteins or the muscle motor myosin, the structure of kinesin remained nearly unchanged. This highlights the stability of kinesin's ADP state in the absence of microtubules. Surprisingly, even after hydrolysis of ADP to AMP by apyrase a strong density peak remains at the position of the beta-phosphate which is compatible either with a phosphate or a sulfate from the solvent and appears to stabilize the nucleotide-binding pocket through several hydrogen bonds.

Adenine Nucleotides↗